36 results about "Membranous nephropathy" patented technology

The invention provides a deep learning pathological image segmentation method for assisting membranous nephropathy diagnosis, and belongs to the technical field of image segmentation analysis. The deep learning pathological image segmentation method specifically comprises the following steps: S1, manually marking an abnormal tissue region in a full-resolution pathological image by a professional physician; s2, adjusting a membranous nephropathy pathological image data set and carrying out local data labeling; marking abnormal areas according to professional physicians, and carrying out standardized data marking; s3, inputting the marked training set image into the SAM network model; and then initializing an image encoder, converting the abnormal tissue mask into an embedded vector by adopting a prompt encoder, fusing the embedded vector with image features, generating a segmentation mask and a confidence score by adopting a mask decoder, and finally obtaining a nephropathy pathological abnormal region segmentation map. According to the method, multi-scale labeling is carried out on abnormal tissues of membranous nephropathy, and a data set is finely adjusted by using a current relatively front SAM model architecture, so that the model is converged, considerable precision is achieved, and efficient and reliable technical support is provided for automatic analysis of membranous nephropathy pathological images.

The invention provides a traditional Chinese medicine composition for treating nephropathy as well as a preparation method and application thereof, and the anti-renal fibrosis effect is remarkably improved by optimizing a leech extraction process and a novel preparation technology. Animal experiments show that urine protein of model animals can be reduced by 67% and serum creatinine can be reduced by 42% after 12 weeks of continuous administration. Clinical tests prove that the traditional Chinese medicine composition has a definite curative effect on IgA nephropathy, membranous nephropathy and the like, and a new choice is provided for treating chronic kidney diseases.

The invention discloses a diagnostic marker for ANCA (Angiovasculitis) related vasculitis. It is found for the first time that the CD19 + CD38 + CD27-CD24 + cell can be used as the diagnosis marker of ANCA related vasculitis, and the diagnosis efficiency is high; in addition, it is found that the CD19 + CD38 + CD27-CD24 + cells can remarkably distinguish ANCA related vasculitis and membranous nephropathy or ANCA related vasculitis and lupus nephritis, a new direction is provided for diagnosis and subsequent treatment of ANCA related vasculitis, and the application has wide application prospects clinically.

The application discloses a urine small extracellular vesicle PLA2R1 membrane protein detection method for distinguishing membranous nephropathy, and belongs to the technical field of biomedical detection. The detection method comprises the following steps: preparing an anti-CD63 antibody surface fixed plasmonic metasurface sensing chip to directly capture small extracellular vesicles in urine; preparing an anti-PLA2R1 antibody modified biofunctionalized gold nanoparticle complex to specifically combine with the PLA2R1 membrane protein on the surface of the small extracellular vesicles; detecting the reflection spectrum of the chip after antibody fixation and gold nanoparticle combination through a spectrometer with an integrated optical fiber probe; calculating the resonance wavelength shift amount; measuring the expression level of the PLA2R1 membrane protein; and realizing accurate distinction of healthy people, membranous nephropathy gray area and confirmed patients. The non-invasive detection method is simple in operation and rapid in detection, the sensitivity and the specificity are improved by means of the gold nanoparticle signal amplification effect, and is suitable for large-scale clinical screening and early diagnosis.

The application provides a PLA2R monoclonal antibody and an ELISA kit comprising the antibody. Specifically, the application provides a monoclonal antibody which specifically binds to PLA2R, wherein the antibody only binds to non-reduced PLA2R antigen with a conformational epitope, does not bind to reduced PLA2R antigen, and does not bind to another antigen THSD7A of primary membranous nephropathy. An ELISA kit prepared based on the antibody can more efficiently and accurately detect primary membranous nephropathy than existing commercial kits.

The invention provides a Mama-based membranous nephropathy multi-mode pathological image quantitative analysis system and method, and belongs to the crossing field of biomedical engineering and artificial intelligence. The problems that in an existing membranous nephropathy diagnosis system, the diagnosis process is high in subjectivity, single-mode analysis is limited, lesion feature quantification is insufficient, and model calculation is complex are solved. According to the technical scheme, the system comprises an image preprocessing module, the image preprocessing module is in communication connection with a macroscopic lesion analysis module, a microstructure analysis module and a thickness quantification module, and the macroscopic lesion analysis module and the thickness quantification module are both in communication connection with a feature fusion and prediction module. The macroscopic lesion analysis module, the microstructure analysis module, the thickness quantification module and the feature fusion and prediction module are all in communication connection with the result visualization module, and multi-modal pathological image quantitative analysis of membranous nephropathy is realized; the method is applied to multi-mode pathological image analysis of membranous nephropathy.

The application belongs to the technical field of kidney disease differential diagnosis, and particularly relates to a microbial gene marker for differentiating diabetic nephropathy and membranous nephropathy and application thereof. The application provides sufficient evidence for the differentiation and treatment of clinical diagnosis of diabetic nephropathy and pathological diagnosis of membranous nephropathy based on four microbial markers of Blautia, Akkermansia, Sphingomonas and Granulicatella.

This disclosure provides methods for treating a disease chosen from membranous nephropathy (MN), IgG4-related diseases, and antiphospholipid syndrome (APS) in a mammal using, for example, a therapeutically effective amount of the BTK inhibitor 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile or a pharmaceutically acceptable salt thereof.

The invention provides an application of a BCMA-CD19 bispecific CAR (Chimeric Antigen Receptor)-immune cell in the treatment of membranous nephropathy. Specifically, the invention provides a BCMA-CD19 bispecific CAR or a coding nucleic acid thereof, or a carrier thereof, or an application of a CAR-immune cell thereof, and the BCMA-CD19 bispecific CAR or the coding nucleic acid thereof, or the carrier thereof, or the CAR-immune cell thereof is used for (i) preparing a medicine for preventing and / or treating membranous nephropathy (MN); (ii) preparing a medicine for reducing the urine protein level; (iii) preparing a medicine for reducing the PLA2R antibody titer; (iv) preparing a medicine for improving the serum albumin level; and / or (v) preparing a medicine for improving the renal function eGFR level. The invention also provides a method for reducing urine protein level, reducing PLA2R antibody titer, increasing serum albumin level and / or increasing renal function eGFR level and a method for preventing and / or treating membranous nephropathy (MN) by using the BCMA-CD19 bispecific CAR or a coding nucleic acid thereof, or a carrier thereof, or a CAR-immune cell thereof, or a pharmaceutical composition. The BCMA-CD19 bispecific CAR-immune cell provided by the invention has very good safety and effectiveness, and can achieve the purpose that patients with high-risk, recurrent or refractory membranous nephropathy can continuously obtain clinical deep relief treatment.

The invention relates to the field of artificial intelligence in environmental health, discloses an innovative method of fusing machine learning, causal inference and high-dimensional interaction analysis, and discloses a high-dimensional interaction recognition-based heavy metal mixed exposure membranous nephropathy prediction method and a high-dimensional interaction recognition-based heavy metal mixed exposure membranous nephropathy prediction system. The method comprises the following steps: firstly, collecting a data set containing multiple heavy metal exposure data, individual information and an MN diagnosis result, and preprocessing the data set; then, constructing a prediction model by adopting multiple machine learning algorithms, comprehensively screening an optimal model through cross validation and multiple performance indexes, and preliminarily evaluating feature importance by utilizing an SHAP value; furthermore, a causal structure based on a directed acyclic graph is introduced, hybrid variables are controlled by applying a dual machine learning method, and the causal effect of individualized metal exposure on MN is estimated. On the basis of the optimal model, an SHAP interaction value and high-dimensional model representation method is applied, the nonlinear collaborative or antagonistic interaction effect between metals is systematically identified and quantified, and the pathogenic danger threshold and high-risk exposure window of the metals are identified.

A method of treating a subject suffering from an immune-mediated disease (e.g., IgA nephropathy, primary membranous nephropathy, an antibody-mediated rejection, lupus nephritis, systemic lupus erythematosus (SLE), Graves' Disease, Myasthenia Gravis, Anti-PLA2R positive Membranous Glomerulonephritis (aMN), Pemphigus, Sjögren's syndrome, and / or Anti-NMDA encephalitis) by administering to the subject a regimen of at least five doses of felzartamab and measuring a level of CD19+CD27hiCD38hi plasmablasts, a level of CD19+ B lymphocytes, or levels of CD19+CD27hiCD38hi plasmablasts and CD19+ B lymphocytes in a blood sample taken from the subject.

The traditional Chinese medicine composition disclosed by the invention adopts a method of warming yang and relieving exterior syndrome to achieve the effects of freeing lung and inducing diuresis, tonifying spleen and warming kidney, and strengthening defensive qi and diminishing swelling, and is prepared to be used for treating the immune-related glomerular diseases, especially membranous nephropathy and minimal lesion nephropathy. The traditional Chinese medicine composition is a pure traditional Chinese medicine preparation, clinical observation and in-vivo and in-vitro basic tests show that the prescription can remarkably improve edema, massive proteinuria, hypoproteinemia and the like, meanwhile, compared with the prior art, the traditional Chinese medicine composition has a better effect on symptoms such as stomachache and diarrhea, has an anti-inflammatory effect and does not have obvious side effects in clinical application. The traditional Chinese medicine composition has an excellent effect on patients suffering from membranous nephropathy and minimal lesion nephropathy caused by syndrome differentiation of spleen-kidney yang deficiency, internal rheumatism and water-fluid overflowing.

This invention provides the use of a reagent for detecting Effector CD4+ T cells in peripheral blood of subjects in the preparation of products for diagnosing membranous nephropathy, lupus nephritis, or ANCA-associated vasculitis. This invention also provides the use of peripheral blood Effector CD4+ T cells in the preparation of diagnostic models for membranous nephropathy, lupus nephritis, or ANCA-associated vasculitis. This invention detects this biomarker by flow cytometry, and the results show that Effector CD4+ T cells are significantly elevated in patients with membranous nephropathy, effectively distinguishing membranous nephropathy from healthy controls (validation set AUC 0.8098), and can help differentiate membranous nephropathy from lupus nephritis (validation set AUC 0.8686) and ANCA-associated vasculitis (validation set AUC 0.8968), and its level is correlated with the refractory nature of membranous nephropathy.

The invention discloses a method for detecting a membranous nephropathy target antigen, which comprises the following steps: adding a protein extracting solution into a glomerular tissue to be detected, and incubating; adding a mixed enzyme of a LysC enzyme and a Trypsin enzyme, and incubating; adding a dithiothreitol solution, and incubating; adding an iodo-acetamide solution, and incubating at room temperature in a dark place; adding a precipitating agent, performing ultrasonic treatment and centrifugation, taking supernate, loading the supernate to a C18 small column, eluting the small column, and collecting eluent; freezing the eluent, blow-drying the eluent, and redissolving the eluent with a loading solution to obtain a test solution; and carrying out liquid chromatography-tandem mass spectrometry detection on the test solution. By adopting the detection method disclosed by the invention, the target antigen of membranous nephropathy can be accurately detected when the sampling volume is obviously reduced, so that the sampling difficulty is greatly reduced, and the application of the laser microdissection and liquid chromatography-mass spectrometry combined technology in the detection of the target antigen of membranous nephropathy is greatly promoted. The method is simple in process and short in detection time.

The application relates to the field of bioinformatics and clinical auxiliary decision-making technology, in particular to a high-dimensional weighted membranous nephropathy gene co-expression network construction method, which integrates biomolecular interaction, disease pathways and health baseline data to construct an initial topological matrix, uses a Riemann manifold optimization algorithm to inject high-dimensional transcription sequencing data into the matrix and update edge weights, generates a high-dimensional weighted network of a target biological sample, accurately locks an abnormal gene module by calculating the topological residual error of the network and the health baseline and the dynamic offset of the eigenvector centrality, compares module features with a target point database to screen candidate drug targets, and stores network weight eigenvalues into a vector database, so that gene co-expression network construction and drug target screening based on biological priori and data driving are realized; and the application accurately retains weak but key local nonlinear cascade signals.

The application belongs to the technical field of nephropathy diagnosis medicine or reagent, and particularly relates to application of multiple groups of metabolic markers in differential diagnosis of different pathological types of nephrotic syndrome. The multiple groups of metabolic markers for diagnosing different pathological types of nephrotic syndrome (including membranous nephropathy and minimal change nephropathy) are provided, and the existing diagnosis means cannot realize non-invasive, rapid and effective pathological type differential diagnosis of primary nephrotic syndrome. The markers include markers for diagnosing membranous nephropathy and / or markers for diagnosing minimal change nephropathy. The markers can be used for preparing differential diagnosis products of different pathological types of nephrotic syndrome, the sample of a subject is pretreated, the level of the marker in the sample is determined and analyzed, the type of nephropathy of the subject is diagnosed, and the application has important clinical application value.

This document relates to methods and materials involved in identifying and / or treating mammals having membranous nephropathy (e.g., membranous nephropathy with an elevated level of a neural epidermal growth factor (EGF)-like 1 (NELL-1) polypeptide in the glomerular basement membrane (GBM)). For example, methods and materials for administering one or more immunosuppressive agents (e.g., corticosteroids, cyclosporine, or a B-cell reduction or depletion agent such as Rituximab) to treat a mammal (e.g., a human) having membranous nephropathy are provided.

The present invention provides a composition comprising a first polypeptide comprising a dimerization domain and a first fragment of an extracellular domain of PLA2R1 or an analog or derivative thereof, and a second polypeptide comprising a dimerization domain and a second fragment of an N-terminal extracellular domain of PLA2R1 or an analog or derivative thereof. A polypeptide comprising a fragment of an extracellular domain of PLA2R1 is also provided. Also provided are pharmaceutical compositions comprising the compositions, polypeptides, nucleic acid systems and nucleic acid molecules encoding the polypeptides of the compositions of the invention, and methods of using the compositions or polypeptides for treatment and for determining the suitability of treatment; and methods of making the compositions or proteins.

The present disclosure relates to a drug, a dosage scheme, an administration interval, and an administration mode for treating membranous nephropathy with a TACI-Fc fusion protein. Results show that the TACI-Fc fusion protein provided by the present disclosure shows relatively good clinical curative effect and good safety in the process of treating a patient with membranous nephropathy.

The invention provides novel methods for treatment of patients with membranous nephropathy by administration of compositions comprising a therapeutic agent for the treatment of membranous nephropathy. According to the invention, the therapeutic agent for the treatment of membranous nephropathy may be an anti-CD19 antibody.

This document relates to methods and materials involved in identifying and / or treating mammals having membranous nephropathy (e.g., membranous nephropathy with an elevated level of a Semaphorin 3B polypeptide in the glomerular basement membrane (GBM)). For example, methods and materials for administering one or more immunosuppressive agents (e.g., corticosteroids, cyclosporine, or a B-cell reduction or depletion agent such as Rituximab) to treat a mammal (e.g., a human) having membranous nephropathy are provided.

The application relates to the technical field of disease diagnosis, and particularly relates to application of CEACAM21 as a serum marker in diagnosis of membranous nephropathy. Based on the marker, risk stratification and treatment decision of the membranous nephropathy can be carried out, and the application has significant clinical significance.

The present invention relates to a drug, a dosage scheme, an administration interval, and an administration mode for treating membranous nephropathy with a TACI-Fc fusion protein. Results show that the TACI-Fc fusion protein provided by the present invention shows relatively good clinical curative effect and good safety in the process of treating a patient with membranous nephropathy.

The invention provides a method and a kit for accurate grading diagnosis of PLA2R antibody positive primary membranous nephropathy. The method and the kit can be used for clinical diagnosis, classification and prognosis analysis of primary membranous nephropathy (PMN). Specifically, the invention provides a method for detecting the PLA2R antibody recognition epitope, and the method can be used for clinically diagnosing PLA2R antibody positive patients, classifying the patients based on the PLA2R antibody recognition epitope in patient serum, and can be used for prognosis analysis of the patients.

The invention relates to the technical field of knowledge graph and medical fusion, in particular to a membranous nephropathy intelligent staging and diagnosis and treatment method based on knowledge graph reasoning, which comprises the following steps of: constructing a membranous nephropathy exclusive causal graph model, integrating multi-source data and defining a core node; hierarchical analysis, tendency score matching and a backdoor adjustment formula are combined to process hybrid variables, interference is effectively stripped, real causal association of drugs and curative effects is defined, the limitation that in the prior art, dependency correlation analysis is prone to generating false association is broken through, and accurate logic support is provided for diagnosis and treatment decisions. On the basis of an STRING database adaptation algorithm, a target protein network and a causal link are coupled, a drug onset molecular mechanism is mined, dual verification of virtual and in-vitro cell experiments is combined, a biological basis is enhanced, and the problems that a traditional method is fuzzy in mechanism and single in verification are solved. And an adaptive drug screening model is constructed in combination with disease staging, so that personalized sorting is realized.

The invention provides a biomarker combination for in-vitro diagnosis of membranous nephropathy. The biomarker combination comprises non-classical mononuclear cells, CD4 + T cells, effector CD4 + T cells, 2-type helper T cells, double-negative T cells, central memory CD4 + T cells, plasma cell-like dendritic cells, antibody secreting cells, total T cells, unconverted memory B cells, classical mononuclear cells and natural killer cells. The invention also provides a construction method of the membranous nephropathy diagnosis model. The construction method comprises a step of screening the characteristic biomarkers and a step of constructing the diagnosis model and evaluating the performance. According to the method, the optimal marker combination is screened out from the high-dimensional flow cytometry data by applying a random forest recursive feature elimination algorithm, and a random forest diagnosis model is constructed. The invention shows excellent performance in distinguishing membranous nephropathy patients from healthy controls, and shows high accuracy in independent verification including a diagnosis difficulty subgroup of PLA2R antibody negative.

The invention provides novel methods for treatment of patients with membranous nephropathy by administration of compositions comprising a therapeutic agent for the treatment of membranous nephropathy. According to the invention, the therapeutic agent for the treatment of membranous nephropathy may be an anti-CD19 antibody.

This document relates to methods and materials involved in identifying and / or treating mammals having membranous nephropathy (e.g., membranous nephropathy with an elevated level of a protocadherin FAT1 (FAT1) polypeptide in the glomerular basement membrane (GBM)). For example, methods and materials for administering one or more immunosuppressive agents to treat a mammal (e.g., a human) having membranous nephropathy are provided.