The persistence of covalently closed circular DNA(cccDNA)in hepatitis B virus(HBV)-infected hepatocytes remains a major obstacle to effective antiviral treatment.Understanding the molecular mechanisms regulating HBV c...The persistence of covalently closed circular DNA(cccDNA)in hepatitis B virus(HBV)-infected hepatocytes remains a major obstacle to effective antiviral treatment.Understanding the molecular mechanisms regulating HBV cccDNA transcription is essential for developing novel therapeutic strategies.In this study,we investigated the role of RNA binding motif protein 25(RBM25)in HBV replication,focusing on its interaction with cccDNA and its regulation of host transcription factors.The results demonstrated that RBM25 knockdown markedly inhibited HBV replication,reducing levels of HBV DNA,hepatitis B e antigen(HBeAg),hepatitis B surface antigen(HBsAg),HBV RNA,and L-HBs in HBV-replicating and infected cell models.Consistent results were observed in a mouse model hydrodynamically injected with 1.2HBV plasmid.Conversely,RBM25 overexpression significantly enhanced HBV replication.Mechanistically,RBM25 promoted HBV promoter activities by binding to cccDNA through its RE/RD and PWI domains.This effect was mediated by increased Yin Yang 1(YY1)expression,which enhanced acetylation of cccDNA-bound histones,promoting HBV transcription.Furthermore,RBM25 expression was upregulated and translocated to the nucleus following core protein expression and accumulation,while overexpression of RBM25 promoted core protein degradation.In conclusion,this study demonstrates that RBM25 is a novel host factor that enhances HBV replication by upregulating YY1-dependent transcriptional activation of cccDNA.It also reveales a reciprocal regulatory mechanism between the HBV core protein and RBM25,which helps sustain HBV replication.展开更多
Naturally occurred precore(PC,G1896A)and/or basal core promoter(BCP,A1762T/G1764A)mutations are prevalent in chronic HBV-infected patients,especially those under HBeAg-negative status.However,the replicative capacity ...Naturally occurred precore(PC,G1896A)and/or basal core promoter(BCP,A1762T/G1764A)mutations are prevalent in chronic HBV-infected patients,especially those under HBeAg-negative status.However,the replicative capacity of HBV with PC/BCP mutations remains ambiguous.Herein,meta-analysis showed that,only under HBeAg-negative status,the serum HBV DNA load in patients with PC mutation was 7.41-fold higher than those without the mutation.Both PC mutation alone and BCPþPC mutations promoted HBV replication in cell and hydrodynamic injection mouse models.In human hepatocyte chimeric mouse model,BCPþPC mutations led to elevated replicative capacity and intrahepatic core protein accumulation.Mechanistically,preC RNA harboring PC mutation could serve as mRNA to express core and P proteins,and such pgRNA-like function favored the maintenance of cccDNA pool under HBeAg-negative status.Additionally,BCPþPC mutations induced more extensive and severe human hepatocyte damage as well as activated endoplasmic reticulum stress and TNF signaling pathway in livers of chimeric mice.This study indicates that HBeAg-negative patients should be monitored on HBV mutations regularly and are expected to receive early antiviral treatment to prevent disease progression.展开更多
Dear Editor,Hepatitis B virus(HBV)infection remains a major cause of liver diseases worldwide,which affects approximately 250 million people globally(Yuen et al.2018).Individuals with chronic HBV infection are at high...Dear Editor,Hepatitis B virus(HBV)infection remains a major cause of liver diseases worldwide,which affects approximately 250 million people globally(Yuen et al.2018).Individuals with chronic HBV infection are at high risk of developing liver cirrhosis,and ultimately hepatocellular carcinoma(HCC).HBV is a Hepadnavirus DNA virus,which specifically infects and efficiently replicates in hepatocytes.It has been proposed for decades that HBV replicates preferentially in non-dividing quiescent hepatocytes(Ozer et al.1996).展开更多
On April 5,2022,United Kingdom(UK)reported 10 cases of severe acute hepatitis with unknown cause among children under 10 years old.The initial symptoms of these cases could date back to March 2022.A rapidly increasing...On April 5,2022,United Kingdom(UK)reported 10 cases of severe acute hepatitis with unknown cause among children under 10 years old.The initial symptoms of these cases could date back to March 2022.A rapidly increasing number of cases lasted for a month and the growth seems to be slightly slowing down in May.As of May 27,2022,the total number of children with acute hepatitis in UK reached to 222(UKHSA,2022a).European Union and European Economic Area reported 305 cases across 17 countries and none as epidemiologically linked as of May 31,2022(ECDC-WHO,2022).展开更多
In the issue of Gastroenterology published October 2018,the article by Moon et al.1 demonstrated that screening patients with cirrhosis for hepatocellular carcinoma(HCC)by ultrasound scan(USS),measurement of serumα-f...In the issue of Gastroenterology published October 2018,the article by Moon et al.1 demonstrated that screening patients with cirrhosis for hepatocellular carcinoma(HCC)by ultrasound scan(USS),measurement of serumα-fetoprotein(AFP),each alone or in combination,was not associated with the decreased HCC-related mortality.In this matched case control study,all the study patients were registered in detail in the U.S.Department of Veterans Affairs.The study included 238 cases who died of HCC with cirrhosis,and the same number of matched controls with cirrhosis who had been enrolled in U.S.Department of Veterans Affairs care for the 4 years before the index date and alive at the time of their matched case's death.The study retrospectively collected each case's USS and AFP screening data for 4 years before the date of HCC diagnosis or the equivalent index date in controls.Authors found that there was no significant difference of frequency of routine screening between the cases and controls.Therefore,the authors interpreted these results as indicating that the routine screening would not reduce cancer-related mortality.展开更多
The stability mechanisms of ecosystem functions have been a hot topic in ecology. However, in wetland ecosystems, the mechanisms by which biotic and abiotic factors interact to affect ecosystem stability in changing e...The stability mechanisms of ecosystem functions have been a hot topic in ecology. However, in wetland ecosystems, the mechanisms by which biotic and abiotic factors interact to affect ecosystem stability in changing environments remain largely unclear. This study investigated the key factors and underlying mechanisms that regulate the spatial variability of wetland productivity by measuring community productivity, multiple components of biodiversity (i.e. species diversity, community functional composition and diversity) and environmental factors along a well-characterized gradient of wetland degradation in the lower reaches of the Yellow River. The results showed that the spatial variability of productivity in wetlands increased with intensified degradation. The spatial variability of wetland productivity was not related to species richness but was mainly affected by changes in community functional composition and diversity. Furthermore, degradation-induced changes in soil nutrients drove the spatial variability of productivity to increase with shifts in functional composition towards more conservative traits (i.e. higher leaf dry matter content and root tissue density), and to decrease with higher functional trait diversity. These findings reveal the driving mechanism of spatial variability in wetland productivity under degradation, and suggest that reduced nutrient availability, by altering plant resource strategies, can affect the spatial reliability of key ecosystem functions in wetlands.展开更多
Although the efficacy of nucleos（t）ide analogue （NA） has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and d...Although the efficacy of nucleos（t）ide analogue （NA） has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and disease relapse. In this review, the RNA virion-like particles of hepatitis B virus （HBV） are integrated into the Hfe cycle of HBV replication, and the potential significance of serum HBV RNA is systematically described. The production of HBV RNA virion-like particles should not be blocked by NA; in this regard, serum HBV RNA is found to be a suitable surrogate marker for the activity of intrahepatic covalently closed circular DNA （cccDNA）, particularly among patients receiving NA therapy. Therefore, the concept of virological response is redefined as persistent loss of serum HBV DNA and HBV RNA. In contrast to hepatitis B surface antigen （HBsAg） that can originate from either the cccDNA or the integrated HBV DNA fragment, serum HBV RNA, with pregenomic RNA origination, can only be transcribed from cccDNA. Therefore, the loss of serum HBV RNA would likely be a promising predicator for safe drug discontinuation. The clinical status of consistent loss of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a ＂para-functional cure,＂ a status nearly close to the functional cure of chronic hepatitis B, to distinguish the ＂functional cure＂ characterized as serum HBsAg loss with or without anti-HBs seroconversion.展开更多
This guideline is established to standardize the prevention,diagnosis and antiviral therapy of chronic hepatitis B(CHB).For other treatment regimens and methods involving CHB,please refer to relevant guidelines and co...This guideline is established to standardize the prevention,diagnosis and antiviral therapy of chronic hepatitis B(CHB).For other treatment regimens and methods involving CHB,please refer to relevant guidelines and consensuses.The Chinese Society of Hepatology,Chinese Medical Association(CMA)and the Society of Infectious Diseases,CMA organized relevant native experts to establish this Guideline of Prevention and Treatment for Chronic Hepatitis B(1st version)in 2005,and made the first revision in 2010.In the past 5 years,great progress has been made in the native and foreign fundamental and clinical research with respect to CHB,necessitating additional revision of this guideline.展开更多
Background and Aims:The poor outcomes of hepatocellular carcinoma(HCC)patients may be due to not only malignant tumors but also limited liver function.Therefore,as stated in major guidelines,only patients with relativ...Background and Aims:The poor outcomes of hepatocellular carcinoma(HCC)patients may be due to not only malignant tumors but also limited liver function.Therefore,as stated in major guidelines,only patients with relatively normal liver function(Child-Pugh A)would be referred for curative hepatectomy.Even so,the postsurgery survival rate of patients is still extremely poor.Direct curative resection may benefit most patients.This study aimed to improve the prognosis predicting accuracy of the Child-Pugh scoring system.Methods:This study included two cohorts:cohort A being composed of 613 HCC patients,with a 23-month median postsurgery follow-up time;and cohort B being composed of 554 tumor-free chronic liver disease patients.Kaplan-Meier test and Cox model were used for survival analysis.Independent-samples t test or one-way ANOVA was used to test the differences between different groups.Results:Serum prealbumin levels were found inversely correlated with worsening of flbrotic scores(r=-0.482,p<0.001).Lower levels of presurgery prealbumin was an independent factor of poor postsurgery prognosis in Child-Pugh A patients,with a hazard ratio of 0.731(p=0.001).By integrating prealbumin together with total bilirubin level,serum albumin concentration and prothrombin time,a modified liver disease prognosis scoring system was developed to define traditional Child-Pugh A HCC patients as Modified Child-Pugh MCP-1,MCP-2 and MCP-3,with median postsurgery overall survival times of 44.00,28.00 and 11.00 months respectively.Conclusions:Preoperative serum prealbumin is a valuable prognosis predicting biomarker for Child-Pugh A HCC patients who may be under consideration for curative resection.With serum prealbumin included as one of the parameters,the MCP scoring system might improve the postsurgery survival predicting accuracy for HCC patients.展开更多
Circulating monocyte subsets with distinct functions play important roles in hepatitis C virus （HCV） infection. However, the mechanisms have not been well studied. In this study, we analyzed the distributions and ph...Circulating monocyte subsets with distinct functions play important roles in hepatitis C virus （HCV） infection. However, the mechanisms have not been well studied. In this study, we analyzed the distributions and phenotypic characteristics of three circulating monocyte subsets--CD14^＋＋CD16^-, CD14^＋＋CD16^＋ and CD14^＋＋mCD16^——in chronic HCV-infected patients, HCV spontaneous resolvers and healthy controls, and we evaluated the possible link between HCV viremia and disease progression. Our results indicated that the frequency of the CD 14^＋＋CD 16^＋ monocyte subset was decreased, and negatively correlated with HCV RNA and core antigen levels during chronic HCV infection. PD-L1 expression and the PD-L1/CD86 ratio in CD14^＋＋CD16^＋ monocytes were higher during chronic HCV infection than in spontaneous HCV resolvers and healthy controls. The PD-L1/CD86 ratio positively correlated with HCV viral load and core antigen levels. Finally, PD-L1 was significantly increased, while cytokine secretions were dramatically decreased upon Toll-like receptor （TLR） ligand binding and HCV JFH-lstimulation. These findings indicates the compromised immune status of the CD14^＋＋CD16^＋ monocytes during chronic HCV infection and provides new insights into the specific role of the CD14^＋＋CD16^＋ monocytes and their significance in chronic HCV infection.展开更多
Background and Aims: Non-invasive evaluation of liver nec-roinflammation in patients with chronic liver disease is an un-met need in clinical practice.The diagnostic accuracy of transient elastography-based liver stif...Background and Aims: Non-invasive evaluation of liver nec-roinflammation in patients with chronic liver disease is an un-met need in clinical practice.The diagnostic accuracy of transient elastography-based liver stiffness measurement(LSM)for liver fibrosis could be affected by liver necroinflam-mation,the latter of which could intensify stiffness of the liver.Such results have prompted us to explore the diagnosis potential of LSM for liver inflammation.Methods: Three cross-sectional cohorts of liver biopsy-proven chronic liver dis-ease patients were enrolled,including 1417 chronic hepatitis B(CHB)patients from 10 different medical centers,106 non-al-coholic steatohepatitis patients,and 143 patients with auto-immune-related liver diseases.Another longitudinal cohort of 14 entecavir treatment patients was also included.The re-ceiver operating characteristic(ROC)curve was employed to explore the diagnostic value of LSM.Results: In CHB patients,LSM value ascended with the increased severity of liver nec-roinflammation in patients with the same fibrosis stage.Such positive correlation between LSM and liver necroinflammation was also found in non-alcoholic steatohepatitis and autoim-mune-related liver diseases populations.Furthermore,the ROC curve exhibited that LSM could identify moderate and se-vere inflammation in CHB patients(area under the ROC curve as 0.779 and 0.838)and in non-alcoholic steatohepatitis pa-tients(area under the ROC curve as 0.826 and 0.871),respec-tively.Such moderate diagnostic value was also found in autoimmune-related liver diseases patients.In addition,in the longitudinal entecavir treated CHB cohort,a decline of LSM values was observed in parallel with the control of inflam-matory activity in liver.Conclusions: Our study implicates a diagnostic potential of LSM to evaluate the severity of liver necroinflammation in chronic liver disease patients.展开更多
The pregenomic RNA(pgRNA)of hepatitis B virus(HBV)serves not only as a bicistronic message RNA to translate core protein(Cp)and DNA polymerase(Pol),but also as the template for reverse transcriptional replication of v...The pregenomic RNA(pgRNA)of hepatitis B virus(HBV)serves not only as a bicistronic message RNA to translate core protein(Cp)and DNA polymerase(Pol),but also as the template for reverse transcriptional replication of viral DNA upon packaging into nucleocapsid.Although it is well known that pgRNA translates much more Cp than Pol,the molecular mechanism underlying the regulation of Cp and Pol translation efficiency from pgRNA remains elusive.展开更多
Background and Aims:Disease progression of chronic hepatitis B virus(HBV)infection is driven by the interactions between viral replication and the host immune response against the infection.This study aimed to clarify...Background and Aims:Disease progression of chronic hepatitis B virus(HBV)infection is driven by the interactions between viral replication and the host immune response against the infection.This study aimed to clarify the relationship between HBV replication and hepatic inflammation during disease progression.Methods:Two cross-sectional,one validation cohort,and meta-analyses were used to explore the relationship between HBV replication and liver inflammation.Spearman analysis,multiple linear regression,and logistic regression were used to explore the relationship between variables.Results:In the cross-sectional cohorts A and B including 1,350 chronic hepatitis B patients,Spearman analysis revealed a negative relationship between HBV replication(such as HBV DNA)and liver inflammation(such as ALT)in HBeAg-positive patients with higher HBV DNA>2×10^(6) IU/mL(rho=0.278 and 0.260)and HBeAg-negative patients(rho=0.450 and 0.363).After adjustment for sex,age,and anti-HBe,results from logistic regression and multiple linear regression showed the opposite relationship still existed in HBeAg-positive patients with different DNA levels;the opposite relationship in HBeAg-positive patients with different DNA levels was validated in a third cohort;the opposite relationship in patients with different HBeAg status was partially confirmed by meta-analysis(overall R:-0.004 vs 0.481).Conclusions:These results suggested a negative relationship between viral replication and liver inflammation in HBeAgpositive patients with high HBV DNA,which changed to a positive relationship for those HBeAg-positive patients with DNA less than 2×10^(6) IU/mL and HBeAg-negative patients.展开更多
Chronic hepatitis B virus (HBV) infection is a major global public health problem. Approximately 887,000 people die of HBV infection-related diseases annually, with cirrhosis and hepatocellular carcinoma (HCC) being t...Chronic hepatitis B virus (HBV) infection is a major global public health problem. Approximately 887,000 people die of HBV infection-related diseases annually, with cirrhosis and hepatocellular carcinoma (HCC) being the principal causes of mortality.[1] Timely antiviral therapy greatly reduces the risks of cirrhosis and HCC. However, unfortunately, of those patients who are eligible for antiviral treatment, only 25% of patients in clinic settings and 12% of those in community settings obtain timely antiviral therapy.[2] Therefore, reliable means of identifying patients with chronic HBV infection that require antiviral therapy are necessary, particularly for use in the community.展开更多
Background and Aims:As a hepatocellular carcinoma biomarker,serum Golgi protein 73(GP73)is reportedly related to inflammation.Acute-on-chronic liver failure(ACLF)is characterized by severe systemic inflammation.In thi...Background and Aims:As a hepatocellular carcinoma biomarker,serum Golgi protein 73(GP73)is reportedly related to inflammation.Acute-on-chronic liver failure(ACLF)is characterized by severe systemic inflammation.In this study,we aimed to explore the association between the GP73 level and short-term mortality in patients with alcohol-associated liver disease-related ACLF(ALD-ACLF).Methods:This retrospective cohort study involved 126 Chinese adults with ALD-ACLF.Baseline serum GP73 level was measured using enzymelinked immunosorbent assay.Patients were followed-up for 90 d and outcomes were assessed.Data were analyzed using multivariate Cox regression and piecewise linear regression analyses.The predictive value of GP73 and classic models for the short-term prognosis of participants were evaluated and compared using receiver operating characteristic curves.Results:The serum GP73 level was independently associated with an increased mortality risk in patients with ALD-ACLF.Compared with the lowest tertile,the highest serum GP73 level predisposed patients with ALD-ACLF to a higher mortality risk in the fully adjusted model[at 28 days:hazard ratio(HR):4.29(0.99–18.54),p=0.0511;at 90 days:HR:3.52(1.15–10.79),p=0.0276].Further analysis revealed a positive linear association.GP73 significantly improved the accuracy of the Child-Turcotte-Pugh score,model for end-stage liver disease score,and model for end-stage liver diseasesodium score in predicting short-time prognosis of patients with ALD-ACLF.Conclusions:The serum GP73 level is a significant predictor of the subsequent risk of death in patients with ALD-ACLF.GP73 improved the predictive value of classic prognostic scores.展开更多
基金supported by the National Key R&D Program of China(No.2022YFA1303600 and No.2023YFC2306800)the National Natural Science Foundation of China(No.82372235 and No.82272315)the Sanming Project of Medicine in Shenzhen(No.SZSM202311032).
文摘The persistence of covalently closed circular DNA(cccDNA)in hepatitis B virus(HBV)-infected hepatocytes remains a major obstacle to effective antiviral treatment.Understanding the molecular mechanisms regulating HBV cccDNA transcription is essential for developing novel therapeutic strategies.In this study,we investigated the role of RNA binding motif protein 25(RBM25)in HBV replication,focusing on its interaction with cccDNA and its regulation of host transcription factors.The results demonstrated that RBM25 knockdown markedly inhibited HBV replication,reducing levels of HBV DNA,hepatitis B e antigen(HBeAg),hepatitis B surface antigen(HBsAg),HBV RNA,and L-HBs in HBV-replicating and infected cell models.Consistent results were observed in a mouse model hydrodynamically injected with 1.2HBV plasmid.Conversely,RBM25 overexpression significantly enhanced HBV replication.Mechanistically,RBM25 promoted HBV promoter activities by binding to cccDNA through its RE/RD and PWI domains.This effect was mediated by increased Yin Yang 1(YY1)expression,which enhanced acetylation of cccDNA-bound histones,promoting HBV transcription.Furthermore,RBM25 expression was upregulated and translocated to the nucleus following core protein expression and accumulation,while overexpression of RBM25 promoted core protein degradation.In conclusion,this study demonstrates that RBM25 is a novel host factor that enhances HBV replication by upregulating YY1-dependent transcriptional activation of cccDNA.It also reveales a reciprocal regulatory mechanism between the HBV core protein and RBM25,which helps sustain HBV replication.
基金supported by National Key R&D Program of China(2023YFC2306800)National Natural Science Foundation of China(No.82072280 and No.82272315)Beijing Municipal Natural Science Foundation(No.7212063 and No.7222108).
文摘Naturally occurred precore(PC,G1896A)and/or basal core promoter(BCP,A1762T/G1764A)mutations are prevalent in chronic HBV-infected patients,especially those under HBeAg-negative status.However,the replicative capacity of HBV with PC/BCP mutations remains ambiguous.Herein,meta-analysis showed that,only under HBeAg-negative status,the serum HBV DNA load in patients with PC mutation was 7.41-fold higher than those without the mutation.Both PC mutation alone and BCPþPC mutations promoted HBV replication in cell and hydrodynamic injection mouse models.In human hepatocyte chimeric mouse model,BCPþPC mutations led to elevated replicative capacity and intrahepatic core protein accumulation.Mechanistically,preC RNA harboring PC mutation could serve as mRNA to express core and P proteins,and such pgRNA-like function favored the maintenance of cccDNA pool under HBeAg-negative status.Additionally,BCPþPC mutations induced more extensive and severe human hepatocyte damage as well as activated endoplasmic reticulum stress and TNF signaling pathway in livers of chimeric mice.This study indicates that HBeAg-negative patients should be monitored on HBV mutations regularly and are expected to receive early antiviral treatment to prevent disease progression.
基金This work was supported by the National S&T Major Project for Infectious Diseases of China(Nos.2017ZX10202202,2017ZX10202203)Beijing Natural Science Foundation(7182079).
文摘Dear Editor,Hepatitis B virus(HBV)infection remains a major cause of liver diseases worldwide,which affects approximately 250 million people globally(Yuen et al.2018).Individuals with chronic HBV infection are at high risk of developing liver cirrhosis,and ultimately hepatocellular carcinoma(HCC).HBV is a Hepadnavirus DNA virus,which specifically infects and efficiently replicates in hepatocytes.It has been proposed for decades that HBV replicates preferentially in non-dividing quiescent hepatocytes(Ozer et al.1996).
基金supported by grants from the Natural Science Foundation of China(No.8214100646)Construction Project of Highlevel Technology Talents in Public Health(Discipline leader-01-12)
文摘On April 5,2022,United Kingdom(UK)reported 10 cases of severe acute hepatitis with unknown cause among children under 10 years old.The initial symptoms of these cases could date back to March 2022.A rapidly increasing number of cases lasted for a month and the growth seems to be slightly slowing down in May.As of May 27,2022,the total number of children with acute hepatitis in UK reached to 222(UKHSA,2022a).European Union and European Economic Area reported 305 cases across 17 countries and none as epidemiologically linked as of May 31,2022(ECDC-WHO,2022).
基金the National S&T Major Project for Infectious Diseases(No.20177X10201201)
文摘In the issue of Gastroenterology published October 2018,the article by Moon et al.1 demonstrated that screening patients with cirrhosis for hepatocellular carcinoma(HCC)by ultrasound scan(USS),measurement of serumα-fetoprotein(AFP),each alone or in combination,was not associated with the decreased HCC-related mortality.In this matched case control study,all the study patients were registered in detail in the U.S.Department of Veterans Affairs.The study included 238 cases who died of HCC with cirrhosis,and the same number of matched controls with cirrhosis who had been enrolled in U.S.Department of Veterans Affairs care for the 4 years before the index date and alive at the time of their matched case's death.The study retrospectively collected each case's USS and AFP screening data for 4 years before the date of HCC diagnosis or the equivalent index date in controls.Authors found that there was no significant difference of frequency of routine screening between the cases and controls.Therefore,the authors interpreted these results as indicating that the routine screening would not reduce cancer-related mortality.
基金supported jointly by Henan Province Xixiayuan Water Conservancy Hub Water Supply and Irrigation District Engineering Research ProjectHenan Province Natural Resources Research Project(2023-382-4)+3 种基金Sichuan Science and Technology Program (2023ZYD0102)China Postdoctoral Science Foundation (2023M743206)the Scientific Research Foundation for Academician of CAS Teamof Zhengzhou University (13432340370)the National Natural Science Foundation of China(32201517)。
文摘The stability mechanisms of ecosystem functions have been a hot topic in ecology. However, in wetland ecosystems, the mechanisms by which biotic and abiotic factors interact to affect ecosystem stability in changing environments remain largely unclear. This study investigated the key factors and underlying mechanisms that regulate the spatial variability of wetland productivity by measuring community productivity, multiple components of biodiversity (i.e. species diversity, community functional composition and diversity) and environmental factors along a well-characterized gradient of wetland degradation in the lower reaches of the Yellow River. The results showed that the spatial variability of productivity in wetlands increased with intensified degradation. The spatial variability of wetland productivity was not related to species richness but was mainly affected by changes in community functional composition and diversity. Furthermore, degradation-induced changes in soil nutrients drove the spatial variability of productivity to increase with shifts in functional composition towards more conservative traits (i.e. higher leaf dry matter content and root tissue density), and to decrease with higher functional trait diversity. These findings reveal the driving mechanism of spatial variability in wetland productivity under degradation, and suggest that reduced nutrient availability, by altering plant resource strategies, can affect the spatial reliability of key ecosystem functions in wetlands.
文摘Although the efficacy of nucleos（t）ide analogue （NA） has been confirmed for treatment of chronic hepatitis B, long-term therapy has been recommended due to the high frequency of off-therapy viral DNA rebound and disease relapse. In this review, the RNA virion-like particles of hepatitis B virus （HBV） are integrated into the Hfe cycle of HBV replication, and the potential significance of serum HBV RNA is systematically described. The production of HBV RNA virion-like particles should not be blocked by NA; in this regard, serum HBV RNA is found to be a suitable surrogate marker for the activity of intrahepatic covalently closed circular DNA （cccDNA）, particularly among patients receiving NA therapy. Therefore, the concept of virological response is redefined as persistent loss of serum HBV DNA and HBV RNA. In contrast to hepatitis B surface antigen （HBsAg） that can originate from either the cccDNA or the integrated HBV DNA fragment, serum HBV RNA, with pregenomic RNA origination, can only be transcribed from cccDNA. Therefore, the loss of serum HBV RNA would likely be a promising predicator for safe drug discontinuation. The clinical status of consistent loss of serum HBV RNA accompanied with low serum HBsAg levels might be implicated as a ＂para-functional cure,＂ a status nearly close to the functional cure of chronic hepatitis B, to distinguish the ＂functional cure＂ characterized as serum HBsAg loss with or without anti-HBs seroconversion.
文摘This guideline is established to standardize the prevention,diagnosis and antiviral therapy of chronic hepatitis B(CHB).For other treatment regimens and methods involving CHB,please refer to relevant guidelines and consensuses.The Chinese Society of Hepatology,Chinese Medical Association(CMA)and the Society of Infectious Diseases,CMA organized relevant native experts to establish this Guideline of Prevention and Treatment for Chronic Hepatitis B(1st version)in 2005,and made the first revision in 2010.In the past 5 years,great progress has been made in the native and foreign fundamental and clinical research with respect to CHB,necessitating additional revision of this guideline.
基金supported by the SZSM201612071the National S&T Major Project for Infectious Diseases(2017YFC0908100,2017ZX10302201,2017ZX10201201)the project from Beijing Municipal Science and Technology Commission(No.Z161100000116047)
文摘Background and Aims:The poor outcomes of hepatocellular carcinoma(HCC)patients may be due to not only malignant tumors but also limited liver function.Therefore,as stated in major guidelines,only patients with relatively normal liver function(Child-Pugh A)would be referred for curative hepatectomy.Even so,the postsurgery survival rate of patients is still extremely poor.Direct curative resection may benefit most patients.This study aimed to improve the prognosis predicting accuracy of the Child-Pugh scoring system.Methods:This study included two cohorts:cohort A being composed of 613 HCC patients,with a 23-month median postsurgery follow-up time;and cohort B being composed of 554 tumor-free chronic liver disease patients.Kaplan-Meier test and Cox model were used for survival analysis.Independent-samples t test or one-way ANOVA was used to test the differences between different groups.Results:Serum prealbumin levels were found inversely correlated with worsening of flbrotic scores(r=-0.482,p<0.001).Lower levels of presurgery prealbumin was an independent factor of poor postsurgery prognosis in Child-Pugh A patients,with a hazard ratio of 0.731(p=0.001).By integrating prealbumin together with total bilirubin level,serum albumin concentration and prothrombin time,a modified liver disease prognosis scoring system was developed to define traditional Child-Pugh A HCC patients as Modified Child-Pugh MCP-1,MCP-2 and MCP-3,with median postsurgery overall survival times of 44.00,28.00 and 11.00 months respectively.Conclusions:Preoperative serum prealbumin is a valuable prognosis predicting biomarker for Child-Pugh A HCC patients who may be under consideration for curative resection.With serum prealbumin included as one of the parameters,the MCP scoring system might improve the postsurgery survival predicting accuracy for HCC patients.
文摘Circulating monocyte subsets with distinct functions play important roles in hepatitis C virus （HCV） infection. However, the mechanisms have not been well studied. In this study, we analyzed the distributions and phenotypic characteristics of three circulating monocyte subsets--CD14^＋＋CD16^-, CD14^＋＋CD16^＋ and CD14^＋＋mCD16^——in chronic HCV-infected patients, HCV spontaneous resolvers and healthy controls, and we evaluated the possible link between HCV viremia and disease progression. Our results indicated that the frequency of the CD 14^＋＋CD 16^＋ monocyte subset was decreased, and negatively correlated with HCV RNA and core antigen levels during chronic HCV infection. PD-L1 expression and the PD-L1/CD86 ratio in CD14^＋＋CD16^＋ monocytes were higher during chronic HCV infection than in spontaneous HCV resolvers and healthy controls. The PD-L1/CD86 ratio positively correlated with HCV viral load and core antigen levels. Finally, PD-L1 was significantly increased, while cytokine secretions were dramatically decreased upon Toll-like receptor （TLR） ligand binding and HCV JFH-lstimulation. These findings indicates the compromised immune status of the CD14^＋＋CD16^＋ monocytes during chronic HCV infection and provides new insights into the specific role of the CD14^＋＋CD16^＋ monocytes and their significance in chronic HCV infection.
基金the National S&T Major Project for Infectious Diseases(2017ZX10201201,2017ZX10202202,2017ZX10302201 and 2017ZX10202203)the project from Beijing Municipal Science & Technology Commission(Z161100000116047)+1 种基金Project funded by China Postdoc-toral Science Foundation(2017M620544,2018T110014)Project funded by Shenzhen Municipal Health Commission(SZSM201612071)
文摘Background and Aims: Non-invasive evaluation of liver nec-roinflammation in patients with chronic liver disease is an un-met need in clinical practice.The diagnostic accuracy of transient elastography-based liver stiffness measurement(LSM)for liver fibrosis could be affected by liver necroinflam-mation,the latter of which could intensify stiffness of the liver.Such results have prompted us to explore the diagnosis potential of LSM for liver inflammation.Methods: Three cross-sectional cohorts of liver biopsy-proven chronic liver dis-ease patients were enrolled,including 1417 chronic hepatitis B(CHB)patients from 10 different medical centers,106 non-al-coholic steatohepatitis patients,and 143 patients with auto-immune-related liver diseases.Another longitudinal cohort of 14 entecavir treatment patients was also included.The re-ceiver operating characteristic(ROC)curve was employed to explore the diagnostic value of LSM.Results: In CHB patients,LSM value ascended with the increased severity of liver nec-roinflammation in patients with the same fibrosis stage.Such positive correlation between LSM and liver necroinflammation was also found in non-alcoholic steatohepatitis and autoim-mune-related liver diseases populations.Furthermore,the ROC curve exhibited that LSM could identify moderate and se-vere inflammation in CHB patients(area under the ROC curve as 0.779 and 0.838)and in non-alcoholic steatohepatitis pa-tients(area under the ROC curve as 0.826 and 0.871),respec-tively.Such moderate diagnostic value was also found in autoimmune-related liver diseases patients.In addition,in the longitudinal entecavir treated CHB cohort,a decline of LSM values was observed in parallel with the control of inflam-matory activity in liver.Conclusions: Our study implicates a diagnostic potential of LSM to evaluate the severity of liver necroinflammation in chronic liver disease patients.
基金This work is supported by grants from the National Natural Science Foundation of China(82272315)the Natural Science Foundation of Beijing Municipality(7222108)National Key R&D Program of China(2022YFA1303600).
文摘The pregenomic RNA(pgRNA)of hepatitis B virus(HBV)serves not only as a bicistronic message RNA to translate core protein(Cp)and DNA polymerase(Pol),but also as the template for reverse transcriptional replication of viral DNA upon packaging into nucleocapsid.Although it is well known that pgRNA translates much more Cp than Pol,the molecular mechanism underlying the regulation of Cp and Pol translation efficiency from pgRNA remains elusive.
基金supported by the National Natural Science Foundation of China(No.82072280)Beijing Natural Science Foundation(No.7212063).
文摘Background and Aims:Disease progression of chronic hepatitis B virus(HBV)infection is driven by the interactions between viral replication and the host immune response against the infection.This study aimed to clarify the relationship between HBV replication and hepatic inflammation during disease progression.Methods:Two cross-sectional,one validation cohort,and meta-analyses were used to explore the relationship between HBV replication and liver inflammation.Spearman analysis,multiple linear regression,and logistic regression were used to explore the relationship between variables.Results:In the cross-sectional cohorts A and B including 1,350 chronic hepatitis B patients,Spearman analysis revealed a negative relationship between HBV replication(such as HBV DNA)and liver inflammation(such as ALT)in HBeAg-positive patients with higher HBV DNA>2×10^(6) IU/mL(rho=0.278 and 0.260)and HBeAg-negative patients(rho=0.450 and 0.363).After adjustment for sex,age,and anti-HBe,results from logistic regression and multiple linear regression showed the opposite relationship still existed in HBeAg-positive patients with different DNA levels;the opposite relationship in HBeAg-positive patients with different DNA levels was validated in a third cohort;the opposite relationship in patients with different HBeAg status was partially confirmed by meta-analysis(overall R:-0.004 vs 0.481).Conclusions:These results suggested a negative relationship between viral replication and liver inflammation in HBeAgpositive patients with high HBV DNA,which changed to a positive relationship for those HBeAg-positive patients with DNA less than 2×10^(6) IU/mL and HBeAg-negative patients.
基金This work was supported by the National Natural Science Foundation of China(No. 81902115)National Key Research and Development Program of China(No. SQ2020YFF0426358)National S and T Major Project for Infectious Diseases(No. 2017ZX10201201)。
文摘Chronic hepatitis B virus (HBV) infection is a major global public health problem. Approximately 887,000 people die of HBV infection-related diseases annually, with cirrhosis and hepatocellular carcinoma (HCC) being the principal causes of mortality.[1] Timely antiviral therapy greatly reduces the risks of cirrhosis and HCC. However, unfortunately, of those patients who are eligible for antiviral treatment, only 25% of patients in clinic settings and 12% of those in community settings obtain timely antiviral therapy.[2] Therefore, reliable means of identifying patients with chronic HBV infection that require antiviral therapy are necessary, particularly for use in the community.
基金supported by a grant from the Capital’s Funds for Health Improvement and Research,China(NO.2020-1-5031).
文摘Background and Aims:As a hepatocellular carcinoma biomarker,serum Golgi protein 73(GP73)is reportedly related to inflammation.Acute-on-chronic liver failure(ACLF)is characterized by severe systemic inflammation.In this study,we aimed to explore the association between the GP73 level and short-term mortality in patients with alcohol-associated liver disease-related ACLF(ALD-ACLF).Methods:This retrospective cohort study involved 126 Chinese adults with ALD-ACLF.Baseline serum GP73 level was measured using enzymelinked immunosorbent assay.Patients were followed-up for 90 d and outcomes were assessed.Data were analyzed using multivariate Cox regression and piecewise linear regression analyses.The predictive value of GP73 and classic models for the short-term prognosis of participants were evaluated and compared using receiver operating characteristic curves.Results:The serum GP73 level was independently associated with an increased mortality risk in patients with ALD-ACLF.Compared with the lowest tertile,the highest serum GP73 level predisposed patients with ALD-ACLF to a higher mortality risk in the fully adjusted model[at 28 days:hazard ratio(HR):4.29(0.99–18.54),p=0.0511;at 90 days:HR:3.52(1.15–10.79),p=0.0276].Further analysis revealed a positive linear association.GP73 significantly improved the accuracy of the Child-Turcotte-Pugh score,model for end-stage liver disease score,and model for end-stage liver diseasesodium score in predicting short-time prognosis of patients with ALD-ACLF.Conclusions:The serum GP73 level is a significant predictor of the subsequent risk of death in patients with ALD-ACLF.GP73 improved the predictive value of classic prognostic scores.
