85 results about "Pathophysiology" patented technology

The invention discloses a disease risk assessment method and screening device based on a multi-group student physical collaborative digital network, and relates to the field of intelligent medical detection. In order to solve the defect that multi-omics-level system collaborative analysis and robust risk assessment are difficult to realize in the prior art, the technical scheme provided by the invention is as follows: acquiring a plasma sample, acquiring a spectral signal by adopting an attenuated total reflection Fourier transform infrared spectrum, and establishing a plasma spectrum digital information space; the method comprises the following steps: constructing a biological collaborative digital network containing four nodes of protein, lipid, saccharides and nucleic acid based on pathophysiology priori knowledge, and defining node strength, edge weight and network collaborative efficiency; a health baseline configuration file is established by using a health sample, a standardized deviation score of a to-be-tested sample is calculated, a comprehensive risk score is obtained, a disease screening result is output in combination with a machine learning model, and digital evaluation of multi-omics collaborative characteristics is realized. The method is suitable for non-invasive rapid screening and risk assessment work of neurodegenerative diseases and mental diseases.

The invention discloses a pyrimidinedione derivative as well as a preparation method and application thereof. Molecules of the pyrimidinedione derivative have better myosin inhibitory activity, also have antioxidant effects of DPPH and / or MDA and the like and anti-ferroptosis activity, and can be applied to treatment / prevention of heart myosin, anti-oxidative stress and anti-ferroptosis mechanism related diseases. The diseases or symptoms mainly comprise hypertrophic cardiomyopathy, diastolic heart failure, left ventricular hypertrophy, heart diseases with pathophysiological characteristics related to the hypertrophic cardiomyopathy, or other disease states and conditions which are obvious to those skilled in the art, or a prodrug thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof. Or a hydrate or solvate thereof, and a pharmaceutical composition containing the same.

The invention discloses a preeclampsia mouse model. The preeclampsia mouse model is constructed by the following method: (1) combining a female mouse with a male mouse; (2) in the middle stage of pregnancy, intragastric administration of hypoxanthine and oteracil potassium salt is carried out on the pregnant mouse for a period of time; the invention also discloses a construction method and application of the gene. The invention provides a novel preeclampsia modeling mode, hypoxanthine and oteracil potassium salt are combined for use, and the administration dosage and the administration mode of hypoxanthine and oteracil potassium salt are controlled, so that the serum uric acid level of a model mouse is stably increased, preeclampsia change occurs in the model mouse, and the model mouse can be used for treating preeclampsia. The stability, specificity and pathophysiology characteristics of the model are ensured to be similar to those of human preeclampsia, so that the uric acid-induced preeclampsia mouse model is successfully constructed. The uric acid induced preeclampsia mouse model provides a valuable tool for researching the pathogenesis of preeclampsia, evaluating a new treatment method and understanding the effect of serum hyperuricemia in preeclampsia.

The invention discloses an injury condition simulation system based on treatment feedback and a treatment evaluation method, and relates to the technical field of injury condition treatment simulation, and the system comprises a simulation definition module which generates initial vital sign parameters and natural evolution increment under a non-intervention condition according to an injury condition type defined in a treatment scene, the physical injury condition simulation dummy comprises a physical injury condition simulation dummy, a treatment detection module for analyzing and quantifying treatment actions of practicers and generating corresponding intervention signals, a central control module for calculating and outputting vital sign parameters and body surface performance parameters based on pathophysiology laws and an intervention mapping model, and a state feedback module for driving each execution unit of the physical injury condition simulation dummy. The system can analyze and score execution parameters of each treatment action of practicers, generate action quality indexes and intervention signals, provide quantifiable and comparable operation feedback for students, and map treatment action effects to dynamic update of injury states, so that vital signs and body surface manifestation change along with operation.

The invention belongs to the technical field of medical image processing and neural image analysis, and particularly discloses a cerebral apoplexy prognosis prediction method which comprises the following steps: step 1, performing whole cerebral vessel segmentation and morphological feature extraction on a CTA image to obtain 40 blood vessel morphological features; 2, extracting high-throughput omics characteristics from an infarction core and a half-dark band region in the DWI image, and obtaining 1026 image omics characteristics; 3, screening high-resolution features based on minimum absolute contraction and a selection operator, establishing a support vector machine classification model, and predicting a prognosis classification result of a three-month improved Rankin scale of the stroke patient; the deep learning network is used for automatically segmenting the whole brain blood vessel, so that subjective difference of manual recognition is reduced; starting from pathophysiology of occurrence and development of cerebral apoplexy, vascular morphological characteristics and infarction region imageomics characteristics are comprehensively incorporated to carry out prognosis prediction on cerebral apoplexy.

Lung fibroblast play an important role in lung cancer tumor microenvironment (TME). Senescence is involved in the pathophysiology of tumorogenesis. analyze how sPLA2 influenced lung cancer cell malignant properties. The inventors show that secreted PLA2 XIIA (sPLA2 XIIA) play a key role in lung cancer cell malignant properties. They demonstrate that sPLA2 XIIA increases the proliferation, the migration and organoid growth of both lung cancer cell lines (NCI and A549). Indeed, they shows that sPLA2 XIIA induces notably the epithelial mesenchymal transition (EMT), which is involved in the invasion of cancer cells and in the formation of metastasis. They also demonstrate that the effect of sPLA2 XIIA is mediated in particular by syndecan 1 and 4. Taken altogether, these data define sPLA2 XIIA as a circulating biomarker of poor prognosis in lung cancer and establish a requirement for sPLA2 XIIA inhibition for the treatment or prevention of cancer, especially lung cancer in the COPD patients.

The invention discloses application of a mitochondrial differentiation expression gene in preparation of a depression diagnostic agent and a depression treatment drug, and relates to the technical field of depression diagnosis and treatment. And the mitochondrial differentiation expression gene comprises one or more of TFAM (Transforming Factor Amplification Molecular), SURF1 and NDUFB9. According to the present invention, the SURF1 gene simultaneously expressed in inhibitory neurons and excitatory neurons is focused on, the key effect of the SURF1 in CUMS-induced depression-like behaviors is found, the CUMS-induced molecular and behavior changes are effectively reversed by the overexpression of the SURF1, and the potential anti-depression effect is displayed; besides, animal experiments find that overexpression of the SURF1 can effectively recover the function of an electron transport chain, ATP generation is enhanced, mitochondrial membrane potential is maintained, and oxidative stress is reduced. The effects jointly relieve depression-like behaviors induced by CUMS, and further support the protection effect of the SURF1 in a depression model, which provides evidence for the new effect of the SURF1 in the pathophysiology of depression.

The present invention relates to an application and product of mitochondrial DNA G-tetramer in sperm in male infertility detection, and belongs to the field of biomedical technology. The level of mitochondrial DNA G-tetramer in sperm is used as a reference indicator for semen analysis, and is applied to male infertility detection products, providing an effective theoretical reference for male infertility in sperm pathophysiology; then, an adapted TPE-mTO fluorescent probe is used as a relevant detection means to detect the level of mitochondrial DNA G-tetramer in sperm, thereby achieving efficient and convenient clinical detection. In addition, a mitochondrial autophagy inducer is used to restore abnormal fertilization caused by increased sperm mitochondrial DNA G-tetramer levels, and the application and product of the mitochondrial autophagy inducer in abnormal fertilization are proposed, providing a new potential treatment reference and theoretical basis for patients with sperm mitochondrial DNA G-tetramer dysfunction.

The present invention relates to a method of treating PIK3CA-Related Overgrowth Spectrum (PROS) more particularly, Congenital, Lipomatous, Overgrowth, Vascular Malformations, Epidermal Nevi and Spinal / Skeletal Anomalies and / or Scoliosis (CLOVES) syndrome. To date, there are no specific treatments for patients and no animal models of PROS to better understand the physiopathology of the disorder. Inventors developed a genetic mouse model of PROS that recapitulates the human disease and demonstrated the efficacy of BYL719. Based on these results they treated two patients, one adult and one child, with severe CLOVES syndrome using BYL719. The drug had a robust efficiency on disease in the two patients inducing quick recovery of all affected organs. Thus, the invention relates to a method of treating PROS in a subject in need thereof comprising the step of administrating the subject with a therapeutically effective amount of BYL719.

The invention relates to the technical field of biological medicines, and provides an application of blocking CYLD (Cytochrome-Yield-Diode) shearing at a D215 site in preparation of a sepsis treatment medicine, and a substance for blocking CYLD shearing at the D215 site is selected from a combination of any one or more of the following conditions: (1) a Caspase8 or FADD inhibitor, (2) a CYLD inhibitor, (3) a CYLD inhibitor, (4) a CYLD inhibitor, and (5) a CYLD inhibitor; and (2) a system for editing the 215 site of the CYLD. The invention further provides a recombinant expression vector and a sepsis treatment pharmaceutical composition, based on the discovery of the invention, the pathophysiology of sepsis inflammatory diseases can be better known, and a new opportunity is provided for diagnosis and treatment of sepsis, so that the clinical service of patients with sepsis inflammatory diseases is improved.

The present invention relates to a method of treating PIK3CA-Related Overgrowth Spectrum (PROS) more particularly, Congenital, Lipomatous, Overgrowth, Vascular Malformations, Epidermal Nevi and Spinal / Skeletal Anomalies and / or Scoliosis (CLOVES) syndrome. To date, there are no specific treatments for patients and no animal models of PROS to better understand the physiopathology of the disorder. Inventors developed a genetic mouse model of PROS that recapitulates the human disease and demonstrated the efficacy of BYL719. Based on these results they treated two patients, one adult and one child, with severe CLOVES syndrome using BYL719. The drug had a robust efficiency on disease in the two patients inducing quick recovery of all affected organs. Thus, the invention relates to a method of treating PROS in a subject in need thereof comprising the step of administrating the subject with a therapeutically effective amount of BYL719.

Extracellular vesicles and / or exosomes (EVs) remain sparsely studied in hemorrhagic transformations, including stroke and intracranial hemorrhages and could provide key insights into stroke pathophysiology. We assessed plasma levels of neuron-derived EVs (NDEs), astrocyte-derived EVs (ADEs), and oligodendrocyte-derived EVs (ODEs) in 58 patients 5, 15, and 30 days post-ischemic stroke along with 46 matched controls using sandwich immunoassays. Hemorrhagic transformation was a better predictor of ADE levels than lesion volume in linear regression models. These findings suggest that ADE levels are preferentially increased over the first month post-stroke compared to EVs from other neural cell types. ADEs may be of additional interest as biomarkers of blood-brain barrier breakdown to predict hemorrhagic transformation at earlier time points after stroke.

The present invention relates to the field of medical therapy of lesions detrimental to a body. The system is capable of treatment with a non-invasive, ionizing kV energy radiation source. Locally focused energy can be used to definitively treat, or as an adjuvant to enhance immune modulators, to eliminate tumors. Distributed external beam entry points produce a significant advantageous dose profile at depth as intersecting beams accumulate in a narrow focus to treat a selected volume. Targeted disease may have enhanced sensitivity to the radiation by taking up an ionizing-radiation, treatment-localizing agent. This increases the effectiveness of an energy dose in the lesion. The pattern of beam output is effectively directed towards a desired location and kV x-rays traveling towards undesired locations, such as healthy tissue, are quenched. Targeting a lesion within the body with volumetrically discrete energy dose deposition can beneficially impact harmful lesions. Aiming the beam at a pathologic target is done while moving an x-ray source mechanically around a patient to distribute surface dose. The purpose of the focused energy deposition is to destroy and disable pathologic physiology, such as malignant masses. More specifically this invention relates to a system, which optimizes delivery of ionizing kV beams to a lesion alone or one containing treatment-localizing agents in higher concentration than the surrounding normal tissues. Thereby an optimal delivery of ionizing radiation becomes more destructive to a mass of abnormal cells upon interaction with the targeted site.

Compounds and pharmaceutical compositions include inhibitors of apoptosis inducing factor (AIF). Pharmaceutical compositions for the treatment and / or mitigation of diseases in which increased rates of apoptosis are part of the disease pathophysiology, particularly, but not exclusively, when levels or activities of AIF are increased.

The invention relates to a hepatocellular carcinoma organoid-T cell co-culture system as well as a construction method and application thereof. The system comprises a liver cancer organoid culture medium and a T cell amplification culture medium which are mixed according to a specific ratio, and can be used for rapidly evaluating the efficacy of the immunosuppressor in vitro or screening candidate drugs. The construction method of the system comprises the steps of construction of hepatocellular carcinoma (HCC) organs, amplification of T cells, co-culture of hepatocellular carcinoma organs-T cells, and detection of efficacy killing evaluation of a PD-1 inhibitor. According to the HCC organ-T cell co-culture system constructed by the invention, the HCC organs maintain genomes, forms and pathophysiology characteristics of parental tumors of the HCC organs, the PD-1 inhibitor drug sensitivity result evaluated by the co-culture system is consistent with the clinical result, and a new model is provided for PD1 drug screening.

The invention relates to the technical field of medical information, and discloses a diabetic neuropathy dynamic early warning method based on deep learning. The method comprises the following steps: acquiring multi-modal physiological data through a sensor array, and converting the multi-modal physiological data into a feature vector sequence through preprocessing and pathophysiology-based mapping; the core of the method is that a dynamic feature selection mechanism is adopted to adaptively screen out a feature subset most related to neuropathy progress to replace a traditional fixed feature set; and constructing a multi-time scale risk prediction model, generating an individualized risk evolution track, and setting a dynamic early warning threshold according to the individualized risk evolution track. And triggering graded early warning by comparing the real-time risk index with a personalized threshold value, and completing adaptive updating of the model. The accuracy of individual risk signal capturing is improved through dynamic feature selection, real prospective early warning is achieved based on a dynamic threshold value of an individual trajectory, and therefore the accuracy and timeliness of early warning are improved.

The present disclosure relates to the use of compound (I) and any of its salts for the treatment of a neoplasm characterized by high expression of toll-like receptor 4 (TLR4) in the tumor or its microenvironment, associated with at least one of the pathophysiological complications including immunosuppression, angiogenesis, fibrosis, or metastasis.

The present disclosure provides methods of training a deep learning (DL)-based classifier to classify a digital histopathology image with respect to a phenotype, methods of classifying a digital histopathology image with respect to a phenotype, and methods of identifying a biological mediator associated with a pathology, pathophysiology, or other clinical characteristic. The disclosure further provides systems for implementation of these methods.

Targeting mitochondrial function is a strategy for preventing metabolic disorders, but restoring mitochondria diurnal regulation remains to be explored. Using targeted metabolomics, we identified 24-hour mitochondrial rhythms promoted by nocturnal time-restricted feeding (TRF) in mice fed a high-fat diet (HFD). Preceding its metabolic benefits, TRF promoted mitochondrial daily rhythms by converging on the enzyme dihydroorotate dehydrogenase (DHODH), which coordinates pyrimidine biosynthesis and mitochondrial oxidative metabolism. The inhibition of DHODH activity by the short half-life inhibitor BAY-2402234 modulated mitochondrial oxidative metabolism, thereby preventing diet-induced obesity, but only when injected at the transition between night and day. This timed inhibition of DHODH promoted oscillations in mitochondrial metabolic pathways and oscillations in the CoQ / CoQH2 ratio, improving metabolic adaptation to the HFD challenge. Our results highlight the role of mitochondrial daily rhythms in the pathophysiology of obesity and open avenues for chronopharmacological treatments targeting these rhythms. Thus, the present invention pertains to a method for treating or preventing obesity in a subject in need thereof. This method includes administering to the subject, at a specific time of the circadian rhythm, a therapeutically effective amount of a dihydroorotate dehydrogenase inhibitor that exhibits an inhibitory duration of less than 24 hours, and more specifically, a short half-life of less than 24 hours.

TRPV1 is an integral cation channel widely expressed in various tissues and involved in critical biological functions, such as thermosensation. It is polymodally activated by distinct stimuli, including chemical ligands, heat, and protons (pH). However, dozens of clinical trials targeting various types of TRPV1 -mediated pain have generally failed, primarily due to hyperthermia (increased body temperature). Meta-analysis of clinical data suggests that mode-selectivity is essential to realizing the therapeutic potential of TRPV1. TRPV1 is regulated allosterically, with vanilloids and other chemical ligands binding to the voltage-sensing-like domain (VSLD), resulting in the gating of the pore domain. Therefore, compositions and methods for modulating TRPV1 to treat human pathophysiologies, such as pain, are described herein.

This invention relates to the field of medical image processing technology, specifically to an automatic detection and classification method and system for intracranial hemorrhage based on three-window CT fusion and label-dependent graph neural network, including the following steps: S100, acquiring the original CT slice image of the head to be detected, performing grayscale mapping on the original slice image based on preset brain window, subdural window and bone window respectively, and stacking the three mapped images along the channel dimension to generate a three-channel fused image; This invention greatly enriches the model's global perception ability of multi-level physiological structures such as brain parenchyma, microhematomas and skull lesions through innovative three-window physical mapping and channel fusion; it introduces a hybrid adjacency matrix graph neural network that combines prior knowledge of neuroradiology with data-driven approach, explicitly establishing pathophysiological causal relationships between various hemorrhage subtypes at the model architecture level, effectively eliminating logical contradictions in predictions that violate clinical common sense.

This application relates to the field of biomedical signal processing and discloses a method for identifying postoperative intestinal dysfunction based on intestinal stimulation feedback, comprising the following steps: S1. A linear frequency modulated (LFM) scanning signal is emitted to the abdomen of the subject, and the mechanical vibration response signal of the abdominal medium to the LFM scanning signal is acquired. The dominant mechanical response frequency characterizing the abdominal medium in the current state is calculated and determined based on the LFM scanning signal and the mechanical vibration response signal. The dominant mechanical response frequency of the intestinal tissue is locked by baseline scanning, and resonant micro-perturbation is implemented at this frequency. The stress response of the intestine is captured synchronously using a dual-modal sensor of mechanical and electrophysiological sensors. By calculating the two-dimensional feature vector composed of the phase-locked value and the dynamic mechanical input impedance, the system can accurately distinguish between a simple decrease in electrical activity and a high-tension state caused by obstruction, thereby providing clinicians with a deeper pathophysiological diagnostic basis.

A method may include identifying a simulated three-dimensional representation corresponding to an internal anatomy of a subject based on a match between a computed two-dimensional image corresponding to the simulated three-dimensional representation and a two-dimensional image depicting the internal anatomy of the subject. Simulations of the electrical activities measured by a recording device with standard lead placement and nonstandard lead placement may be computed based on the simulated three-dimensional representation. A clinical electrogram and / or a clinical vectorgram for the subject may be corrected based on a difference between the simulations of electrical activities to account for deviations arising from patient-specific lead placement as well as variations in subject anatomy and pathophysiology.

Provided herein include compounds, compositions, kits and methods for preventing and treating psychiatric disorders. The composition and methods described herein can prophylactically treat a subject prior to and / or after a stressor and / or prior to the recurrence of a stressor, thereby preventing or delaying a relapse of depression or depression-like and / or stress-induced behaviors and disorders. The composition can comprise a serotonin 4 receptor (S-HUR) agonist and an N- methyl-D-aspartate (NMDAR) antagonist and a pharmaceutically acceptable salt, analog, derivative or metabolite thereof.

The invention relates to the technical field of medical image analysis, and particularly discloses a three-dimensional reconstruction and risk prediction system and method based on preoperative image features. The method comprises the following steps: acquiring an MRI / CT image and segmenting a focus area; constructing a pathophysiology knowledge graph; and fusing the space and the pathological rule to construct a dynamic graph structure. The method is characterized in that a graph convolutional neural network is adopted to aggregate and update graph node features, and multi-focus joint three-dimensional reconstruction is realized; and a graph attention mechanism is used to calculate a risk conduction weight conforming to a pathological law between focuses, and finally a joint risk thermodynamic diagram fusing prior knowledge is generated. According to the method, data driving and knowledge driving are deeply fused through the neural network model, the defect that relevance between lesions is neglected in a traditional method is overcome, high-precision three-dimensional reconstruction and accurate risk prediction are achieved, and intelligent decision support is provided for preoperative planning.

The present disclosure provides for imaging agents and methods of making and using the same. The imaging agent comprises a luminol component comprising a luminol moiety or functional analogue thereof; a chelator; a linker group bonding or complexing the luminol component to the chelator; and a radiolabel component bound to the chelator. The imaging agent described herein is capable of monitoring, targeting, or imaging oxidative stress, reactive oxygen species (ROS), superoxide generation, or hydrogen peroxide generation, mediating pathophysiology of different disease states.

The present invention relates to a method of treating PIK3CA-Related Overgrowth Spectrum (PROS) more particularly, Congenital, Lipomatous, Overgrowth, Vascular Malformations, Epidermal Nevi and Spinal / Skeletal Anomalies and / or Scoliosis (CLOVES) syndrome. To date, there are no specific treatments for patients and no animal models of PROS to better understand the physiopathology of the disorder. Inventors developed a genetic mouse model of PROS that recapitulates the human disease and demonstrated the efficacy of BYL719. Based on these results they treated two patients, one adult and one child, with severe CLOVES syndrome using BYL719. The drug had a robust efficiency on disease in the two patients inducing quick recovery of all affected organs. Thus, the invention relates to a method of treating PROS in a subject in need thereof comprising the step of administrating the subject with a therapeutically effective amount of BYL719.

AMD is a complex, multifactorial disease lacking curative therapy. Understanding of AMD pathophysiology highlights mechanisms such as mitochondrial dysfunction, visual cycle defects, autophagy impairment, and unresolved inflammation and oxidative stress. However, current therapies only target select aspects of AMD pathology. As described herein, variants in the ELOVL2 gene are utilized to predict the progression of age-related central nervous system conditions, including AMD, and to assess susceptibility to treatment. This approach enables more effective early intervention and personalized therapeutic strategies.

The present invention relates to a composition containing gintonin as an active ingredient for the prevention and treatment of ischemic cerebrovascular disorders, including cerebral infarction. The gintonin of the present invention can reduce the volume of cerebral infarction and increase survival rates after cerebral infarction, making it useful for the prevention and treatment of cerebral infarction. Furthermore, pretreatment of human brain microvascular endothelial cells (HBMECs) with gintonin has been shown to have neuroprotective and injury-preventing effects, while posttreatment with gintonin has been shown to have neuroprotective and therapeutic effects. Mechanism verification revealed that gintonin is effective in restoring reduced nitric oxide (NO) levels, which are known to be involved in the onset and pathophysiology of cerebral infarction. Therefore, the use of the present invention may improve the prevention and treatment of ischemic cerebrovascular disorders, including cerebral infarction, and reduce medical costs.

The present invention discloses systems and methods for mapping gastric activity with an electrode array patch disposed over an abdomen skin surface of a patient. A method may include measuring electrical signals associated with gastric activity of the patient with the electrode array patch over a predetermined time period and concurrently receiving patient symptom information, determining one or more normalized biometrics from the measured electrical signals, correlating the one or more normalized biometrics and the patient symptom information, determining a measure of correlation, determining a measure of temporal association, and determining a gastrointestinal phenotype of the patient based at least in part on the measure of correlation and the measure of temporal association. The present invention advantageously enables mapping of gut motility patterns at high spatial resolution for the identification of gastric disorders and provides biomarkers of pathophysiology which include correlations with symptom severity profiles.