30 results about "Hepatitis B" patented technology

The present application relates to the technical field of knowledge graph, in particular to a multi-task hepatitis B drug screening method and system based on knowledge graph assistance, comprising the following steps: based on hepatitis B virus genotype sequence data recorded over time, patient drug use records and drug sensitivity. In the present application, multi-dimensional dynamic time series data such as virus genotype sequence data, patient drug use records and drug sensitivity are integrated, the interaction events between entities are marked by time stamp, the dynamic characteristics such as virus variation track and drug efficacy change are embedded in the graph node attributes, so that the knowledge representation can reflect the time dependence in the real scene. Based on biological pathway annotation information and protein interaction data, the hyperedge connection multi-entity set is defined, the limitation of traditional knowledge graph which only supports binary relationship is expanded, the drug combination and multi-target synergistic mechanism are explicitly modeled, and the misjudgment of combination effect caused by the simplification of interaction relationship is avoided.

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 present application provides a compound of formula (I), or an optical isomer thereof, a pharmaceutically acceptable salt, a solvated form, or a prodrug. The compound may modulate NTCP function for the prevention and / or treatment of HBV / HDV and hepatitis virus-related diseases, bile acid-related cholestasis disorders, metabolic disorders, and / or liver diseases. Additionally, the present application relates to a pharmaceutical composition comprising such a compound and a method for modulating NTCP.

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 invention discloses a plasma near-infrared spectrum mode recognition method for detecting latent hepatitis B. The method comprises the following steps: S1, collecting spectral data of a plasma sample to be tested in a near-infrared band; s2, acquiring multi-repetition near infrared spectrum data of each sample, and constructing a spectrum data set; s3, grouping samples of a latent hepatitis B infection group and a normal control group in the spectral data set; s4, constructing an OBI-normal control spectrum discrimination model of the plasma sample based on a classifier primitive algorithm; s5, preprocessing parameters are optimized based on the discriminant performance of the classifier; s6, constructing an optimal wavelength combination; and S7, checking the optimal model. Compared with the prior art, the plasma near infrared spectrum mode recognition method for detecting the latent hepatitis B has the advantage that a solution can be provided for developing a small special blood analyzer for detecting latent hepatitis B infection.

The present application relates to the technical field of medical data mining, in particular to a whole-course management system based on fusion analysis of hepatitis B serological and virological indexes, which comprises a serum index collection module, an evolution path construction module, a characteristic section extraction module, an intervention response classification module and a fusion structure induction module.In the present application, based on the index sequence matrix formed by continuous sampling, the trend trajectory is generated by tracking the change direction of the index concentration at each time node, the change fragments with structural differences are extracted in combination with the biochemical response markers, the index combination relationship under different interventions is classified and arranged, the matching mapping between the intervention behavior and the response path is established, the regular characteristics of the intervention effect are reflected through the combination of multiple indexes, and then the induction analysis result set covering the whole treatment process is generated, thereby providing clear data basis for dynamic intervention evaluation and treatment path adjustment.

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 present invention relates to the use of methylene blue in the treatment of treatment of hepatitis B (HBV) and / or hepatitis D (HDV) infection of a human patient as well as pharmaceutical compositions applicable in this treatment.

The application belongs to the technical field of pharmaceutical chemistry, and discloses a compound for inhibiting hepatitis B surface antigen and application thereof. It is proved through research that the recombinant plasmid S-HiBiT constructed can characterize the expression and secretion of HBs, and can be used for screening the compound for inhibiting HBs, and a cell model for screening anti-HBV drugs targeting HBsAg, i.e. HepG2-PB-S-HiBiT stable expression cell line. It is verified through experiments that the model is particularly suitable for high-throughput screening of compounds. Compound 1 and compound 3 capable of inhibiting HBsAg are found through screening of a compound library by using the model, the drug has the potential to be further developed into a hepatitis B treatment candidate drug, and a new drug is provided for the treatment of 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.

Disclosed herein are identified compound fragments, compounds and their pharmaceutically acceptable salts, isotopes or solvates, useful as antiviral drug and / or as a hepatic-targeted drug, such as for the treatment of HBV, HDV and / or HIV.

The present application relates to the technical field of immunological detection, in particular to hepatitis B PreS1 antigen and its preparation method and application. The present application first selects an active PreS1 polypeptide sequence, which is coupled to a hepatitis B surface antigen HBsAg molecule through a crosslinking agent to obtain a hepatitis B PreS1 antigen having both hepatitis B surface antigen activity and PreS1 antigen activity, which can be used as a calibrator and positive control in a hepatitis B PreS1 antigen detection kit. The kit uses anti-PreS1 antibody as coating and anti-HBsAg antibody as enzyme label. The artificial coupled hepatitis B PreS1 antigen prepared by the present application can effectively replace the currently used PreS1 real positive sample on the market, has no biological safety risk, stable source, and various indexes such as reactivity, vehicle stability and thermal stability, which are all better than those of the real positive sample, and has high innovation and applicability.

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.

Disclosed herein are processes for the preparation of fused heteroaryl dihydro pyrimidine compounds, or salts or stereoisomers thereof, which are useful for the treatment and prophylaxis of hepatitis B virus infections using compounds of formula IX or stereoisomers thereof,wherein a disclosed process comprisesa. reacting a compound formula IIwith hydrogen in the presence of a solvent and a palladium catalyst or a platinum catalyst, to form a compound of formula III:b. reacting the compound of formula III, or a salt or stereoisomer thereof, with a hydrolase selected from the group consisting of an amidase and a peptidase, or a mixture thereof, to form a compound of formula I:or a salt or stereoisomer thereof,c. protecting the compound of formula I, or a salt or stereoisomer thereof, with an amino protecting group (PG) selected from the group consisting of di-tert-butyl dicarbonate (Boc2O) and 2-(tert-butoxycarbonyloxyimino)-2-phenylacetonitrile, to form a compound of formula IV:d. reacting the compound of formula IV, or a salt or stereoisomer thereof, with a compound of the following formula: —R7—NH2 in the presence of a base and the coupling agent, carbonyldiimidazole (CDI), to form a compound of formula V:or a salt or stereoisomer thereof,e. reacting the compound of formula V above, or a salt or stereoisomer thereof, with oxalyl chloride to form a compound of formula VIf. reacting the compound of formula VI above, or a stereoisomer thereof, with a reducing agent selected from the group consisting of BH3·THF and NaBH4, to form a compound of formula VII:g. deprotecting the compound of formula VII above, or a stereoisomer thereof, with concentrated HCl in methyl isobutyl ketone (MIBK), to form a compound of formula IX:

This invention belongs to the field of biomedical technology, specifically providing the application of TL1A as a biomarker in the diagnosis of cirrhosis. This invention is the first to discover that the TL1A gene promoter exhibits a hypomethylated state in patients with hepatitis B-related cirrhosis, suggesting a close correlation between the methylation level of the TL1A gene promoter and the diagnosis of hepatitis B-related cirrhosis. Therefore, quantitative detection of TL1A gene promoter methylation can indicate the occurrence and progression of hepatitis B-related cirrhosis, thereby assisting in clinical diagnosis and possessing significant practical application value.

Compounds, methods, and compositions for treating or preventing viral infections using nucleoside compounds. The nucleoside compounds have increased antiviral activity potential with the result of inhibiting at least one of flaviviruses, herpesviruses, polyomaviruses, alphaviruses, enteroviruses, filoviruses matonaviruses, phenuiviruses, Hepatitis B virus, and / or coronaviruses.

The invention generally relates to the field of diagnostics and prognostics. In particular, the invention relates to a method for determining the responsiveness of a chronic hepatitis B (CHB) patient to IFN-alpha treatment. In an aspect of the invention, there is provided a method for determining the responsiveness of a chronic hepatitis B (CHB) patient to IFN-alpha treatment, comprising: (a) measuring an expression level of at least one biomarker of a prognostic biomarker panel selected from the group consisting of NQO2, MBL2, IGKV3D-20, PKHD1L1, PGLYRP1, KHSRP, LCN2, and ROBO1 in a biological sample obtained from the patient, and (b) comparing the expression level of the at least one biomarker to corresponding expression level of a known non-responder, wherein an expression level higher than the corresponding expression level is indicative of a likelihood of a positive response to IFN-alpha treatment.

This invention relates to the field of hepatitis B pharmacology, and discloses a method for identifying targets of traditional Chinese medicine (TCM) for chronic hepatitis B based on graph neural networks. First, the active ingredients and potential targets of at least two TCM formulas are extracted, and "TCM-component-target" networks are constructed respectively. From a TCM systems pharmacology database network, the degree centrality, betweenness centrality, and eigenvector centrality of node i in the data network are used as identification indicators for key nodes. Topological analysis is used to screen key nodes in the network, and then the importance of node i is comprehensively ranked using the PageRank algorithm. The core components and targets that rank highly in all TCM formulas are calculated. By constructing a modular network, the common components and target groups in the TCM formulas are calculated. Simultaneously, GO function and KEGG pathway enrichment analyses are performed to calculate the biological functions and signaling pathways associated with key targets. This invention utilizes molecular docking technology to verify the interaction between core targets and small drug molecules.

The present application provides a novel double-stranded siRNA, conjugates thereof and uses thereof. The present application also provides uses of the double-stranded siRNA and conjugates thereof in the preparation of a medicament for treating and / or preventing hepatitis B disease. The present application relates to a novel compound, and uses of the compound in the raw material for DNA nucleotide solid-phase synthesis, the raw material for siRNA drug synthesis, the research of siRNA drug, the research of gene function and / or the screening of whole gene library, especially in the raw material for the synthesis of the double-stranded siRNA drug. Furthermore, the present application also relates to a novel nucleotide residue, and its application in the research of siRNA drug, the research of gene function and / or the screening of whole gene library, and its application as an oligonucleotide intercalating group.

This invention relates to pharmaceuticals and methods for clearing hepatitis B virus (HBV) cccDNA from the livers of hepatitis B virus-infected individuals. Specifically, this invention provides the use of HBV entry inhibitors that inhibit HBV entry into hepatocytes and, optionally, immunomodulatory agents that regulate anti-HBV immunity in the preparation of pharmaceutical combinations or kits used in methods for clearing HBV cccDNA from hepatitis B patients. This invention also provides corresponding pharmaceutical combinations and kits for the above-mentioned uses.

This invention relates to enhancing antisense oligonucleotides that are complementary to distal upstream element-binding protein 1 (FUBP1) and capable of reducing FUBP1 target nucleic acids, such as FUBP1 mRNA. This invention relates to enhancing antisense oligonucleotides or conjugates thereof targeting FUBP1 for the treatment and / or prevention of hepatitis B virus (HBV) infection, particularly chronic HBV infection. This invention particularly relates to the use of said enhancing antisense oligonucleotides or conjugates thereof targeting FUBP1 for destabilizing cccDNA, such as HBV cccDNA. This invention further relates to enhancing antisense oligonucleotides or conjugates thereof targeting FUBP1 for the treatment of cancer. This invention also includes a pharmaceutical composition and its use in the treatment and / or prevention of HBV infection, or its use in the treatment of cancer.

The present invention provides a method for identifying compounds that prevent, improve, and / or suppress hepatitis B virus (HBV) infection. [Solution] The present invention relates to a method for identifying compounds that (i) reduce the expression and / or activity of PAP-related domain-containing protein 5 (PAPD5) and / or PAP-related domain-containing protein 7 (PAPD7) and / or (ii) bind to PAPD5 and / or PAPD7 and inhibit the proliferation of HBV, as compounds for preventing, improving and / or suppressing HBV infection. The present invention also provides PAPD5 and / or PAPD7 inhibitors for use in the treatment and / or prevention of HBV infection, as well as mixed formulations comprising PAPD5 inhibitors and PAPD7 inhibitors for simultaneous or sequential use in the treatment and / or prevention of HBV infection. Pharmaceutical compositions for use in the treatment and / or prevention of HBV infection, and methods for monitoring treatment outcomes during the treatment of HBV infection are also included in the present invention.

The present disclosure provides, in part, 5-membered heteroaryl formamide compounds useful for disrupting HBV core protein assembly and pharmaceutical compositions thereof and methods of treating hepatitis B (HBV) infection.

The application discloses a convenient-to-use hepatitis B detection kit, which comprises an outer box body, a label plaque is fixedly installed on the front side of the outer box body, a protective cover is hingedly connected to the upper end of the outer box body, the protective cover and the outer box body are fixed to each other through a lock catch, a containing block is fixedly connected to the inside of the outer box body, a guide groove for inserting a reagent tube is arranged on the containing block, a jacking limiting part is arranged in the guide groove, the jacking limiting part is used for limiting the inserted reagent tube, and is used for jacking up the reagent tube after the protective cover is opened, and a pressing block for applying pressure to the reagent tube is fixedly installed on the protective cover. The convenient-to-use hepatitis B detection kit can improve the stability of the kit and a desktop through negative pressure adsorption when the kit is placed, prevents the kit from being knocked down and falling after being subjected to external force, and facilitates the ejection of the reagent tube when the reagent tube is taken, thereby improving the convenience of taking the reagent tube.

The application provides a method for constructing a double humanized hepatitis B mouse model characterized by T cell immune reconstruction. The method is characterized by promoting humanized T cell reconstruction, and comprises the steps of constructing a human liver chimeric immunodeficient mouse model, infecting the human liver chimeric immunodeficient mouse with HBV, and implanting human immune cells. The results show that hAlb, HBV DNA and HBsAg can be continuously detected in the blood of the constructed mouse, HBsAg and HBcAg can be detected in the liver, and human immune cell infiltration mainly in the form of CD3+ T cells can be detected in the blood, liver and other organs, thereby forming a double humanized hepatitis B mouse model of the liver and the immune system. The humanized mouse model construction technology of the application can be used to study the interaction mechanism of HBV and immune cells in the process of hepatitis B. The technical scheme provides a good animal model for the research of hepatitis B progression, immune cell exhaustion mechanism and clinical hepatitis B drug treatment.

This invention provides an application of a reagent for detecting the expression level of lncRNA-NONHSAT178169.1, belonging to the field of biomedical technology. Research results showed significant differences in BTLA expression in peripheral blood T cells of CHB patients at different stages, with the highest expression in the IT phase, and CD8 expression... + T-cell differential expression was more pronounced. RNA-seq identified 29 differentially expressed lncRNAs, among which lncRNA-NONHSAT178169.1 was continuously downregulated under αBTLA treatment and validated by qPCR. Detection of lncRNA-NONHSAT178169.1 expression levels in test samples can specifically and sensitively predict or diagnose the immune tolerance phase of chronic hepatitis B. lncRNA-NONHSAT178169.1 provides more targets for predicting or diagnosing the immune tolerance phase of chronic hepatitis B.

本发明属于生物医学检测技术领域，具体涉及一种定量检测HBV preS2蛋白并鉴定血清亚型的方法。包括：采用LC‑MS / MS采集各亚型preS2蛋白特异性离子对信号；以标准曲线结合内标校正计算蛋白含量；同时提取血清HBV DNA，对preS2区进行PCR扩增和测序，与已知亚型参考序列比对确认亚型归属。本发明检测下限达100 pg / mL，可同时区分adw、adr、adr‑m、ayw、ayr五种亚型。在HBsAg阴性的隐匿性乙型肝炎患者中，该方法的preS2蛋白检出率达60%；在功能性治愈患者中，preS2蛋白检出率达70%。本发明通过质谱定量与核酸测序双重验证，为HBV特殊人群提供了可靠检测手段。