A system and device for constructing a spinal cord glioma animal model

Abstract

This specification provides a system and apparatus for constructing an animal model of spinal glioma, relating to the field of intelligent medicine. The system, executed by a robot, includes: a puncture point localization module configured to locate the highest point of the spine in its natural state as the puncture point; a spine exposure module configured to locate points at a first distance above and below the highest point of the spine along the spinal direction, forming a line segment; controlling the cutting of the dorsal skin of the animal sample along the line segment to expose the spine; a puncture needle insertion module configured to control the puncture needle to penetrate the puncture point perpendicular to the vertebral interface at a first speed until the puncture needle penetrates the spinal cord tissue; controlling the puncture needle to retract a third distance and pause for a first time; a cell suspension injection module; and a puncture needle withdrawal module configured to control the withdrawal of the puncture needle, thus obtaining the animal model. This application provides insights for clinical research on the molecular characteristics of spinal glioma and the identification of potential therapeutic targets.

Description

Technical Field

[0001] This invention relates to the field of intelligent medicine, and more specifically, to a system and apparatus for constructing an animal model of spinal cord glioma. Background Technology

[0002] In clinical practice, the clinical manifestations of spinal cord gliomas largely depend on the location and extent of tumor infiltration. They are most commonly found in the cervical and thoracic spinal cords, and less frequently in the lumbar spinal cord. Patients often present with diffuse, nonspecific axial pain as the initial symptom, including back pain, radicular pain, and central pain, often accompanied by progressive motor or sensory deficits. Furthermore, some patients may experience bladder or gastrointestinal dysfunction, severely impacting their quality of life.

[0003] For patients with well-defined, low-grade spinal cord gliomas, surgical resection within the maximum safe range can achieve good local control of the disease. However, high-grade spinal cord gliomas have severe local infiltration, making it difficult to distinguish their boundary from normal spinal cord tissue under a surgical microscope, resulting in incomplete surgical resection and extremely poor patient prognosis. A retrospective clinical study reported that the median survival of patients with primary high-grade spinal cord astrocytomas was only 20.2 months, significantly lower than the median survival of patients with other common cancers. Due to the extremely low incidence of spinal cord gliomas, they have not received sufficient attention from clinicians and researchers worldwide, resulting in a lack of effective treatment options. Therefore, the 2021 NCCN guidelines recommend that patients with high-grade spinal cord gliomas participate in various clinical trials to seek survival benefits.

[0004] Recent studies have confirmed that spinal cord gliomas possess unique clinicopathological features due to their different locations, with significant differences in gene mutations and molecular genetic phenotypes compared to intracranial gliomas. Therefore, studying the molecular characteristics of spinal cord gliomas and identifying potential therapeutic targets is urgently needed in clinical treatment. However, the current lack of effective animal models for spinal cord tumors has limited research progress in this field.

[0005] Currently, the evaluation of drug treatment for spinal cord gliomas widely relies on animal models constructed from intracranial tumor cells. However, due to differences in tumor molecular genetic background and tumor microenvironment, intracranial tumor models cannot accurately reflect the treatment efficacy of spinal cord gliomas. A common method uses C6 rats as experimental animals, exposing the spinal cord by biting off the spinous processes with forceps, and then injecting G55 or U87 human astrocytoma cells into the spinal cord. The experiment then examines tumor growth and spinal cord injury-induced autonomic dysfunction in rats. While this method simulates the growth pattern of intramedullary tumors and demonstrates the process of astrocytoma infiltration into the spinal cord, these procedures disrupt the anatomical structure and enclosed space of the spine. Furthermore, the tumor cells injected into the experimental models are all derived from gliomas of the brain, failing to simulate the sensitivity to treatment of tumors with the molecular genetic characteristics of spinal cord astrocytomas. These complex procedures make model standardization difficult. Additionally, these models do not provide specific puncture points and depths, or injection doses, leading to unstable construction results. Summary of the Invention

[0006] This invention aims to address at least one of the technical problems existing in the prior art. To this end, this invention provides a system and apparatus for constructing a spinal glioma animal model; by utilizing patient-derived tumor cells to develop a novel spinal glioma xenograft animal model, it provides insights for clinical research on the molecular characteristics of spinal glioma and the identification of potential therapeutic targets.

[0007] The first aspect of this application discloses a system for constructing an animal model of spinal cord glioma, the system being executed by a robot, comprising: The puncture point localization module is configured to locate the highest point of the spine of the animal sample in its natural state as the puncture point. The spine exposure module is configured to locate points at a first distance above and below the highest point of the spine along the spinal direction, with the three points forming a line segment; and to control the cutting of the back skin of the animal sample along the line segment to expose the spine. The puncture needle insertion module is configured to control the puncture needle to penetrate the puncture point perpendicular to the vertebral interface at a first speed until the puncture needle penetrates the spinal cord tissue; control the puncture needle to retract a third distance and pause for a first time; The cell suspension injection module is configured to control the puncture needle to inject cell suspension at a third speed, injecting a first volume of cell suspension; after the injection is completed, the puncture needle is controlled to remain stationary in its original position for a second time. The puncture needle withdrawal module is configured to control the withdrawal of the puncture needle to obtain an animal model.

[0008] In some embodiments, the highest point of the spine is the thoracic vertebra T13; Optionally, the animal specimen is placed in a prone position on the restraint device; Optionally, the first distance is 4.5-5.5 mm, preferably 5 mm.

[0009] In some embodiments, the determination of whether the puncture needle has penetrated the spinal cord tissue is as follows: the depth of the puncture needle penetrating the skin is the second distance, and the first twitching of the hind limb of the animal sample is detected. Optionally, the second distance is 1-2 mm, preferably 1.5 mm; Optionally, the third distance is 0.25-0.45 mm, preferably 0.3 mm; Optionally, the initial time is 50-70 seconds, preferably 1 minute.

[0010] In some embodiments, the cell suspension is tumor cells with molecular genetic characteristics of spinal astrocytoma (including primary human spinal glioma cells); Optionally, the first volume is 2.5-3.5 μL, preferably 3 μL; Optionally, the second time is 1.5-2.5 min, preferably 2 min; Optionally, the third velocity is 0.8-1.2 μL / min, preferably 1 μL / min.

[0011] In some embodiments, the system further includes: The incision care module is configured to control a first tool to apply a second volume of skin adhesive to the incision site on the back skin; The incision alignment module is configured to control the second tool to align the skin on both sides of the incision to obtain an animal model; Optionally, the second volume is determined based on the actual situation of the incision; Optionally, the first tool is a robotic arm; Optionally, the second tool is tweezers.

[0012] In some embodiments, the system further includes: a postoperative adjustment module configured to control the examination device to check and confirm the insertion position of the puncture needle; It is also configured to adjust the position of the puncture needle in response to the offset of the puncture needle position being greater than a preset offset threshold, so that the insertion position of the puncture needle is aligned with the puncture point.

[0013] In some embodiments, the system further includes installing a navigation system, the navigation system comprising: The step-by-step guidance module is configured to provide real-time prompts for the sequence of surgical steps; The operation monitoring unit is configured to acquire surgical field image data via an image monitoring device; The early warning module is configured to generate early warning information and trigger audible and visual alerts in response to the triggering of early warning conditions; The processing module is configured as follows: Based on surgical field image data, the instrument position and tissue characteristics within the surgical field are tracked and obtained; Based on instrument location and tissue characteristics, the surgical steps are updated and displayed to the user using the step guidance module.

[0014] The second aspect of this application discloses an apparatus for constructing an animal model of spinal cord glioma, the apparatus comprising: one or more processors and a memory; the memory for storing one or more computer programs; and the following steps performed when the one or more computer programs are executed by the one or more processors: The highest point of the spine in the animal sample under natural conditions is the puncture point; Locate the first distance points above and below the highest point of the spine along the spine direction; these three points form a line segment; control the cutting of the animal sample's back skin along the line segment to expose the spine; Control the puncture needle to be perpendicular to the vertebral interface and insert it into the puncture point at the first speed until the puncture needle penetrates the spinal cord tissue; control the puncture needle to retract a third distance and pause for a first time; Control the puncture needle to inject the cell suspension at a third speed, injecting the first volume of cell suspension; after the injection is completed, control the puncture needle to remain stationary in the original position for a second time; The puncture needle was withdrawn to obtain an animal model.

[0015] In some embodiments, the steps further include: The first tool is used to apply a second volume of skin glue to the incision site on the back skin; The second tool is used to align the skin on both sides of the incision to obtain an animal model.

[0016] In some embodiments, the apparatus includes: a spreader for fully exposing the spine, a puncture needle, a fixation device for securing the animal specimen, and skin glue; Optionally, the device may also include: tumor cells with molecular genetic characteristics of spinal astrocytoma; Optionally, the device may also include tweezers.

[0017] This application has the following beneficial effects: This application innovatively discloses a system for constructing an animal model of spinal cord glioma. The system optimizes the initial steps of the model construction process. First, by setting up a stereotactic device that can fix the mouse's position, it not only ensures high repeatability but also enables vertical puncture, avoiding unnecessary damage to the spinal cord caused by oblique punctures. Second, by reconstructing the puncture point at the T13 thoracic vertebra, it is not only easier to identify, but also, due to the enlarged spinal cord and larger medullary cavity at the T13 thoracic vertebra, it is more conducive to tumor cell growth. Furthermore, the incision site centered on T13 results in less bleeding, a clearer surgical field, and more complete exposure. In addition, before puncturing tumor cells, this application also improves the puncture method and puncture depth of the puncture needle, changing it from the traditional oblique needle insertion of 0.9mm to a needle insertion perpendicular to the vertebral body cross section of 1.5mm, reducing animal mortality and improving the success rate of modeling; during the puncture process, by withdrawing the needle a certain distance (e.g., 0.3mm) after puncture and then pausing for a certain time (1min), the leakage of tumor cell fluid is further prevented, ensuring that the tumor cell spheres after tumor formation can exhibit a similar appearance to human spinal cord glioma, which is consistent with the actual growth pattern of tumors.

[0018] Furthermore, in actual tumor cell injection, compared to the conventional model which requires waiting one minute after injecting each microliter of tumor cell suspension to allow for good tumor cell diffusion, and then leaving the syringe in place for three minutes before removal, this application improves the injection method by leaving the puncture needle in place for two minutes immediately after injection to allow for sufficient diffusion of tumor cells within the spinal cord tissue cavity. The construction of this model not only results in shorter injection times but also less damage, which is beneficial for postoperative recovery in animals.

[0019] Finally, regarding wound treatment, compared to the conventional method of suturing wounds with needles and sutures, this application directly uses 3M skin adhesive to treat the incision, which is simple and non-invasive, requires no additional disinfection steps, and is less likely to cause infection. Attached Figure Description

[0020] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0021] Figure 1 This is a schematic diagram of the treatment system provided in the first aspect of the present invention; Figure 2 This is a schematic diagram of gross observation of mouse spinal cord tissue provided in an embodiment of the present invention; wherein, the green arrows are the puncture sites of this model, and the blue arrows are the puncture sites of the conventional model; Figure 3These are the survival curves of 10 model mice provided in this embodiment of the invention; where red represents the conventional model and blue represents the present model, it can be seen that the survival time of the mice is significantly prolonged; Figure 4 This is a schematic diagram illustrating the successful modeling of the present invention (live imaging technology) provided in an embodiment of the present invention. Figure 5 This is a schematic diagram of successful modeling of the present invention provided in an embodiment of the invention (MRI technology); wherein, the round lesion indicated by the green arrow is a mouse spinal cord glioma; Figure 6 This is a schematic diagram of successful modeling of the present invention (HE staining image); where the green arrow points to a mouse spinal cord glioma; Figure 7 This is a schematic diagram of the conventional cervical spinal cord modeling process provided in the embodiments of the present invention; Figure 8 This is a schematic diagram of the conventional cervical spinal cord puncture and injection process provided in the embodiments of the present invention; Figure 9 This is a schematic diagram of the thoracic spinal cord modeling process provided in this embodiment of the invention; Figure 10 This is a schematic diagram of the thoracic spinal cord puncture and injection process provided in this embodiment of the invention. Detailed Implementation

[0022] To enable those skilled in the art to better understand the present invention, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings.

[0023] In some of the processes described in the specification, claims, and accompanying drawings of this invention, multiple operations appearing in a specific order are included. However, it should be clearly understood that these operations may not be executed in the order they appear herein, or may be executed in parallel. The operation numbers, such as 101, 102, etc., are merely used to distinguish different operations and do not represent any execution order. Furthermore, these processes may include more or fewer operations, and these operations may be executed sequentially or in parallel. It should be noted that the descriptions such as "first," "second," etc., in this document are used to distinguish different messages, devices, modules, etc., and do not represent a sequential order, nor do they limit "first" and "second" to different types.

[0024] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0025] Figure 1 This is a schematic diagram of a system for constructing a spinal cord glioma animal model according to an embodiment of the present invention. Specifically, the system is executed by a robot and includes: The puncture point localization module is configured to locate the highest point of the spine of the animal sample in its natural state as the puncture point. In some embodiments, the terms “animal sample” or “subject” or “test subject” or “sample to be tested” as used herein refer to any animal (e.g., a mammal), including but not limited to humans, non-human primates, rodents, etc., which will become the recipient of a particular treatment. Generally, the terms “subject” and “patient” are used interchangeably herein when referring to human subjects. Preferably, the animal sample is a mouse.

[0026] In some embodiments, the highest point of the spine is the thoracic vertebra T13; In some embodiments, the animal specimen is placed in a prone position on the restraint device; The spine exposure module is configured to locate points at a first distance above and below the highest point of the spine along the spinal direction, with the three points forming a line segment; and to control the cutting of the back skin of the animal sample along the line segment to expose the spine. In some embodiments, the first distance is 4.5-5.5 mm, preferably 5 mm.

[0027] The puncture needle insertion module is configured to control the puncture needle to penetrate the puncture point perpendicular to the vertebral interface at a first speed until the puncture needle penetrates the spinal cord tissue; control the puncture needle to retract a third distance and pause for a first time; the first time is 50s-70s, preferably 1min. The third distance is 0.25-0.45 mm, preferably 0.3mm.

[0028] In some embodiments, the method for determining whether the puncture needle has penetrated the spinal cord tissue is as follows: the depth of the puncture needle penetrating the skin is the second distance, and the first twitching of the hind limb of the animal sample is detected; the second distance is 1-2 mm, preferably 1.5 mm; The cell suspension injection module is configured to control the puncture needle to inject the cell suspension at a third speed, injecting a first volume of cell suspension; after injection, the puncture needle is controlled to remain stationary at the original position for a second time; in some embodiments, the cell suspension is tumor cells with molecular genetic characteristics of spinal astrocytoma (including primary human spinal glioma cells); the first volume is 2.5-3.5 μL, preferably 3 μL; the second time is 1.5-2.5 min, preferably 2 min; the third speed is 0.8-1.2 μL / min, preferably 1 μL / min.

[0029] The puncture needle withdrawal module is configured to control the withdrawal of the puncture needle to obtain an animal model.

[0030] In some embodiments, the system further includes: The incision care module is configured to control a first tool to apply a second volume of skin adhesive to the incision site on the back skin; the second volume is determined according to the actual situation of the incision; the first tool is a robotic arm. The incision alignment module is configured to control the second tool to align the skin on both sides of the incision to obtain an animal model; the second tool is tweezers.

[0031] In some embodiments, the system further includes: a postoperative adjustment module configured to control the examination device to check and confirm the insertion position of the puncture needle; It is also configured to adjust the position of the puncture needle in response to the offset of the puncture needle position being greater than a preset offset threshold, so that the insertion position of the puncture needle is aligned with the puncture point.

[0032] In some embodiments, the system further includes installing a navigation system, the navigation system comprising: The step-by-step guidance module is configured to provide real-time prompts for the sequence of surgical steps; The operation monitoring unit is configured to acquire surgical field image data via an image monitoring device; The early warning module is configured to generate early warning information and trigger audible and visual alerts in response to the triggering of early warning conditions; The processing module is configured to: track and acquire instrument positions and tissue features within the surgical field based on surgical field image data; update surgical steps based on instrument positions and tissue features; and display these steps to the user based on the step guidance module.

[0033] The second aspect of this application discloses an apparatus for constructing an animal model of spinal cord glioma, the apparatus comprising: one or more processors and a memory; the memory for storing one or more computer programs; and the following steps performed when the one or more computer programs are executed by the one or more processors: By retrieving the computer program from the memory and using the processor to perform S101, the highest point of the spine of the animal sample in its natural state is located as the puncture point. By retrieving the computer program from the memory and using the processor in step S102, points at a first distance above and below the highest point of the spine are located along the spine direction, and the three points form a line segment; the back skin of the animal sample is cut along the line segment to expose the spine. By retrieving the computer program from the memory, the processor performs S103, controlling the puncture needle to be perpendicular to the vertebral interface and inserted into the puncture point at a first speed until the puncture needle penetrates the spinal cord tissue; controlling the puncture needle to retract a third distance and pause for a first time. By retrieving the computer program from the memory, the processor performs S104, controlling the puncture needle to inject the cell suspension at a third speed, injecting a first volume of cell suspension; after the injection is completed, the puncture needle is controlled to remain stationary in its original position for a second time. By retrieving the computer program from the memory and using the processor to perform S105, the puncture needle is controlled to withdraw, thus obtaining an animal model. In some embodiments, the steps further include: By retrieving the computer program from the memory and using the processor in step S106, the first tool is controlled to apply a second volume of skin glue to the incision site on the back skin. By retrieving the computer program from the memory and using the processor in step S107, the second tool is controlled to align the skin on both sides of the incision to obtain an animal model.

[0034] In some embodiments, the apparatus includes: a spreader for fully exposing the spine, a puncture needle, a fixation device for securing the animal specimen, and skin glue; Optionally, the device may also include: tumor cells with molecular genetic characteristics of spinal astrocytoma; Optionally, the device may also include tweezers.

[0035] The experimental method is explained in detail below: Cell culture: Primary human spinal cord glioma cells SCA-S01 (WHO grade IV) were transfected with Luciferase virus. After transfection, the cells were conjugated with luciferase antibody and detected by in vivo imaging. Cells were cultured in Neurobasal / DMEM / F12 medium (B27, N2, L-glutamine, β-mercaptoethanol, non-essential amino acids, penicillin, streptomycin) and incubated at 37°C with 5% CO2. Cells were passaged every 3 days.

[0036] Experimental animals: BALB / c nude mice, female, 5 weeks old, 20g.

[0037] Cell collection: Discard the culture medium in the T75 culture flask. Wash the SCA-S01 cells twice with 3 mL of cold PBS and discard the PBS. Add 2 mL of Accutase solution to the culture flask and incubate at 37°C with 5% CO2 for 5 min. Dilute the Accutase solution with 4 mL of culture medium and collect the cell suspension in a 15 mL centrifuge tube. Centrifuge at 1500 rpm for 5 min, discard the supernatant, resuspend the cells in 1 mL of culture medium, and count the cells using a CellCounter instrument. Set the final cell suspension concentration to 100,000 cells / μL. Collect the cells in a 1.5 mL EP tube and place on ice.

[0038] Model Construction: A 2.5% solution of 2,2,2-tribromoethane was prepared using physiological saline. 300 μL of this solution was injected intraperitoneally using a 1 mL syringe to anesthetize mice. Anesthetized mice were placed prone on a stereotactic apparatus, with the highest point of the spine in its natural state located at the thoracic vertebra T13. Using T13 as the center point, the skin on the mouse's back was longitudinally incised 5 mm above and below it with tissue scissors, and a small retractor was used to fully expose the spine. The cell suspension was thoroughly mixed, and 5 μL of the suspension was drawn using a microsyringe and attached to the stereotactic apparatus. The injection point was the midpoint of the T13 vertebral body, perpendicular to the vertebral section. The needle depth was set to 1.5 mm. After slow needle insertion, a rapid twitching of the mouse's hind limb was observed, confirming that the needle had penetrated the spinal cord tissue. After reaching the puncture depth, the needle was withdrawn 0.3 mm and held for 1 minute to allow for tissue clearance. The cell suspension was injected at a rate of 1 μL / min, for a total of 3 μL, which is equivalent to 300,000 human spinal cord glioma cells (SCA-S01 cells). After injection, the puncture needle was left in place for 2 minutes to allow the tumor cells to fully diffuse within the spinal cord tissue cavity. The puncture needle was then slowly withdrawn, and 300 μL of skin adhesive was evenly applied to the skin incision site on the mouse's back. The skin was then aligned with forceps, and the mouse was placed in a cage. After the anesthesia wore off, the mouse was given food and water, and its condition and activity were observed.

[0039] In vivo imaging: Tumor growth in mice was assessed 14 days after tumor cell injection. A 15 mg / mL stock solution of D-Luciferin potassium was prepared using sterile DPBS, filtered through a 0.2 μm filter for sterilization, and stored at -80°C. Mice were anesthetized by intraperitoneal injection of 300 μL of 2.5% 2,2,2-tribromoethane solution. Five minutes later, 200 μL of the D-Luciferin potassium stock solution was injected intraperitoneally. The mice were then placed on a plate in an in vivo imaging system and allowed to stand for 10 minutes. Subsequently, the growth of spinal cord tumors was detected using bioluminescence on an IVIS spectral in vivo imaging system, and the results were statistically analyzed using Live Image software. Results are as follows: Figure 4 As shown, the tumor is growing well.

[0040] Small animal magnetic resonance imaging (MRI): MRI was performed on mice 14 days after tumor cell injection to assess tumor growth. Mice were anesthetized by intraperitoneal injection of 300 μL of 2.5% 2,2,2-tribromoethane solution. Five minutes later, the mice were placed on a 7T small animal MRI machine. The MRI detection coil was fixed with the T13 vertebral body as the midpoint, and the mice were secured to the machine using tape and a plastic board. T1- and T2-weighted imaging sequences were set, and the mouse spinal cord was scanned to acquire spinal cord MRI images. Results are as follows: Figure 5As shown, the green arrow points to a mouse spinal cord glioma, which is growing well.

[0041] HE staining of spinal cord tissue: After in vivo imaging and magnetic resonance imaging (MRI) were completed, mice were euthanized, their thoracic cavities were opened to expose the heart, and an intravenous infusion needle was inserted into the left ventricle. The heart was perfused with 20 mL of cold PBS until the blood was drained, followed by perfusion with 20 mL of cold 4% paraformaldehyde. The entire segment of the spinal cord tissue was completely isolated, dehydrated and fixed overnight using a dehydrator, and then embedded in paraffin to obtain paraffin blocks. The spinal cord tissue was sliced ​​into 5 μm thick sections using a microtome and dewaxed in a 65°C oven for 3 hours. The sections were then sequentially immersed in a solution of xylene I for 10 min, xylene II for 10 min, anhydrous ethanol I for 10 min, anhydrous ethanol II for 10 min, 95% ethanol I for 5 min, 95% ethanol II for 5 min, 75% ethanol for 5 min, and rinsed with tap water for 5 min. The sections were then stained with hematoxylin for 2 min, rinsed with tap water for 2 min, differentiated with 1% hydrochloric acid alcohol for 5 s, rinsed with tap water for 2 min, and then blued with 0.6% ammonia solution, rinsed with running water for 10 min. The sections were then stained with eosin for 2 min. Finally, the sections were sequentially dehydrated and cleared in 95% ethanol I for 5 min, 95% ethanol II for 5 min, anhydrous ethanol I for 5 min, anhydrous ethanol II for 5 min, xylene I for 5 min, and xylene II for 5 min. The sections were then removed from the xylene, allowed to air dry slightly, and the xylene around the tissue was wiped away with lens paper. The sections were then mounted with neutral resin, observed under a microscope, and images were acquired. The results are as follows: Figure 6 As shown, the green arrow points to a mouse spinal cord glioma, which is growing well.

[0042] To facilitate understanding, the construction process of the conventional model and that of this model are compared here to highlight the advantages of the construction process of this model. See Table 1 below for details: Table 1. Detailed comparison of the construction process of this model and the conventional model.

[0043] To further demonstrate the advantages of this model, in this embodiment, mice were divided into two groups: the model group and the conventional model group, with 10 mice in each group. The success rate and survival time of these groups were statistically analyzed. The survival time results showed that, compared with the mice in the conventional model group, the mice in the model-construction group had a significantly longer survival time. (See details...) Figure 3In the table, red represents the conventional model and blue represents the current model, showing a significant extension in mouse survival. Statistical results show that the success rate of constructing the model using this method is 90%, far exceeding the 50% success rate of the conventional model group (see Table 2 for details).

[0044] Table 2 Comparison of the total number and success rate of spinal cord glioma modeling between this model and the conventional model group.

[0045] The exemplary embodiments of this disclosure described in detail above are merely illustrative and not restrictive. Those skilled in the art will understand that various modifications and combinations can be made to these embodiments or their features without departing from the principles and spirit of this disclosure, and such modifications should fall within the scope of this disclosure.

Claims

1. A system for constructing an animal model of spinal cord glioma, characterized in that, The system is executed by a robot and includes: The puncture point localization module is configured to locate the highest point of the spine of the animal sample in its natural state as the puncture point. The spine exposure module is configured to locate points at a first distance above and below the highest point of the spine along the spinal direction, with the three points forming a line segment; control the cutting of the back skin of the animal sample along the line segment to expose the spine; the highest point of the spine is the thoracic vertebra T13; the first distance is 4.5-5.5 mm; The puncture needle insertion module is configured to control the puncture needle to penetrate the puncture point perpendicular to the vertebral interface at a first speed until the puncture needle penetrates the spinal cord tissue; control the puncture needle to retract a third distance and pause for a first time; the first time is 50s-70s, the third distance is 0.25-0.45 mm, and the method for determining whether the puncture needle has penetrated the spinal cord tissue is: the depth of the puncture needle penetrating the skin is the second distance, and the first twitching of the hind limb of the animal sample is detected, the second distance is 1-2 mm; The cell suspension injection module is configured to control the puncture needle to inject a cell suspension at a third speed, injecting a first volume of cell suspension; after injection, the puncture needle is controlled to remain stationary in its original position for a second time; the first volume is 2.5-3.5 μL, the second time is 1.5-2.5 min, and the third speed is 0.8-1.2 μL / min. The puncture needle withdrawal module is configured to control the withdrawal of the puncture needle to obtain an animal model.

2. The system for constructing a spinal cord glioma animal model according to claim 1, wherein The animal specimen was placed in a prone position on the fixation device.

3. The system for constructing a spinal glioma animal model according to claim 1, wherein The first distance is 5mm.

4. The system for constructing a spinal glioma animal model according to claim 1, wherein The second distance is 1.5mm.

5. The system for constructing a spinal glioma animal model according to claim 1, wherein The third distance is 0.3mm.

6. The system for constructing a spinal glioma animal model according to claim 1, wherein The first time is 1 minute.

7. The system for constructing a spinal glioma animal model according to claim 1, wherein The cell suspension consists of tumor cells with molecular genetic characteristics of spinal astrocytoma.

8. The system for constructing a spinal glioma animal model according to claim 1, wherein The first volume is 3 μL.

9. The system for constructing a spinal glioma animal model according to claim 1, wherein The second time is 2 minutes.

10. The system for constructing a spinal glioma animal model according to claim 1, wherein The third speed is 1 μL / min.

11. The construction system of a spinal cord glioma animal model according to claim 1, wherein The system also includes: The incision care module is configured to control a first tool to apply a second volume of skin adhesive to the incision site on the back skin; The incision alignment module is configured to control the second tool to align the skin on both sides of the incision to obtain an animal model.

12. The system for constructing a spinal glioma animal model according to claim 11, wherein The second volume is determined based on the actual situation of the incision.

13. The system for constructing a spinal glioma animal model according to claim 11, wherein The first tool is a robotic arm.

14. The system for constructing a spinal glioma animal model according to claim 11, wherein The second tool is tweezers.

15. The construction system of a spinal cord glioma animal model according to claim 1, wherein The system also includes a postoperative adjustment module, configured to control the examination equipment to check and confirm the insertion position of the puncture needle; It is also configured to adjust the position of the puncture needle in response to an offset of the position of the puncture needle being greater than a preset offset threshold, so that the insertion position of the puncture needle is aligned with the puncture point.

16. The construction system of a spinal cord glioma animal model according to any one of claims 1 to 15, wherein The system also includes an installation navigation system, the installation navigation system comprising: The step-by-step guidance module is configured to provide real-time prompts for the sequence of surgical steps; The operation monitoring unit is configured to acquire surgical field image data via an image monitoring device; The early warning module is configured to generate early warning information and trigger audible and visual alerts in response to the triggering of early warning conditions; The processing module is configured as follows: Based on the surgical field image data, the instrument positions and tissue characteristics within the surgical field are tracked and obtained; Based on the instrument location and tissue characteristics, the surgical steps are updated and displayed to the user using the step guidance module.

17. A device for constructing a spinal cord glioma animal model, characterized by, The device includes: one or more processors and a memory; the memory is used to store one or more computer programs; when the one or more computer programs are executed by the one or more processors, the following steps are performed: The highest point of the spine in the animal sample under natural conditions is the puncture point; Locate points at a first distance above and below the highest point of the spine along the spinal direction, forming a line segment; control the cutting of the back skin of the animal sample along the line segment to expose the spine; the highest point of the spine is the thoracic vertebra T13; the first distance is 4.5-5.5mm; The puncture needle is controlled to be perpendicular to the vertebral interface and inserted into the puncture point at a first speed until the puncture needle penetrates the spinal cord tissue; the puncture needle is controlled to retract a third distance and pause for a first time; the first time is 50s-70s, the third distance is 0.25-0.45 mm, and the method for determining whether the puncture needle penetrates the spinal cord tissue is: the depth of the puncture needle penetrating the skin is the second distance, and the first twitching of the hind limb of the animal sample is detected, the second distance is 1-2 mm; The puncture needle is controlled to inject the cell suspension at a third speed, injecting a first volume of cell suspension; after injection, the puncture needle is held in place for a second time; the first volume is 2.5-3.5 μL, the second time is 1.5-2.5 min, and the third speed is 0.8-1.2 μL / min. The puncture needle was withdrawn to obtain an animal model.

18. The apparatus according to claim 17, wherein the apparatus is used for constructing a spinal cord glioma animal model. The steps also include: The first tool is used to apply a second volume of skin glue to the incision site on the back skin; The second tool is used to align the skin on both sides of the incision to obtain an animal model.

19. The apparatus according to claim 17, wherein the apparatus is used for constructing a spinal cord glioma animal model. The device includes: a spreader for fully exposing the spine, a puncture needle, a fixation device for securing the animal specimen, and skin glue.

20. The apparatus according to claim 17, wherein the apparatus is used for constructing a spinal cord glioma animal model. The device also includes tumor cells with molecular genetic characteristics of spinal astrocytoma.

21. The apparatus according to claim 17, wherein the apparatus is used for constructing a spinal cord glioma animal model. The device also includes tweezers.

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