44 results about "Chronic hepatitis" patented technology

The invention provides a polypeptide for activating cellular immunity in chronic hepatitis B and application of the polypeptide, and belongs to the technical field of biological medicine. A polypeptide library is designed and synthesized on the basis of a preS1 structural domain for coding HBV large HBsAg, a full-length core protein Core, a polymerase protein fragment rich in T cell epitopes and an mRNA-PreS1CPX holoantigen sequence (as shown in SEQ ID NO.1) of full-length X protein HBX, and peptide fragments capable of activating T cell immunity are screened by utilizing ELISPOT and flow cytometry. Experimental results show that the polypeptide sequences as shown in SEQ ID NO.2-15 can promote HBV antigen specific immune response by stimulating CD8 + T lymphocytes to secrete IFN-gamma, so that immune activation treatment of hepatitis B is realized.

Described are methods for treating alpha-1 antitrypsin deficiency (AATD) in a human patient in need of treatment, using pharmaceutical compositions that include AAT RNAi agents. The pharmaceutical compositions disclosed herein that include AAT RNAi agents, when administered to a human patient in need thereof, treat liver diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, increased risk of hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, fulminant hepatic failure, and other liver-related diseases.

The invention relates to the technical field of bioinformatics, and relates to a construction method and application of a children chronic hepatitis B prediction model based on machine learning. The construction method comprises the following steps: S1, acquiring corresponding information and data of a research object, and preprocessing the acquired data; s2, screening and determining characteristic indexes of chronic hepatitis B of children; s3, constructing a prediction model; s4, evaluating and comparing the model of the children chronic hepatitis B prediction algorithm; and S5, generating a network calculator and calculating the prediction probability of the chronic hepatitis B of children. The constructed prediction model can predict the probability that children suffer from chronic hepatitis B, the network calculator generated according to the model can be applied to medical electronic cases, children suffering from chronic hepatitis B can be recognized more effectively clinically, effective early intervention can be achieved, and therefore potential hazards caused by chronic hepatitis B to children health are reduced.

The application relates to the field of biological medicine, in particular to application of TDF in serum cholesterol regulation and a verification method. The application discloses that tenofovir disoproxil fumarate (TDF) can inhibit intestinal cholesterol absorption by specifically down-regulating the expression level of NPC1L1 protein in the intestinal tract, so as to reduce serum cholesterol. The regulation has tissue specificity, and TDF has no significant influence on the expression of key genes of liver cholesterol metabolism. The application also provides a method for verifying the regulation of TDF on serum cholesterol, which is evaluated by detecting blood lipid indexes and the gene and / or protein expression level of NPC1L1 in duodenal tissue. The application provides a treatment scheme with antiviral and cholesterol-lowering effects for patients with chronic hepatitis B combined with hypercholesterolemia, and provides a new idea for developing a lipid-lowering strategy targeting intestinal cholesterol absorption.

The application discloses a DNA methylation site marker for detecting hepatocellular carcinoma, a multiplex dPCR kit and a diagnostic model construction method. The DNA methylation site marker comprises cg02829688, cg13080379, cg03760839, cg10703826, cg12664119, cg16990168 and cg23371746 sites. The application designs a primer probe group for the above sites, constructs a multiplex dPCR kit of a double reaction system, realizes quantification of target DNA methylation sites, takes the methylation levels of the 7 sites as characteristic variables, adopts an XGBoost algorithm and / or an LR algorithm to construct a diagnostic model. Experimental verification shows that the model can effectively distinguish hepatocellular carcinoma patients from liver cirrhosis, chronic hepatitis B, metabolic dysfunction-related fatty liver disease patients and healthy individuals, especially shows good efficiency in auxiliary diagnosis of early hepatocellular carcinoma, and provides a new technical scheme for clinical diagnosis and screening of hepatocellular carcinoma.

The present disclosure relates to double stranded RNA agents targeting the hepatitis B virus (HBV) genome, and methods of using such agents to inhibit expression of one or more HBV genes and methods of treating subjects having an HBV infection or HBV-associated disorder, e.g., chronic hepatitis B infection.

Provided herein are methods for administering hepatitis B virus surface antigen (HBsAg) to a subject suffering from chronic hepatitis B to differentiate between responder subjects and non-responder subjects that the administration of HBsAg results in an increased response to HBV antibody levels, and treating chronic hepatitis B in responder subjects using HBV therapy. Also provided are methods of excluding unresponded subjects outside a clinical study.

The present invention relates to compositions and methods for therapeutic immunization for treatment of chronic hepatitis B virus (CHB). Methods of the invention include a method generating a high titer hybrid-hepatitis B virus (HBV) vector, methods of treating and / or preventing HBV infection and / or CHB, and methods of inducing a memory T and B cell immune response against HBV infection in a subject administered the VLV composition produced thereby. Furthermore, the invention encompasses a pharmaceutical composition for vaccinating a subject to protect the subject against infection with HBV.

The application discloses application of a low-dose anti-PD-1 antibody in a limited course of treatment in treatment of hepatitis B. Anti-PD-1 antibody treatment is carried out on a chronic hepatitis B patient receiving nucleoside analogue or nucleotide analogue treatment, 100 mg is injected intravenously each time, once every three weeks, and the course of treatment is ended after 12 weeks or 24 weeks. The application blocks the combination of the PD-1 receptor highly expressed on the surface of T cells of the CHB patient with a ligand by blocking the CHB patient T cell surface high expression of the PD-1 receptor, thereby reversing the T cell exhaustion state, enhancing the HBV specific T cell immune response, and promoting HBsAg clearance. The application uses a limited course of treatment and a low-dose alpha PD-1 to enhance the HBV specific T cell immune response of the patient and promote the clearance of HBsAg while ensuring good safety. Compared with the traditional 48-week Peg-IFN alpha or several years or even decades of NAs treatment of the CHB patient, the 12-week or 24-week course of alpha PD-1 is shorter and has a smaller economic burden on the patient.

The invention provides application of a compound as shown in a formula (I), a solvate, a hydrate, a prodrug or a pharmaceutically acceptable salt of the compound in preparation of drugs for treating or preventing chronic hepatitis B with hepatic fibrosis. Clinical research proves that the compound can effectively reverse hepatic fibrosis; and particularly, the traditional Chinese medicine composition has a better effect on treating fibrosis in a converging region, remarkable fibrosis, hepatic fibrosis in a progressive stage or liver cirrhosis.

The invention discloses an intelligent construction method and system for a chronic hepatitis B pathological image analysis model. The method comprises the following steps: inputting a WSI image into a system, preprocessing, and cutting into an image block set with a fixed size; inputting the image block set into a UNI feature extraction model, and extracting a multi-scale embedded vector through a self-attention mechanism; the embedded vector is transmitted into an attention module of a CLAM multi-instance learning model, and an attention score is calculated; clustering the image blocks according to the attention score, endowing a pseudo label, and calculating a loss function to perform network parameter training; performing click operation on the attention score and the embedded vector to obtain a feature vector subjected to attention calibration, and performing full connection processing to obtain prediction probability distribution; generating an attention heat map to visualize the model decision process; network parameters are optimized through a cross entropy loss function and a back propagation algorithm, and finally a grading and staging result is output and verified through a standard scoring system.

The application discloses a traditional Chinese medicine granule for treating jaundice and a preparation method and application thereof. The traditional Chinese medicine granule is prepared from the following traditional Chinese medicine raw materials in parts by mass: radix rehmanniae 14-16 parts, radix et rhizoma rhei 6.5-8.5 parts, fructus aurantii immaturus 6.5-8.5 parts, radix pini 6.5-8.5 parts, herba taraxaci 14-16 parts. The traditional Chinese medicine granule is used for treating jaundice, acute and chronic hepatitis mainly manifested as jaundice (yellowish urine), and the clinical manifestations are yellowish urine, abdominal distension or abdominal distension and pain, poor appetite, yellow urine, dysuria, constipation or diarrhea, red or dark red tongue, yellow tongue fur, and slow and thin pulse. The traditional Chinese medicine granule is determined through years of clinical application, and the results show that the traditional Chinese medicine granule can be used for treating jaundice caused by various acute and chronic hepatitis, and the curative effect is very good, the effect is fast, the curative effect is accurate, the medicine is less, and the cost is low.

The application provides a chronic hepatitis B treatment method and device based on a molecular typing model, and the method comprises the following steps: obtaining a tissue sample of a chronic hepatitis B patient; determining the type of chronic hepatitis B of the chronic hepatitis B patient according to the tissue sample of the chronic hepatitis B patient based on a constructed molecular typing model; and determining the targeted treatment drug for the chronic hepatitis B patients of each type according to the type of chronic hepatitis B of the chronic hepatitis B patient. The application can perform molecular typing on the tissue sample of the chronic hepatitis B patient through the construction of the molecular typing model and the molecular typing model, and give the targeted treatment drug according to the type of chronic hepatitis B of the chronic hepatitis B patient. From the perspective of disease heterogeneity, the application provides a new idea for the treatment of drug-resistant patients and a new stratification suggestion for CHB patients.

The invention provides application of a BTLA inhibitor in preparation of a medicine for preventing and / or treating chronic hepatitis B, and belongs to the technical field of biological medicine. Research finds that antagonistic B and T lymphocyte attenuation factors (BTLA) can promote removal of hepatitis B surface antigen (HBsAg), reduce the expression level of HBeAg, promote activation and proliferation of T cells and enhance host immune response, so that the purpose of preventing and / or treating chronic hepatitis B is achieved, and functional cure of chronic hepatitis B (CHB) is achieved. The invention provides more choices for medicines for clinically preventing and / or treating chronic hepatitis B.

The invention belongs to the field of biological medicines, and relates to a pharmaceutical composition and application thereof in preparation of medicines for preventing and treating hepatitis B virus. Comprising a nucleic acid drug and a carrier for loading the nucleic acid drug, the carrier can specifically target liver Kupffer cells, the nucleic acid drug is mRNA, and a gene sequence for coding the mRNA comprises nucleotide sequences shown as SEQ ID NO: 1 and SEQ ID NO: 2. The pharmaceutical composition provided by the invention can specifically activate Notch signal channels of Kupffer cells, and can play a role in treating and preventing hepatitis B; meanwhile, the anti-HBV effect of the pharmaceutical composition depends on the participation of Kupffer cells, and the pharmaceutical composition becomes a potential novel strategy for clinical treatment of chronic hepatitis B.

This invention relates to a fusion antigen mRNA molecule, which encodes a protein comprising at least two of the following: hepatitis B surface antigen protein sHBsAg, hepatitis B core antigen protein Core, hepatitis B X antigen protein HBxAg, and hepatitis B preS1 antigen protein PreS1, preferably comprising hepatitis B surface antigen protein sHBsAg, hepatitis B core antigen protein, and hepatitis B PreS1 antigen protein, denoted as sHBsAg-Core-PreS1, and its amino acid sequence is shown in SEQ ID No. 17; the above-mentioned fusion antigen mRNA molecule can be prepared into an mRNA-LNP vaccine composition and used to treat chronic hepatitis B virus infection. The preferred sHBsAg-Core-PreS1 mRNA-LNP of this invention can normally express and present each encoded target antigen in vivo, and achieve cross-presentation, cross-activation and enhanced expression, inducing target antigen-specific humoral and cellular immune responses. It can also effectively overcome immune tolerance in a mouse model of chronic hepatitis B, and has excellent antiviral and immunotherapeutic effects. Compared with existing related therapeutic HBV mRNA-LNP vaccines, it effectively improves the immune tolerance breakthrough threshold, providing a candidate vaccine and a new immunotherapy strategy for the immunotherapy of patients with chronic HBV infection.

This invention discloses the application of β-1,4-galactosyltransferase 1 and its inhibitors in liver diseases, particularly acute liver injury and liver failure. The application of β-1,4-galactosyltransferase 1 and its inhibitors in acute liver injury and liver failure provides the correlation between β-1,4-galactosyltransferase 1 and acute liver injury and liver failure, confirming that inhibiting the activity of β-1,4-galactosyltransferase 1 can alleviate acute liver injury and liver failure. β-1,4-galactosyltransferase 1 can serve as a drug target for screening acute and chronic hepatitis, liver injury, fatty liver, liver fibrosis, and acute and chronic liver failure. This invention also confirms the alleviating effect of β-1,4-galactosyltransferase 1 inhibitors on acute liver failure. β-1,4-galactosyltransferase 1 inhibitors improve acute liver failure by reducing the enzyme activity or protein expression of β-1,4-galactosyltransferase 1.

Virus-Like Particles derived from the subfamilies, Parahepevirinae, which infect trout and salmon, and the Orthohepevirinae, which infect mammals and birds, particularly those of the species Paslahepevirus balayani, which can cause acute hepatitis in humans and several mammalian species, and chronic conditions in immunocompromised patients are also disclosed. Major aspects of the invention relate to compositions of Virus-Like Particles comprising viral capsid proteins capable of assembly in cultured cells that may be purified, disassembled, and reassembled in the presence of other molecules suitable for use as therapeutic drug products to facilitate the targeting and delivery of cargo molecules to specific cells or tissues, or as antigenic agents designed to stimulate responses to heterologous epitopes exposed on the surfaces of Virus-Like Particles. Preferred aspects relate to functional capsids comprising polypeptide sequences comprising one or more amino acid substitutions, insertions, or deletions of amino acid encoded by a consensus of ORF2 genes, wherein said variant polypeptides are functionally-similar or have enhanced properties compared to capsid polypeptides encoded by naturally-occurring viruses obtained from clinical samples or prototype Hepatitis E Viruses (HEV). Other aspects include the design and assembly of modified vectors to facilitate the basic and applied studies leading to the development and commercialization of novel drug products, and as tools advancing the interests of institutions involved in animal and human healthcare.

There is provided a method of curing chronic hepatitis B infection in a human, the method comprising administering to a subject in need thereof an effective amount of one or both of an exogenous anti-HBs antibody or an anti-HBs antibody producing carrier, the present invention relates to a method for reducing cellular and blood hepatitis B surface antigen (HBsAg) by providing continuously increased levels of anti-HBs antibodies in the subject.

The present invention provides liver cancer-associated serum microRNA markers and a new method for diagnosing liver cancer, wherein the liver cancer-associated serum microRNA markers consist of hsa-miR-122, hsa-miR-21, hsa-miR-2115, hsa-miR-221, hsa-miR-27 and hsa-miR-4499; relative expression level of the liver cancer-associated serum microRNA markers in serum is tested using Real-time PCR method, and reagents for the testing contains primers of the liver cancer-associated serum microRNA markers. The present invention can be used to diagnose hepatocellular carcinoma, in particular early hepatocellular carcinoma or to distinguish the serum of at least one patient with hepatocellular carcinoma from the serum of at least one healthy individual, the serum of at least one patient with chronic hepatitis B or the serum of at least one patient with liver cirrhosis.

The invention relates to the technical field of biological molecular diagnosis of hepatitis B related diseases, and particularly discloses a group of HBV related liver injury diagnostic markers and application thereof. According to the serum exosomes tRF-Val-TAC, tRF-Lys-CTT and tRF-Lys-TTT provided by the invention, the tRFs marker is tRFs combined detection of any one or combination of the sequences, and has the index advantages of high AUC value, high sensitivity and strong specificity; the method can solve the problem of difficulty in early and accurate diagnosis of hepatitis B-related chronic plus acute liver failure (HBV-ACLF) caused by pure dependence on traditional biochemical and blood coagulation indexes, and can meet various diagnosis requirements of ACLF, chronic hepatitis B and cirrhosis.

Provided herein are methods for treating chronic hepatitis B (CHB) infections in human subjects. In some embodiments, the methods involve administering a lipid nanoparticle carrying an epigenetic-modifying DNA targeting system composed of polynucleotides for targeting repression of total Hepatitis B Viral (HBV) transcripts. Also provided is a lipid nanoparticle carrying the polynucleotides.

This invention discloses a compound preparation of toad skin and its preparation method, which is made by processing dried toad skin, astragalus, and tortoise shell powder in a certain proportion. Compared with the prior art, this invention has the effects of invigorating qi and tonifying the kidney, detoxifying and relieving pain. The formulation of this invention is more reasonable, and it has significant curative effects on mid-to-late stage tumors, chronic hepatitis B and other diseases, without any toxic side effects.

The invention relates to the technical field of biological medicine, in particular to fusion protein and application thereof in preparation of products for treating or preventing hepatitis B virus. PreS1 is used as a core antigen component and modified IgM is used as a basic skeleton to obtain a preS1-IgM monomer, then J chain connection is performed to obtain fusion protein, the fusion protein is used as an active component to construct the therapeutic vaccine, anti-preS1 antibody response can be effectively stimulated, and Th1 / Th2 immune response can be synergistically activated. Experiments show that serum HBsAg, HBV DNA and intrahepatic virus antigen levels of a chronic HBV infection model can be remarkably reduced by using the vaccine alone, and serological conversion of part of animals is realized; when the compound is combined with entecavir, the compound shows an excellent synergistic effect. According to the vaccine, the treatment effect is remarkably improved, meanwhile, remarkable liver injury is not caused, and an innovative immunotherapy with prevention and treatment functions is provided for chronic hepatitis B treatment.

The present application relates to the technical field of biological medicine, and particularly relates to a fusion protein and application thereof in preparation of a product for treating or preventing hepatitis B virus. The present application takes preS1 as a core antigen component and takes an improved IgM as a basic skeleton to obtain a preS1-IgM monomer, and then connects the preS1-IgM monomer through a J chain to obtain a fusion protein. The fusion protein is taken as an active component to construct a therapeutic vaccine, which can effectively stimulate an anti-preS1 antibody response and synergistically activate a Th1 / Th2 immune response. Experiments show that the vaccine alone can significantly reduce the serum HBsAg, HBV DNA and intrahepatic virus antigen levels of a chronic HBV infection model, and realize seroconversion of part of the animals. When the vaccine is used in combination with entecavir, a remarkable synergistic effect is exhibited. The vaccine significantly improves the therapeutic effect without causing significant liver damage, and provides an innovative immunotherapy with both prevention and treatment functions for chronic hepatitis B treatment.

This invention belongs to the field of biomedical technology and provides an application of a ferroptosis inhibitor in the treatment of hepatitis. This invention reveals that a GRIM-19 gene defect specifically induces ferroptosis in hepatocytes, rather than other cell death mechanisms such as apoptosis, necrosis, or autophagy. This invention provides a ferroptosis inhibitor with Ferrostatin-1 as the active ingredient, solving the technical problem of insufficient intervention against the ferroptosis mechanism in existing hepatitis treatments. This inhibitor can significantly increase the expression level of GPX4 in liver tissue, effectively clear lipid peroxides, a core toxic product in the ferroptosis process, and block the ferroptosis process; in addition, it can significantly inhibit the activation of the NLRP3 inflammasome and reduce the expression of downstream inflammatory factors, thereby alleviating inflammatory cell infiltration and fibrotic lesions in the liver. This invention is applicable to the treatment of GRIM-19 deficiency-related chronic hepatitis, providing a new strategy for targeted therapy of liver diseases.

The invention relates to an anti-HBsAg antibody, an antibody fragment and application thereof in preventing and treating hepatitis D virus infection and related diseases. The present invention provides a method of neutralizing hepatitis delta virus infection comprising administering an effective amount of the antibody or antigen-binding fragment thereof to a patient in need thereof by injection or infusion.

The invention discloses a system, equipment and medium for predicting the progress of chronic hepatitis B cirrhosis based on ordered logistic regression, and relates to the technical field of intelligent diagnosis and treatment. According to the method, a traditional ordered logistic regression model is improved, a self-adaptive threshold extension ordered logistic regression model is obtained, and a model for predicting the progress of chronic hepatitis B cirrhosis is constructed based on the quantitative data of the optimal serum marker obtained through screening. According to the present invention, in the two scenes of F < 2 + > and F < 3 + > prediction, the performance exceeds the XGB Classifier, the Random Forest Classifier and the Logistic Regression, and is superior to the classic hepatic fibrosis scoring model APRI model, the FIB-4 model and the GPR model, such that the important clinical application value is provided.

The invention relates to a metabolic biomarker for malignant transformation of chronic hepatitis B and application of the metabolic biomarker, and belongs to the technical field of biomedicine. The invention provides aldehyde oxidase 1 (AOX1) and its downstream metabolite pyridoxal phosphate (PLP) as metabolic biomarkers for chronic hepatitis B malignant transformation. Through metabonomics and transcriptomics analysis, a'first-rising and second-falling 'dynamic trajectory of PLP rising in a chronic hepatitis B stage and falling in a liver cancer stage is found, and HBx reduces the PLP level by inhibiting AOX1 expression. The marker can be used for preparing a detection reagent, a kit or an integrated device, and dynamic monitoring and early warning of the vicious transformation risk are realized by detecting the AOX1 / PLP level in samples such as serum. The marker has the advantages of being clear in mechanism, high in dynamic relevance, suitable for clinical transformation and the like, and a new means is provided for liver cancer risk monitoring of chronic hepatitis B patients.