AIM： To investigate the risk factors for gallstone disease in the general population of Chengdu, China. METHODS： This study was conducted at the West China Hospital. Subjects who received a physical examination at t...AIM： To investigate the risk factors for gallstone disease in the general population of Chengdu, China. METHODS： This study was conducted at the West China Hospital. Subjects who received a physical examination at this hospital between January and December 2007 were included. Body mass index, blood pressure, fasting plasma glucose, serum lipid and lipoproteins concentrations were analyzed. Gallstone disease was diagnosed by ultrasound or on the basis of a history of cholecystectomy because of gallstone disease. Unconditional logistic regression analysis was used to investigate the risk factors for gallstone disease, and the Chi-square test was used to analyze differences in the incidence of metabolic disorders between subjects with and without gallstone disease. RESULTS： A total of 3573 people were included, 10.7% （384/3573） of whom had gallstone diseases. Multiple logistic regression analysis indicated that the incidence of gallstone disease in subjects aged 40-64 or ≥65 years was significantly different from that in those aged 18-39 years （P 〈 0.05）; the incidence was higher in women than in men （P 〈 0.05）. In men,a high level of fasting plasma glucose was obvious in gallstone disease （P 〈 0.05）, and in women, hypertriglyceridemia or obesity were significant in gallstone disease （P 〈 0.05）. CONCLUSION： We assume that age and sex are profoundly associated with the incidence of gallstone disease; the metabolic risk factors for gallstone disease were different between men and women.展开更多
BACKGROUND： Vitamin D is a fat-soluble sterol derivative that is predominantly synthesized in the liver and has multiple functions. The accumulative data showed that the clinical manifestations and prognosis of chron...BACKGROUND： Vitamin D is a fat-soluble sterol derivative that is predominantly synthesized in the liver and has multiple functions. The accumulative data showed that the clinical manifestations and prognosis of chronic liver diseases are associated with serum vitamin D levels. DATA SOURCES： A PubMed and Google Scholar search using terms： ＂vitamin D＂, ＂25 （OH）D＂, ＂liver disease＂, ＂viral hepatitis＂, ＂non-alcoholic fatty liver disease＂, ＂liver fibrosis＂, ＂cirrhosis＂, ＂hepatocellular carcinoma＂ and ＂autoimmune liver disease＂ was performed, and relevant articles published in English between January 2000 and March 2014 were reviewed. Fulb text publications relevant to the field were selected and relevant articles from reference lists were also included. RESULTS： The insufficiency or deficiency of vitamin D is common in various kinds of chronic liver diseases including viral hepatitis B and C. Serum 25-hydroxyvitamin D and vitamin D receptors are possibly interrelated with the incidence, treatment and prognosis of diseases. Though the evidence of vitamin D supplementation in viral hepatitis and associated liver diseases is still limited, there is great potential to apply this adjuvant therapy to improve the treatments. CONCLUSIONS： Although the exact role and mechanisms of vitamin D have not been fully elucidated in chronic liver diseases, it is potentially beneficial in the treatment of chronic liver diseases. Further mechanistic studies are needed to validate its clinical application.展开更多
This minireview focuses on psychological distress and treatment adherence-issues in patients with chronic hepatitis B(CHB).It begins by discussing the epidemiology and disease burden of CHB,and addresses the relations...This minireview focuses on psychological distress and treatment adherence-issues in patients with chronic hepatitis B(CHB).It begins by discussing the epidemiology and disease burden of CHB,and addresses the relationship between psychological distress and treatment adherence.Next,it delves into the current status and risk factors for psychological distress among patients with CHB,and explores the challenges and risk factors related to treatment adherence.Subsequently,it explores the development and implementation of integrated nursing strategies,including psychological interventions and support,self-efficacy enhancement strategies,social support-system optimization,personalized medical care,and technological innovation.Finally,it highlights the limitations of current interventions and clarifies future research priorities.This minireview aims to provide a comprehensive theoretical basis and practical guidance for improving treatment outcomes and quality of life of patients with CHB.In summary,we reveal that psychological distress significantly impacts treatment adherence in patients with CHB and that it is essential to adopt integrated nursing strategies to address these challenges.These findings highlight the need to consider the psychological states of individuals and develop targeted interventions to improve treatment outcomes.展开更多
BACKGROUND Chronic hepatitis B virus(HBV)infection acquired in childhood frequently presents with mild or nonspecific symptoms,yet a distinct subset of pediatric patients develops rapid progression to liver cirrhosis(...BACKGROUND Chronic hepatitis B virus(HBV)infection acquired in childhood frequently presents with mild or nonspecific symptoms,yet a distinct subset of pediatric patients develops rapid progression to liver cirrhosis(LC)before adulthood.AIM To identify clinical and pathological characteristics of pediatric HBV-related LC.METHODS A total of 1332 pediatric patients with chronic HBV infection from the Fifth Medical Center of PLA General Hospital from January 2010 to January 2023 were included in this study.We identified 62 pediatric HBV-related LC by liver biopsy from the group.Subsequently,we described the clinical and pathological characteristics of pediatric LC.And 64 pediatric chronic hepatitis B(CHB;age and sex were matched with pediatric LC group)and 69 adult HBV-related LC(sex were matched with pediatric LC group)were enrolled to further demonstrate clinical and pathological differences between pediatric LC,pediatric CHB and adult LC.RESULTS We enrolled 62 pediatric LC,including 54(87.1%)males and 8(12.9%)females.The median age was 11(4-14)years old.The pediatric LC group showed significantly lower median quantitative HBV DNA loads(log10IU/mL:6.3 vs 17.4,P<0.001),reduced HBsAg titers(log10IU/mL:3.11 vs 8.956,P<0.0001),and diminished hepatitis B e antigen-positive positive rate(81.4%vs 93.8%,P<0.05)compared with pediatric CHB.A higher proportion of pediatric patients were asymptomatic(77.4%)compared to adult patients(11.6%)as they first diagnosed as LC,pediatric LC showed milder initial symptoms compared with adult patients such as fatigue(4.8%vs 27.5%),abdominal discomfort(9.7%vs 23.2%),nausea(0%vs 10.1%),and poor appetite(6.5%vs 8.7%;all P<0.0001).Notably,pediatric LC can achieve a significant percentage of functional cure compared with adult LC as 17.4%and 0%.The incidence of progression of LC in children after antiviral therapy continues to be much lower than that in adult LC(hazard ratio=6.102,95%confidence interval:1.72-21.65,P=0.00051).While the incidence of LC remission in children after antiviral therapy continues to be much higher than that in adult LC(hazard ratio=0.055,95%confidence interval:0.07128-0.2802,P<0.0001).CONCLUSION Pediatric patients with HBV-related cirrhosis exhibit elevated virological parameters and heightened transaminase levels than adult patients.However,the frequent paucity of overt clinical symptoms contributes to diagnostic challenges.Notably,early initiation of antiviral therapy in this population substantially improved clinical outcomes.展开更多
With organ transplantation facing many dilemmas,tissue and organ regeneration as an alternative has bright prospects.In regenerative medicine,Three-dimensional(3D)printing technology and stem cells has been widely app...With organ transplantation facing many dilemmas,tissue and organ regeneration as an alternative has bright prospects.In regenerative medicine,Three-dimensional(3D)printing technology and stem cells has been widely applied to the treatment of diseases related to tissue or organ replacement in dentistry,respectively.However,there are very few studies on the combination of the two,and even fewer clinical studies have been reported in dentistry.In this review,the current oral tissue engineering in vivo and in vitro based on 3D printing and stem cell technology will be summarized,and the discussion on the development prospects of this research direction will be given.Besides,the working principles and advantages&disadvantages of several types of 3D printers,as well as the mechanism of stem cells in tissue engineering will be elucidated.This review provides clinicians and researchers with the current state of research and trends in the combination of stem cells and 3D printing technology to treat oral-related diseases.In the future,3D bioprinters are poised for ongoing innovation with the advancement of relevant technologies,catalyzing an increase in clinical studies focused on treating oral diseases using stem cells and 3D scaffolds.Consequently,these developments will further advance the field of oral tissue engineering.展开更多
Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates sub...Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates substantial quantities of pro-inflammatory intracellular substances,thereby accelerating the advancement of liver fibrosis.Consequently,directing therapeutic efforts towards inhibiting pyroptosis could po-tentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.Methods:GSDMD-NT^(ki/wt)mice and Alb-cre^(ki/wt)mice were generated using CRISPR/Cas9 technology.After crossing the two strains together,we induced conditional cell death by doxycycline to construct a mouse model of liver fibrosis.We analyzed differ-entially expressed genes by RNA sequencing and explored their biological functions.The efficacy of obeticholic acid(OCA)in the treatment of liver fibrosis was assessed.Results:Doxycycline-treated GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice showed severe liver damage,vacuolation of hepatocytes,increased collagen fibers,and accumulation of lipid droplets.The expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse liver.RNA-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses,cell activation,and metabolic processes.Treatment with OCA alleviated the liver fibrosis,with reduced ALT and AST levels seen in the GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice.Conclusions:We successfully constructed a novel mouse model for liver fibrosis.This GSDMD-NT-induced fibrosis may be mediated by abnormal lipid metabolism.Our re-sults demonstrated that we successfully constructed a mouse model of liver fibrosis,and GSDMD-NT induced fibrosis by mediating lipid metabolism.展开更多
Tigecycline is one of the most critical drugs for treating Gram-negative bacterial infections;however,the emergence of the tigecycline resistance efflux pump TMexCD1-TOprJ1 poses a global health threat.The evolutionar...Tigecycline is one of the most critical drugs for treating Gram-negative bacterial infections;however,the emergence of the tigecycline resistance efflux pump TMexCD1-TOprJ1 poses a global health threat.The evolutionary relationships and epidemiological trends of tmexCD1-toprJ1-positive strains across various ecological niches remain largely unexplored.In this study,we employed whole-genome sequencing(WGS)of tmexCD1-toprJ1-positive bacteria from humans,food,animals,and the environment in China to assess the epidemiological and genomic features of these strains,analyzing both newly collected strains and data from the GenBank database.From 3434 samples collected during 2019-2022,145tmexCD1-toprJ1-carrying strains(4.5%)were isolated.The majority of the tmexCD1-toprJ1-positive Enterobacterales exhibited resistance to nearly all antimicrobials,including colistin(42.13%).tmexCD1-toprJ1 was predominantly identified in Klebsiella pneumoniae(K.pneumoniae)from chicken feces in China but was also detected in multiple ecological niches and other countries.Phylogenetic analysis revealed the clonal transmission of tmexCD1-toprJ1-positive ST37 K.pneumoniae across diverse ecological niches as well as the international spread of the ST15 K.pneumoniae clone-producing TMexCD1-TOprJ1.tmexCD1-toprJ1 is mainly carried by Klebsiella spp.specific narrow host range plasmids,which may limit the spread of tmexCD1-toprJ1 across different bacterial species.Notably,due to the fitness cost posed by tmexCD1-toprJ1,the occurrence of tmexCD1-toprJ1-positive Enterobacterales in both food animals and humans in China has declined significantly following the withdrawal of antibiotics as growth promoters in food animals in China since 2020.However,tmexCD1-toprJ1 has been captured by broad-host-range plasmids and hypervirulent carbapenem-resistant K.pneumoniae ST11-KL64 strains in healthcare settings.The frequent use of tetracyclines in chicken farming likely contributes to the high detection rate of tmexCD1-toprJ1;therefore,to reduce the threat of tmexCD1-toprJ1-positive K.pneumoniae,continuous monitoring of tmexCD1-toprJ1 across different ecological niches and strict enforcement of antimicrobial policies in animal husbandry,particularly in the poultry industry,are urgently required.展开更多
Hepatitis B virus(HBV) associated acute-on-chronic liver failure(ACLF) is an increasingly recognized fatal liver disease encompassing a severe acute exacerbation of liver function in patients with chronic hepatitis B(...Hepatitis B virus(HBV) associated acute-on-chronic liver failure(ACLF) is an increasingly recognized fatal liver disease encompassing a severe acute exacerbation of liver function in patients with chronic hepatitis B(CHB). Despite the introduction of an artificial liver support system and antiviral therapy, the short-term prognosis of HBV-ACLF is still extremely poor unless emergency liver transplantation is performed. In such a situation, stopping or slowing the progression of CHB to ACLF at an early stage is the most effective way of reducing the morbidity and mortality of HBV-ACLF. It is well-known that the occurrence and progression of HBV-ACLF is associated with many factors, and the outcomes of HBV-ACLF patients can be significantly improved if timely and appropriate interventions are provided. In this review, we highlight recent developments in early warning and clinical outcome prediction in patients with HBV-ACLF and provide an outlook for future research in this field.展开更多
AIM:To evaluate the prognosis of patients with acute fatty liver of pregnancy(AFLP)6 mo or longer after discharge.METHODS:The records of pregnant patients diagnosed with AFLP at Beijing Ditan Hospital over a 16-year p...AIM:To evaluate the prognosis of patients with acute fatty liver of pregnancy(AFLP)6 mo or longer after discharge.METHODS:The records of pregnant patients diagnosed with AFLP at Beijing Ditan Hospital over a 16-year period were reviewed in November 2012.Patients weremonitored using abdominal ultrasound,liver and kidney functions,and routine blood examination.RESULTS:A total of 42 patients were diagnosed with AFLP during the study period,and 25 were followed.The mean follow-up duration was 54.5 mo(range:6.5-181 mo).All patients were in good physical condition,but one patient had gestational diabetes.The renal and liver functions normalized in all patients after recovery,including in those with pre-existing liver or kidney failure.The ultrasound findings were normal in12 patients,an increasingly coarsened echo-pattern and increased echogenicity of the liver in 10 patients,and mild to moderate fatty liver infiltration in 3 patients.Cirrhosis or liver nodules were not observed in any patient.CONCLUSION:Acute liver failure and acute renal failure in AFLP patients is reversible.Patients do not require any specific long-term follow-up after recovery from AFLP if their liver function tests have normalized and they remain well.展开更多
AIM:To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure(ACLF).METHODS:This was a si...AIM:To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure(ACLF).METHODS:This was a single center,prospective cohort study.Eligible,consecutive hospitalized patients received either entecavir 0.5 mg/d or lamivudine 100mg/d.All patients were given standard comprehensive internal medicine.The primary endpoint was survival rate at day 60,and secondary endpoints were reduction in hepatitis B virus(HBV)DNA and alanine aminotransferase(ALT)levels,and improvement in Child-Turcotte-Pugh(CTP)and model for end-stage liver disease(MELD)scores at day 60 and survival rate at week 52.RESULTS:One hundred and nineteen eligible subjects were recruited from 176 patients with severe acute exacerbation of chronic hepatitis B:65 were included in the entecavir group and 54 in the lamivudine group(full analysis set).No significant differences were found in patient baseline clinical parameters.At day 60,entecavir did not improve the probability of survival(P=0.066),despite resulting in faster virological suppression(P<0.001),higher rates of virological response(P<0.05)and greater reductions in the CTP and MELD scores(all P<0.05)than lamivudine.Intriguingly,at week 52,the probability of survival was higher in the entecavir group than in the lamivudine group[42/65(64.6%)vs 26/54(48.1%),respectively;P=0.038].The pretreatment MELD score(B,1.357;95%Cl:2.138-7.062;P=0.000)and virological response at day30(B,1.556;95%Cl:1.811-12.411;P=0.002),were found to be good predictors for 52-wk survival.CONCLUSION:Entecavir significantly reduced HBV DNA levels,decreased the CTP and MELD scores,and thereby improved the long-term survival rate in patients with spontaneous reactivation of hepatitis B presenting as ACLF.展开更多
AIM： To establish a rapid and convenient animal model with hepatitis B virus （HBV） replication.METHODS： A naked DNA solution of HBV-replicationcompetent plasmid was transferred to BALB/C mice via the tail vein, us...AIM： To establish a rapid and convenient animal model with hepatitis B virus （HBV） replication.METHODS： A naked DNA solution of HBV-replicationcompetent plasmid was transferred to BALB/C mice via the tail vein, using a hydrodynamic in vivo transfection procedure. After injection, these mice were sacrificed on d 1, 3, 4, 5, 7 and 10. HBV DNA replication intermediates in the liver were analyzed by Southern blot hybridization. The expression of hepatitis B core antigen （HBcAg） and hepatitis B surface antigen （HBsAg） in the liver was checked by immunohistochemistry. Serum HBsAg and hepatitis B e antigen （HBeAg） was detected by enzyme- linked immunosorbent assay （ELISA）. Inhibition of HBV replication was compared in HBV replication model mice treated intraperitoneally with polyinosinic-polytidylin acid （polyIC） or phosphate-buffered saline （PBS）.RESULTS： After hydrodynamic in vivo transfection, HBV DNA replication intermediates in the mouse liver were detectable on d 1 and abundant on d 3 and 4, the levels were slightly decreased and remained relatively stable between d 5 and 7, and were almost undetectable on d 10. The expression patterns of HBcAg and HBsAg were similar to that of HBV replication intermediate DNA, except that they reached a peak on d 1 after injection. No obvious differences in HBV DNA replication intermediates were observed in the left, right and middle lobes of the liver. After treatment with polyIC, the level of HBV intermediate DNA in the liver was lower than that in the control mice injected with PBS.CONCLUSION： A rapid and convenient mouse model with a high level of HBV replication was developed and used to investigate the inhibitory effect of polyIC on HBV replication, which provides a useful tool for future functional studies of the HBV genome.展开更多
BACKGROUND: Controlled attenuation parameter (CAP) is a non-invasive method for diagnosing hepatic steatosis based on vibration-controlled transient elastography. The objective of this study was to investigate the eff...BACKGROUND: Controlled attenuation parameter (CAP) is a non-invasive method for diagnosing hepatic steatosis based on vibration-controlled transient elastography. The objective of this study was to investigate the effect of high value of CAP on antiviral therapy in patients with chronic hepatitis B (CHB). METHODS: Patients with CHB receiving enticavir for initial antiviral therapy were studied; they were divided into the high CAP group and normal CAP group at baseline according to the CAP values. The effect of the antiviral therapy between the two groups were compared at week 12, 24 and 48. Patients with high CAP value at baseline were divided into three subgroups, mild, moderate and severe elevation; the therapeutic response were compared among patients with normal CAP and subgroups of patients with elevated CAP. RESULTS: A total of 153 patients were enrolled. Among them, 63 were in the high CAP group and 90 in the normal CAP group. Patients with high CAP had lower rates of ALT normalization and HBV DNA clearance in response to antiviral therapy compared with those with normal CAP at week 12, 24 and 48. Further analysis showed that the rate of ALT normalization in patients with mildly and moderately elevated CAP were significant lower than those with normal CAP at week 12 and 24; while the difference was not significant between the patients with normal CAP and those with severely elevated CAP. The rate of HBV DNA clearance was significantly lower in patients with severely elevated CAP compared with those with normal CAP at week 12, 24 and 48. CONCLUSION: CHB patients with high CAP had poor response to antiviral therapy.展开更多
BACKGROUND: The liver, as the main iron storage compart-ment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Exces-sive accumulation of iron is an import...BACKGROUND: The liver, as the main iron storage compart-ment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Exces-sive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. DATA SOURCES: PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease pro-gression. We have also included literature on adjuvant thera-peutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis. RESULTS: Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identiifcation of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause signiifcant improvement of liver functions in patients with iron overload. Phlebotomy can have beneifcial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology. CONCLUSION: Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and avail-able data suggest that it can be considered as target for adju-vant therapy in this condition.展开更多
Background:Post-liver transplantation(LT)hepatocellular carcinoma(HCC)recurrence still occurs in approximately 20%of patients and drastically affects their survival.This study aimed to evaluate the efficacy of various...Background:Post-liver transplantation(LT)hepatocellular carcinoma(HCC)recurrence still occurs in approximately 20%of patients and drastically affects their survival.This study aimed to evaluate the efficacy of various treatments for recurrent HCC after LT in a Chinese population.Methods:A total of 64 HCC patients with tumor recurrence after LT were enrolled in this study.Univariate and multivariate analyses were performed to identify factors affecting post-recurrence survival.Results:Of the 64 patients with recurrent HCC after LT,those who received radical resection followed by nonsurgical therapy had a median overall survival(OS)of 20.9 months after HCC recurrence,significantly superior to patients who received only nonsurgical therapy(9.4 months)or best supportive care(2.4 months).The one-and two-year OS following recurrence was favorable for patients receiving radical resection followed by nonsurgical therapy(93.8%,52.6%),poor for patients receiving only nonsurgical therapy(30.8%,10.8%),and dismal for patients receiving best supportive care(0%,0%;overall P<0.001).Median OS in sorafenib-tolerant patients treated with lenvatinib was 19.5 months,far surpassing the patients that discontinued sorafenib or were treated with regorafenib after sorafenib failure(12 months,P<0.001).Compared with tacrolimus-based immunosuppressive therapy,OS was significantly increased with sirolimus-based therapy at one and two years after HCC recurrence(P=0.035).Multivariate analysis showed radical resection combined with nonsurgical therapy for recurrent HCC and sorafenib-lenvatinib sequential therapy were independent favorable factors for post-recurrence survival.Conclusions:Aggressive surgical intervention in well-selected patients significantly improves OS after recurrence.A multidisciplinary treatment approach is required to slow down disease progression for patients with unresectable recurrent HCC.展开更多
Chronic hepatitis B (CHB) is currently medically managed with either interferon-alpha or one of the five nucleos(t)ide analogs. However, there are still a large number of CHB patients whose response to the above thera...Chronic hepatitis B (CHB) is currently medically managed with either interferon-alpha or one of the five nucleos(t)ide analogs. However, there are still a large number of CHB patients whose response to the above therapies remains less than satisfactory, and their incomplete or non-response to antiviral therapies has plagued clinicians worldwide. In recent years, a newly proposed optimization therapy has provided us with a new approach to solve this problem. The key points in this optimization therapy are to initiate antiviral therapy with an appropriate agent at the correct time point, and to adjust treatments in patients with poor early responses by adding a second agent or switching to another more potent agent. In this review, we summarize recent developments in optimization therapy for the treatment of CHB, and provide an outlook for future research in this field. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.展开更多
The past two decades have witnessed an explosion of research and clinical application of stem cells, transforming the field of regenerative medicine. Stem cell transplantation has already been performed to treat patie...The past two decades have witnessed an explosion of research and clinical application of stem cells, transforming the field of regenerative medicine. Stem cell transplantation has already been performed to treat patients with cancer,liver diseases, and various types of chronic diseases. Indeed, stem cell-based therapies are effective in many diseases, and provide novel insights into the treatment of end-stage liver disease. Several clinical trials have indicated the efficacy profiles of stem cell transplantation in patients with end-stage liver disease, including liver cirrhosis, liver failure, and liver tumors. Animal models of acute liver failure have also provided important insights into the safety,mechanisms, and efficacy of stem cell therapies. Nevertheless, excitement due to this promising field must be tempered with careful and calculated research. In particular, studies on the quality, safety, and efficacy of stem cell transplantation are needed to ensure that qualified products are tested in well-designed clinical trials and approved by governments. Therefore, further investigations are required to effectively balance the safety with the innovation of stem cell transplantation research toward the effective treatment of end-stage liver disease.展开更多
BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA...BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA viral load.AIM To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection.METHODS In total,395 patients(30–65 years old)with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk.Endpoints to evaluate therapeutic efficacy included:(1)HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96;and(2)HBeAg clearance and seroconversion rates at weeks 48 and 96.RESULTS HBV DNA levels≤4 log10 IU/mL were 10.05%at week 48 and 18.59%at week 96 in the treatment group.The HBeAg clearance and conversion rates were 8.54%and 8.04%at week 48 and 16.08%and 14.57%at week 96,respectively.However,HBV DNA levels≤4 log10 IU/mL were 2.55%and 2.55%at weeks 48 and 96,respectively,and the HBeAg clearance rates were 3.06%and 5.61%at weeks 48 and 96,respectively,in the control group.The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance.CONCLUSION High rates of HBV DNA reduction,HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase.The ability of the compound to modulate host immune function probably contributed to this effect.展开更多
Background:The progress of liver diseases may not stop after viral eradication.This study aimed to provide data on long-term prognosis of patients with hepatitis C virus(HCV)infection who underwent pegylated interfero...Background:The progress of liver diseases may not stop after viral eradication.This study aimed to provide data on long-term prognosis of patients with hepatitis C virus(HCV)infection who underwent pegylated interferon plus ribavirin(PR)regimen and achieved a sustained virological response 24 weeks post-treatment(SVR24).Methods:Responders to the PR regimen in our hospital from January 2011 to June 2014 were enrolled and prospectively followed up.Baseline characteristics were profiled.The incidence of hepatocellular carcinoma(HCC),progression of liver disease(increase in liver stiffness or occurrence of decompensated complication),and HCV recurrence was all monitored.The accumulative and annualized incidence rates(AIRs)of these adverse events were analyzed,and the risk factors were also examined.Results:In total,151 patients reached a median follow-up time of 103 weeks.Among them,two had an incidence of HCC during the surveillance with AIR of 0.68%(95%CI:0.00-1.63%).Six patients showed progression of liver disease with AIR of 2.05%(95%CI:0.42%-3.68%).Three patients who had risky behaviors encountered HCV reinfection.The cirrhotic patients faced higher risk of poor prognosis than non-cirrhotic patients,including HCC and progression of liver disease(AIR:6.17%vs.1.42%,P=0.039).Conclusions:The incidence of HCC and progression of liver disease was evident in PR responders during the long-term follow-up period,but the risk level was low.Cirrhotic responders were more vulnerable to develop HCC post SVR24 compared with non-cirrhotic ones.HCV recurrence was rare in responders with SVR24 who had corrected their risky behaviors.展开更多
The AKT/mTOR and NF-κB signalings are crucial pathways activated in cancers including nasopharyngeal carcinoma(NPC), which is prevalent in southern China and closely related to Epstein-Barr virus(EBV) infection.How t...The AKT/mTOR and NF-κB signalings are crucial pathways activated in cancers including nasopharyngeal carcinoma(NPC), which is prevalent in southern China and closely related to Epstein-Barr virus(EBV) infection.How these master pathways are persistently activated in EBV-associated NPC remains to be investigated. Here we demonstrated that EBV-encoded latent membrane protein 1(LMP1) promoted cyclophilin A(CYPA) expression through the activation of NF-κB. The depletion of CYPA suppressed cell proliferation and facilitated apoptosis.CYPA was able to bind to AKT1, thus activating AKT/mTOR/NF-κB signaling cascade. Moreover, the use of mTOR inhibitor, rapamycin, subverted the activation of the positive feedback loop, NF-κB/CYPA/AKT/mTOR. It is reasonable that LMP1 expression derived from initial viral infection is enough to assure the constant potentiation of AKT/mTOR and NF-κB signalings. This may partly explain the fact that EBV serves as a tumor-promoting factor with minimal expression of the viral oncoprotein LMP1 in malignancies. Our findings provide new insight into the understanding of causative role of EBV in tumorigenicity during latent infection.展开更多
BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening program...BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.AIM To determine the role of the combination of SCCA-IgM and AFP in predicting mid-and long-term appearance of HCC.METHODS Two-hundred and three cirrhotic patients(Child A 74.9%,B 21.2%,C 3.9%)were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines.The estimation cohort was recruited in Italy(30.5%;62/203)and validation cohort from Spain(69.5%;141/203).Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay(Hepa-IC,Xeptagen,Italy)and AFP levels at baseline.Patients were followed-up for 60 mo,being censored at the time of the appearance of HCC.RESULTS There were 10.8%and 23.1%of HCC development at two-and five-years followup.Patients with HCC showed higher levels of SCCA-IgM than those without it(425.72±568.33 AU/mL vs 195.93±188.40 AU/mL,P=0.009)during the fiveyear follow-up.In multivariate analysis,after adjusting by age,sex,aspartate transaminase and Child-Pugh,the following factors were independently associated with HCC:SCCA-IgM[Hazard ratio(HR)=1.001,95%CI:1.000-1.002;P=0.003],AFP(HR=1.028,95%CI:1.009-1.046;P=0.003)and creatinine(HR=1.56495%CI:1.151-2.124;P=0.004).The log-rank test of the combination resulted in 7.488(P=0.024)in estimation cohort and 11.061(P=0.004)in the validation cohort,and a 100%of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.CONCLUSION We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method,which could be followed by tailored HCC surveillance for individual patients,especially for those cirrhotic patients belonging to the subgroup identified as low-risk of HCC development.展开更多
基金The National Natural Science Foundation of China,No.30571640the National Basic Research Program of China,No.2006CB504302 and No.2007CB512902
文摘AIM： To investigate the risk factors for gallstone disease in the general population of Chengdu, China. METHODS： This study was conducted at the West China Hospital. Subjects who received a physical examination at this hospital between January and December 2007 were included. Body mass index, blood pressure, fasting plasma glucose, serum lipid and lipoproteins concentrations were analyzed. Gallstone disease was diagnosed by ultrasound or on the basis of a history of cholecystectomy because of gallstone disease. Unconditional logistic regression analysis was used to investigate the risk factors for gallstone disease, and the Chi-square test was used to analyze differences in the incidence of metabolic disorders between subjects with and without gallstone disease. RESULTS： A total of 3573 people were included, 10.7% （384/3573） of whom had gallstone diseases. Multiple logistic regression analysis indicated that the incidence of gallstone disease in subjects aged 40-64 or ≥65 years was significantly different from that in those aged 18-39 years （P 〈 0.05）; the incidence was higher in women than in men （P 〈 0.05）. In men,a high level of fasting plasma glucose was obvious in gallstone disease （P 〈 0.05）, and in women, hypertriglyceridemia or obesity were significant in gallstone disease （P 〈 0.05）. CONCLUSION： We assume that age and sex are profoundly associated with the incidence of gallstone disease; the metabolic risk factors for gallstone disease were different between men and women.
基金supported by grants from the National Twelve-Five Project of China (2012ZX10002007-001-003)the Chinese Foundation for Hepatitis PreventionControl-TianQing Liver Disease Research Fund (cfhpc20132047)
文摘BACKGROUND： Vitamin D is a fat-soluble sterol derivative that is predominantly synthesized in the liver and has multiple functions. The accumulative data showed that the clinical manifestations and prognosis of chronic liver diseases are associated with serum vitamin D levels. DATA SOURCES： A PubMed and Google Scholar search using terms： ＂vitamin D＂, ＂25 （OH）D＂, ＂liver disease＂, ＂viral hepatitis＂, ＂non-alcoholic fatty liver disease＂, ＂liver fibrosis＂, ＂cirrhosis＂, ＂hepatocellular carcinoma＂ and ＂autoimmune liver disease＂ was performed, and relevant articles published in English between January 2000 and March 2014 were reviewed. Fulb text publications relevant to the field were selected and relevant articles from reference lists were also included. RESULTS： The insufficiency or deficiency of vitamin D is common in various kinds of chronic liver diseases including viral hepatitis B and C. Serum 25-hydroxyvitamin D and vitamin D receptors are possibly interrelated with the incidence, treatment and prognosis of diseases. Though the evidence of vitamin D supplementation in viral hepatitis and associated liver diseases is still limited, there is great potential to apply this adjuvant therapy to improve the treatments. CONCLUSIONS： Although the exact role and mechanisms of vitamin D have not been fully elucidated in chronic liver diseases, it is potentially beneficial in the treatment of chronic liver diseases. Further mechanistic studies are needed to validate its clinical application.
文摘This minireview focuses on psychological distress and treatment adherence-issues in patients with chronic hepatitis B(CHB).It begins by discussing the epidemiology and disease burden of CHB,and addresses the relationship between psychological distress and treatment adherence.Next,it delves into the current status and risk factors for psychological distress among patients with CHB,and explores the challenges and risk factors related to treatment adherence.Subsequently,it explores the development and implementation of integrated nursing strategies,including psychological interventions and support,self-efficacy enhancement strategies,social support-system optimization,personalized medical care,and technological innovation.Finally,it highlights the limitations of current interventions and clarifies future research priorities.This minireview aims to provide a comprehensive theoretical basis and practical guidance for improving treatment outcomes and quality of life of patients with CHB.In summary,we reveal that psychological distress significantly impacts treatment adherence in patients with CHB and that it is essential to adopt integrated nursing strategies to address these challenges.These findings highlight the need to consider the psychological states of individuals and develop targeted interventions to improve treatment outcomes.
基金Supported by National Key R&D Program of China,No.2023YFC2308104Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support,No.ZLRK202301National Natural Science Foundation of China,No.92159305.
文摘BACKGROUND Chronic hepatitis B virus(HBV)infection acquired in childhood frequently presents with mild or nonspecific symptoms,yet a distinct subset of pediatric patients develops rapid progression to liver cirrhosis(LC)before adulthood.AIM To identify clinical and pathological characteristics of pediatric HBV-related LC.METHODS A total of 1332 pediatric patients with chronic HBV infection from the Fifth Medical Center of PLA General Hospital from January 2010 to January 2023 were included in this study.We identified 62 pediatric HBV-related LC by liver biopsy from the group.Subsequently,we described the clinical and pathological characteristics of pediatric LC.And 64 pediatric chronic hepatitis B(CHB;age and sex were matched with pediatric LC group)and 69 adult HBV-related LC(sex were matched with pediatric LC group)were enrolled to further demonstrate clinical and pathological differences between pediatric LC,pediatric CHB and adult LC.RESULTS We enrolled 62 pediatric LC,including 54(87.1%)males and 8(12.9%)females.The median age was 11(4-14)years old.The pediatric LC group showed significantly lower median quantitative HBV DNA loads(log10IU/mL:6.3 vs 17.4,P<0.001),reduced HBsAg titers(log10IU/mL:3.11 vs 8.956,P<0.0001),and diminished hepatitis B e antigen-positive positive rate(81.4%vs 93.8%,P<0.05)compared with pediatric CHB.A higher proportion of pediatric patients were asymptomatic(77.4%)compared to adult patients(11.6%)as they first diagnosed as LC,pediatric LC showed milder initial symptoms compared with adult patients such as fatigue(4.8%vs 27.5%),abdominal discomfort(9.7%vs 23.2%),nausea(0%vs 10.1%),and poor appetite(6.5%vs 8.7%;all P<0.0001).Notably,pediatric LC can achieve a significant percentage of functional cure compared with adult LC as 17.4%and 0%.The incidence of progression of LC in children after antiviral therapy continues to be much lower than that in adult LC(hazard ratio=6.102,95%confidence interval:1.72-21.65,P=0.00051).While the incidence of LC remission in children after antiviral therapy continues to be much higher than that in adult LC(hazard ratio=0.055,95%confidence interval:0.07128-0.2802,P<0.0001).CONCLUSION Pediatric patients with HBV-related cirrhosis exhibit elevated virological parameters and heightened transaminase levels than adult patients.However,the frequent paucity of overt clinical symptoms contributes to diagnostic challenges.Notably,early initiation of antiviral therapy in this population substantially improved clinical outcomes.
基金supported by 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University(No.ZYGD23030)National Natural Science Foundation of China(No.82172254)Science and Technological Supports Project of Sichuan Province,China(No.2024YFFK0214).
文摘With organ transplantation facing many dilemmas,tissue and organ regeneration as an alternative has bright prospects.In regenerative medicine,Three-dimensional(3D)printing technology and stem cells has been widely applied to the treatment of diseases related to tissue or organ replacement in dentistry,respectively.However,there are very few studies on the combination of the two,and even fewer clinical studies have been reported in dentistry.In this review,the current oral tissue engineering in vivo and in vitro based on 3D printing and stem cell technology will be summarized,and the discussion on the development prospects of this research direction will be given.Besides,the working principles and advantages&disadvantages of several types of 3D printers,as well as the mechanism of stem cells in tissue engineering will be elucidated.This review provides clinicians and researchers with the current state of research and trends in the combination of stem cells and 3D printing technology to treat oral-related diseases.In the future,3D bioprinters are poised for ongoing innovation with the advancement of relevant technologies,catalyzing an increase in clinical studies focused on treating oral diseases using stem cells and 3D scaffolds.Consequently,these developments will further advance the field of oral tissue engineering.
基金National Natural Science Foundation of China,Grant/Award Number:82174292Key Project of Jiangsu Provincial Administration of Traditional Chinese Medicine,Grant/Award Number:ZD202312+2 种基金Natural Science Foundation of Laboratory Medicine School in Chengdu Medical College,Grant/Award Number:JYZK202203Sichuan Province Science and Technology Program,Grant/Award Number:2024NSFSC0577 and 2021YFG0316Technology innovation group project of Foshan 2019,Grant/Award Number:FS0AA-KJ919-4402-0027。
文摘Background:The emerging incidence of pathogenic liver conditions is turning into a major concern for global health.Induction of pyroptosis in hepatocytes instigates cel-lular disintegration,which in turn liberates substantial quantities of pro-inflammatory intracellular substances,thereby accelerating the advancement of liver fibrosis.Consequently,directing therapeutic efforts towards inhibiting pyroptosis could po-tentially serve as an innovative approach in managing inflammation related chronic hepatic disorders.Methods:GSDMD-NT^(ki/wt)mice and Alb-cre^(ki/wt)mice were generated using CRISPR/Cas9 technology.After crossing the two strains together,we induced conditional cell death by doxycycline to construct a mouse model of liver fibrosis.We analyzed differ-entially expressed genes by RNA sequencing and explored their biological functions.The efficacy of obeticholic acid(OCA)in the treatment of liver fibrosis was assessed.Results:Doxycycline-treated GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice showed severe liver damage,vacuolation of hepatocytes,increased collagen fibers,and accumulation of lipid droplets.The expression of liver fibrosis related genes was greatly increased in the doxycycline-treated mouse liver compared with untreated mouse liver.RNA-sequencing showed that upregulated differentially expressed genes were involved in inflammatory responses,cell activation,and metabolic processes.Treatment with OCA alleviated the liver fibrosis,with reduced ALT and AST levels seen in the GSDMD-NT^(ki/wt)×Alb-cre^(ki/wt)mice.Conclusions:We successfully constructed a novel mouse model for liver fibrosis.This GSDMD-NT-induced fibrosis may be mediated by abnormal lipid metabolism.Our re-sults demonstrated that we successfully constructed a mouse model of liver fibrosis,and GSDMD-NT induced fibrosis by mediating lipid metabolism.
基金funded by the Guangdong Major Project of Basic and Applied Basic Research(2020B0301030007)the National Natural Science Foundation of China(32141002)+1 种基金the National Key Research and Development Program of China(2022YFC2303900)the Science and Technology Program of Guangzhou,China(2023A04J0755 and 202201010300)。
文摘Tigecycline is one of the most critical drugs for treating Gram-negative bacterial infections;however,the emergence of the tigecycline resistance efflux pump TMexCD1-TOprJ1 poses a global health threat.The evolutionary relationships and epidemiological trends of tmexCD1-toprJ1-positive strains across various ecological niches remain largely unexplored.In this study,we employed whole-genome sequencing(WGS)of tmexCD1-toprJ1-positive bacteria from humans,food,animals,and the environment in China to assess the epidemiological and genomic features of these strains,analyzing both newly collected strains and data from the GenBank database.From 3434 samples collected during 2019-2022,145tmexCD1-toprJ1-carrying strains(4.5%)were isolated.The majority of the tmexCD1-toprJ1-positive Enterobacterales exhibited resistance to nearly all antimicrobials,including colistin(42.13%).tmexCD1-toprJ1 was predominantly identified in Klebsiella pneumoniae(K.pneumoniae)from chicken feces in China but was also detected in multiple ecological niches and other countries.Phylogenetic analysis revealed the clonal transmission of tmexCD1-toprJ1-positive ST37 K.pneumoniae across diverse ecological niches as well as the international spread of the ST15 K.pneumoniae clone-producing TMexCD1-TOprJ1.tmexCD1-toprJ1 is mainly carried by Klebsiella spp.specific narrow host range plasmids,which may limit the spread of tmexCD1-toprJ1 across different bacterial species.Notably,due to the fitness cost posed by tmexCD1-toprJ1,the occurrence of tmexCD1-toprJ1-positive Enterobacterales in both food animals and humans in China has declined significantly following the withdrawal of antibiotics as growth promoters in food animals in China since 2020.However,tmexCD1-toprJ1 has been captured by broad-host-range plasmids and hypervirulent carbapenem-resistant K.pneumoniae ST11-KL64 strains in healthcare settings.The frequent use of tetracyclines in chicken farming likely contributes to the high detection rate of tmexCD1-toprJ1;therefore,to reduce the threat of tmexCD1-toprJ1-positive K.pneumoniae,continuous monitoring of tmexCD1-toprJ1 across different ecological niches and strict enforcement of antimicrobial policies in animal husbandry,particularly in the poultry industry,are urgently required.
基金Supported by National Natural Science Foundation of China,No.81300319Science and Technology Support Program of Sichuan Province,China,No.2015SZ0049
文摘Hepatitis B virus(HBV) associated acute-on-chronic liver failure(ACLF) is an increasingly recognized fatal liver disease encompassing a severe acute exacerbation of liver function in patients with chronic hepatitis B(CHB). Despite the introduction of an artificial liver support system and antiviral therapy, the short-term prognosis of HBV-ACLF is still extremely poor unless emergency liver transplantation is performed. In such a situation, stopping or slowing the progression of CHB to ACLF at an early stage is the most effective way of reducing the morbidity and mortality of HBV-ACLF. It is well-known that the occurrence and progression of HBV-ACLF is associated with many factors, and the outcomes of HBV-ACLF patients can be significantly improved if timely and appropriate interventions are provided. In this review, we highlight recent developments in early warning and clinical outcome prediction in patients with HBV-ACLF and provide an outlook for future research in this field.
文摘AIM:To evaluate the prognosis of patients with acute fatty liver of pregnancy(AFLP)6 mo or longer after discharge.METHODS:The records of pregnant patients diagnosed with AFLP at Beijing Ditan Hospital over a 16-year period were reviewed in November 2012.Patients weremonitored using abdominal ultrasound,liver and kidney functions,and routine blood examination.RESULTS:A total of 42 patients were diagnosed with AFLP during the study period,and 25 were followed.The mean follow-up duration was 54.5 mo(range:6.5-181 mo).All patients were in good physical condition,but one patient had gestational diabetes.The renal and liver functions normalized in all patients after recovery,including in those with pre-existing liver or kidney failure.The ultrasound findings were normal in12 patients,an increasingly coarsened echo-pattern and increased echogenicity of the liver in 10 patients,and mild to moderate fatty liver infiltration in 3 patients.Cirrhosis or liver nodules were not observed in any patient.CONCLUSION:Acute liver failure and acute renal failure in AFLP patients is reversible.Patients do not require any specific long-term follow-up after recovery from AFLP if their liver function tests have normalized and they remain well.
基金Supported by Grants from the National Key Technology R and D Program,No.2008ZX10005 and No.2009ZX10005
文摘AIM:To investigate the short-term and long-term efficacy of entecavir versus lamivudine in patients with spontaneous reactivation of hepatitis B presenting as acute-on-chronic liver failure(ACLF).METHODS:This was a single center,prospective cohort study.Eligible,consecutive hospitalized patients received either entecavir 0.5 mg/d or lamivudine 100mg/d.All patients were given standard comprehensive internal medicine.The primary endpoint was survival rate at day 60,and secondary endpoints were reduction in hepatitis B virus(HBV)DNA and alanine aminotransferase(ALT)levels,and improvement in Child-Turcotte-Pugh(CTP)and model for end-stage liver disease(MELD)scores at day 60 and survival rate at week 52.RESULTS:One hundred and nineteen eligible subjects were recruited from 176 patients with severe acute exacerbation of chronic hepatitis B:65 were included in the entecavir group and 54 in the lamivudine group(full analysis set).No significant differences were found in patient baseline clinical parameters.At day 60,entecavir did not improve the probability of survival(P=0.066),despite resulting in faster virological suppression(P<0.001),higher rates of virological response(P<0.05)and greater reductions in the CTP and MELD scores(all P<0.05)than lamivudine.Intriguingly,at week 52,the probability of survival was higher in the entecavir group than in the lamivudine group[42/65(64.6%)vs 26/54(48.1%),respectively;P=0.038].The pretreatment MELD score(B,1.357;95%Cl:2.138-7.062;P=0.000)and virological response at day30(B,1.556;95%Cl:1.811-12.411;P=0.002),were found to be good predictors for 52-wk survival.CONCLUSION:Entecavir significantly reduced HBV DNA levels,decreased the CTP and MELD scores,and thereby improved the long-term survival rate in patients with spontaneous reactivation of hepatitis B presenting as ACLF.
基金Supported by the National Science Fund for Distinguished Young Scholars from the National Natural Science Foundation of China,No.30325036a grant from the National Natural Science Foundation of China,No.30571640
文摘AIM： To establish a rapid and convenient animal model with hepatitis B virus （HBV） replication.METHODS： A naked DNA solution of HBV-replicationcompetent plasmid was transferred to BALB/C mice via the tail vein, using a hydrodynamic in vivo transfection procedure. After injection, these mice were sacrificed on d 1, 3, 4, 5, 7 and 10. HBV DNA replication intermediates in the liver were analyzed by Southern blot hybridization. The expression of hepatitis B core antigen （HBcAg） and hepatitis B surface antigen （HBsAg） in the liver was checked by immunohistochemistry. Serum HBsAg and hepatitis B e antigen （HBeAg） was detected by enzyme- linked immunosorbent assay （ELISA）. Inhibition of HBV replication was compared in HBV replication model mice treated intraperitoneally with polyinosinic-polytidylin acid （polyIC） or phosphate-buffered saline （PBS）.RESULTS： After hydrodynamic in vivo transfection, HBV DNA replication intermediates in the mouse liver were detectable on d 1 and abundant on d 3 and 4, the levels were slightly decreased and remained relatively stable between d 5 and 7, and were almost undetectable on d 10. The expression patterns of HBcAg and HBsAg were similar to that of HBV replication intermediate DNA, except that they reached a peak on d 1 after injection. No obvious differences in HBV DNA replication intermediates were observed in the left, right and middle lobes of the liver. After treatment with polyIC, the level of HBV intermediate DNA in the liver was lower than that in the control mice injected with PBS.CONCLUSION： A rapid and convenient mouse model with a high level of HBV replication was developed and used to investigate the inhibitory effect of polyIC on HBV replication, which provides a useful tool for future functional studies of the HBV genome.
基金supported by grants from the National Science and Technology Major Project of China(2012ZX10002007-001-003 and 2013ZX10002005-002-003)the WBE Liver Fibrosis Foundation(XJS20120204)
文摘BACKGROUND: Controlled attenuation parameter (CAP) is a non-invasive method for diagnosing hepatic steatosis based on vibration-controlled transient elastography. The objective of this study was to investigate the effect of high value of CAP on antiviral therapy in patients with chronic hepatitis B (CHB). METHODS: Patients with CHB receiving enticavir for initial antiviral therapy were studied; they were divided into the high CAP group and normal CAP group at baseline according to the CAP values. The effect of the antiviral therapy between the two groups were compared at week 12, 24 and 48. Patients with high CAP value at baseline were divided into three subgroups, mild, moderate and severe elevation; the therapeutic response were compared among patients with normal CAP and subgroups of patients with elevated CAP. RESULTS: A total of 153 patients were enrolled. Among them, 63 were in the high CAP group and 90 in the normal CAP group. Patients with high CAP had lower rates of ALT normalization and HBV DNA clearance in response to antiviral therapy compared with those with normal CAP at week 12, 24 and 48. Further analysis showed that the rate of ALT normalization in patients with mildly and moderately elevated CAP were significant lower than those with normal CAP at week 12 and 24; while the difference was not significant between the patients with normal CAP and those with severely elevated CAP. The rate of HBV DNA clearance was significantly lower in patients with severely elevated CAP compared with those with normal CAP at week 12, 24 and 48. CONCLUSION: CHB patients with high CAP had poor response to antiviral therapy.
基金supported by a grant from Polish National Science Centre(2011/01/B/NZ6/00320)
文摘BACKGROUND: The liver, as the main iron storage compart-ment and the place of hepcidin synthesis, is the central organ involved in maintaining iron homeostasis in the body. Exces-sive accumulation of iron is an important risk factor in liver disease progression to cirrhosis and hepatocellular carcinoma. Here, we review the literature on the molecular pathogenesis of iron overload and its clinical consequences in chronic liver diseases. DATA SOURCES: PubMed was searched for English-language articles on molecular genesis of primary and secondary iron overload, as well as on their association with liver disease pro-gression. We have also included literature on adjuvant thera-peutic interventions aiming to alleviate detrimental effects of excessive body iron load in liver cirrhosis. RESULTS: Excess of free, unbound iron induces oxidative stress, increases cell sensitivity to other detrimental factors, and can directly affect cellular signaling pathways, resulting in accelerated liver disease progression. Diagnosis of liver cirrhosis is, in turn, often associated with the identiifcation of a pathological accumulation of iron, even in the absence of genetic background of hereditary hemochromatosis. Iron depletion and adjuvant therapy with antioxidants are shown to cause signiifcant improvement of liver functions in patients with iron overload. Phlebotomy can have beneifcial effects on liver histology in patients with excessive iron accumulation combined with compensated liver cirrhosis of different etiology. CONCLUSION: Excessive accumulation of body iron in liver cirrhosis is an important predictor of liver failure and avail-able data suggest that it can be considered as target for adju-vant therapy in this condition.
基金the grants from National S&T Major Project(2017ZX10203205)the Medical Science and Technology Project of Zhejiang Province(2014KYA082)+1 种基金the Fundamental Research Funds for the Central Universities(2018FZA7002)the Shulan Talent Foundation.
文摘Background:Post-liver transplantation(LT)hepatocellular carcinoma(HCC)recurrence still occurs in approximately 20%of patients and drastically affects their survival.This study aimed to evaluate the efficacy of various treatments for recurrent HCC after LT in a Chinese population.Methods:A total of 64 HCC patients with tumor recurrence after LT were enrolled in this study.Univariate and multivariate analyses were performed to identify factors affecting post-recurrence survival.Results:Of the 64 patients with recurrent HCC after LT,those who received radical resection followed by nonsurgical therapy had a median overall survival(OS)of 20.9 months after HCC recurrence,significantly superior to patients who received only nonsurgical therapy(9.4 months)or best supportive care(2.4 months).The one-and two-year OS following recurrence was favorable for patients receiving radical resection followed by nonsurgical therapy(93.8%,52.6%),poor for patients receiving only nonsurgical therapy(30.8%,10.8%),and dismal for patients receiving best supportive care(0%,0%;overall P<0.001).Median OS in sorafenib-tolerant patients treated with lenvatinib was 19.5 months,far surpassing the patients that discontinued sorafenib or were treated with regorafenib after sorafenib failure(12 months,P<0.001).Compared with tacrolimus-based immunosuppressive therapy,OS was significantly increased with sirolimus-based therapy at one and two years after HCC recurrence(P=0.035).Multivariate analysis showed radical resection combined with nonsurgical therapy for recurrent HCC and sorafenib-lenvatinib sequential therapy were independent favorable factors for post-recurrence survival.Conclusions:Aggressive surgical intervention in well-selected patients significantly improves OS after recurrence.A multidisciplinary treatment approach is required to slow down disease progression for patients with unresectable recurrent HCC.
基金Supported by The National Twelve-Five Project of China,No.2012ZX10002007-001-003,and No.2013ZX10002001
文摘Chronic hepatitis B (CHB) is currently medically managed with either interferon-alpha or one of the five nucleos(t)ide analogs. However, there are still a large number of CHB patients whose response to the above therapies remains less than satisfactory, and their incomplete or non-response to antiviral therapies has plagued clinicians worldwide. In recent years, a newly proposed optimization therapy has provided us with a new approach to solve this problem. The key points in this optimization therapy are to initiate antiviral therapy with an appropriate agent at the correct time point, and to adjust treatments in patients with poor early responses by adding a second agent or switching to another more potent agent. In this review, we summarize recent developments in optimization therapy for the treatment of CHB, and provide an outlook for future research in this field. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.
文摘The past two decades have witnessed an explosion of research and clinical application of stem cells, transforming the field of regenerative medicine. Stem cell transplantation has already been performed to treat patients with cancer,liver diseases, and various types of chronic diseases. Indeed, stem cell-based therapies are effective in many diseases, and provide novel insights into the treatment of end-stage liver disease. Several clinical trials have indicated the efficacy profiles of stem cell transplantation in patients with end-stage liver disease, including liver cirrhosis, liver failure, and liver tumors. Animal models of acute liver failure have also provided important insights into the safety,mechanisms, and efficacy of stem cell therapies. Nevertheless, excitement due to this promising field must be tempered with careful and calculated research. In particular, studies on the quality, safety, and efficacy of stem cell transplantation are needed to ensure that qualified products are tested in well-designed clinical trials and approved by governments. Therefore, further investigations are required to effectively balance the safety with the innovation of stem cell transplantation research toward the effective treatment of end-stage liver disease.
基金Supported by the National Natural Science Foundation of China,No.81174263National Science and Technology Major Project during the 12th Five-year Plan Period,No.2012ZX1005006+1 种基金Sanming Project of Medicine in Shenzhen,Guangdong Province,China,No.SZSM201612074and Science and Technology Planning Project of Guangdong Province,China,No.2017A020213016.
文摘BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA viral load.AIM To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection.METHODS In total,395 patients(30–65 years old)with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk.Endpoints to evaluate therapeutic efficacy included:(1)HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96;and(2)HBeAg clearance and seroconversion rates at weeks 48 and 96.RESULTS HBV DNA levels≤4 log10 IU/mL were 10.05%at week 48 and 18.59%at week 96 in the treatment group.The HBeAg clearance and conversion rates were 8.54%and 8.04%at week 48 and 16.08%and 14.57%at week 96,respectively.However,HBV DNA levels≤4 log10 IU/mL were 2.55%and 2.55%at weeks 48 and 96,respectively,and the HBeAg clearance rates were 3.06%and 5.61%at weeks 48 and 96,respectively,in the control group.The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance.CONCLUSION High rates of HBV DNA reduction,HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase.The ability of the compound to modulate host immune function probably contributed to this effect.
基金supported by the Research Project of Health Commission of Sichuan Province(No.17PJ006)。
文摘Background:The progress of liver diseases may not stop after viral eradication.This study aimed to provide data on long-term prognosis of patients with hepatitis C virus(HCV)infection who underwent pegylated interferon plus ribavirin(PR)regimen and achieved a sustained virological response 24 weeks post-treatment(SVR24).Methods:Responders to the PR regimen in our hospital from January 2011 to June 2014 were enrolled and prospectively followed up.Baseline characteristics were profiled.The incidence of hepatocellular carcinoma(HCC),progression of liver disease(increase in liver stiffness or occurrence of decompensated complication),and HCV recurrence was all monitored.The accumulative and annualized incidence rates(AIRs)of these adverse events were analyzed,and the risk factors were also examined.Results:In total,151 patients reached a median follow-up time of 103 weeks.Among them,two had an incidence of HCC during the surveillance with AIR of 0.68%(95%CI:0.00-1.63%).Six patients showed progression of liver disease with AIR of 2.05%(95%CI:0.42%-3.68%).Three patients who had risky behaviors encountered HCV reinfection.The cirrhotic patients faced higher risk of poor prognosis than non-cirrhotic patients,including HCC and progression of liver disease(AIR:6.17%vs.1.42%,P=0.039).Conclusions:The incidence of HCC and progression of liver disease was evident in PR responders during the long-term follow-up period,but the risk level was low.Cirrhotic responders were more vulnerable to develop HCC post SVR24 compared with non-cirrhotic ones.HCV recurrence was rare in responders with SVR24 who had corrected their risky behaviors.
基金supported by the Natural Science Foundations of China(81974427)Graduate Research and Innovation Projects of Central South University(2021zzts0931)
文摘The AKT/mTOR and NF-κB signalings are crucial pathways activated in cancers including nasopharyngeal carcinoma(NPC), which is prevalent in southern China and closely related to Epstein-Barr virus(EBV) infection.How these master pathways are persistently activated in EBV-associated NPC remains to be investigated. Here we demonstrated that EBV-encoded latent membrane protein 1(LMP1) promoted cyclophilin A(CYPA) expression through the activation of NF-κB. The depletion of CYPA suppressed cell proliferation and facilitated apoptosis.CYPA was able to bind to AKT1, thus activating AKT/mTOR/NF-κB signaling cascade. Moreover, the use of mTOR inhibitor, rapamycin, subverted the activation of the positive feedback loop, NF-κB/CYPA/AKT/mTOR. It is reasonable that LMP1 expression derived from initial viral infection is enough to assure the constant potentiation of AKT/mTOR and NF-κB signalings. This may partly explain the fact that EBV serves as a tumor-promoting factor with minimal expression of the viral oncoprotein LMP1 in malignancies. Our findings provide new insight into the understanding of causative role of EBV in tumorigenicity during latent infection.
基金Supported by Sara Borrell postdoctoral fellowships from Instituto de Salud Carlos Ⅲ to support ángela Rojas postdoctoral contract,Consejería de Salud y Familias,Junta de Andalucía supporting Antonio Gil-Gómez contract,PI19/01404 Grant from Spanish Ministry of Economy,Innovation and Competition,the Instituto de Salud Carlos Ⅲ,PI19/00589/Spanish Ministry of Economy,Innovation and Competition,the Instituto de Salud Carlos Ⅲ,and the Xeptagen,Italy,provided the ELISA kits for the measurements of SCCA-IgM.
文摘BACKGROUND The combination of alpha-fetoprotein(AFP)and squamous cell carcinoma antigen immunocomplex(SCCA-IgM)have been proposed for its use in the screening of hepatocellular carcinoma(HCC).Current screening programs for all cirrhotic patients are controversial and a personalized screening is an unmet need in the precision medicine era.AIM To determine the role of the combination of SCCA-IgM and AFP in predicting mid-and long-term appearance of HCC.METHODS Two-hundred and three cirrhotic patients(Child A 74.9%,B 21.2%,C 3.9%)were followed-up prospectively every six months to screen HCC by ultrasound and AFP according to European Association for the Study of the Liver guidelines.The estimation cohort was recruited in Italy(30.5%;62/203)and validation cohort from Spain(69.5%;141/203).Patients underwent to evaluate SCCA-IgM by enzyme-linked immunosorbent assay(Hepa-IC,Xeptagen,Italy)and AFP levels at baseline.Patients were followed-up for 60 mo,being censored at the time of the appearance of HCC.RESULTS There were 10.8%and 23.1%of HCC development at two-and five-years followup.Patients with HCC showed higher levels of SCCA-IgM than those without it(425.72±568.33 AU/mL vs 195.93±188.40 AU/mL,P=0.009)during the fiveyear follow-up.In multivariate analysis,after adjusting by age,sex,aspartate transaminase and Child-Pugh,the following factors were independently associated with HCC:SCCA-IgM[Hazard ratio(HR)=1.001,95%CI:1.000-1.002;P=0.003],AFP(HR=1.028,95%CI:1.009-1.046;P=0.003)and creatinine(HR=1.56495%CI:1.151-2.124;P=0.004).The log-rank test of the combination resulted in 7.488(P=0.024)in estimation cohort and 11.061(P=0.004)in the validation cohort,and a 100%of correctly classified rate identifying a low-risk group in both cohorts in the two-year follow-up.CONCLUSION We have constructed a predictive model based on the combination of SCCA-IgM and AFP that provides a new HCC screening method,which could be followed by tailored HCC surveillance for individual patients,especially for those cirrhotic patients belonging to the subgroup identified as low-risk of HCC development.
