59 results about "Membranous nephropathy" patented technology

The invention discloses a method for constructing a differential diagnosis model for lupus nephritis and membranous nephropathy, and belongs to the technical field of intelligent medical treatment. The modeling method comprises the following steps: S1, respectively collecting flow cytometry detection data of lupus nephritis patients and healthy control personnel; s2, performing data cleaning and conversion on the flow cytometry detection data, and converting non-numerical features into digits; carrying out implication on the missing value by adopting a k nearest neighbor algorithm from an implication packet; s3, random sampling is carried out on the cleaned and converted data set, and samples are divided into a training set and a verification set according to the proportion of 7: 3; s4, dividing a training subset and a test set from the training set, and iteratively selecting the types of cells incorporated into the constructed model as pDC, CD4T, effector CD4T, Th2, CD8T, CD38 + HLA-DR + CD8T, and CD38 + PD-1 + CD8T by adopting an RFE method, wherein the types of the cells incorporated into the constructed model are pDC, CD4T, effector CD4T, Th2, CD8T, CD38 + HLA-DR + CD8T and CD38 + PD-1 + CD8T; and S5, performing a classification task by adopting TabPFNClassifier, performing training from features selected from the training data set, then evaluating the performance of the model, performing model training by utilizing detection data, and performing evaluation to construct a lupus nephritis prediction model with high accuracy.

The invention discloses a method and system for predicting membranous nephropathy based on machine learning, and relates to the technical field of medical diagnosis and treatment, and the method comprises the steps: collecting multi-source heterogeneous data of a patient; preprocessing the multi-source heterogeneous data, constructing a mapping relation between the traditional Chinese medicine syndrome type and the molecular biomarker, and generating a traditional Chinese and western medicine fusion feature matrix; screening a feature subset related to membranous nephropathy prediction from the traditional Chinese and western medicine fusion feature matrix; constructing a membranous nephropathy multi-level prediction framework according to the feature subset, and training each prediction model in the framework; and applying the trained and optimized membranous nephropathy multi-level prediction framework to the feature subset data of the new patient to generate a membranous nephropathy multi-dimensional prediction result. By establishing the Chinese and western medicine feature mapping relation, deep fusion of traditional Chinese medicine diagnosis and modern medical indexes is realized, and comprehensiveness and accuracy of disease diagnosis are improved.

The invention provides an application of a reagent for detecting an effector CD4 + T cell in peripheral blood of a subject in preparation of a product for diagnosing membranous nephropathy, lupus nephritis or ANCA-related vasculitis. The invention also provides an application of the effector CD4 + T cell in peripheral blood in preparation of a diagnostic model for diagnosing membranous nephropathy, lupus nephritis or ANCA-related vasculitis. The marker is detected through flow cytometry, and the result shows that the Ejector CD4 + T cell is remarkably increased in a patient with membranous nephropathy, can effectively distinguish membranous nephropathy from healthy control (verification set AUC 0.8098), can assist in identifying membranous nephropathy, lupus nephritis (verification set AUC 0.8686) and ANCA-related vasculitis (verification set AUC 0.8968), and the level of the Ejector CD4 + T cell is related to whether membranous nephropathy is difficult to treat or not.

The invention discloses a lupus nephritis marker and application thereof, and belongs to the technical field of biomarkers. The marker for the lupus nephritis, disclosed by the invention, comprises one or more of CD8, CD38 and PD-1. By detecting specific cell surface markers in patient blood, early diagnosis of LN is assisted in a minimally invasive mode, and based on deep comparative analysis of LN patients and healthy people, the specificity and sensitivity of the biomarkers in LN diagnosis are ensured through screening of the biomarkers. In the aspect of differential diagnosis, a clinician is assisted to distinguish LN from other types of kidney diseases, such as membranous nephropathy (MN) and anti-neutrophil cytoplasm antibody related vasculitis (AAV), by analyzing specific biomarker modes of different nephropathy. The dependence on kidney puncture is reduced, related potential risks and inconvenience are avoided, and meanwhile more accurate and timely diagnosis is provided for an SLE patient.

The present invention relates to a double-stranded siRNA analogue for inhibiting expression of mannan-binding lectin-related serine protease 2 (MASP2), and a preparation method and use thereof, the double-stranded siRNA analogue can inhibit expression of MASP2, and is used for preventing and / or treating MASP2-related diseases and symptoms, such as MASP2-related diseases and disorders. The diseases and symptoms comprise IgA nephropathy, membranous nephropathy, lupus nephritis, thrombotic microangiopathy, systemic lupus erythematosus and the like.

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 present invention provides a kit, method and application for detecting human membranous nephropathy-related indicators. Through multiple mutation screenings of the coding nucleotide sequences of PLA2R antigen and THSD7A antigen, the most optimized sequences of PLA2R antigen and THSD7A antigen are obtained. The dialysis fluid formula in the preparation and purification processes of PLA2R antigen and THSD7A antigen, as well as the preservation fluid formula of PLA2R antigen and THSD7A antigen, are optimized. Highly pure PLA2R antigen and THSD7A antigen are prepared, and the problems of instability and batch-to-batch variation of PLA2R antigen and THSD7A antigen are solved to the greatest extent. The prepared kit can significantly improve the accuracy and sensitivity of detection, control batch-to-batch variation, and achieve rapid, accurate, simple and efficient detection of human membranous nephropathy-related indicators.

The invention relates to the technical field of detection, and discloses a kit for detecting a PLA2R antibody in urine, which comprises a non-invasive urine sampling device, a pore plate detection module and a time-resolved fluorescence detection module, the non-invasive urine sampling device comprises a urine collecting cup, a collecting cup and a U-shaped siphon which are matched up and down; a spiral flow guide groove for guiding the collection cup is formed in the inner wall of the urine collection cup; the collecting cup is located at the bottom of the urine collecting cup, and scale marks are arranged on the side wall of the collecting cup; the inlet end of the U-shaped siphon is communicated with the side wall of the collecting cup and is higher than the bottom of the collecting cup, and the outlet end of the U-shaped siphon extends into the urine collecting cup. According to the kit, urine is used for replacing serum to serve as a PLA2R-IgG antibody detection sample, the problems that traditional serological detection cannot achieve real-time monitoring and is high in cost are solved through the simplified process of non-invasive sampling-time resolution detection, and a convenient solution can be provided for rapid screening of membranous nephropathy.

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.

Provided are a diagnostically useful carrier coated with a recombinant polypeptide comprising SEQ ID NO: 1, an isolated autoantibody binding specifically to a polypeptide having SEQ ID NO: 1, a kit comprising the carrier, a method for the diagnosis of a membranous nephropathy (MN) that includes detecting the presence or absence of an autoantibody binding specifically to a polypeptide having SEQ ID NO: 1 in a liquid sample comprising antibodies from a subject, a use of an autoantibody binding specifically to a polypeptide having SEQ ID NO: 1 or a polypeptide comprising SEQ ID NO: 1, and a aqueous solution comprising an autoantibody binding specifically to a polypeptide having SEQ ID NO: 1.

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 invention discloses a method for evaluating the drug effect of rituximab on primary membranous nephropathy. According to the method, an SNP (Single Nucleotide Polymorphism) site rs396991 of FCGR3A is mutated into AC or CC from wild type AA, and the 158th amino acid coded by the SNP site rs396991 is mutated into phenylalanine from valine; according to the invention, an iMLDR typing technology is adopted to detect an FGCR3A base mutation site, if rs396991 is AA type, the rs396991 is considered to be effective to an RTX drug, and if the rs396991 is detected to be AC type or CC type, the rs396991 is considered to be insensitive or ineffective to an RTX reaction; therefore, the rituximab can be used for effectively evaluating the drug effect of the rituximab on the primary membranous nephropathy.

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 invention provides application of ATP6V1D as an IgA nephropathy diagnosis and / or disease risk assessment marker, and belongs to the technical field of in-vitro diagnosis. The invention provides an application of ATP6V1D as a marker for IgA nephropathy diagnosis and / or disease risk assessment. The research finds that the ATP6V1D protein has different expressions in IgA nephropathy and healthy people, membranous nephropathy and slight lesion nephropathy, and can be used as a marker for IgA nephropathy diagnosis and / or disease risk assessment. The invention further provides a kit for detecting the ATP6V1D, and compared with an existing KM55 kit, the kit provided by the invention is low in price and high in detection sensitivity and specificity.

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.

Provided are a traditional Chinese medicine composition for treating membranous nephropathy, a preparation method therefor, and use thereof. The traditional Chinese medicine composition comprises the following traditional Chinese medicine raw materials in parts by weight: 3-9 parts of Taxus chinensis, 9-12 parts of Curcuma zedoaria, 15-30 parts of Astragalus membranaceus, 6-12 parts of Panax notoginseng, and 10-20 parts of Gynostemma pentaphyllum. At the animal level, the traditional Chinese medicine composition can reduce proteinuria, regulate the lipid metabolism disorder, and protect the kidney. Furthermore, it is proved that the traditional Chinese medicine composition can alleviate the vacuolar degeneration of GBM or GBM thickening in experimental rats. Immunohistochemical analysis demonstrates that the formula can reduce the expression level of TGF-β1 in the renal interstitium, reduce the expression of ɑ-SMA and Col-IV collagen, reduce the deposition of ECM in the renal interstitium, and delay glomerulosclerosis and renal interstitial fibrosis.

Provided here are methods of treating primary membranous nephropathy in a patient in need thereof, comprising administering to said patient a BTK inhibitor, e.g., (S)-7-(1-acryloylpiperidin-4-yl)-2-(4-phenoxyphenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidine-3-carboxamide, or a pharmaceutically acceptable salt, tautomer, stereoisomer, enantiomer, isotopologue, solvate, or prodrug 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 relates to the technical field of immunodetection, and discloses a PLA2R antigen epitope peptide for membranous nephropathy and application thereof. The antigen epitope is selected from at least one of Ricin, CTLD1, CTLD7 and CTLD8. The PLA2R antigen epitope of membranous nephropathy can be combined with a self-reaction B cell and is presented to a T helper cell through a major histocompatibility complex (MHC) II type receptor, the stimulated T cell releases cytokines and feeds back the cytokines to the B cell to stimulate division and differentiation of plasma cells and generate an antibody and memory B cells, and a physiological target of immune response of membranous nephropathy is formed. The important value is realized on the diagnosis and prognosis of membranous nephropathy.

The invention belongs to the technical field of biological medicines, and particularly relates to application of songorine to preparation of a medicine for treating autoimmune diseases. According to the application disclosed by the invention, the songorine is used for intervening a rat model with membranous nephropathy and a mouse Treg cell in-vitro differentiation model, the songorine is found to be capable of effectively treating the rat model with membranous nephropathy, the curative effect of the songorine is equivalent to that of an existing clinical common medicine for treating membranous nephropathy, the songorine has the advantages of curative effect and safety, and the effect of the songorine for promoting Treg cell differentiation is disclosed for the first time; different from existing reports of anti-inflammatory curative effects, the anti-inflammatory composition has remarkable innovation.

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.