Relationship between HBV genotypes and anti-viral therapeutic efficacy of interferon-alpha

BACKGROUND: Much evidence demonstrates that the genotypes of hepatitis B virus (HBV) present differences in pathogenicity and outcomes owing to differences in genetic structure. This study aimed to investigate the influences of HBV genotypes on the anti-viral therapeutic efficacy of interferon-alpha (IFN-alpha) in chronic hepatitis B patients, and to determine the relationship between HBV genotypes and levels of viral replication or gene variations. METHODS: The chronic hepatitis B patients who were treated with IFN-alpha were selected randomly. Anti-viral therapeutic efficacy was monitored in these patients. The HBV genotypes were detected by PCR microplate hybridization ELISA. The levels of serum HBV-DNA were determined by fluorescence quantitative PCR. HBV gene variation at pre-C and basic core promoter (BCP) regions were assayed by gene chip technology. RESULTS: Genotypes B and C were predominant in 94 chronic hepatitis B patients. A, E and F genotypes were not found in these patients. The HBV-DNA levels of genotype C and mixed genotypes were significantly higher than those of genotype B. The response to IFN-alpha in patients with genotype B was markedly better than in those with genotypes C and D, and the complete response to IFN-alpha was only observed in genotype B. The response to IFN-alpha in patients with mixed genotypes was the least sensitive. The negative transition of HBeAg was correlated with variations in the HBV pre-C and BCP regions in patients with partial or no response to IFN-alpha. The variation rates of HBV pre-C and BCP regions were clearly higher in genotype C than in genotype B. CONCLUSIONS: The results suggest that HBV genotype is correlated with the serum levels of HBV-DNA, HBV gene variations and therapeutic efficacy of IFN-alpha. The regular detection of HBV genotypes in the clinic will be of benefit for disease prognosis and planning of anti-viral therapeutic strategies.

Era of direct acting anti-viral agents for the treatment of hepatitis C

Hepatitis C infection is universal and the most common indication of liver transplantation in the United States. The period of less effective interferon therapy with intolerable side effects has gone. Now we have stepped into the era of direct acting anti-viral agents(DAAs) against hepatitis C virus. Treatment of hepatitis C is now extremely effective, tolerable and requires a short duration of intake of oral agents. Less monitoring is required with the current therapy and drug-drug interactions are less than the previous regimen. The current treatment options of chronic hepatitis C with various DAAs are discussed in this article.

Anti-viral Effect of Caulis Tripterygii Wilfordii

There have appeared more and more antibiotics to antagonize against causative organism, but in comparison few antivirals have. Hence, many viral diseases remain refractory and fatal due to lack of effective medicine.Caulis Tripterygii wilfordii (TW) is a specific and potent Chinese medicine, and its effect in treating various intractable diseases, such as systemic lupus erythematosus, dermatomyositis, scleroderma, psoriasis and eczema has been confirmed by many medical researches. Pharmacological researches also proved that TW has anti-inflammatory and immunomodulatory actions. It is interesting that some effective components isolated from TW have an antiviral effect and more and more intention has been paid to related achievements at home and abroad.

Strong earthquake activity all over the world and strong-moderate earthquake ac-tivity within and near China (April 2007～May 2007)

All the data in this catalog are chosen from the ＂Preliminary Seismological Report of Chinese Seismic Stations＂ （Its abbreviation is ＂Monthly Report＂）. The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The ＂Monthly Report＂ is monthly compiled by the Ninth Section of Institute of Geophysics, China Earthquake Administration.

Strong earthquake activity all over the world and strong-moderate earthquake ac-tivity within and near China (December 2006～January 2007)

All the data in this catalog are chosen from the ＂Preliminary Seismological Report of Chi- nese Seismic Stations＂ （Its abbreviation is ＂Monthly Report＂）. The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The ＂Monthly Report＂ is monthly compiled by the Ninth Section of Institute of Geophysics, China Earthquake Administration.

Strong earthquake activity all over the world and strong-moderate earthquake ac-tivity within and near China (February,2006～March,2006)

All the data in this catalog are chosen from the ＂Preliminary Seismological Report of Chinese Seismic Stations＂ （Its abbreviation is ＂Monthly Report＂）. The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The ＂Monthly Report＂ is monthly compiled by the Ninth Section of Institute of Geoohysics, China Earthquake Administration.

Strong earthquake activity all over the world and strong-moderate earthquake ac-tivity within and near China (April,2006～May,2006)

Illustration All the data in this catalog are chosen from the ＂Preliminary Seismological Report of Chinese Seismic Stations＂ （Its abbreviation is ＂Monthly Report＂）. The catalog includes the events of M≥4.7 in and near China and M≥6 all over the world. The ＂Monthly Report＂ is monthly compiled bv the Ninth Section of Institute of Geophysics, China Earthquake Administration.

COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

Predictions in Clinical Efficiency of SARS-CoV-2 RNA-Dependent RNA Polymerase (RdRp) Inhibitors by Molecular Docking

This study utilizes the enzyme-substrate complex theory to predict the clinical efficacy of COVID-19 treatments at the biological systems level, using molecular docking stability indicators. Experimental data from the Protein Data Bank and molecular structures generated by AlphaFold 3 were used to create macromolecular complex templates. Six templates were developed, including the holo nsp7-nsp8-nsp12 (RNA-dependent RNA polymerase) complex with dsRNA primers (holo-RdRp-RNA). The study evaluated several ligands—Favipiravir-RTP, Remdesivir, Abacavir, Ribavirin, and Oseltamivir—as potential viral RNA polymerase inhibitors. Notably, the first four of these ligands have been clinically employed in the treatment of COVID-19, allowing for comparative analysis. Molecular docking simulations were performed using AutoDock 4, and statistical differences were assessed through t-tests and Mann-Whitney U tests. A review of the literature on COVID-19 treatment outcomes and inhibitors targeting RNA polymerase enzymes was conducted, and the inhibitors were ranked according to their clinical efficacy: Remdesivir > Favipiravir-RTP > Oseltamivir. Docking results obtained from the second and third templates aligned with clinical observations. Furthermore, Abacavir demonstrated a predicted efficacy comparable to Favipiravir-RTP, while Ribavirin exhibited a predicted efficacy similar to that of Remdesivir. This research, focused on inhibitors of SARS-CoV-2 RNA-dependent RNA polymerase, establishes a framework for screening AI-generated drug templates based on clinical outcomes. Additionally, it develops a drug screening platform based on molecular docking binding energy, enabling the evaluation of novel or repurposed drugs and potentially accelerating the drug development process.

淫羊藿苷抗自发性高血压大鼠肾小管上皮细胞凋亡的作用

目的观察淫羊藿苷(icariin,Ica)对自发性高血压大鼠(spontaneously hypertensive rats,SHR)肾小管上皮细胞凋亡的影响,探讨其可能的机制。方法将21只14周龄♂SHR随机分为模型组,Ica低、高剂量组(20、40 mg·kg-1,ig,bid,至26周龄),14周龄♂同源京都大鼠(WKY)为对照组,各组动物数均为7只。WKY组、模型组同期灌胃等体积双蒸水。采用HE染色观察肾脏病理学变化;原位缺口末端标记法检测肾小管上皮细胞凋亡;real time RT-PCR法检测肾Bok、Bcl-2、Bax mRNA水平;Western blot法检测肾Bcl-2、Bax、Active caspase-3蛋白表达。结果与WKY组相比,模型组肾小球囊腔狭窄且不规则,肾小球系膜基质增多,细胞排列紊乱,毛细血管扩张充血,个别肾小球出现皱缩,肾小管上皮细胞水肿、管腔狭窄;肾小管上皮细胞凋亡明显,Bok和Bax mRNA水平、Bax和Active caspase-3蛋白表达均明显上调,Bcl-2 mRNA和蛋白的水平明显下调(P<0.05或P<0.01)。与模型组比较,Ica-L组、Ica-H组肾小球囊腔增宽,肾小球系膜基质增生减少,细胞排列紊乱有所改善,毛细血管扩张充血、肾小管管腔狭窄均减轻;肾小管上皮细胞凋亡以及Bok、Bax mRNA水平和Bax蛋白表达均明显下调,IcaH组肾Bcl-2 mRNA水平和蛋白表达明显上调,Active caspase-3蛋白表达明显下调(P<0.05或P<0.01)。结论淫羊藿苷可抑制SHR肾小管上皮细胞凋亡,其机制可能与下调Bax、Active caspase-3、Bok,上调Bcl-2表达有关。

In vitro Antimicrobial Activity of Golden Buckwheat Extract and Therapeutic Effect of its Preparation on Chicken Mycoplasma Infection

[Objective] This study aimed to identify the in vitro antibacterial activity of golden buckwheat extract and investigate the therapeutic effect of its preparation on mycoplasma infection. [Method] Through measuring the minimum inhibitory concentra-tion, the in vitro antibacterial activity of golden buckwheat water extract was deter-mined; meanwhile, the therapeutic effect of golden buckwheat oral solution on my-coplasma infection was determined by artificial y infecting chickens with Mycoplasma gal isepticum culture. [Results] The golden buckwheat water extract had obvious in-hibitory effects against Pseudomonas aeruginosa and Escherichia coli, and a certain inhibitory effect on Salmonel a and Staphylococcus aureus; administration of golden buckwheat oral solution at the dose of 0.5%-1.0% continuously for 5 d had a good therapeutic effect against mycoplasma infection. [Conclusion] The study provides sci-entific bases for further study on the antibacterial activity of golden buckwheat and its application.

Molecular biology of liver disorders:the hepatitis C virus and molecular targets for drug development

INTRODUCTIONMolecular biology has made a tremendous impact on thediagnosis and treatment of liver diseases.In particular,advances in molecular biology made possible the

Hepatitis B virus genotypes:Global distribution and clinical importance

At least 600000 individuals worldwide annually die of hepatitis B virus(HBV)-related diseases,such as chronic hepatitis B(CHB),liver cirrhosis(LC),and hepatocellular carcinoma(HCC).Many viral factors,such as viral load,genotype,and specific viral mutations,are known to affect disease progression.HBV reverse transcriptase does not have a proofreading function,therefore,many HBV genotypes,sub-genotypes,mutants,and recombinants emerge.Differences between genotypes in response to antiviral treatment have been determined.To date,10 HBV genotypes,scattered across different geographical regions,have been identified.For example,genotype A has a tendency for chronicity,whereas viral mutations are frequently encountered in genotype C.Both chronicity and mutation frequency are common in genotype D.LC and progression to HCC are more commonly encountered with genotypes C and D than the other genotypes.Pathogenic differences between HBV genotypes explain disease intensity,progression to LC,and HCC.In conclusion,genotype determination in CHB infection is important in estimating disease progression and planning optimal antiviral treatment.

Hepatitis B:Who should be treated?-managing patients with chronic hepatitis B during the immune-tolerant and immunoactive phases

New hepatitis B virus(HBV)infections are decreasing owing to improved antiviral therapy and increased HBV vaccination worldwide;however,the number of HBV infections remains a major cause of liver carcinogenesis.HBV triggers cytotoxic immunity to eliminate HBV-infected cells.Therefore,the HBV pathophysiology changes in persistently infected individuals depending on host immune responses and HBV DNA proliferation state.To prevent liver cirrhosis and carcinogenesis caused by HBV,it is important to treat HBV infection at an early stage.Active treatment is recommended for the immunoactive hepatitis B surface-antigen-positive and-negative phase,but not during the immune-inactive phase or immune-tolerant phase;instead,follow-up is recommended.However,these patients should be monitored through regular blood tests to accurately diagnose the immune-inactive or-tolerant phases.The treatment regimen should be determined based on the age,sex,family history of liver cancer,and liver fibrosis status of patients.Early treatment is often recommended due to various problems during the immune-tolerant phase.This review compares the four major international practice guidelines,including those from the Japanese Society of Hepatology,and discusses strategies for chronic hepatitis B treatment during the immune-tolerant,immune-inactive,and resolved phases.Finally,recommended hepatitis B antiviral therapy and follow-up protocols are discussed.

COVID-19 in cancer patients:risk,clinical features,and management

A novel coronavirus known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has spread across the world,prompting the World Health Organization to declare the coronavirus disease of 2019(COVID-19)a public health emergency of international concern.Cancer patients are regarded as a highly vulnerable population to SARS-CoV-2 infection and development of more severe COVID-19 symptoms,which is possibly due to the systemic immunosuppressive state caused directly by tumor growth and indirectly by effects of anticancer treatment.Currently,much effort has been directed toward studying the pathogenesis and treatment of COVID-19,but the risk profiles,prognoses,and treatment outcomes in cancer patients remain unclear.Based on the current literature,we summarize the risk profiles,clinical and biochemical characteristics,and therapy outcomes of COVID-19 infections in cancer patients.The challenges in the clinical care of cancer patients with COVID-19 are discussed.The goal of this review is to stimulate research to better understand the biological impact and prognoses of COVID-19 infections in cancer patients,thus facilitating improvement of the clinical management of these patients.

EV713C protease cleaves host anti-viral factor OAS3 and enhances virus replication

The global spread of enteroviruses(EVs)has become more frequent,severe and life-threatening.Intereron(IFN)I has been proved to control EVs by regulating IFN-stimulated genes(ISG)expression.20-50-oligoadenylate synthetases 3(OAS3)is an important ISG in the OAS/RNase L antiviral system.The relationship between OAS3 and EVs is still unclear.Here,we reveal that OAS3,superior to OAS1 and OAS2,significantly inhibited EV71 replication in vitro.However,EV71 utilized autologous 3C protease(3C^(pro))to cleave intracellular OAS3 and enhance viral replication.Rupintrivir,a human rhinovirus 3C protease inhibitor,completely abolished the cleavage of EV713C^(pro)on OAS3.And the proteolytically deficient mutants H40G,E71A,and C147G of EV713C^(pro)also lost the ability of OAS3 cleavage.Mechanistically,the Q982-G983 motif in C-terminal of OAS3 was identified as a crucial 3C^(pro)cutting site.Further investigation indicated that OAS3 inhibited not only EV71 but also Coxsackievirus B3(CVB3),Coxsackievirus A16(CA16),Enterovirus D68(EVD68),and Coxsackievirus A6(CA6)subtypes.Notably,unlike other four subtypes,CA163C^(pro)could not cleave OAS3.Two key amino acids variation Ile36 and Val86 in CA163C^(pro)might result in weak and delayed virus replication of CA16 because of failure of OAS and 3AB cleavage.Our works elucidate the broad anti-EVs function of OAS3,and illuminate a novel mechanism by which EV71 use 3C^(pro)to escape the antiviral effect of OAS3.These findings can be an important entry point for developing novel therapeutic strategies for multiple EVs infection.

Fulminant hepatic failure in a case of autoimmune hepatitis in hepatitis C during peg-interferon-alpha 2b plus ribavirin treatment

A 27-year-old Caucasian female with hepatitis C virus (HCV) infection treated with interferon (IFN) who developed severe autoimmune hepatitis (AIH) is described. The infecting viral strain was of genotype Ib and the pre-treatment HCV viral load was at a high level. The patient was treated with pegylated IFN-alpha 2b and ribavirin,and her HCV-RNA became negative at wk 12,but after that she developed fulminant hepatic failure. The patient recovered after steroid pulse therapy consisting of methylprednisolone 1000 mg/d for three days which was administered twice. A needle liver biopsy revealed the typical pathological findings of AIH.

Two-year Observation of the Clinical Efficacy in Treating Chronic Hepatitis B Patients with Ganxian Recipe (肝纤方) and Lamivudine

Objective: To evaluate the clinical efficacy of Ganxian recipe (肝纤方, GXR) and lamivudine (LVD) in a two-year treatment of chronic hepatitis B (CHB). Methods: One hundred and twenty patients with CHB were randomly divided into the combinedly treated group (combined group) of 40 CHB patients who were treated with GXR combined with LVD. Another 40 CHB patients were treated with LVD alone (WM group), and still another 40 CHB patients were treated with GXR alone (TCM group). All these cases were randomly controlled and observed for two years. Results: Comprehensive efficacy: Total effective rate of the combined group (complete response and partial response) was 92.5%, while that of the WM group was 67.5% and TCM group 57.5%, respectively, with the difference between them was significant ( P <0.01); after treatment, the hepatic functions (AST, ALT, SB) of the three groups were all reduced, and the reduction in the combined group was particularly significant in comparison with the WM group or TCM group, P <0.05 or P < 0.01 respectively, suggesting that the effect in the combined group was better than that in the other two groups; the rate of tyrosine-methionine-aspartate-aspartate (YMDD) virus mutation: it was 7.5% in the combined group, 40.0% in the WM group, and 5.0% in the TCM group; liver fibrosis improvement parameter: after treatment, the results in the combined group got better than those in the other two groups. Conclusion: GXR could inhibit the appearance of YMDD after long-term application of LVD, and combined use has marked synergism.

Potent antiviral therapy improves survival in acute on chronic liver failure due to hepatitis B virus reactivation

Acute on chronic liver failure(ACLF)is a disease entity with a high mortality rate.The acute event arises from drugs and toxins,viral infections,bacterial sepsis,interventions(both surgical and non-surgical)and vascular events on top of a known or occult chronic liver disease.ACLF secondary to reactivation of chronic hepatitis B virus is a distinct condition;the high mortality of which can be managed in the wake of new potent antiviral therapy.For example,lamivudine and entecavir use has shown definite short-term survival benefits,even though drug resistance is a concern in the former.The renoprotective effects of telbivudine have been shown in a few studies to be useful in the presence of renal dysfunction.Monotherapy with newer agents such as tenofovir and a combination of nucleos(t)ides is promising for improving survival in this special group of liver disease patients.This review describes the current status of potent antiviral therapy in patient with acute on chronic liver failure due to reactivation of chronic hepatitis B,thereby providing an algorithm in management of such patients.