Cure of chronic hepatitis B virus （HBV） infection is the ultimate goal in HBV-related research， and exploring potential curative pathways may help to identify key research directions. Covalently closed circular DNA （cccDNA）， as the most difficult genetic material to be eliminated within the HBV replication cycle， is not only a primary impediment to achieving cure， but also a key issue for establishing an analytical framework for cure strategies. This article reviews the thinking framework of “cccDNA dynamics”， further elaborates on its core implications， and systematically discusses the main strategies to promote cccDNA decay.

Objective:To investigate the effect of DExH-box helicase 9(DHX9)O-linked N-acetylglucosamine(O-GlcNAc)modifi-cation(O-GlcNAcylation)on the proliferation of hepatitis B virus(HBV)-associated hepatoma cells.Methods:The pAdTrack-TO4-DHX9-3Flag recombinant adenovirus plasmid was constructed by molecular cloning and transfected into HEK293 cells for packaging and amplification of the recombinant adenovirus AdDHX9.The interaction between DHX9 and O-GlcNAc transferase(OGT)was con-firmed using co-immunoprecipitation.The co-localization between DHX9 and OGT was measured by immunofluorescence.The level of DHX9 O-GlcNAcylation was determined using succinylated wheat germ agglutinin(sWGA)and glycosylated immunoprecipitation(IP).The effect of DHX9 O-GlcNAcylation on the proliferation of HBV-associated hepatoma cells was assessed using the colony-forming assay and cell growth curves.Results:The recombinant adenovirus AdDHX9 was successfully obtained,and DHX9 expression was confirmed by Western blot.DHX9 interacted with OGT,and the two proteins were co-localized on the nucleus.The sWGA and gly-cosylated IP experiments showed that DHX9 underwent O-GlcNAcylation,which was further enhanced by HBV infection.The colony-forming assay demonstrated that the number of cell clones was increased in the AdDHX9 group(386.667±15.630)compared with the AdGFP control group(142.667±7.572,P<0.001).Moreover,cell growth curves demonstrated that the overall cell growth rate was en-hanced in the AdDHX9 group(22.860±0.770)compared with the AdGFP control group(13.670±0.517,P<0.001).Conclusion:HBV infection promotes DHX9 O-GlcNAcylation,which enhances the proliferation of HBV-associated hepatoma cells.

With the widespread implementation of immunoprophylaxis strategies, the primary challenge in HBV infection prevention and control in China has shifted to reducing the burden of existing infections. A crucial approach to decreasing the burden of existing infections is to develop the effective treatment methods to achieve clinical or functional cures within a limited treatment duration for infected patients. The existing infections can be divided into two parts: those that are easy to cure and those that are difficult to treat. Patients who meet the current drug withdrawal criteria and at the same time have HBsAg<100 IU/mL following treatment with nucelos(t)ide analogue therapy are the easier one to treat, accounting for about 12% of the total infections, and the remaining 88% are difficult to cure. A necessary step toward clinical cure is pushing the HBsAg levels of patients to <100 IU/mL, but this driving effect must stem from effective immune reconstitution against HBV. Recent prevention and control, certain characteristics and implementation of clinical cure, and the safe drug withdrawal are discussed here to offer new perspectives on issues related to hepatitis B.

With the widespread implementation of immunoprophylaxis strategies, the primary challenge in HBV infection prevention and control in China has shifted to reducing the burden of existing infections. A crucial approach to decreasing the burden of existing infections is to develop the effective treatment methods to achieve clinical or functional cures within a limited treatment duration for infected patients. The existing infections can be divided into two parts: those that are easy to cure and those that are difficult to treat. Patients who meet the current drug withdrawal criteria and at the same time have HBsAg<100 IU/mL following treatment with nucelos(t)ide analogue therapy are the easier one to treat, accounting for about 12% of the total infections, and the remaining 88% are difficult to cure. A necessary step toward clinical cure is pushing the HBsAg levels of patients to <100 IU/mL, but this driving effect must stem from effective immune reconstitution against HBV. Recent prevention and control, certain characteristics and implementation of clinical cure, and the safe drug withdrawal are discussed here to offer new perspectives on issues related to hepatitis B.

The persistent infection of hepatitis B virus (HBV) is the result of lacking specific immunity against the virus. This state is also called immune tolerance to HBV. In most cases, acute HBV infection in adults can induce specific immune response which can clear the virus. Perinatal HBV infection, however, usually progresses to chronic infection, indicating a defect in HBV-specific immune response. A typical specific immune response includes four processes, which were antigen presentation, specific CD4 + T cell activation, specific CD8 + T cell activation and B cell activation. There must be some dysfunctions in some or all of the four processes during chronic HBV infection. This article discussed the relationship between chronic HBV infection and cellular immunity, hoping to provide a reference for further study on the reconstitution of specific immunity against HBV.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is the template for HBV transcription and replication and exists stably in hepatocytes in the form of minichromosome. Based on the mechanism of cccDNA inactivation or clearance and the development of related drugs, this article introduces the current knowledge on the formation, transcription, and degradation of cccDNA and reviews the research advances in cccDNA-targeted drugs and biological techniques.

The construction of "Double First-class" has started a new journey of higher education in China. Scientific, reasonable and objective evaluation on universities is the foundation and important guarantee for the construction of first-class universities. On the basis of introducing the main university evaluation system at home and abroad, the selection of representative Chinese and world university evaluation system for comparative study has strong guiding significance for the establishment of first-class university evaluation system. Under the background of "Double First-Class" construction, based on Chinese characteristics, the author puts forward some thoughts and suggestions on perfecting the university evaluation system in China.

Direct-acting antivirals (DAAs) play a critical role for the therapy of chronical hepatitis B. DAAs can decrease the production of viral progeny of hepatitis B virus (HBV), breaking the viral dynamic equilibrium between: (1) virion production from hepatocytes and clearance from circulation; (2) replenishment and decay of covalently closed circular (ccc)DNA pool inside infected hepatocytes. Nucleos(t)ide analogues can potently shift the first balance to undetectable viremia in the blood, but have limited or no effect on the second one, thus making it imperative to develop new agents targeting additional step(s) of HBV life cycle. We herein briefly introduce the DAAs currently in development by classifying them as agents affecting the replenishment or the decay of cccDNA pool.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is stably maintained in hepatocytes in the form of minichromosome and is considered the most important cause of chronicity of HBV infection, presence of HBV after antiviral therapy, and recurrence of hepatitis after drug withdrawal. However, due to a lack of antiviral regimens targeting cccDNA itself or the formation and transcription of cccDNA, there is an urgent need for treatment strategies targeting cccDNA. With the gradual understanding of epigenetic modification of histones of the cccDNA minichromosome, epigenetic therapy is expected to become a potential therapy for HBV. This article reviews the current status and future directions of HBV DNA methylation and cccDNA-bound histone modification, in order to provide new thoughts for epigenetic therapy for HBV.

Objective To investigate the seroepidemiology of Epstein-Barr virus (EBV) and human immunodeficiency virus (HIV) in adult men who have sex with men (MSM) in Chongqing area. Methods Nonprobability sampling method was used to test EB-CA-IgG, EB-NA-IgG and EB-VCA-IgM in the sera of 1082 MSMs from the clinical trials of HIV/AIDS treatments in Chongqing area from 2012 to 2015, and 1059 healthy individuals by means of enzyme-linked immunosorbent assay. The results were analyzed by Chi-square test. The difference was considered statistically significant when P<0.05. Results The 1082 MSM included 130 HIV positive and 952 HIV negative subjects. The prevalence of prior EBV infection was 92.6% in total MSM population, 88.5% in HIV-positive MSM, and 93.2% in HIV-negative MSM. The prevalence in total MSM and HIV negative MSM was significantly higher than that in control group (89.9%). Prior EBV infection was not?found?in?0.5%?of?the?total?MSM,?0.8%?of?HIV?positive?MSM?and?0.4%?of?HIV?negative?MSM,?all?significantly?lower?than?that?of control group (5.0%) (P<0.05).?Finally,?the?rate?of?EBV?reactivation?in?HIV?positive?MSM?(10.0%)?was?significantly?higher?than?that in control group (3.8%) and in HIV negative MSM group(4.1%) (P<0.005). Conclusions EBV infection is highly prevalent in MSM, higher than that in the general population. The rate of EBV reactivation in HIV negative MSM is similar to that in general population. The rate of seroepidemiology-based EBV reactivation is significantly higher in HIV positive MSM, which may be associated with the immunocompromised status post HIV infection.