Intermittent high-low oxygen system and high-low oxygen adaptation training method
By using a gas separation and detection device in an intermittent high-low oxygen system, dynamic control of the oxygen concentration in the output gas is achieved, solving the problem of unstable gas concentration in existing equipment, improving training effectiveness and safety, and making it suitable for high-low oxygen adaptation training equipment.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-12-15
- Publication Date
- 2026-04-03
AI Technical Summary
Existing high and low oxygen adaptation training equipment has difficulty in achieving precise control of the oxygen concentration of the output gas and is easily affected by environmental and equipment fluctuations, resulting in unstable training effects.
By using an intermittent high and low oxygen system, employing a gas separation unit and a gas output unit, combined with a gas detection device, the oxygen concentration of the target gas can be dynamically controlled to ensure that the oxygen concentration of the output gas is within the expected range. A gas separation membrane and an air compressor are used to separate oxygen-rich and nitrogen-rich gases, and a flow regulating valve and a mixing chamber are used to achieve precise adjustment of the gas ratio. A closed-loop feedback control system is used to maintain a stable gas concentration.
It achieves precise control over the oxygen concentration of the inhaled gas of the trainees, reduces the impact of environmental and equipment fluctuations, and improves the stability and safety of training effects. It is suitable for hypoxia adaptation training for anti-immunoaging and tumor growth inhibition.
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Figure CN121775413A_ABST
Abstract
Description
Technical Field
[0001] This disclosure relates to the field of medical device technology, and in particular to an intermittent hyper-hypoxia system and a hyper-hypoxia adaptation training method. Background Technology
[0002] Hypoxic conditioning refers to the endogenous protective mechanism that an organism or its cells develop after being subjected to one or more brief, non-lethal hypoxic stimuli. This mechanism can induce a series of beneficial physiological changes. Hypoxic conditioning is usually achieved using specialized equipment. Summary of the Invention
[0003] This disclosure provides an intermittent hyper-hypoxia system, a hyper-hypoxia adaptation training method, a hypoxia adaptation training device for anti-immunoaging, and a hypoxia adaptation training device for inhibiting tumor growth. By dynamically regulating the oxygen concentration of the output target gas, the system ensures that the oxygen concentration of the output target gas remains within the expected range, avoiding the influence of environmental factors, equipment fluctuations, or the breathing patterns of the trainees on the equipment output, thereby improving the accuracy of the equipment's oxygen supply.
[0004] In a first aspect, embodiments of this disclosure provide an intermittent high / low oxygen system, comprising: a gas supply device and a gas detection device.
[0005] The gas supply device includes a gas separation unit and a gas output unit connected in series; the gas separation unit is used to separate the initial gas into at least one enriched gas, the oxygen concentration of the enriched gas being different from that of the initial gas; the gas output unit is used to output a target gas in response to a control signal, the target gas including at least one enriched gas and at least one of the initial gas; the control signal is used to characterize the target oxygen concentration of the target gas.
[0006] The gas detection device is used to detect the actual oxygen concentration of the target gas output by the gas output unit. The gas output unit also adjusts the ratio of enriched gas to initial gas in the target gas output by the gas output unit according to reference indicators, including the target oxygen concentration and the actual oxygen concentration.
[0007] The intermittent hyper-hypoxia system disclosed herein achieves dynamic regulation of the oxygen concentration of the target gas through a closed-loop adjustment of "target oxygen concentration - actual oxygen concentration - target gas component ratio adjustment", ensuring that the oxygen concentration of the output target gas remains within the expected range, avoiding the influence of environmental and equipment fluctuations or the breathing of the training subjects, and improving the accuracy of equipment oxygen supply.
[0008] In some embodiments, the gas separation unit includes an air compressor, a separation chamber, and a gas separation membrane.
[0009] A gas separation membrane is disposed in the separation chamber, dividing the separation chamber into a first sub-chamber and a second sub-chamber. The first sub-chamber is connected to the output end of the air compressor and the first input end of the gas output unit, and the second sub-chamber is connected to the second input end of the gas output unit.
[0010] The air compressor's input is connected to the atmosphere, and its output is also connected to the third input of the gas output unit; the air compressor is used to pressurize air and output compressed gas; the initial gas is compressed gas.
[0011] In this process, the permeation rate of oxygen through the gas separation membrane is greater than that of nitrogen. A portion of the compressed gas entering the first sub-chamber passes through the gas separation membrane into the second sub-chamber to become oxygen-enriched gas, while the remaining portion remains in the first sub-chamber to become nitrogen-enriched gas. The enriched gas includes both nitrogen-enriched and oxygen-enriched gases.
[0012] In some embodiments, the gas output unit includes a mixing chamber and a plurality of flow regulating valves.
[0013] The first input terminal of the mixing chamber is connected to the first sub-chamber, the second input terminal of the mixing chamber is connected to the second sub-chamber, the third input terminal of the mixing chamber is connected to the output terminal of the air compressor, and the output terminal of the mixing chamber is used to output the target gas.
[0014] A flow control valve is configured to correspond to an input terminal of the mixing chamber. The flow control valve is used to regulate the flow rate of gas flowing into the mixing chamber through its corresponding input terminal. The opening degree of the flow control valve is related to the target oxygen concentration.
[0015] In some embodiments, the intermittent hyper-hypoxia system further includes a breathing device; the breathing device is connected to a gas output unit and is used to output a target gas from the gas output unit. A gas detection device is used to detect the actual oxygen concentration of the target gas output by the breathing device.
[0016] In some embodiments, the breathing apparatus includes: a breathing mask, and / or, a breathing chamber.
[0017] In some embodiments, the intermittent hyper-hypoxia system further includes a breathing device and a physiological parameter monitoring device. The breathing device is used to deliver the target gas to the trainee. The physiological parameter monitoring device is used to acquire the trainee's physiological parameters; the physiological parameters include at least one of the trainee's blood oxygen saturation, brain oxygen saturation, heart rate, and respiratory rate. Reference indicators also include physiological parameters.
[0018] In some embodiments, the oxygen concentration of the target gas is less than or equal to 38%.
[0019] Secondly, this disclosure provides a method for high and low oxygen training, comprising: periodically and alternately exposing the trainee to a first oxygen concentration gas and a second oxygen concentration gas with different oxygen concentrations; one alternation of the first oxygen concentration gas and the second oxygen concentration gas constitutes one cycle, 3 to 40 cycles are performed daily, and high and low oxygen adaptation training is performed 1 to 7 times per week for 1 to 15 weeks.
[0020] In each cycle, the training subjects were exposed to the first oxygen concentration gas for 4 to 10 minutes, and in each cycle, the training subjects were exposed to the second oxygen concentration gas for 4 to 10 minutes.
[0021] In some embodiments, the oxygen concentration of one of the first oxygen concentration gas and the second oxygen concentration gas is 10% to 20%, and the oxygen concentration of the other is 20% to 22%.
[0022] In some embodiments, the oxygen concentration of one of the first oxygen concentration gas and the second oxygen concentration gas is 10% to 20%, and the oxygen concentration of the other is 22% to 38%.
[0023] In some embodiments, the oxygen concentration of one of the first oxygen concentration gas and the second oxygen concentration gas is 20% to 22%, and the oxygen concentration of the other is 22% to 38%.
[0024] Thirdly, embodiments of this disclosure also provide a hypoxia adaptation training device for anti-immunoaging, comprising: an intermittent hyper-hypoxia system as provided in the first aspect of this disclosure. The intermittent hyper-hypoxia system is used to alternately output a first oxygen concentration gas and a second oxygen concentration gas with different oxygen concentrations, both of which are target gases as described above. The oxygen concentration of the first oxygen concentration gas and the second oxygen concentration gas with the lower oxygen concentration is 10%–18%, and the oxygen concentration of the other with the higher oxygen concentration is 20%–38%.
[0025] Fourthly, embodiments of this disclosure also provide a hypoxia adaptation training device for inhibiting tumor growth, comprising: an intermittent hyper-hypoxia system as provided in the first aspect of this disclosure. The intermittent hyper-hypoxia system is used to alternately output a first oxygen concentration gas and a second oxygen concentration gas with different oxygen concentrations, both of which are target gases as described above. The oxygen concentration of the first oxygen concentration gas and the second oxygen concentration gas with the lower oxygen concentration is 10%–18%, and the oxygen concentration of the other with the higher oxygen concentration is 20%–38%. Attached Figure Description
[0026] The accompanying drawings, which are incorporated in and form a part of this specification, illustrate embodiments consistent with this disclosure and, together with the description, serve to explain the principles of this disclosure.
[0027] To more clearly illustrate the technical solutions in the embodiments of this disclosure or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, for those skilled in the art, other drawings can be obtained based on these drawings without creative effort.
[0028] Figure 1 A structural block diagram of an intermittent high-low oxygen system provided in an embodiment of this disclosure; Figure 2 Another structural block diagram of the intermittent high-low oxygen system provided in this embodiment of the disclosure; Figure 3 A structural block diagram of a gas supply device provided in an embodiment of this disclosure; Figure 4 This is a schematic diagram of the structure of a gas supply device provided in an embodiment of the present disclosure; Figure 5 Data graphs of bone marrow cell subsets in aged mice from the 3-month-old normoxic control group, the 18-month-old normoxic control group, and the 18-month-old intermittent hypoxia training group. Figure 6 A graph showing data on thymocyte subsets in aged mice from the 3-month-old normoxic control group, the 18-month-old normoxic control group, and the 18-month-old intermittent hypoxia training group. Figure 7 Data graphs of lungs and spleen in aged mice from the 3-month-old normoxic control group, the 18-month-old normoxic control group, and the 18-month-old intermittent hypoxia training group; Figure 8 Data graphs of spleen and thymus in aged mice in normoxic, 2-week hypoxic training, 4-week hypoxic training, and 6-week hypoxic training groups. Figure 9 This is a graph showing data on lung metastases in the intermittent hypoxia preconditioning group and the normoxia control group; Figure 10 A statistical chart showing the survival rates of the intermittent hypoxia preconditioning group and the normoxic control group; Figure 11 A graph showing tumor volume data for the intermittent hypoxia preconditioning group and the normoxia control group; Figure 12 This is a graph showing experimental data for colorectal cancer. Figure 13 Comparison of tumor tissue samples before and after hypoxia adaptation training; Figure 14 A comparative graph showing the levels of CD8, GZMB, and Cleaved Caspase 3 cells before and after hypoxia adaptation training. Detailed Implementation
[0029] To better understand the above-mentioned objectives, features, and advantages of this disclosure, the solutions disclosed herein will be further described below. It should be noted that, unless otherwise specified, the embodiments and features described herein can be combined with each other.
[0030] Numerous specific details are set forth in the following description in order to provide a full understanding of this disclosure, but this disclosure may also be implemented in other ways different from those described herein; obviously, the embodiments in the specification are only some, and not all, of the embodiments of this disclosure.
[0031] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. The terminology used herein in the specification of this invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.
[0032] Unless otherwise specified, the reagents, methods, and equipment used in this invention are conventional reagents, methods, and equipment in this technical field. Unless otherwise specified, the reagents and materials used in the following examples are all commercially available.
[0033] This disclosure provides an intermittent hyper-hypoxia system.
[0034] In some embodiments, such as Figure 1 and Figure 2 As shown, the intermittent high / low oxygen system includes a gas supply device, which comprises a gas separation unit and a gas output unit connected in series. The gas separation unit separates the initial gas into at least one enriched gas, the oxygen concentration of which differs from that of the initial gas. The gas output unit outputs a target gas in response to a control signal, the target gas comprising at least one enriched gas and at least one of the initial gas; the control signal characterizes the target oxygen concentration of the target gas.
[0035] In the intermittent hyper-hypo-oxygen system provided in this disclosure, such as Figure 1 and Figure 2 As shown, the gas separation unit can separate the initial gas into one, two, or more enriched gases, each with a different oxygen concentration, and the oxygen concentration of each enriched gas is different from that of the initial gas. Target gases with different oxygen concentrations are obtained by mixing at least one enriched gas and / or the initial gas in different proportions. That is, by adjusting the ratio of enriched gas to the initial gas in the target gas output by the gas output unit, the gas supply device can output target gases with different oxygen concentrations.
[0036] For example, the composition of the target gas output by the gas output unit in the gas supply device includes, but is not limited to, the following: (1) Includes only the initial gas; (2) Includes only one enriched gas; (3) Includes at least one enriched gas and an initial gas mixture; (4) A mixture of gases including at least two enriched gases.
[0037] In summary, in the intermittent high and low oxygen system provided by some embodiments of this disclosure, a gas enrichment gas with a different oxygen concentration than the initial gas is obtained through a gas separation unit. The gas output unit can controllably output a gas with a target oxygen concentration (target gas) by adjusting the mixing ratio of the enriched gas and / or the initial gas (when only one of them is included, the mixing ratio is 100%; when two or more of them are included, the sum of the mixing ratios of the multiple gases with different oxygen concentrations is 100%). The oxygen concentration of the output target gas is continuously adjustable.
[0038] For example, the initial gas is air or compressed air. In this way, the gas supply device can obtain the initial gas from the atmosphere and separate it to obtain enriched gas, without the need for additional devices (such as high-pressure gas cylinders, chemical gasification devices, etc.) to supply the initial gas. This not only avoids the safety risks of storing external gas (such as high-pressure leakage, gas pollution), but also greatly simplifies the system structure.
[0039] When this intermittent hyper-hypoxia system is applied to hyper-hypoxia adaptation training equipment, the design of obtaining initial gas from the atmosphere by the gas supply device facilitates the lightweight and portable design of the hyper-hypoxia adaptation training equipment (such as home desktop equipment or mobile medical equipment), reducing the size and weight of the equipment, lowering manufacturing costs and the threshold for end-user use.
[0040] Taking compressed air as the initial gas as an example, the gas separation unit can separate the initial gas into nitrogen-rich gas and / or oxygen-rich gas.
[0041] Specifically, such as Figure 1 As shown, taking the gas separation unit for separating the initial gas into a enriched gas as an example, the target gas output by the gas output unit can be: only the enriched gas, or only the initial gas, or a mixture of the initial gas and the enriched gas.
[0042] It should be noted that the gas output unit is configured to prohibit the output of the enriched gas alone when the oxygen concentration of the enriched gas is lower than a preset low oxygen threshold; and when outputting the enriched gas, it must be mixed with another enriched gas or an initial gas with an oxygen concentration higher than the low oxygen threshold to ensure that the oxygen concentration of the output target gas is higher than the low oxygen threshold. In this way, the intermittent high / low oxygen system forcibly locks the oxygen concentration of the output target gas above the low oxygen threshold, fundamentally eliminating the possibility of outputting dangerous low-oxygen gas due to parameter missetting or program errors, thus achieving proactive safety protection.
[0043] Since the oxygen concentration of the enriched gas is different from that of the initial gas, the oxygen concentration of the target gas will be different when the target gas includes only one enriched gas or only the initial gas. At the same time, when the target gas is a mixture of the initial gas and the enriched gas, the oxygen concentration of the target gas will also be different when the enriched gas and the initial gas are mixed in different proportions.
[0044] For example, taking the enriched gas as a nitrogen-rich gas, the gas output unit can output only the initial gas to achieve the supply of normal oxygen gas; or, the gas output unit can output a mixture of nitrogen-rich gas and the initial gas to achieve the supply of low oxygen gas.
[0045] For example, taking oxygen-enriched gas as the enriched gas, the gas output unit can output only the initial gas to achieve the supply of normal oxygen gas; or, the gas output unit can output only oxygen-enriched gas to achieve the supply of high oxygen gas; or, the gas output unit can output a mixture of oxygen-enriched gas and initial gas to achieve the supply of high oxygen / normal oxygen gas (depending on the mixing ratio of oxygen-enriched gas and initial gas, the oxygen concentration of the target gas output after mixing oxygen-enriched gas and initial gas may fall within the normal oxygen range or the high oxygen range, which is specifically related to the low oxygen, normal oxygen, and high oxygen ranges set by the intermittent high and low oxygen system).
[0046] The term "normal oxygen gas" as used herein refers to a gas with the same or similar oxygen concentration as air. Furthermore, the term "normal oxygen gas" can also encompass other gases; for example, when the oxygen concentration of the output target gas is in the range of 20% to 22% (including extreme values), the target gas output by the gas output unit can be considered as normal oxygen gas.
[0047] It should be noted that the oxygen concentration range of the ambient gas described herein is only an exemplary description of one possible implementation of this disclosure, and can be adapted to suit specific needs in practical applications.
[0048] like Figure 2As shown, taking the example of a gas separation unit capable of separating an initial gas into two enriched gases (hereinafter referred to as the first enriched gas and the second enriched gas, respectively). Where the initial gas is air or compressed air, one of the first enriched gas and the second enriched gas may have a higher oxygen concentration than the initial gas, while the other has a lower oxygen concentration.
[0049] Based on this, the target gas output by the gas output unit can be: only the initial gas, or only the first enriched gas, or only the second enriched gas, or a mixture of the first enriched gas and the second enriched gas, or a mixture of the first enriched gas and the initial gas, or a mixture of the second enriched gas and the initial gas.
[0050] Since the oxygen concentrations of the first enriched gas, the second enriched gas, and the initial gas are all different, the oxygen concentration of the target gas will differ depending on whether it includes only the first enriched gas, only the second enriched gas, or only the initial gas. Furthermore, when the target gas is a mixture (target gas) obtained by mixing at least two of the initial gas, the first enriched gas, and the second enriched gas, the oxygen concentration of the target gas will also differ when the initial gas, the first enriched gas, and the second enriched gas are mixed in different proportions.
[0051] In summary, in the gas supply device, the initial gas is separated into at least one enriched gas by the gas separation unit, and the gas output unit adjusts the proportion of enriched gas and / or initial gas in the target gas based on the control signal carrying the target oxygen concentration information, so that the oxygen concentration of the target gas output by the gas output unit can be adaptively adjusted according to actual needs to achieve the output of the target gas with the target oxygen concentration.
[0052] The aforementioned intermittent hyper-hypoxia system can be applied to hyper-hypoxia adaptation training equipment. By outputting target gases with varying oxygen concentrations through the intermittent system, the equipment can provide either hypoxia or hyperxia adaptation training to the trainees. Multiple gas combination modes can be flexibly adapted to different training scenarios and populations.
[0053] For example, outputting a mixture of nitrogen-enriched gas and initial gas can achieve hypoxia training, while outputting only oxygen-enriched gas can achieve hyperxia intervention. The combination of the two can form an alternating "hypoxia-hypoxia" mode. The combination of initial gas and enriched gas can fine-tune the concentration of normoxic / hypoxia / hypoxia. Without changing the gas source or adding an extra gas storage module, it can meet the needs of multiple scenarios such as anti-aging for healthy people, conditioning for people with weak immune function, and auxiliary intervention for cancer patients, thus improving the versatility and applicability of the system.
[0054] Specifically, the gas output unit can achieve continuous adjustment of the target oxygen concentration by flexibly adjusting the mixing ratio of the enriched gas and the initial gas. Compared with the jump-change output of fixed oxygen concentration levels, it has a wider range of applications. Moreover, the switching between different oxygen concentrations of the target gas output can not only achieve jump-change switching (e.g., alternating output of target gas with oxygen concentration of 15% and target gas with oxygen concentration of 21%, with the oxygen concentration of the target gas jumping directly during the alternation), but also achieve gradual / gradual change switching (e.g., alternating output of target gas with oxygen concentration of 15% and target gas with oxygen concentration of 21%, with the oxygen concentration of the target gas gradually increasing to 21% or gradually decreasing to 15% during the alternation, thereby reducing the trainee's perception of changes in gas oxygen concentration). This provides core technical support for "personalized oxygen concentration intervention" in medical and health scenarios. When this intermittent high and low oxygen system is applied to high and low oxygen adaptation training equipment, it can ensure the stability and repeatability of training effects.
[0055] Based on the above embodiments, when the intermittent hyperoxia system is applied to hyperoxia training equipment, the low oxygen threshold, as the minimum safe oxygen concentration threshold preset by the system, is a key parameter to ensure the safety of the training subjects. The setting of this threshold is based on the physiological data of mammals (especially humans).
[0056] In a resting state, the minimum short-term oxygen concentration that a healthy adult can tolerate is about 10% to 12%. Therefore, the aforementioned low oxygen threshold can optionally be set to 10%, 11%, or 12%, etc.
[0057] Furthermore, to ensure the safety and comfort of long-term training and to avoid risks to trainees due to individual differences or cardiopulmonary insufficiency, the aforementioned low oxygen threshold can also be set at a level higher than the physiological limit, such as 12% to 16%. Based on this, the aforementioned low oxygen threshold can optionally be set to 12.5%, 13%, 14%, 15%, or 16%.
[0058] Based on the above, it can be understood that the low oxygen threshold set in the intermittent hyper-hypoxia system can be adaptively adjusted according to the specific training subjects (such as athletes, elderly patients, and animals). The above description of the low oxygen threshold and the specific values given are only illustrative examples of some possible implementations of this disclosure and are not intended to limit this disclosure.
[0059] In some embodiments, such as Figure 1 and Figure 2 As shown, the intermittent high / low oxygen system also includes a control device, which is communicatively connected to the gas supply device. The control device is used to issue commands to the gas supply device to control the gas supply device to output the target gas.
[0060] For example, the control device is communicatively connected to the gas output unit. The control device outputs a control signal, and the gas output unit outputs the target gas in response to the control signal from the control device. The control signal carries information about the target oxygen concentration of the target gas.
[0061] In some embodiments, such as Figure 3 As shown, the gas separation unit includes an air compressor, a separation chamber, and a gas separation membrane. The gas separation membrane is disposed within the separation chamber and divides the separation chamber into a first sub-chamber and a second sub-chamber. The first sub-chamber is connected to the output end of the air compressor and the first input end of the gas output unit, and the second sub-chamber is connected to the second input end of the gas output unit.
[0062] The air compressor's input is connected to the atmosphere, and its output is also connected to the third input of the gas output unit; the air compressor is used to pressurize air and output compressed gas; the initial gas is compressed gas.
[0063] In this process, the permeation rate of oxygen through the gas separation membrane is greater than that of nitrogen. A portion of the compressed gas entering the first sub-chamber passes through the gas separation membrane into the second sub-chamber to obtain oxygen-rich gas, while the other portion remains in the first sub-chamber to obtain nitrogen-rich gas.
[0064] The "enriched gas" mentioned above in "gas separation unit for separating initial gas into at least one enriched gas" includes nitrogen-enriched gas and oxygen-enriched gas.
[0065] like Figure 3 As shown, the gas separation membrane has different permeation rates for different gas components. Since the permeation rate of the gas separation membrane for oxygen is greater than that for nitrogen, the oxygen carried in the initial gas will form an oxygen-rich flow that preferentially permeates through the gas separation membrane into the second sub-chamber to form oxygen-rich gas, while the nitrogen carried in the initial gas will remain in the first sub-chamber to form nitrogen-rich gas.
[0066] By adjusting the output parameters of the air compressor, the intake pressure and flow rate of the compressed air entering the separation chamber can be regulated. This allows for control of the production ratio and concentration of nitrogen-rich and oxygen-rich gases within a certain range, providing an additional control dimension for the system. The system can optimize the production of raw material gas according to different target concentrations. In conjunction with the downstream mixing control, it can achieve high-precision and high-efficiency output within a safe oxygen concentration range (e.g., 10%–38%), avoiding the problem of low mixing efficiency at extreme concentration points.
[0067] For example, the air compressor and the separation chamber are connected by a connecting pipe.
[0068] In some embodiments of the present disclosure, the gas separation unit integrates an air compressor, a separation chamber, a gas separation membrane, and connecting pipelines into a compact unit. Compared with traditional nitrogen / oxygen generation technologies (such as pressure swing adsorption PSA and cryogenic methods), it eliminates the need for traditional large and complex tower or tank separation devices, resulting in a compact structure and high integration, which is conducive to the miniaturization of equipment.
[0069] In this way, when the intermittent hyper-hypoxia system is applied to hyper-hypoxia training equipment, the size and weight of the hyper-hypoxia training equipment can be greatly reduced, realizing the transformation of hyper-hypoxia adaptation training equipment from "large cabin equipment" to "desktop or portable equipment".
[0070] For example, the gas separation membrane may be a hollow fiber membrane module (including one, two or more hollow fiber membranes).
[0071] The system achieves separation of oxygen-enriched and nitrogen-enriched gases through membrane separation, offering rapid response and stable gas concentration output. Gas permeation within the membrane is an instantaneous and continuous physical diffusion process. Once the air compressor starts and provides stable pressure, nitrogen-enriched and oxygen-enriched gases are generated almost instantly, eliminating the cycle waiting time of PSA technology. This provides an immediate and stable source of raw materials for rapid and precise adjustment of the downstream gas output unit. The system can quickly respond to concentration change commands set by the training subjects (such as switching from normoxic to hypoxic oxygen), achieving rapid dynamic switching.
[0072] At the same time, separating oxygen-enriched gas and nitrogen-enriched gas through membrane separation is a physical sieving process that does not involve chemical reactions and does not produce new chemical substances or byproducts. This avoids damage to the respiratory tract and membrane components caused by oil or chemical pollution, ensuring the safety of high and low oxygen adaptation training and extending the service life of the high and low oxygen adaptation training equipment.
[0073] The separation of oxygen-rich and nitrogen-rich gases via membrane separation is a significant improvement over traditional PSA methods (which require frequent valve switching and cryogenic methods require extremely low temperatures). The entire process is quieter and involves no moving parts, resulting in significantly reduced operating noise and energy consumption. This greatly enhances the training experience, making training / treatment sessions that can last for tens of minutes and several weeks quieter and more comfortable. Furthermore, the lower operating costs meet the requirements of both medical and home-use equipment for long-term reliability and cost-effectiveness.
[0074] In some embodiments, such as Figure 4 As shown, the gas supply device also includes a multi-stage combined filtration device. The input end of the multi-stage combined filtration device is connected to the output end of the air compressor, and the output end of the multi-stage combined filtration device is connected to the first sub-chamber of the separation chamber.
[0075] After being pressurized by the air compressor, the air first enters the multi-stage combined filtration device. The multi-stage combined filtration device can remove particulate matter (such as dust particles), oil mist, moisture and volatile organic compounds carried in the compressed air. After being filtered by the multi-stage combined filtration device, the compressed air enters the separation chamber to ensure that the gas entering the separation chamber is clean and dry, and to avoid contamination or performance degradation of the gas separation membrane.
[0076] Based on the above embodiments, during the process of outputting the target gas in the intermittent high-low oxygen system, the actual oxygen concentration of the final output target gas may deviate from the expected oxygen concentration due to the influence of the components in the intermittent high-low oxygen system.
[0077] For example, during the process of separating the initial gas into enriched gas, the gas separation unit may be affected by factors such as the intake pressure of the compressed air entering the separation chamber, the temperature of the compressed air, the aging of the gas separation membrane, and blockage / leakage of the airflow pipeline, which may affect the stability of the ratio of nitrogen-enriched / oxygen-enriched flow.
[0078] To avoid the impact of external factors and equipment aging on the accuracy of the oxygen concentration of the target gas output by the system, in some embodiments, such as Figure 1 and Figure 2 As shown, the intermittent high and low oxygen system also includes a gas detection device, which is used to detect the actual oxygen concentration of the target gas output by the gas output unit.
[0079] The gas output unit is also used to adjust the proportion of enriched gas and initial gas in the target gas output by the gas output unit according to reference indicators; the reference indicators include the target oxygen concentration and the actual oxygen concentration.
[0080] The gas separation unit generates enriched gas with a different oxygen concentration than the initial gas. Combined with the real-time feedback and closed-loop regulation logic of the gas detection device, the gas output unit dynamically optimizes the mixing ratio of the enriched gas and the initial gas, thereby achieving controllable output of the target oxygen concentration gas (target gas).
[0081] By setting a gas detection device at the gas output end of the gas output unit, the actual oxygen concentration of the output target gas can be monitored in real time and compared with the preset value (target oxygen concentration). Once a deviation is detected, dynamic correction is achieved by adjusting the mixing ratio of the enriched gas and / or the initial gas, forming a closed-loop feedback control. This enables precise, stable and adaptive control of the oxygen concentration of the output target gas, overcomes internal and external disturbances, and reduces or even eliminates the deviation between the actual oxygen concentration and the expected oxygen concentration of the target gas.
[0082] It fundamentally overcomes the problem of unstable concentration output caused by internal and external factors such as fluctuations in inlet pressure / temperature, degradation of membrane component performance, changes in breathing tubing pressure drop, and differences in the breathing patterns of trainees. It ensures that throughout the entire training / treatment cycle, regardless of changes in the equipment's operating status, the oxygen concentration of the gas inhaled by the trainee remains within the preset safe and effective range, thus guaranteeing the consistency and repeatability of the treatment / training program.
[0083] The closed-loop control system has an extremely short response time (down to the millisecond level). Through rapid response and dynamic adaptation of the target gas oxygen concentration adjustment, it can quickly track and correct concentration deviations, meeting the requirements of intermittent high and low oxygen training to complete rapid and accurate switching of gas oxygen concentration within minutes. It ensures the switching speed and the stability of the concentration after the switch, enabling the equipment to strictly and reliably execute the preset complex high and low oxygen alternation program (such as 5 minutes of low oxygen / 5 minutes of normoxic cycle), ensuring that the concentration curve of each cycle is completely consistent with the preset plan, thereby accurately inducing the expected physiological adaptation effect.
[0084] Meanwhile, the gas detection device serves not only for control but also as a continuous safety monitor. If the actual concentration consistently and significantly deviates from the target value (e.g., output approaching pure nitrogen due to valve malfunction), the deviation signal can be identified by the system, immediately triggering safety alarms (such as audible and visual alarms) and protective interventions (such as switching to a safe mode and outputting high-oxygen gas). This shifts safety monitoring from reliance on external sensors and manual observation to a built-in, automated, core-parameter-based proactive defense, providing crucial additional safety for trainees (especially patients or the elderly), preventing the risk of hypoxia or hyperxia due to equipment malfunctions. This allows the device to be used in higher-risk clinical and home environments.
[0085] When key components such as gas separation membranes experience slow performance degradation due to long-term use (e.g., decreased separation efficiency), the closed-loop control system can automatically detect and compensate for this degradation. By fine-tuning the mixing ratio, it maintains the accuracy of the oxygen concentration in the output gas, reducing the need for frequent manual calibration or replacement due to slow changes in component performance. This significantly improves the long-term reliability, stability, and maintenance-free period of the equipment, and reduces the total life-cycle cost and maintenance complexity.
[0086] In summary, this intermittent high and low oxygen system achieves a leap from "trainee setting parameters → equipment mechanical execution" to "trainee setting goals → equipment intelligent realization and maintenance". Trainees do not need to worry about complex equipment status and external conditions. They only need to set the required gas oxygen concentration and training plan to obtain stable and reliable results, which greatly simplifies the operation process.
[0087] For example, the gas detection device includes an oxygen concentration sensor. The oxygen concentration sensor enables real-time detection of the oxygen concentration of the target gas output by the gas output unit.
[0088] For example, the control device described above is also communicatively connected to the gas detection device. The control device is also used to acquire detection data from the gas detection device and process the detection data.
[0089] In some embodiments, the intermittent hyper-hypoxia system further includes a breathing device. The breathing device is connected to a gas output unit and is used to output a target gas from the gas output unit. A gas detection device is used to detect the actual oxygen concentration of the target gas output by the breathing device.
[0090] For example, the input end of the breathing device is connected to the output end of the gas output unit.
[0091] For example, the breathing device can be a breathing mask or a breathing chamber. A breathing mask conforms to the human face to stably deliver a high-precision gas mixture to the training subject. A breathing chamber is used to contain the animal.
[0092] The breathing device breaks through the limitations of traditional single-scenario adaptability and adopts a dual-option structure of "breathing mask + breathing chamber" to achieve precise adaptation to different users. The dual-scenario adaptability design takes into account the differentiated needs of "humans" and "animals".
[0093] For breathing masks designed to fit the human body and face closely, fit optimization (such as flexible sealing edges) can ensure a tight fit to the facial contours, preventing gas leakage, reducing the mixing of outside air, and ensuring that the output high and low oxygen mixed gas concentration (such as any set value within the range of 0% to 38%) remains unchanged and stable during delivery. This ensures that the trainee can stably inhale the mixed gas at the set concentration and avoids oxygen concentration fluctuations caused by poor mask fit.
[0094] The specially designed breathing chamber allows for flexible adjustment of the internal space according to the body size of the trainee, and strictly follows the preset oxygen concentration switching program (such as a cycle of 5 minutes of low oxygen + 5 minutes of normal oxygen) to ensure that the trainee receives a stable and precise concentration of gas in a closed environment.
[0095] For example, the breathing chamber may be used to accommodate a human body or an animal (such as a rat, mouse, rabbit, monkey, etc.), and this disclosure does not limit it.
[0096] Furthermore, the gas detection device can be located inside the breathing apparatus. Alternatively, the gas detection device can also be located in the connecting pipeline between the breathing apparatus and the gas output unit.
[0097] By placing the gas detection device inside the breathing apparatus (such as a mask or breathing chamber), the actual oxygen concentration of the gas to be inhaled by the trainee is directly detected, achieving true end-to-end precision control. This ensures that the oxygen concentration of the target gas supplied to the trainee is at or close to the expected concentration, avoiding concentration attenuation or fluctuations caused by leakage, adsorption, dead space gas mixing, or animal respiratory disturbances when the target gas output from the gas output unit flows through the mask, interface, or breathing chamber. In this way, the aforementioned closed-loop control system can make feedback adjustments based on the most realistic inhalation concentration, ensuring that regardless of the breathing apparatus, the oxygen concentration ultimately delivered to the trainee's alveoli for gas exchange is the same as or close to the preset oxygen concentration. This achieves ultimate precision delivery of the target gas, which is the fundamental prerequisite for obtaining predictable and repeatable physiological effects.
[0098] It should be noted that the gas detection device may also be located in the mixing chamber or the gas flow pipeline, and this disclosure does not limit it in this respect.
[0099] In some embodiments, the gas detection device includes an oxygen concentration sensor. In other embodiments, the gas detection device also includes a gas flow meter.
[0100] The gas detection device is communicatively connected to the control device. Using an oxygen concentration sensor and a gas flow meter, the oxygen concentration and flow rate of the target gas are monitored in real time, and closed-loop feedback control is implemented via the control device (e.g., a microprocessor). The detection data from the gas detection device is transmitted to the control device in real time. If the oxygen concentration of the target gas deviates from the expected range, the control device can immediately trigger adjustment commands (e.g., controlling the gas output unit to adjust the mixing ratio of gases with different oxygenation concentrations in the target gas). Through real-time correction of the oxygen concentration of the target gas, a closed-loop control of "monitoring-analysis-correction" is formed, ensuring that the gas concentration remains stable within the target range throughout the entire training / treatment process, avoiding the impact of abnormal concentrations on therapeutic effects (e.g., insufficient oxygen concentration leading to weakened immune activation).
[0101] In some embodiments, the gas output unit includes a mixing chamber and a plurality of flow regulating valves.
[0102] The first input terminal of the mixing chamber is connected to the first sub-chamber, the second input terminal of the mixing chamber is connected to the second sub-chamber, the third input terminal of the mixing chamber is connected to the output terminal of the air compressor, and the output terminal of the mixing chamber is used to output the target gas.
[0103] A flow control valve is configured to correspond to an input end of a mixing chamber. The flow control valve is used to regulate the flow rate of gas flowing into the mixing chamber through the input end of its corresponding mixing chamber. The opening degree of the flow control valve is related to the target oxygen concentration.
[0104] Multiple flow control valves are used to control the flow rates of oxygen-enriched gas, nitrogen-enriched gas, and initial gas entering the mixing chamber. By employing a gas output unit architecture that includes a mixing chamber and multiple independent high-precision flow control valves, independent, precise, and coordinated control of the three gas streams—oxygen-enriched gas, nitrogen-enriched gas, and initial gas (compressed air)—is achieved.
[0105] By controlling the flow rates of nitrogen-enriched (low-oxygen feed), oxygen-enriched (high-oxygen feed), and air (reference and diluent) with three independent flow control valves, the system achieves three degrees of freedom of control. This allows a single device to cover all application scenarios from extreme hypoxia to therapeutic hyperoxia, greatly expanding the device's application scope and research value.
[0106] High-response flow control valves (such as proportional valves or high-speed switching valves) can adjust their opening within milliseconds based on control signals, thereby changing the instantaneous flow rate of each airflow. When periodic switching between different oxygen concentrations is required (e.g., from 21% normoxic to 13% hypoxic), the valve can act rapidly, redistributing the proportions of the three airflows, allowing the concentration of the gas output from the mixing chamber to transition quickly and smoothly to the new set value. This ensures the accuracy of timing and the sharpness of concentration switching in intermittent hyperoxic and hypoxic training programs.
[0107] The mixing chamber provides ample space and flow channels for the three airflows to mix thoroughly. Precise control of the inlet flow rate via valves ensures a constant proportion of gases entering the chamber. This avoids uneven mixing caused by flow fluctuations, and even when the outlet flow rate changes drastically due to the subject's breathing, the output concentration remains stable because the inlet proportion is locked in a closed loop. This guarantees the consistency of the output gas concentration in time and space (throughout the entire respiratory cycle), providing a stable and reliable gas environment for the subject and avoiding ineffective stimulation or safety risks caused by concentration fluctuations.
[0108] The three-source gas design provides redundancy and flexibility. For example, if a slight concentration drift occurs in one enrichment gas path due to changes in membrane performance, the system can compensate by dynamically adjusting the ratio of the other two gas streams, still accurately outputting the target concentration. This adds a "correction" dimension to concentration control, making the system independent of the absolute accuracy of any single path. This significantly improves the long-term reliability of the system, reduces over-reliance on the output accuracy of the upstream gas separation unit, extends the effective life of key components (such as the gas separation membrane), and enhances the overall reliability of the equipment.
[0109] This multi-input, independently controllable structure provides the physical platform for backend intelligent control algorithms (such as PID, fuzzy control, and even machine learning algorithms) to function. The PID algorithm can calculate the optimal combination of opening degrees for the three valves based on real-time feedback from the gas detection device and signals from the physiological parameter monitoring device, enabling complex control strategies for concentration, flow rate, and even delivery mode. Upgrading the equipment from "manual / fixed program adjustment" to "closed-loop intelligent adjustment" lays a solid hardware foundation for realizing personalized adaptive hyper- and hypoxic treatment programs based on individual physiological responses.
[0110] For example, the gas detection device also includes multiple gas flow meters. Each input end of the mixing chamber is equipped with a gas flow meter, which measures the flow rate of different gases (enriched gas, initial gas, etc.) entering the mixing chamber through each input end.
[0111] By integrating high-precision gas flow meters at each gas input end (nitrogen-enriched gas, oxygen-enriched gas, compressed air) in the mixing chamber, direct, real-time, and independent measurement of the flow rate of each raw material gas is achieved. A dual closed-loop control system of "flow monitoring-concentration detection" is constructed to realize "feedforward-feedback" composite control, which greatly improves the dynamic response speed and steady-state accuracy of the system.
[0112] The flow meter provides real-time flow data for each airflow, forming a feedforward control channel. The control device can quickly calculate the estimated opening of each valve based on the target concentration and execute the calculation immediately. Simultaneously, a concentration sensor located at the target gas output provides feedback signals to finely correct minor errors in the feedforward control. Compared to a simple concentration feedback closed loop (adjusting only after a deviation is detected), the composite control can proactively compensate for deviations before they occur, especially for rapid disturbances caused by upstream pressure fluctuations or sudden changes in the trainee's breathing. This results in faster adjustment of the oxygen concentration of the target gas, smaller overshoot, and less steady-state fluctuation, maintaining stable inhaled concentration throughout the entire process of changes in the trainee's breathing rhythm.
[0113] Each flow meter continuously monitors the flow rate in its corresponding gas path. Based on this data and valve opening commands, the control device performs cross-validation and logical judgment to enhance system safety and reliability. If the flow meter reading in a certain path is significantly inconsistent with the valve opening command (e.g., valve jamming, pipeline blockage / leakage), the system can immediately identify which path is malfunctioning and trigger a precise alarm.
[0114] For example, when set to output low oxygen, if the oxygen enrichment flow meter unexpectedly detects a significant flow rate, the system can determine that a valve malfunction has caused the introduction of hazardous gas, immediately cut off the gas supply, and trigger an alarm. This elevates the system's reliability from "preventing concentration errors" to "preventing malfunctions" and "rapidly locating the source of the malfunction," providing a deeper level of protection for the safe operation of medical equipment and facilitating rapid repair by maintenance personnel.
[0115] Under the premise of stable performance of the gas separation unit, there is a theoretical relationship between the flow rate and concentration of each enrichment gas path. By long-term monitoring of the actual flow rate of the enrichment gas path under the same valve opening, the performance changes of the gas separation membrane (such as the decrease in gas production efficiency due to aging) can be indirectly inferred. The system can establish a flow rate baseline, and when a trend deviation is detected, it can prompt the training object to perform preventive maintenance or initiate a self-calibration program to avoid slow performance degradation that will eventually affect output accuracy. This realizes predictive maintenance of the equipment, changing "repair after failure" to "intervention before performance degradation", which greatly improves the long-term availability of the equipment and reduces the risk of unexpected downtime.
[0116] Precise data on the flow rates of each gas path is fundamental for in-depth analysis of system status, establishment of accurate mathematical models, and implementation of advanced control strategies (such as Model Predictive Control, MPC). Algorithms can more accurately understand the dynamic relationship between "valve action - flow rate change - concentration change," thereby making better predictions and control decisions. This transforms the equipment from a tool executing preset programs into an intelligent system capable of learning, adapting, and optimizing, enabling truly personalized, adaptive high- and low-oxygen training that is "tailored to the individual and adapts to the time."
[0117] In some embodiments, the intermittent hyperoxia system further includes a physiological parameter monitoring device. The physiological parameter monitoring device is used to acquire the physiological parameters of the training subject; the physiological parameters include at least one of the subject's blood oxygen saturation, brain oxygen saturation, heart rate, and respiratory rate. Reference indicators also include physiological parameters.
[0118] For example, the physiological parameter monitoring device collects key physiological indicators of the training subjects in real time, including but not limited to in-depth indicators such as blood oxygen saturation (SpO2), brain oxygen saturation (rSO2), heart rate variability (HRV), and immune indicators (CD8+ T cell ratio).
[0119] This design gives the system strong compatibility and scalability: on the one hand, it can dynamically adjust the gas combination and concentration ratio according to the physiological state of the training subjects (such as immune cell activity and oxygen partial pressure in the tumor microenvironment) to achieve closed-loop control of "physiological indicators-oxygen concentration"; on the other hand, it can adapt to the personalized needs of different disease intervention and health management scenarios by increasing or decreasing the types of enriched gases and adjusting the mixing ratio range, avoiding the limitations of the "one-size-fits-all" approach of traditional equipment.
[0120] By integrating physiological parameter monitoring devices and incorporating multimodal physiological parameters into the closed-loop control reference indicators, a fundamental leap has been achieved from "open-loop stimulation based on preset gases" to "closed-loop treatment based on physiological feedback." The system no longer applies a fixed concentration-time protocol to all training subjects; instead, it dynamically adjusts the target gas concentration based on real-time indicators such as blood oxygen saturation (SpO2) and heart rate variability (HRV), enabling intelligent adjustment of high and low oxygen adaptation training programs.
[0121] For example, when the SpO2 of a training subject is detected to be below a preset safety threshold (e.g., 90%), the system will immediately and automatically increase the output oxygen concentration, regardless of the current program, to prevent potential hypoxia risks. This is especially suitable for cancer patients or the elderly with poor cardiopulmonary reserve. Based on feedback from brain oxygenation (rSO2) or immune indicators (e.g., post-treatment cycle testing), the system can automatically optimize the intensity of the next training session (e.g., the difference between high and low oxygen concentrations, alternation frequency) to find the optimal "dosage" for the individual. This upgrades the traditional "one-size-fits-all" training model to a personalized adaptive treatment approach, actively seeking and locking in the most effective stimulation scheme for the individual while ensuring safety, greatly improving the success rate and efficiency of treatment.
[0122] By monitoring deep biomarkers directly related to the final therapeutic effect (such as immune indicators: CD8+ T cell ratio), the process control of hyperoxia training is linked to the therapeutic goal in real time. In animal experiments or future companion diagnostics, if the activation of specific immune cell subsets is not as expected, the system can automatically adjust the concentration or timing of hypoxia / hyperoxia to stimulate the target pathway in a stronger or gentler manner. This transforms the device from a mere treatment executor into a treatment exploration and validation platform. It not only implements treatment but also scientifically verifies the effectiveness of treatment through real-time or periodic physiological feedback, intelligently guiding the direction of treatment and supporting clinical research and the development of new therapies.
[0123] Integrating multiple parameters such as blood oxygen, brain oxygen, heart rate, and respiratory rate, a comprehensive vital sign assessment matrix is constructed. A normal single indicator (such as blood oxygen) does not guarantee absolute safety. Multi-parameter cross-validation (e.g., normal blood oxygen but a sharp decrease in heart rate variability (HRV) or an abnormally rapid increase in respiratory rate) can more sensitively and specifically detect physiological stress or potential discomfort in users, offering far greater early warning value than single gas concentration monitoring. This provides hospital-level safety assurance for high-risk users (such as critically ill patients). The system can identify abnormal patterns based on complex algorithms, providing early warnings or interventions before users experience significant discomfort, thus maximizing safety.
[0124] All physiological parameters and corresponding treatment parameters (gas concentration, time) are recorded synchronously and continuously, forming a complete digital therapy log. This provides doctors / researchers with a solid data foundation for evaluating efficacy and adjusting treatment plans, making the treatment process completely transparent and quantifiable. It also creates a visualized health record for users / patients, intuitively showing the physiological improvements brought about by treatment (such as increased HRV and decreased resting heart rate), enhancing treatment confidence and compliance. The massive amount of "treatment parameter-physiological response" data accumulated by the product provides reliable data references for optimizing algorithms and developing new applications.
[0125] This system fully realizes an intelligent closed loop of "perception-analysis-decision-execution." It goes beyond simply responding; it understands the physiological state of the training subject, forming an adaptive life regulation system. It dynamizes static medical devices and activates passive treatment processes, providing programmable and interactive intelligent hardware solutions for chronic disease management, rehabilitation medicine, and anti-aging. The device possesses biosensing and intelligent decision-making capabilities, transforming treatment from an externally applied operation into a continuous dialogue with the user's body.
[0126] In some embodiments, the oxygen concentration of the target gas is less than or equal to 38%.
[0127] The adjustable oxygen concentration of the target gas output by the intermittent high-low oxygen system is 0% to 38%.
[0128] For example, the intermittent high and low oxygen system may include multiple operating modes, and the gas output unit is used to output target gas with different oxygen concentrations in different operating modes.
[0129] For example, the intermittent high-low oxygen system operates in the first working mode, with the gas output unit alternately outputting low-oxygen gas and normal-oxygen gas; or, alternately outputting low-oxygen gas and high-oxygen gas.
[0130] For example, the intermittent high-low oxygen system operates in the second working mode, with the gas output unit alternately outputting normal oxygen gas and high-oxygen gas.
[0131] For example, the oxygen volume percentage is 0% to 20% during low oxygen output and 30% to 38% during high oxygen output.
[0132] Prolonged or improper inhalation of excessively high concentrations of oxygen (>50%) may lead to oxygen toxicity, damaging the lungs and central nervous system. For target user groups such as cancer patients and the elderly, whose bodies may be in a relatively vulnerable state, their tolerance to high concentrations of oxygen requires more careful assessment. The gas supply device provided in this disclosure sets the upper limit of the oxygen concentration of the output gas to 38%, actively limiting the oxygen concentration of the output gas within a mild range, ensuring that the device remains within a relatively safe concentration range in all preset treatment and training programs (such as intermittent hyperoxia).
[0133] In conjunction with the above embodiments, in some embodiments, the control device includes a central processing unit, which is communicatively connected to various functional modules in the intermittent hyper-hypoxia system (e.g., gas supply device, gas detection device, and physiological function monitoring device, etc.) to issue instructions to each functional module and collect and process data.
[0134] For example, the central processing unit includes: a control unit, an arithmetic unit, a storage unit, a data bus, an address bus, registers, and a floating-point arithmetic unit; the control unit and the arithmetic unit work together, and the efficiency is improved by combining high-speed cache; the data / address bus enables communication between modules, and together they complete instruction execution and data processing tasks.
[0135] By introducing an integrated central processing unit (CPU), which includes core components for control, computation, storage, and communication, a unified, efficient, and scalable intelligent control platform is constructed. This achieves a qualitative leap from mechanical linkage to an intelligent system. The CPU rapidly acquires real-time data from gas detection devices (concentration), multiple flow meters (flow rate), and physiological parameter monitoring devices (blood oxygen, heart rate, etc.) via a data / address bus. Leveraging the powerful computing capabilities of its arithmetic and floating-point units, it can run complex control algorithms (such as multivariable PID and model predictive control) within milliseconds, simultaneously processing multiple information sources including concentration deviation, flow feedforward, and physiological feedback, and calculating the optimal control commands for multiple flow regulating valves in real time. This ensures that the entire system can achieve a rapid, accurate, and coordinated response under dynamically changing respiratory disturbances and user physiological fluctuations, stably maintaining the target oxygen concentration at the design value.
[0136] The cache and storage units enable the system to cache real-time data streams and store a large amount of preset treatment plans, user historical data, and device operation logs. By analyzing the stored user historical physiological data, the CPU can optimize subsequent treatment parameters, enabling personalized iteration of the treatment plan and providing the necessary hardware support for running more complex algorithms (such as machine learning-based individual efficacy prediction and abnormal pattern recognition). This upgrades the device from a tool that executes fixed programs to an intelligent terminal capable of learning, remembering, and optimizing, laying the hardware foundation for true digital therapy and long-term health management.
[0137] Through a unified data / address bus and communication protocol, the central processing unit (CPU) acts as the core hub, exchanging standardized instructions and data with all functional modules (gas supply, detection, physiological monitoring, etc.). Each functional module can be developed, tested, and replaced independently, as long as it adheres to the unified communication interface, reducing system complexity. The CPU can monitor the communication status and data integrity of each module, quickly locate faulty modules, and may implement isolation or safe degraded operation, greatly improving the overall system's engineering reliability, maintainability, and upgradeability.
[0138] The central processing unit (CPU) is the carrier of local intelligence within the device and also serves as the gateway for interaction with the remote data management platform. It can preprocess, compress, and encrypt data locally before uploading it to the cloud. Simultaneously, it can securely receive and execute software updates, new treatment algorithms, or ad-hoc doctor instructions from the cloud, realizing an "edge-cloud collaborative" intelligent healthcare model. The device can operate independently and securely offline, while also gaining unlimited computing expansion and medical support through cloud connectivity, enabling continuous evolution of its performance and service capabilities.
[0139] The control unit works in tandem with the computing unit to handle task scheduling, interrupt response, and resource allocation for the entire system. It can simultaneously process real-time control (high priority), user interaction (touchscreen operation), data recording, and communication tasks, ensuring the absolute priority of the control loop while providing a smooth human-computer interaction experience. This ensures that the system remains stable and smooth even under complex operating conditions, preventing core treatment functions from being affected by interface lag or background task blocking, thus enhancing the product's professionalism and user trust.
[0140] In some embodiments, the intermittent hyper-hypoxia system also includes a remote data management platform, which ensures experimental safety and data security through remote monitoring and cloud analysis.
[0141] In some embodiments, the intermittent hyper-hypoxia system further includes a communication device, which includes a GSM communication module and / or a system communication module. The communication device is used to establish communication connections between the various functional modules in the intermittent hyper-hypoxia system.
[0142] For example, GSM communication supports voice, SMS and data transmission, enabling the widespread application of digital mobile communication in hyper-hypoxia training instruments and forming the basis for building remote data management platforms.
[0143] By integrating a communication device with mobile communication modules such as GSM, high-speed, reliable, and wireless data transmission both inside and outside the device is achieved, constructing a collaborative intelligent architecture of "end-edge-cloud". The GSM module utilizes mature mobile communication networks (4G / 5G) to transmit device operating data (gas concentration, flow rate) and the user's core physiological parameters (blood oxygen, heart rate) in real-time with encryption to a remote data management platform or designated medical personnel terminals. This eliminates reliance on local area networks such as Wi-Fi, enabling continuous data reporting from anywhere with cellular signal (home, community, remote areas), providing a crucial remote lifeline for outpatient treatment (such as home rehabilitation and the home phase of clinical trials). Medical personnel can remotely monitor treatment safety and adherence, and immediately intervene via SMS or telephone in case of abnormal data (such as persistently low blood oxygen levels), achieving borderless medical-grade monitoring and greatly expanding the device's application scenarios and security.
[0144] Through GSM data channels, device manufacturers or healthcare service providers can securely push firmware updates, new treatment algorithms, or personalized treatment plans for specific users to the devices. This allows the device's functionality and efficacy to continuously evolve without requiring users to return to the factory or for professionals to visit the device. Doctors can remotely adjust the training parameters on the device based on the user's latest assessment results. This transforms medical devices from "factory-defined" fixed products into "growable and customizable" service terminals, not only extending the product's technological lifecycle but also enabling the remote implementation of precise treatment plans after the separation of diagnosis and treatment.
[0145] All desensitized treatment data and physiological response data generated by networked devices can be automatically aggregated to the cloud data center, realizing the automatic and standardized collection of multi-center, large-sample clinical research data. This avoids the errors and inefficiencies of traditional paper records or manual data export, greatly accelerating the scientific research process and clinical translation in this field, enabling rapid verification of the efficacy of hyperoxia training in different populations, optimization of treatment parameters, and discovery of new biomarkers.
[0146] The equipment can upload data such as self-test logs and the operating status of key components (e.g., membrane pressure differential, valve response count). The server can analyze this data to identify potential fault risks in advance (e.g., filter clogging, sensor drift) and send maintenance reminders to users or service centers. This transforms "post-failure maintenance" into "predictive maintenance," greatly improving equipment availability and user satisfaction, and reducing the risk of sudden equipment downtime to continuous treatment.
[0147] Through integrated SMS or data channels, the platform can send treatment reminders and health education information to patients and receive simple feedback from them, enhancing patients' treatment compliance and sense of participation, forming a lightweight closed-loop communication between doctors and patients, and improving the overall treatment experience and management efficiency.
[0148] In some embodiments, the intermittent hyper-hypoxia system further includes a human-machine interface device, which includes a display device, a touch screen, and control knobs. The display device is communicatively connected to the gas detection device and the parameter monitoring device.
[0149] The trainees set the target oxygen concentration through the human-machine interface. The system dynamically controls the mixing ratio of nitrogen-rich airflow, oxygen-rich airflow and bypass air (compressed air without membrane separation) through a high-precision flow regulating valve, which can achieve low oxygen output of 0% to 20% and high oxygen output of 30% to 38%.
[0150] The trainees set the target oxygen concentration through the human-machine interface. The system dynamically controls the mixing ratio of nitrogen-rich airflow, oxygen-rich airflow and bypass air (compressed air without membrane separation) through a high-precision flow regulating valve, which can achieve low oxygen output of 0% to 20% and high oxygen output of 34% to 38%.
[0151] By integrating a display device and connecting it to the core monitoring modules (gas and physiological parameters), a unified control and monitoring center with centralized information, intuitive interaction, and decision support is constructed. The display screen simultaneously and clearly shows gas control parameters (target oxygen concentration, actual output concentration, and flow rate of each gas path) and physiological monitoring parameters (blood oxygen saturation, brain oxygen, heart rate, etc.). This achieves full parameter transparency and status visualization of the treatment process, enhancing trust and a sense of control, transforming the "black box" operation of the equipment into a "glass box" demonstration. Users and doctors can clearly see "what the set values are," "what the actual output is," and "what the user's physical response is." Operators can confirm in real time whether the equipment accurately executes medical orders, and users can intuitively perceive the correlation between their own physiological changes and treatment, thereby improving treatment confidence and compliance.
[0152] Users or doctors can directly set target oxygen concentrations, select preset programs, and adjust training durations on the device via input methods such as touchscreens or knobs. This simplifies complex multivariate control (which requires adjusting multiple valves) to operations targeting a single clinical goal (such as "setting 13% hypoxia"). The system automatically completes all calculations and valve controls in the background, greatly reducing the barrier to entry and professional training costs.
[0153] The display device, incorporating intelligent algorithms, provides high-priority visual alerts for abnormal states. For example, when blood oxygen saturation falls below a safe threshold, the relevant area on the interface turns red and flashes, while a clear warning message pops up. This delivers warning signals from gas detection and physiological monitoring devices to on-site personnel in the most direct and easily noticeable way. It adds a powerful, vision-based proactive warning barrier to training safety. Even if personnel are not constantly monitoring the data details, they can immediately recognize the risk through the prominent interface changes, facilitating timely intervention.
[0154] The display device provides a historical data curve review function, showing the changing trends of gas concentration and physiological parameters in single or multiple training sessions. Doctors or researchers can directly observe the user's physiological response patterns (such as the trend of heart rate changes during hypoxia) on the device without relying on data exported from a back-end computer, providing data support for real-time evaluation and on-site adjustments to the treatment plan. Doctors can optimize the parameters for the next round of training on the spot based on the response to the previous round, achieving an efficient "evaluation-adjustment" cycle.
[0155] The display device is the final point of convergence for information from the gas control closed loop and the physiological monitoring closed loop. It is not only a "display" but also a window showcasing the collaborative achievements of the entire intelligent system. The stable curves and coordination parameters it presents intuitively demonstrate the technical success of this invention in deeply integrating precise gas supply with physiological feedback, thereby enhancing the product's professional image and user experience.
[0156] The intermittent hyperoxia system described above can be used in humans and animals. The hyperoxia adaptation device is designed based on prior theoretical research, with hyperoxia modes tailored to different disease states considering clinical uncertainties. It integrates a system for monitoring physiological parameters such as tissue physiological parameters and brain oxygenation data, and is supported by telemedicine. It boasts advantages in integrated innovation and guaranteed safety, exhibiting high stability and repeatability, making it easy to promote clinically. The instrument also has data recording, storage, and analysis functions, allowing for long-term evaluation and optimization of the effects of hyperoxia adaptation.
[0157] The system employs a PID control algorithm to achieve precise and rapid adjustment of oxygen concentration, ensuring that the system can dynamically switch between different oxygen concentrations in a short period of time. Simultaneously, a multi-parameter integrated sensor system is developed to monitor key physiological indicators such as blood oxygen saturation (SpO2), cerebral oxygen saturation (rSO2), and heart rate variability (HRV) in real time. Furthermore, a cloud platform system with telemedicine capabilities is built to enable real-time transmission, cloud storage, and intelligent analysis of treatment data, providing data support for clinical decision-making.
[0158] Compared with traditional instruments, it has the characteristics of low cost, small footprint, low consumption, and wide applicability. It also has disease model conditions, physiological monitoring indicators and telemedicine system, which can be used for disease prevention and control.
[0159] In terms of software systems, an adaptive control system based on machine learning algorithms dynamically adjusts oxygen concentration output by analyzing physiological parameters such as patient blood oxygen saturation and heart rate variability in real time, thereby achieving intelligent regulation of the treatment plan. Secondly, a structured treatment database system is constructed, integrating multiple clinically validated pre-set treatment plans, and a personalized treatment plan design module is developed to support doctors in customizing treatment parameters based on individual patient differences.
[0160] When this intermittent hyper-hypoxia system is used in hyper-hypoxia adaptation training equipment, it must strictly follow medical device software development specifications. The equipment needs to complete ISO13485 quality management system certification and electromagnetic compatibility (EMC) testing to ensure system stability and reliability.
[0161] In practical use, hyperoxia modes can be formulated based on prior theoretical research. Parameter settings can be adjusted for different disease states, taking into account clinical uncertainties. The instrument integrates physiological parameters of body tissues and brain oxygenation data, and is supported by telemedicine. It boasts advantages of integrated innovation and guaranteed safety, exhibiting high stability and repeatability, making it easy to promote clinically. The instrument also has data recording, storage, and analysis functions, allowing for long-term evaluation and optimization of hyperoxia adaptation effects.
[0162] This disclosure also provides a hyperoxia adaptation training method, which is used to conduct hyperoxia adaptation training or hypooxia adaptation training on training subjects.
[0163] In some embodiments, the hyperoxia adaptation training method can be used for hyperoxia adaptation training or hypooxia adaptation training. That is, the hyperoxia adaptation training method includes both hyperoxia adaptation training methods and hypooxia adaptation training methods.
[0164] The high and low oxygen acclimatization training method includes: periodically exposing the trainees to a first oxygen concentration gas and a second oxygen concentration gas with different oxygen concentrations; one alternation of the first oxygen concentration gas and the second oxygen concentration gas constitutes one cycle, and 3 to 40 cycles are performed every day, with 1 to 7 high and low oxygen acclimatization training sessions per week, lasting for 1 to 15 weeks.
[0165] In each cycle, the training subjects were exposed to the first oxygen concentration gas for 4 to 10 minutes, and in each cycle, the training subjects were exposed to the second oxygen concentration gas for 4 to 10 minutes.
[0166] This hyperoxia training method can be applied to either hyperoxia adaptation training or hypooxia adaptation training.
[0167] Meanwhile, according to the actual division of intervention, this high- and low-oxygen adaptation training can be as pre-adaptation training (training conducted before anticipated major stress events to improve the body's tolerance and reduce subsequent damage; such as before major surgery, entering a high-altitude environment, or receiving high-intensity radiotherapy and chemotherapy), synchronous intervention training (training conducted during disease treatment or in a specific environment) as a step-by-step treatment or supportive means; such as during chemotherapy cycles, rehabilitation after the acute phase of stroke, or during stays at high altitudes, etc.), or post-adaptation / rehabilitation training (training conducted after major stress events to accelerate recovery, reduce complications, and prevent functional decline; such as after surgery or acute illness), etc.
[0168] According to the purpose of intervention, the high and low oxygen adaptation training can be applied to therapeutic adaptation training (mainly for the treatment or adjuvant treatment of specific diseases, such as the treatment of tumors, chronic obstructive pulmonary disease (COPD), ischemic cardiovascular and cerebrovascular diseases, etc.), rehabilitation and functional improvement adaptation training (mainly for the purpose of promoting functional recovery after disease, delaying age-related physiological function decline, or improving specific physiological indicators, such as improving immune function, metabolic function, etc.), or health promotion and quality improvement training (mainly for the purpose of improving the physiological reserves, exercise endurance, and adaptability to low oxygen environment of healthy people, such as high-altitude travel, diving, etc.).
[0169] In some embodiments, the oxygen concentration of one of the first oxygen concentration gas and the second oxygen concentration gas is 10% to 20%, and the oxygen concentration of the other is 20% to 22%.
[0170] In some embodiments, the oxygen concentration of one of the first oxygen concentration gas and the second oxygen concentration gas is 10% to 20%, and the oxygen concentration of the other is 22% to 38%.
[0171] In some embodiments, the oxygen concentration of one of the first oxygen concentration gas and the second oxygen concentration gas is 20% to 22%, and the oxygen concentration of the other is 22% to 38%.
[0172] For example, some embodiments of this disclosure provide a hyperoxia adaptation training method that can supply gases with different oxygen concentrations through the aforementioned intermittent hyperoxia system. The target gas output by the intermittent hyperoxia system can be adjusted to have an oxygen volume percentage ranging from 0% to 38%.
[0173] For example, an intermittent hyper-hypoxia system can achieve hypoxia output, normoxic output, or hyperoxic output. When outputting hypoxia, the oxygen volume percentage of the target gas output by the intermittent hyper-hypoxia system is 10%–20% (inclusive of 10%, but excluding 20%); when outputting normoxic, the oxygen volume percentage of the target gas output is 20%–22% (inclusive of the extreme value, i.e., inclusive of both 20% and 22%); and when outputting hyperoxic, the oxygen volume percentage of the target gas output is 22%–38% (inclusive of 38%, but excluding 22%). Alternatively, when outputting hypoxia, the oxygen volume percentage of the target gas output by the intermittent hyper-hypoxia system is 0%–20% (excluding the extreme value); when outputting normoxic, the oxygen volume percentage of the target gas output is 20%–22% (inclusive of the extreme value); and when outputting hyperoxic, the oxygen volume percentage of the target gas output is 30%–38% (inclusive of the extreme value).
[0174] The oxygen volume percentage mentioned here refers to the oxygen concentration of the gas mentioned above. The oxygen concentration of the target gas output during low oxygen output, normal oxygen output, or high oxygen output is only an exemplary description of one possible implementation of this disclosure and is not intended to limit this disclosure. In actual use, the oxygen concentration of high oxygen, normal oxygen, and low oxygen gas (which can be a definite value or a range) can be adaptively designed as needed.
[0175] Optionally, a cycle consists of 4 to 10 minutes of hypoxia, 4 to 10 minutes of hyperxia, and 4 to 10 minutes of normoxic conditions. 3 to 30 cycles are performed daily, for a total of 35 to 120 minutes per session, applied 1 to 7 times per week for 1 to 15 weeks.
[0176] Optionally, the hypoxia adaptation training program involves alternating between hypoxia and normoxic conditions, with the oxygen volume ratio in hypoxia being 13% and in normoxic conditions being 21%. Each cycle consists of 5 minutes of hypoxia and 5 minutes of normoxic conditions. Ten cycles are performed daily for eight consecutive weeks. The subjects are elderly animals.
[0177] Optionally, the hypoxia adaptation training program involves alternating between hypoxia and normoxic conditions, with the oxygen volume ratio in hypoxia being 13% and in normoxic conditions being 21%. Each cycle consists of 5 minutes of hypoxia and 5 minutes of normoxic conditions. Ten cycles are performed daily for eight consecutive weeks.
[0178] Optionally, the hypoxia adaptation training program involves alternating between hypoxia and normoxic conditions, with the oxygen volume ratio in hypoxia being 13% and in normoxic conditions being 21%. Each cycle consists of 5 minutes of hypoxia and 5 minutes of normoxic conditions. Ten cycles are performed daily for two consecutive weeks. The target population is the elderly.
[0179] Optionally, the hypoxia adaptation training program involves alternating between hypoxia and normoxic conditions, with the oxygen volume ratio in hypoxia being 13% and in normoxic conditions being 21%. Each cycle consists of 5 minutes of hypoxia and 5 minutes of normoxic conditions. Ten cycles are performed daily for two consecutive weeks.
[0180] Optionally, the hypoxia adaptation training program involves alternating between hyperxia and hypoxia, with the oxygen volume ratio in hyperxia being 36% and in hypoxia being 13%; each cycle consists of 5 minutes of hyperxia and 5 minutes of hypoxia; 10 cycles are performed daily for 4 consecutive weeks.
[0181] Optionally, the hyperoxia acclimatization training program involves alternating between hyperoxia and normoxia, with the oxygen volume ratio of hyperoxia being 36% and normoxia being 21%. Each cycle consists of 5 minutes of hyperoxia and 5 minutes of normoxia. Ten cycles are performed daily for two consecutive weeks.
[0182] Optionally, when the training subject is an animal, the animal can be a rat, mouse, rabbit, pig, dog, cat, or monkey.
[0183] The above-described methods for hyperoxia acclimatization training can be applied to the intermittent hyperoxia equipment mentioned earlier. This equipment can output various combinations of alternating gas pairs, including but not limited to: Mode A (Hypoxia-Normalxia): One of the first and second oxygen concentration gases has a concentration of 10%–20% (hypoxia), and the other has a concentration of 20%–22% (normalxia). This mode can be applied to basic anti-aging and basic hypoxia adaptation training.
[0184] Mode B (Hypoxia-Hypoxia): One of the first and second oxygen concentration gases is 10%–20% (hypoxia), and the other is 22%–38% (hypoxia). This mode can be used to achieve a higher intensity of hypoxia adaptation alternation stimulation.
[0185] Mode C (normo-hyperoxygen): The concentration of one of the first and second oxygen concentration gases is 20%–22% (normo-oxygen), and the other is 22%–38% (hyperoxygen). This mode focuses on hyperoxygen adaptation and oxidative stress regulation.
[0186] Based on the aforementioned gas regulation capabilities, the core time parameters for high and low oxygen adaptation training are as follows: Duration of a single exposure: The duration of each continuous inhalation of hypoxic, hyperxic, or normoxic gas, ranging from 4 to 10 minutes. Specifically, the duration can be 4 minutes, 5 minutes, 6 minutes, 8 minutes, or 10 minutes, etc.
[0187] A single training cycle consists of one exposure to each of two different gas concentrations. For example, a complete cycle could be: hypoxia (5 minutes) → normoxic (5 minutes).
[0188] Daily training intensity: 3-40 cycles can be performed daily. The total daily training time is approximately 35 to 120 minutes.
[0189] Weekly training frequency: 1 to 7 training sessions per week.
[0190] Total treatment duration: A complete intervention cycle can last from 1 to 15 weeks.
[0191] In some embodiments, hypoxia adaptation training is conducted using Mode A (hypoxia-norxxia), where the hypoxia concentration is 13% and the normoxia concentration is approximately 21%, with each exposure lasting 5 minutes. Ten cycles are performed daily, 5–7 times per week, for a total of 8 weeks. This training method can be applied to adjuvant cancer therapy.
[0192] In some embodiments, hypoxia adaptation training is conducted using Mode A (hypoxia-noroxic), where the hypoxia concentration is 13% and the normoxic concentration is approximately 21%, with each exposure lasting 5 minutes. Ten cycles are performed daily, 5–7 times per week, for 6–8 consecutive weeks. This training method can be applied to anti-immunoaging.
[0193] In some embodiments, either Mode A or Mode B may be used. For example, alternating between 12% hypoxia and normoxic conditions, 5–10 cycles per day, for 2–4 weeks before entering high altitude. This training method can be applied to high altitude pre-acclimatization.
[0194] Embodiments of this disclosure also provide a hypoxia adaptation training device for anti-immunoaging, including an intermittent hyper-hypoxia system as provided in any of the preceding embodiments.
[0195] The intermittent high-low oxygen system is used to alternately output a first oxygen concentration gas and a second oxygen concentration gas with different oxygen concentrations; both the first oxygen concentration gas and the second oxygen concentration gas are the target gas; The oxygen concentration of the gas with the lower oxygen concentration is 10% to 18%, and the oxygen concentration of the gas with the higher oxygen concentration is 20% to 38%.
[0196] Optionally, the hypoxia adaptation program involves alternating between hypoxia and normoxic conditions, with the oxygen volume ratio in hypoxia being 13% and in normoxic conditions being 21%. Each cycle consists of 5 minutes of hypoxia and 5 minutes of normoxic conditions. Ten cycles are performed daily for two consecutive weeks. The training can be conducted on elderly individuals.
[0197] Optionally, the hypoxia adaptation program involves alternating between hypoxia and normoxic conditions, with the oxygen volume ratio in hypoxia being 13% and in normoxic conditions being 21%. Each cycle consists of 5 minutes of hypoxia followed by 5 minutes of normoxic conditions. Ten cycles are performed daily for eight consecutive weeks. The training subjects can be older animals.
[0198] Embodiments of this disclosure also provide a hypoxia adaptation training device for inhibiting tumor growth, comprising an intermittent hyper-hypoxia system as described in any of the preceding embodiments. The intermittent hyper-hypoxia system is used to alternately output a first oxygen concentration gas and a second oxygen concentration gas with different oxygen concentrations, both of which are target gases as described above. The oxygen concentration of the first oxygen concentration gas and the second oxygen concentration gas with the lower oxygen concentration is 10%–18%, and the oxygen concentration of the other with the higher oxygen concentration is 20%–38%.
[0199] For example, the hypoxia adaptation training device for inhibiting tumor growth and the hypoxia adaptation training device for anti-immunoaging can be used to implement the high and low oxygen adaptation training method as described in the foregoing embodiments.
[0200] The following describes some embodiments of this disclosure in detail with reference to experimental data.
[0201] Example 1: Application of hypoxia adaptation training equipment in anti-immune aging (1) Applicable to people aged 60 and above and elderly animals.
[0202] Furthermore, aged animals include mice aged 18–24 months, rats aged 20 months and older, rabbits aged 3 years and older, or rhesus monkeys aged 19 years and older.
[0203] (2) Hypoxia adaptation program: The oxygen volume ratio in hypoxia is 10% to 15%, and the oxygen volume ratio in normoxic conditions is 21%; the duration of hypoxia is 4 to 10 minutes, and the duration of normoxic conditions is 4 to 10 minutes, which constitutes one cycle; 3 to 38 cycles are performed every day for 2 to 10 weeks.
[0204] Furthermore, the hypoxia adaptation program involves alternating between hypoxia and normoxic conditions. The oxygen volume ratio during hypoxia is 10%–16%, while the oxygen volume ratio during normoxic conditions is 21%. The duration of hypoxia is 4–10 minutes, and the duration of normoxic conditions is 4–10 minutes, constituting one cycle. 3–38 cycles are performed daily for 2–10 weeks.
[0205] Furthermore, the oxygen volume ratio in the hypoxia phase is 13%, the hypoxia phase lasts for 10 minutes, and the normoxic phase lasts for 10 minutes, which constitutes one cycle; 10 cycles are performed every day for 6 consecutive weeks.
[0206] Furthermore, the oxygen volume ratio in the hypoxia phase is 13%, the hypoxia phase lasts for 5 minutes, and the normoxic phase lasts for 5 minutes, which constitutes one cycle; 10 cycles are performed every day for 8 consecutive weeks.
[0207] (3) Evaluation of hypoxia adaptation effect: After the hypoxia adaptation was completed, the degree of cell senescence, oxidative stress level, degree of mitochondrial dysfunction and genomic instability of aged mice were detected by flow cytometry, immunohistochemistry, immunofluorescence and qPCR.
[0208] Figure 5 This is a graph showing the data of bone marrow cell subsets in aged mice from the 3-month-old normoxic control group, the 18-month-old normoxic control group, and the 18-month-old intermittent hypoxia training group.
[0209] Among them, Nor-3mo (Normoxic, 3-month-old) represents the 3-month-old normoxic control group, serving as a young control group and representing a young and healthy physiological baseline state; Nor-18mo (Normoxic, 18-month-old) represents the 18-month-old normoxic control group, serving as an aging model group and representing a natural aging state; IH-18mo (Intermittent Hypoxic, 18-month-old) represents the 18-month-old intermittent hypoxia training group, serving as a treatment intervention group and representing aging individuals who received intermittent hypoxia adaptation training intervention.
[0210] In this embodiment, the Nor-3mo control group was used to confirm whether the aging model was successfully established. Figure 5 It can be seen that the Nor-18mo control group had worse indicators compared to the Nor-3mo control group; the Nor-18mo control group serves as a benchmark for evaluating the effectiveness of IH training (intermittent hypoxia training). Figure 5 It can be seen that the IH-18mo hypoxia training group has better performance in all indicators compared to the Nor-18mo control group.
[0211] Figure 5 a shows the number of bone marrow (BM) cells in different control groups; Figure 5 b shows the Lin values of different control groups. - The percentage of live cells in the total number of cells analyzed; Figure 5 c shows the percentage of live cells out of the total analyzed cells for LSmLm cells, CLP cells, LSK cells, and HSC cells in different control groups.
[0212] Figure 5 Lin -Lineage-negative cells represent a population of cells that do not express a series of markers of mature immune cells. They are enriched with more primitive cells such as hematopoietic stem cells and progenitor cells, possessing high proliferative and differentiation potential. LSmKm represents hematopoietic stem cell progenitor cells; CLP represents Common Lymphoid Progenitor cells, which differentiate from HSCs / LSKs and are progenitor cells that specifically differentiate into lymphocyte lineages such as T cells, B cells, and NK cells. Their number directly determines lymphocyte production capacity; LSK represents Lin... - Sca-1 + and c-Kit + The cells were a population enriched with HSCs and pluripotent progenitor cells.
[0213] The percentage of live cells in the total analyzed cells is a key indicator for measuring cell population survival and health. Figure 5 The results show that the number of bone marrow cells did not change significantly after hypoxia adaptation, but the proportions of Lineage negative, KSmKm, LSK, and HSC cells increased significantly, indicating that hypoxia adaptation may promote the proliferation and differentiation of bone marrow cells in aged mice.
[0214] Figure 6 This figure shows experimental data on thymocyte subsets in aged mice from a 3-month-old normoxic control group, an 18-month-old normoxic control group, and an 18-month-old intermittent hypoxia training group. Specifically, Figure 6 The experimental data are shown for three groups: a 3-month-old normoxic control group (Nor-3mo), an 18-month-old normoxic control group (Nor-18mo), and an 18-month-old intermittent hypoxia training group (IH-18mo).
[0215] Figure 6 It shows Figure 6 a, Figure 6 b、 Figure 6 c and Figure 6 d. Four experimental data graphs. Among them, Figure 6 Figure a shows the number of thymocytes in different control groups; Figure 6 b and Figure 6 Figure c shows the percentage of live cells in the total analyzed cells from the DN1 to DN4 cell subsets in different control groups; Figure 6 d shows the percentage of live cells out of the total analyzed cells for CD4 SP, CD8 SP, DN, DP, DP1, DP2, and DP3 cells in different control groups.
[0216] Specifically, DN1, DN2, DN3, and DN4 cells are four stages of immature thymocytes in the thymus during T cell development, collectively known as the Double Negative (DN) stage. They are named for the fact that their surface markers CD4 and CD8 are both negative. The division of the DN1 to DN4 stages is based on the dynamic changes of cell surface markers. These stages represent the early key steps in the differentiation of T cells from hematopoietic progenitor cells to mature T cells, reflecting the orderly development of T cells in the thymic cortex.
[0217] During thymocyte development, the proportion of cells at different stages has a relatively stable distribution in healthy individuals, with double-negative cells (DN), double-positive cells (DP), and single-positive cells (SP) being the core stages.
[0218] from Figure 6 It can be seen that the number of thymocytes in the hypoxia-adapted group increased significantly, and the proportion of DN1 to DN4 cell subsets increased, especially DN1, indicating that hypoxia-adaptation is beneficial to promoting the proliferation and differentiation of thymocyte subsets in aged mice.
[0219] Figure 7 Data graphs of lungs and spleens in aged mice from a 3-month-old normoxic control group, an 18-month-old normoxic control group, and an 18-month-old intermittent hypoxia training group. Specifically, Figure 7 The experimental data are shown for three groups: a 3-month-old normoxic control group (Nor-3mo), an 18-month-old normoxic control group (Nor-18mo), and an 18-month-old intermittent hypoxia training group (IH-18mo).
[0220] Figure 7 It shows Figure 7 a and Figure 7 b shows two experimental data graphs. Among them, Figure 7 Figure a shows the total number of lung cells in different control groups; Figure 7 Figure b shows the morphology of lung and spleen tissues in different control groups.
[0221] from Figure 7 The results show that, compared with the normoxic group, the total number of lung cells did not change significantly after hypoxia adaptation, but hypoxia adaptation reduced inflammatory cell infiltration and mucus secretion in aged mice. Compared with young mice, the spleen tissue morphology and structure of aged mice were more disordered, with a significant reduction in the white pulp area, an expansion of the red pulp area, and a decrease in the number of lymphocytes. After hypoxia adaptation, the spleen tissue morphology and structure of aged mice were more intact than those of the normoxic group, with a clear boundary between the white and red pulp, and a significant expansion of the white pulp area. This indicates that hypoxia adaptation can delay the aging process of the lungs and spleen in aged mice.
[0222] Example 2: Application of hypoxia adaptation training equipment in anti-immune aging (1) Applicable to people aged 60 and above and elderly animals.
[0223] (2) Hypoxia adaptation program: Set up normoxic elderly group and multiple hypoxia training elderly groups; different hypoxia training elderly groups all adopt the "hypoxia-noroxic" alternating program for hypoxia adaptation training, or all adopt the "hypoxia-hyperoxic" alternating program for hypoxia adaptation training.
[0224] Taking the elderly group undergoing hypoxia training using a "hypoxia-normative" alternation program as an example, all elderly groups undergoing hypoxia training used the same oxygen volume ratio and duration of hypoxia, as well as the same oxygen volume ratio and duration of normative oxygen, and performed the same number of "hypoxia-normative" cycles every day.
[0225] The difference lies in the duration of the hypoxia acclimatization training for different groups of elderly individuals. For example, the different groups underwent hypoxia acclimatization training for 2 weeks, 4 weeks, and 6 weeks, respectively.
[0226] Figure 8 The experimental data for four control groups are shown, where Nor-Aged represents the normoxic elderly group, 2W-Aged represents the elderly group with 2 weeks of hypoxic training, 4W-Aged represents the elderly group with 4 weeks of hypoxic training, and 6W-Aged represents the elderly group with 6 weeks of hypoxic training.
[0227] Figure 8 It shows Figure 8 A, Figure 8 B Figure 8 C and Figure 8 D shows four experimental data graphs. Among them, Figure 8 A shows the spleen weight in different control groups; Figure 8 B shows the thymus weight in different control groups; bal-HSC represents lymphoid-myeloid balanced hematopoietic stem cells, which dominate youth immune homeostasis and maintain a youthful immune phenotype. Figure 8 C shows the proportion of bal-HSCs to HSCs in different control groups, i.e., the percentage of balanced hematopoietic stem cells (HSCs) among all hematopoietic stem cells; my-HSCs represent myeloid-based hematopoietic stem cells, whose proportion increases significantly with age, becoming the dominant subgroup in old age and driving immunosenescence. Figure 8 D shows the proportion of my-HSC to HSC in different control groups.
[0228] from Figure 8 It can be seen that, compared with the normoxic control group, aged mice that underwent periodic hypoxia adaptation training showed a significant increase or maintained a better level of spleen and thymus weight. Among the four control groups, intermittent hypoxia for 6 weeks better delayed aging in aged mice.
[0229] The spleen and thymus are important immune organs, and their weight and structural integrity are directly related to the generation, development, and functional reserves of immune cells. These data directly demonstrate that hypoxia adaptation training programs can effectively alleviate or reverse age-related atrophy of immune organs.
[0230] Example 3: Application of hypoxia adaptation training equipment in tumor treatment (1) Tumor cell culture: Select mycoplasma-free mouse melanoma cell line B16-F10, colorectal cancer cell line MC38, lung cancer cell line LLC, leukemia cell line C1498, or breast cancer cell line E0771, and culture them in RPMI-1640 or DMEM containing 1% penicillin / streptomycin and 10% fetal bovine serum. (2) Hypoxia adaptation: SPF-grade 6-8 week old female or male wild-type mice were acclimatized to hypoxia according to the hypoxia protocol described above. (3) Constructing a mouse tumor model: After the hypoxia adaptation period, the tumor cells from step (1) were inoculated into the mice in step (2) at a concentration of 5×10^6 to 1×10^7 cells / mL, 100uL per mouse, by tail vein or subcutaneous injection. (4) Evaluation of hypoxia adaptation effect: Regularly monitor mouse body weight, detect tumor volume using in vivo imaging, analyze immune function using flow cytometry, and detect the infiltration of immune cells within the tumor using immunohistochemistry and immunofluorescence.
[0231] Figure 9 This is a data graph showing lung metastases in the intermittent hypoxia preconditioning group and the normoxia control group. Figure 8 The images show morphological diagrams of lung metastases, total luciferase light flux data, and spleen and lung weight data for the intermittent hypoxia preconditioning group and normoxic control group.
[0232] from Figure 9 The results show that after hypoxia acclimatization, the volume of lung metastases and lung mass in mice were significantly smaller than those in the normoxic group and larger than those in the hypoxia preconditioning group. The proportion of apoptotic cells stained by TUNEL was also significantly higher in the mice than in the normoxic group. This indicates that hypoxia acclimatization inhibits tumor growth, but its inhibitory effect is weaker than that of hypoxia preconditioning.
[0233] Figure 10 This is a statistical chart showing the survival rates of the intermittent hypoxia preconditioning group and the normoxic control group.
[0234] Figure 11 This is a graph showing the changes in EO771 tumor growth over time in the intermittent hypoxia preconditioning group and the normoxia control group.
[0235] Figure 12This is a graph showing the changes in tumor volume over time in the intermittent hypoxia preconditioning group and the normoxia control group.
[0236] like Figures 9 to 12 As shown, the tumor volume and lung mass of hypoxia-adapted mice were significantly lower than those of normoxic mice. In breast cancer and colorectal cancer models, the tumor volume of hypoxia-adapted mice was smaller and the growth was slower. Hypoxia-adapted leukemia mice had higher survival rates and fewer tumor cells. This indicates that hypoxia can inhibit the progression of various tumors.
[0237] Example 4: Application of hypoxia adaptation training equipment in tumor treatment (1) Applicable to people aged 60 and above (2) Hypoxia adaptation program: The oxygen volume ratio in hypoxia is 10% to 15%, and the oxygen volume ratio in normoxic conditions is 21%; the duration of hypoxia is 4 to 10 minutes, and the duration of normoxic conditions is 4 to 10 minutes, which constitutes one cycle; 10 to 25 cycles are performed every day for 1 to 2 weeks.
[0238] Furthermore, the hypoxia adaptation program involves alternating between hypoxia and normoxic conditions, with the oxygen volume ratio in hypoxia being 13% and in normoxic conditions being 21%. Each cycle consists of 5 minutes of hypoxia followed by 5 minutes of normoxic conditions. Twenty cycles are performed daily for one week.
[0239] (3) Evaluation of hypoxia adaptation effect: After the hypoxia adaptation is completed, immunohistochemistry is used to detect the infiltration and killing of immune cells in tumor tissue.
[0240] Figure 13 This is a comparison image of tumor tissue samples before and after hypoxia adaptation training. Figure 14 A comparative graph showing the levels of CD8, GZMB, and Cleaved Caspase 3 cells before and after hypoxia adaptation training.
[0241] from Figure 13 and Figure 14 It can be seen that CD8α in tumor tissue after training + The number of infiltrating T cells was significantly higher than before training, indicating that hypoxia adaptation training effectively recruited and / or activated more specific cytotoxic T cells into the tumor lesion; the expression level of GZMB increased significantly after training, and was correlated with CD8α. + The high degree of colocalization of T cell distribution indicates that the infiltrating T cells are in a highly activated functional state and are actively releasing cytotoxic mediators; after training, a large number of cleaved caspase-3 positive cells appeared in the tumor tissue, significantly more than before training, indicating that the aforementioned activated immune cells (CD8α) are active. + The 1999 SARS-CoV-2 and its released weapon (GZMB) successfully induced large-scale apoptosis in tumor cells.
[0242] In other words, immunohistochemical results showed that the proportions of CD8+, GZMB+, and Cleaved Caspase 3+ cells increased significantly after hypoxia adaptation, indicating that hypoxia adaptation increases the infiltration and killing function of CD8+ T cells.
[0243] This disclosure also provides an electronic device, which includes: a memory, a processor, a computer program, and a communication interface; wherein the computer program is stored in the memory and configured to be executed by the processor using the hyperoxia adaptation training method described above.
[0244] In addition, this disclosure also provides a computer-readable storage medium having a computer program stored thereon, the computer program being executed by a processor to implement the high and low oxygen adaptation training method described in the above embodiments.
[0245] Furthermore, this disclosure also provides a computer program product, which includes a computer program or instructions that, when executed by a processor, implement the hyperoxia adaptation training method described above.
[0246] It should be noted that, in this document, relational terms such as "first" and "second" are used merely to distinguish one entity or operation from another, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such a process, method, article, or apparatus. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the process, method, article, or apparatus that includes said element.
[0247] The above description is merely a specific embodiment of this disclosure, enabling those skilled in the art to understand or implement it. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of this disclosure. Therefore, this disclosure is not to be limited to the embodiments described herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims
1. An intermittent high / low oxygen system, characterized in that, include: A gas supply device includes a gas separation unit and a gas output unit connected in series; the gas separation unit is used to separate an initial gas into at least one enriched gas, the oxygen concentration of the enriched gas being different from the oxygen concentration of the initial gas; the gas output unit is used to output a target gas in response to a control signal, the target gas including at least one of the enriched gas and at least one of the initial gas; the control signal is used to characterize a target oxygen concentration of the target gas. A gas detection device is used to detect the actual oxygen concentration of the target gas; The gas output unit is further configured to adjust the proportion of the enriched gas and the initial gas in the target gas output by the gas output unit according to a reference index; the reference index includes the target oxygen concentration and the actual oxygen concentration.
2. The intermittent high / low oxygen system according to claim 1, characterized in that, The gas separation unit includes: an air compressor, a separation chamber, and a gas separation membrane; The gas separation membrane is disposed in the separation chamber and divides the separation chamber into a first sub-chamber and a second sub-chamber; the first sub-chamber is connected to the output end of the air compressor and the first input end of the gas output unit, and the second sub-chamber is connected to the second input end of the gas output unit; The input end of the air compressor is connected to the atmosphere, and the output end of the air compressor is also connected to the third input end of the gas output unit; the air compressor is used to pressurize air and output compressed gas; the initial gas is the compressed gas; Wherein, the permeation rate of the gas separation membrane for oxygen is greater than the permeation rate of the gas separation membrane for nitrogen. A portion of the compressed gas entering the first sub-chamber passes through the gas separation membrane into the second sub-chamber to obtain oxygen-rich gas, while the other portion remains in the first sub-chamber to obtain nitrogen-rich gas. The enriched gas includes the nitrogen-rich gas and the oxygen-rich gas.
3. The intermittent high / low oxygen system according to claim 2, characterized in that, The gas output unit includes: a mixing chamber and multiple flow regulating valves; The first input terminal of the mixing chamber is connected to the first sub-chamber, the second input terminal of the mixing chamber is connected to the second sub-chamber, the third input terminal of the mixing chamber is connected to the output terminal of the air compressor, and the output terminal of the mixing chamber is used to output the target gas; A flow regulating valve is provided corresponding to an input terminal of the mixing chamber. The flow regulating valve is used to regulate the flow rate of gas flowing into the mixing chamber through its corresponding input terminal. The opening degree of the flow regulating valve is related to the target oxygen concentration.
4. The intermittent high / low oxygen system according to claim 1, characterized in that, The intermittent hyper-hypoxia system also includes: A breathing device, connected to the gas output unit, for outputting the target gas from the gas output unit; The gas detection device is used to detect the actual oxygen concentration of the target gas output by the breathing device.
5. The intermittent high / low oxygen system according to claim 1, characterized in that, The intermittent hyper-hypoxia system also includes: A breathing device, connected to the gas output unit, is used to deliver the target gas to the training subject; A physiological parameter monitoring device is used to acquire the physiological parameters of the training subject; the physiological parameters include at least one of the training subject's blood oxygen, brain oxygen, heart rate, and respiratory rate; the reference indicators also include the physiological parameters.
6. The intermittent high / low oxygen system according to claim 1, characterized in that, The oxygen concentration of the target gas is less than or equal to 38%.
7. A method for high and low oxygen adaptation training, characterized in that, include: The trainees are periodically and alternately exposed to a first oxygen concentration gas and a second oxygen concentration gas with different oxygen concentrations; one cycle is defined as one alternation between the first oxygen concentration gas and the second oxygen concentration gas, and 3 to 40 cycles are performed daily, with 1 to 7 high and low oxygen adaptation training sessions per week for 1 to 15 weeks. In each cycle, the training subject is exposed to the first oxygen concentration gas for 4 to 10 minutes, and in each cycle, the training subject is exposed to the second oxygen concentration gas for 4 to 10 minutes.
8. The high and low oxygen adaptation training method according to claim 7, characterized in that, The oxygen concentration of one of the first oxygen concentration gas and the second oxygen concentration gas is 10%–20%, and the oxygen concentration of the other is 20%–22%; or, The oxygen concentration of one of the first oxygen concentration gas and the second oxygen concentration gas is 10%–20%, and the oxygen concentration of the other is 22%–38%; or, The oxygen concentration of one of the first oxygen concentration gas and the second oxygen concentration gas is 20% to 22%, and the oxygen concentration of the other is 22% to 38%.
9. A hypoxia adaptation training device for anti-immune aging, characterized in that, include: Intermittent high-low oxygen system as described in any one of claims 1 to 6; The intermittent high-low oxygen system is used to alternately output a first oxygen concentration gas and a second oxygen concentration gas with different oxygen concentrations; both the first oxygen concentration gas and the second oxygen concentration gas are the target gas; The oxygen concentration of the gas with the lower oxygen concentration is 10% to 18%, and the oxygen concentration of the gas with the higher oxygen concentration is 20% to 38%.
10. A hypoxia adaptation training device for inhibiting tumor growth, characterized in that, include: Intermittent high-low oxygen system as described in any one of claims 1 to 6; The intermittent high-low oxygen system is used to alternately output a first oxygen concentration gas and a second oxygen concentration gas with different oxygen concentrations; both the first oxygen concentration gas and the second oxygen concentration gas are the target gas; The oxygen concentration of the gas with the lower oxygen concentration is 10% to 18%, and the oxygen concentration of the gas with the higher oxygen concentration is 20% to 38%.