As new evidence emerges, treatment strategies toward the functional cure of chronic hepatitis B are evolving. In 2019, a panel of national hepatologists published a Consensus Statement on the functional cure of chronic hepatitis B. Currently, an international group of hepatologists has been assembled to evaluate research since the publication of the original consensus, and to collaboratively develop the updated statements. The 2.0 Consensus was aimed to update the original consensus with the latest available studies, and provide a comprehensive overview of the current relevant scientific literatures regarding functional cure of hepatitis B, with a particular focus on issues that are not yet fully clarified. These cover the definition of functional cure of hepatitis B, its mechanisms and barriers, the effective strategies and treatment roadmap to achieve this endpoint, in particular new surrogate biomarkers used to measure efficacy or to predict response, and the appropriate approach to pursuing a functional cure in special populations, the development of emerging antivirals and immunomodulators with potential for curing hepatitis B. The statements are primarily intended to offer international guidance for clinicians in their practice to enhance the functional cure rate of chronic hepatitis B.

AIMS:Human immunodeficiency virus(HIV) co-infection may cause different immune imprinting, which leads to different hybrid immunity and clinical manifestations of coronavirus disease 2019. This study aims to evaluate the immune imprinting from wild-type(WT) vaccination in people living with HIV(PLWH) and analyze its effect on hybrid immunity and clinical manifestations. MATERIALS AND METHODS:We enrolled 118 PLWH to compared the differences of BA.5-specific immune response in different immune modes. 20 vaccinated healthy individuals(HC) and 30 vaccinated PLWH were matched to compare the differences of the status of Omicron infection, serum neutralizing antibody levels against WT and BA.5, and specific lymphocytes expression, separately. KEY FINDINGS:Hybrid immunity had a higher level of BA.5 IgG than either vaccine immunity only or natural immunity only in PLWH but didn't have a higher level of BA.5-specific lymphocytes responses. PLWH had fewer symptoms than HC after breakthrough infection. The neutralizing inhibition rate of PLWH was higher for BA.5 and lower for WT, while the neutralizing inhibition rate of HC was higher for WT and lower for BA.5. The difference value of specific B lymphocytes/memory B cells/follicular helper T cells of PLWH was greater than that of HC. SIGNIFICANCE:Hybrid immunity of PLWH has a higher level of Omicron-specific IgG without a higher level of Omicron-specific lymphocytes due to immune imprinting. However, there is a stronger neutralizing ability against variants of PLWH due to the weaker immune imprinting of PLWH than that of healthy people, which may lead to fewer symptoms in PLWH after breakthrough infection.

Background: Hepatitis C virus (HCV) infection is prevalent worldwide. Observational studies have shown that HCV infection is associated with extrahepatic cancer. However, the results are inconsistent and causality remains to be established.Methods: A two-sample Mendelian randomization (MR) was conducted to explore whether HCV infection is causally associated with extrahepatic cancers. Based on the summary-level genome-wide association studies (GWAS) data from a publicly available database, the variance weighted inverse (IVW) was applied as the primary method to estimate causality, and other estimators were used as complementary methods.Results: A total of 14 extrahepatic cancer were included in this study and 4 single nucleotide polymorphisms (SNPs) were used as instrumental variables (IVs) for HCV infection. The results of IVW method indicated that genetic liabilities of HCV infection were strongly associated with colorectal cancer (OR: 1.353, P = 4.05e-06) and lung cancer (OR: 1.341, P = 7.03e-04). Also, we found that the genetic liability of HCV infection was suggestively causally associated with gastric cancer (OR: 1.224, P = 0.017). However, HCV infection was not significantly associated with ovarian, cervical cancer, biliary cancer, pancreatic cancer, ovarian cancer, esophageal cancer, pharyngeal and laryngeal cancer, skin cancer, thyroid cancer, endometrial cancer and breast cancer. And no pleiotropy was observed.Conclusions: HCV infection have causal effect on extrahepatic cancers including colorectal and lung cancers. We recommend enhanced screening for extrahepatic cancers in chronically HCV-infected individuals for early detection of cancer.Funding: This work was supported in part by grants from the National Science and Technology Major Project of China (2017ZX10202203008), the National Natural Science Foundation of China (81772171), the Chongqing Talents Project (cstc2021ycjh-bgzxm0150) and the Remarkable Innovation–Clinical Research Project, The Second Affiliated Hospital of Chongqing Medical University.Declaration of Interest: The authors declare that they have no conflict of interest.

AbstractBackgroundThe associations of hypotension with mortality in general population remains incompletely understood. We aimed to investigate whether hypotension is associated with higher all-cause and cardiovascular disease (CVD) mortality in this population.MethodsIn this prospective analysis, we utilized data from the National Health and Nutrition Examination Survey (NHANES, 1999-2018), with mortality information linked until 2019. We used multivariable Cox proportional hazards regression to estimate hazard ratios (HRs) and 95% CIs for the associations of different blood pressure (BP) with all-cause and CVD mortality.FindingsAmong the 37,832 participants, a total of 5261 deaths and 1664 deaths attributed to CVD causes were recorded over a median of 8.4 years of follow-up. The prevalence of hypotension was 7.6%. Both systolic BP and diastolic BP exhibited a J-shaped association with the all-cause and CVD mortality in restricted cubic spline modeling analysis (nonlinear-P <0.01). Compared to the normal BP group, the adjusted HRs for all-cause and CVD mortality in the hypotension group were 1.44 (1.20-1.74) and 1.57 (1.10-2.24), respectively. Subgroup analyses revealed that older individuals (age ≥60 years) and those with obesity exhibited more pronounced HRs for all-cause mortality, with HRs of 1.60 (1.28-2.00) and 1.95 (1.45-2.61), respectively (P for interaction <0.05).InterpretationIn this nationally representative cohort of US adults, hypotension demonstrated a significant association with both all-cause and cardiovascular disease mortality, particularly among elderly and obesity individuals. The findings underscore the significance of paying attention to and optimizing the management of hypotension in the general population.

BackgroundThe worldwide spread of monkeypox (mpox) has witnessed a significant increase, particularly in nonendemic countries. ObjectiveWe aimed to investigate the changing clinical symptoms associated with mpox from 1970 to 2023 and explore their interrelations. MethodsIn this systematic review and meta-analysis, 3 electronic databases were searched for English peer-reviewed studies conducted from January 1970 to April 2023 that reported any symptoms among confirmed mpox cases. We categorized the mpox epidemics into 3 periods: 1970-2002 (period 1, within the African region), 2003-2021(period 2, epidemics outside Africa), and 2022-2023 (period 3, worldwide outbreak). Following PRISMA guidelines, a meta-analysis was performed to estimate the pooled prevalence for each symptom. The correlation among symptoms was analyzed and visualized using network analysis. ResultsThe meta-analysis included 61 studies that reported 21 symptoms in 720 patients from period 1, 39 symptoms in 1756 patients from period 2, and 37 symptoms in 12,277 patients from period 3. The most common symptom among patients from all 3 periods was rash (period 1: 92.6%, 95% CI 78.2%-100%; period 2: 100%, 95% CI 99.9%-100%; and period 3: 94.8%, 95% CI 90.9%-98.8%), followed by lymphadenopathy (period 1: 59.8%, 95% CI 50.3%-69.2%; period 2: 74.1%, 95% CI 64.2%-84.1%; and period 3: 61.1%, 95% CI 54.2%-68.1%). Fever (99%, 95% CI 97%-100%), enlarged lymph nodes (80.5%, 95% CI 75.4%-85.0%), and headache (69.1%, 95% CI 4%-100%) were the main symptoms in period 1, with a significant decrease in period 3: 37.9%, 31.2%, and 28.7%, respectively. Chills/rigors (73.3%, 95% CI 60.9%-85.7%), fatigue (68.2%, 95% CI 51.6%-84.8%), and dysphagia/swallowing difficulty (61.2%, 95% CI 10.5%-100%) emerged as primary new symptoms in period 2 and decreased significantly in period 3. Most other symptoms remained unchanged or decreased in period 3 compared to the former 2 periods. Nausea/vomiting had the highest degree of correlation (with 13 symptoms) and was highly positively correlated with lymphadenopathy (r=0.908) and conjunctivitis (r=0.900) in period 2. In contrast, rash and headache were 2 symptoms with the highest degree of correlation (with 21 and 21 symptoms, respectively) in period 3 and were highly positively correlated with fever (r=0.918 and 0.789, respectively). ConclusionsThe manifestation of symptoms in patients with mpox has become more diverse, leading to an increase in their correlation. Although the prevalence of rash remains steady, other symptoms have decreased. It is necessary to surveil the evolving nature of mpox and the consequential changes in clinical characteristics. Epidemic countries may shift their focus on the potential association among symptoms and the high synergy risk. Trial RegistrationPROSPERO Registration: CRD42023403282; http://tinyurl.com/yruuas5n

The role of dendritic cells and the autophagy state of dendritic cells in the immune response of hepatitis B virus (HBV) infection was still controversial. In this study, we carefully examined the phenotype, function and autophagy pathway of dendritic cells in HBV infection. Monocyte-derived dendritic cells from healthy blood donors and patients with chronic HBV infection were stimulated by lipopolysaccharide, supernatant of HepG2.2.15 cells or supernatant of HepG2 cells respectively. Phenotype of dendritic cells was examined by flow cytometry and cytokines secretion was detected by enzyme-linked immunosorbent assay. Autophagy related proteins were detected by western blot and immunofluorescence analysis. Our results showed that the expression of both major histocompatibility complex II molecules and co-stimulated molecules including cluster of differentiation antigen 80, cluster of differentiation antigen 86 in the monocyte-derived dendritic cells from patients with chronic HBV infection was significantly higher than that from healthy donors when cultured with supernatant of HepG2.2.15 cells. The amount of cytokines, including tumour necrosis factor-α, interleukin-10 and interleukin-12, secreted by monocyte-derived dendritic cells from patients with chronic HBV infection was also significantly higher than that from healthy donors when stimulate by HBV. Interestingly, the expression level of autophagy-related proteins including autophagy-related protein5 and associated protein 1 light chain in dendritic cells from patients with chronic HBV infection was significantly increased when compared with that from healthy donors when re-exposed to HBV. Our results indicated that dendritic cells from patients with chronic HBV infection could intensively present antigen and express co-stimulatory molecules. The increased activation of dendritic cells might be related to the enhanced autophagy of dendritic cells in HBV infection.

AbstractTwo novel coordination polymers based on Cu(II) ions as the metal nodes, {Cu(pydc)(2,2‐bpy)(DMF)}n (1, H2pydc=3,5‐pyridinedicarboxylate, 2,2‐bpy=2,2‐bipyridine) and {[Cu(H2O)2(H2imdc)2](H2O)}n (2, H3imdc=1H‐imidazole‐4,5‐dicarboxylic acid) have been synthesized via the hydrothermal or solvothermal conditions and characterized by techniques of elemental analysis, powder X‐ray diffraction (PXRD) as well as the analysis of single‐crystal X‐ray diffraction. Furthermore, the anti‐tumor activities of compounds 1 and 2 against on U251 brain glioma cells were evaluated in vitro. The Cell Counting Kit‐8 (CCK‐8) detection was performed to assess anti‐tumor activities of compounds 1 and 2 on U251 brain glioma cells. The Annexin V‐FITC/PI approach and Terminal deoxynucleotidyl transferase mediated dUTP nick‐end labeling (TUNEL) staining was used to determine the U251 brain glioma cells apoptosis after compounds treatment. Besides, the ROS assay was utilized to determine the ROS accumulation within U251 brain glioma cells after compounds treatment. The RT‐PCR was conducted to measure the ROS related genes relative expression.

Hepatitis B surface antigen (HBsAg) seroclearance is an optimal therapeutic endpoint, as it reflects the amount of covalently closed circular DNA. The exact mechanisms that contribute to HBsAg reduction are not completely understood. We evaluated adaptive immunity in nucleoside analog-experienced chronic hepatitis B (CHB) pa-tients with low HBsAg levels who received oral antiviral therapy. One hundred and ninety-five CHB patients had hepatitis B virus (HBV) DNA <= 1000 IU/ml and HBsAg < 3000 IU/ml for longer than one year of antiviral therapy. According to HBsAg levels, they were divided into Group 1 (HBsAg reduction >= 0.5 log10) and Group 2 (HBsAg reduction < 0.5 log10). Cytokines, adaptive immune cells, and molecular markers in peripheral blood were detected at follow-up times. In total, 38 (19.5%) of the 195 patients achieved HBsAg reduction >= 0.5 log10. IL4, IL5, IL10, TGF beta, IL17, and PD-1 decreased gradually in these patients. HBsAg reduction had a link to the change in ICOSL+CD19+ B cells and CD40L+CXCR5+CD4+ Tfh cells. More CD8+ naive T lymphocytes differ-entiated into CD4+ TCMs, CD8+ TCMs and CD8+ TEMs in Group 1. Meanwhile, Group 1 exhibited elevated Th1 and Th1/Th2 levels and reduced levels of Treg versus those in Group 2. With the reduction in HBsAg, the imbalance of T-cell subsets was partially corrected; the immune activity of T cells was enhanced, and the state of immune exhaustion was alleviated to a certain extent.

Journal of Medical VirologyVolume 94, Issue 10 p. 4591-4592 LETTER TO THE EDITOR T cell epitopes are largely conserved in the SARS-CoV-2 Omicron subvariant (BA.1, BA.2, BA.3, and GKA) Hu Li, Hu Li Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaSearch for more papers by this authorZhiwei Chen, Zhiwei Chen Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaSearch for more papers by this authorXiaoqing Liu, Xiaoqing Liu Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaSearch for more papers by this authorPeng Hu, Corresponding Author Peng Hu [email protected] [email protected] orcid.org/0000-0001-8481-0841 Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China Correspondence Peng Hu, Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, 76# Linjiang Rd, Yuzhong District, Chongqing 400010, China. Email: [email protected] and [email protected]Search for more papers by this author Hu Li, Hu Li Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaSearch for more papers by this authorZhiwei Chen, Zhiwei Chen Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaSearch for more papers by this authorXiaoqing Liu, Xiaoqing Liu Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, ChinaSearch for more papers by this authorPeng Hu, Corresponding Author Peng Hu [email protected] [email protected] orcid.org/0000-0001-8481-0841 Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China Correspondence Peng Hu, Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, 76# Linjiang Rd, Yuzhong District, Chongqing 400010, China. Email: [email protected] and [email protected]Search for more papers by this author First published: 08 June 2022 https://doi.org/10.1002/jmv.27925 Hu Li, Zhiwei Chen, and Xiaoqing Liu contributed equally to this study. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume94, Issue10October 2022Pages 4591-4592 RelatedInformation