Anluohuaxianwan Alleviates Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats through Upregulation of Peroxisome Proliferator-Activated Receptor-Gamma and Downregulation of Nuclear Factor-Kappa B/IκBα Signaling Pathway

Objective:The aim of this study was to investigate the effects of traditional Chinese medicine Anluohuaxianwan(ALHXW)on peroxisome proliferator-activated receptor-gamma(PPARγ)and nuclear factor-kappa B(NF-κB)signaling pathways using a rat model of carbon model groups were gavaged with saline for 6 weeks.Liver function was measured,and liver fibrosis and necroinflammation were assessed.Protein and messenger RNA expression levels of PPARγ,NF-κB,and Inhibitorαof NF-κB(IκBα)were analyzed by Western blot and reverse transcription–quantitative polymerase chain reaction.Results:ALHXW markedly alleviated liver injury compared with the model group,as indicated by the improvements in disease status,the morphology of liver and spleen,the liver and spleen indexes,and liver function.The extent of liver fibrosis was improved,hepatic stellate cell activation was inhibited,the expression of PPARγand IκBαwas significantly higher,and the expression of NF-κB was significantly lower in the treatment group as compared with the model group.Conclusions:ALHXW treatment can alleviate CCl4-induced liver fibrosis in rats, and the potential antifibrogenic mechanisms may occur through the upregulation of PPARγ expression and downregulation of NF-κB/IκBα signaling pathway.

Serum N-glycan markers for diagnosing liver fibrosis induced by hepatitis B virus

BACKGROUND Hepatitis B virus (HBV) infection is the primary cause of hepatitis with chronic HBV infection,which may develop into liver fibrosis,cirrhosis and hepatocellular carcinoma.Detection of early-stage fibrosis related to HBV infection is of great clinical significance to block the progression of liver lesion.Direct liver biopsy is regarded as the gold standard to detect and assess fibrosis;however,this method is invasive and prone to clinical sampling error.In order to address these issues,we attempted to find more convenient and effective serum markers for detecting HBV-induced early-stage liver fibrosis.AIM To investigate serum N-glycan profiling related to HBV-induced liver fibrosis and verify multiparameter diagnostic models related to serum N-glycan changes.METHODS N-glycan profiles from the sera of 432 HBV-infected patients with liver fibrosis were analyzed.Significant changed N-glycan levels (peaks)(P <0.05) in differentfibrosis stages were selected in the modeling group,and multiparameter diagnostic models were established based on changed N-glycan levels by logistic regression analysis.The receiver operating characteristic (ROC) curve analysis was performed to evaluate diagnostic efficacy of N-glycans models.These models were then compared with the aspartate aminotransferase to platelet ratio index (APRI),fibrosis index based on the four factors (FIB-4),glutamyltranspeptidase platelet albumin index (S index),GlycoCirrho-test,and GlycoFibro-test.Furthermore,we combined multiparameter diagnostic models with alanine aminotransferase (ALT) and platelet (PLT) tests and compared their diagnostic power.In addition,the diagnostic accuracy of N-glycan models was also verified in the validation group of patients.RESULTS Multiparameter diagnostic models constructed based on N-glycan peak 1,3,4and 8 could distinguish between different stages of liver fibrosis.The area under ROC curves (AUROCs) of Model A and Model B were 0.890 and 0.752,respectively differentiating fibrosis F0-F1 from F2-F4,and F0-F2 from F3-F4,and surpassing other serum panels.However,AUROC (0.747) in Model C used for the diagnosis of F4 from F0-F3 was lower than AUROC (0.795) in FIB-4.In combination with ALT and PLT,the multiparameter models showed better diagnostic power (AUROC=0.912,0.829,0.885,respectively) when compared with other models.In the validation group,the AUROCs of the three combined models (0.929,0.858,and 0.867,respectively) were still satisfactory.We also applied the combined models to distinguish adjacent fibrosis stages of 432patients (F0-F1/F2/F3/F4),and the AUROCs were 0.917,0.720 and 0.785.CONCLUSION Multiparameter models based on serum N-glycans are effective supplementary markers to distinguish between adjacent fibrosis stages of patients caused by HBV,especially in combination with ALT and PLT.

A Real-world Prospective Study of Mother-to-child Transmission of HBV in China Using a Mobile Health Application (Shield 01)

Background and Aims:The World Health Organization(WHO)Western Pacific Region set a target of eliminating mother-to-child transmission(MTCT)of hepatitis B virus(HBV)by 2030.To assess the feasibility of this target in China,we carried out an epidemiological study to investigate the status quo of MTCT in the real-world setting.Methods:One thousand and eight hepatitis B surface antigen-positive preg-nant women were enrolled at 10 hospitals.Immunoprophy-laxis was administered to infants.In addition,mothers with HBV DNA level>2,000,000 IU/mL were advised to initiate antiviral therapy during late pregnancy.A health application called SHIELD was used to manage the study.Results:Nine hundred and five of the enrolled mothers,with 924 infants,completed the follow-up.Birth-dose hepatitis B vaccine and hepatitis B immunoglobulin were received by 99.7%and 99.7%of infants,respectively,within 24 h after birth.There ;were 446 mothers who received antiviral therapy,including 72.3%of the mothers with HBV DNA level>2,000,000 IU/mL and 21.0%of the mothers with HBV DNA level<2,000,000 IU/mL.Eight infants were infected with HBV.The overall rate of MTCT was 0.9%.Birth defects were rare(0.5%among in-fants with maternal antiviral exposure versus 0.7%among infants without exposure;p=1.00).Conclusions:The MTCT rate was lower than the WHO Western Pacific Region elimina-tion MTCT target in this real-world study,indicating that a comprehensive management composed of immunoprophy-laxis to infants and antiviral prophylaxis to mothers may be a feasible strategy to achieve the 2030 WHO elimination goal.

Monocyte activation and cardiovascular disease in HIV infection

Antiretroviral therapy(ART)has increased the lifespan of HIVinfected individuals,which is now approaching that of the general population.However,cardiovascular disease(CVD),including myocardial infarction,stroke,heart failure,and arrhythmia,is still a main cause of mortality in HIVpositive population.The risk of CVD in people living with HIV is about 1.5–2-fold higher than that in the general population.1 Even in those successfully treated with ART,the incidence of CVD is still higher than that in uninfected individuals.2 Thus,in addition to the traditional risk factors associated with CVD,other factors(such as ART per se,inflammation,and immune activation caused by HIV infection)may be involved in CVD development.