Hepatitis D virus （HDV）， as a defective virus， relies on the envelope protein of hepatitis B virus （HBV） to complete replication and transmission. Chronic hepatitis B （CHB） patients comorbid with HDV infection may experience significant acceleration of liver disease progression and a significantly higher risk of serious complications such as liver cirrhosis and hepatocellular carcinoma （HCC） compared with the patients with CHB alone， which poses a serious threat to the life and health of patients. At present， the coverage rate of HDV screening needs to be improved， and some patients with HBV/HDV co-infection have not been found in time. Therefore， strengthening the understanding of HDV among clinicians， expanding the scope of HDV screening， identifying patients with infection in a timely manner， and performing standardized antiviral therapy and long-term follow-up management are of great significance for improving the prognosis of patients， reducing disease burden， improving the quality of life of patients， and achieving the global goal of “eliminating viral hepatitis as a public health threat by 2030”.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

Objectives:This study aims to investigate the relationship between neutrophil to high-density lipoprotein cholesterol ratio(NHR)and incidence of cardiovascular disease(CVD)among individuals with metabolic associated fatty liver disease(MAFLD).Methods:We conducted a prospective cohort study utilizing health check-up data from 2006 to 2007 at Kailuan General Hospital and its 10 affiliated hospitals.The study population consisted of employees and retirees diagnosed with MAFLD,excluding those with incomplete neutrophil and high-density lipoprotein cholesterol data or a history of heart failure,myocardial infarction,cerebral hemorrhage,or cerebral infarction.CVD was defined as the presence of heart failure,myocardial infarction,cerebral hemorrhage,or cerebral infarction.Annual follow-ups were conducted from 2006,new-onset CVD cases identified through discharge records from the 11 Kailuan Group hospitals and records from municipal social insurance agencies,the final follow up date was December 31,2022.NHR was calculated as the ratio of neutrophil to high-density lipoprotein cholesterol,and the MAFLD cohort(n=28 952)was stratified into four groups by NHR quartiles:Q1 group(NHR<1.97,n=7 241),Q2 group(1.97≤NHR<2.57,n=7 235),Q3 group(2.57≤NHR<3.36,n=7 240),and Q4 group(NHR≥3.36,n=7 236).The Kaplan-Meier method was employed to plot survival curves for new-onset CVD,and the cumulative incidences of CVD across different NHR quartiles groups were determined.Intergroup comparisons were made using the log-rank test,and a multifactorial Cox proportional hazards regression model was used to assess the association between NHR quartiles and the risk of new-onset CVD in the MAFLD population.Results:The average follow-up duration was(14.03±3.99)years,during which 4 666 new CVD cases were recorded among the study population.The number of CVD cases across Q1 group to Q4 group were 1 061,1 167,1 186 and 1 252,respectively,with an overall incidence density of 11.5 cases per 1 000 person-years.The incidence densities for Q1 group to Q4 group were 10.4,11.4,11.7 and 12.5 cases per 1 000 person-years,respectively.The multifactorial Cox proportional hazards regression analysis revealed that higher NHR quartiles were associated with an increased relative risk of new-onset CVD(Q2 group:HR=1.13,95%CI:1.04-1.23;Q3 group:HR=1.15,95%CI:1.05-1.25;Q4 group:HR=1.22,95%CI:1.12-1.33).Conclusions:The risk of new-onset cardiovascular disease in individuals with MAFLD escalates with increasing NHR.

OBJECTIVE To explore the efficacy and safety of sofosbuvir-velpatasvir(SOF/VEL)combined with or without ribavirin(RBV)in treatment of the patients with genotype 3(GT3)chronic hepatitis C(CHC)and liver cirrhosis.METHODS Totally 230 patients with CT3 CHC and liver cirrhosis who were treated in Traditional Chi-nese Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Hetian Specialized Hospital of Infectious Diseases and Xinjiang Manasi County People's Hospital from Jun.2018 to Mar.2023 were recruited as the research sub-jects.The clinical curative effects were observed after the subjects were treated with single SOF-VEL or the com-bination with RBV for 12 to 24 weeks.The indexes including high-sensitivity hepatitis C RNA(HCV RNA),blood routine indexes,liver function indexes and noninvasive diagnosis indexes for liver fibrosis were observed,and the sustained virological response 12 weeks after the treatment(SVR12)was analyzed.RESULTS The mean age of the enrolled patients was(42.31±11.18)years old,the male patients accounted for 66.52％,and there were 137 cases of GT3a and 93 cases of GT3b 93,there were 183 cases of CHC,44 cases of compensated cirrhosis(CC)and 3 cases of decompensated cirrhosis(DCC).There were 189 cases of single HCV infection,33 cases of mixed infections of HCV and HIV,6 cases of mixed infections of HBV/HCV and 2 cases of triple infections of HBV/HCV/HIV.The overall SVR12 of the 230 patients was 99.57％,the SVR12 of the GT3a type patients was 100.00％,the GT3b type patients 98.92％.The SVR12 of the patients with CHC,CC and DCC were 99.45％,100.00％and 100.00％,respectively.The SVR12 of the patients with single HCV infection,HCV/HIV infec-tion,HBV/HCV infection and HBV/HCV/HIV were 99.47％,100.00％,100.00％and 100.00％,respective-ly.No patient quit the direct-acting antivirals(DAAs)treatment due to the drug-induced adverse reactions.1 pa-tient had relapse due to irregular administration of DAAs.CONCLUSION The virological response rate is high a-mong the patients with GT3 CHC and liver cirrhosis who are treated with single SOF/VEL or the combination with RBV,with the safety favorable.

OBJECTIVE To explore the efficacy and safety of sofosbuvir-velpatasvir(SOF/VEL)combined with or without ribavirin(RBV)in treatment of the patients with genotype 3(GT3)chronic hepatitis C(CHC)and liver cirrhosis.METHODS Totally 230 patients with CT3 CHC and liver cirrhosis who were treated in Traditional Chi-nese Hospital of Xinjiang Uygur Autonomous Region,Xinjiang Hetian Specialized Hospital of Infectious Diseases and Xinjiang Manasi County People's Hospital from Jun.2018 to Mar.2023 were recruited as the research sub-jects.The clinical curative effects were observed after the subjects were treated with single SOF-VEL or the com-bination with RBV for 12 to 24 weeks.The indexes including high-sensitivity hepatitis C RNA(HCV RNA),blood routine indexes,liver function indexes and noninvasive diagnosis indexes for liver fibrosis were observed,and the sustained virological response 12 weeks after the treatment(SVR12)was analyzed.RESULTS The mean age of the enrolled patients was(42.31±11.18)years old,the male patients accounted for 66.52％,and there were 137 cases of GT3a and 93 cases of GT3b 93,there were 183 cases of CHC,44 cases of compensated cirrhosis(CC)and 3 cases of decompensated cirrhosis(DCC).There were 189 cases of single HCV infection,33 cases of mixed infections of HCV and HIV,6 cases of mixed infections of HBV/HCV and 2 cases of triple infections of HBV/HCV/HIV.The overall SVR12 of the 230 patients was 99.57％,the SVR12 of the GT3a type patients was 100.00％,the GT3b type patients 98.92％.The SVR12 of the patients with CHC,CC and DCC were 99.45％,100.00％and 100.00％,respectively.The SVR12 of the patients with single HCV infection,HCV/HIV infec-tion,HBV/HCV infection and HBV/HCV/HIV were 99.47％,100.00％,100.00％and 100.00％,respective-ly.No patient quit the direct-acting antivirals(DAAs)treatment due to the drug-induced adverse reactions.1 pa-tient had relapse due to irregular administration of DAAs.CONCLUSION The virological response rate is high a-mong the patients with GT3 CHC and liver cirrhosis who are treated with single SOF/VEL or the combination with RBV,with the safety favorable.

Objectives:This study aims to investigate the relationship between neutrophil to high-density lipoprotein cholesterol ratio(NHR)and incidence of cardiovascular disease(CVD)among individuals with metabolic associated fatty liver disease(MAFLD).Methods:We conducted a prospective cohort study utilizing health check-up data from 2006 to 2007 at Kailuan General Hospital and its 10 affiliated hospitals.The study population consisted of employees and retirees diagnosed with MAFLD,excluding those with incomplete neutrophil and high-density lipoprotein cholesterol data or a history of heart failure,myocardial infarction,cerebral hemorrhage,or cerebral infarction.CVD was defined as the presence of heart failure,myocardial infarction,cerebral hemorrhage,or cerebral infarction.Annual follow-ups were conducted from 2006,new-onset CVD cases identified through discharge records from the 11 Kailuan Group hospitals and records from municipal social insurance agencies,the final follow up date was December 31,2022.NHR was calculated as the ratio of neutrophil to high-density lipoprotein cholesterol,and the MAFLD cohort(n=28 952)was stratified into four groups by NHR quartiles:Q1 group(NHR<1.97,n=7 241),Q2 group(1.97≤NHR<2.57,n=7 235),Q3 group(2.57≤NHR<3.36,n=7 240),and Q4 group(NHR≥3.36,n=7 236).The Kaplan-Meier method was employed to plot survival curves for new-onset CVD,and the cumulative incidences of CVD across different NHR quartiles groups were determined.Intergroup comparisons were made using the log-rank test,and a multifactorial Cox proportional hazards regression model was used to assess the association between NHR quartiles and the risk of new-onset CVD in the MAFLD population.Results:The average follow-up duration was(14.03±3.99)years,during which 4 666 new CVD cases were recorded among the study population.The number of CVD cases across Q1 group to Q4 group were 1 061,1 167,1 186 and 1 252,respectively,with an overall incidence density of 11.5 cases per 1 000 person-years.The incidence densities for Q1 group to Q4 group were 10.4,11.4,11.7 and 12.5 cases per 1 000 person-years,respectively.The multifactorial Cox proportional hazards regression analysis revealed that higher NHR quartiles were associated with an increased relative risk of new-onset CVD(Q2 group:HR=1.13,95%CI:1.04-1.23;Q3 group:HR=1.15,95%CI:1.05-1.25;Q4 group:HR=1.22,95%CI:1.12-1.33).Conclusions:The risk of new-onset cardiovascular disease in individuals with MAFLD escalates with increasing NHR.