Surveillance for respiratory infectious diseases caused by 6 common viruses in a recruit training site in the Northern region of China

Background: Recruit training sites are places with a high incidence of respiratory infectious diseases. Effective surveillance for acute respiratory infectious diseases in a recruit training site is an important way to prevent disease outbreaks.Methods: Eight hundred recruits(722 males and 78 females) enlisted in autumn 2015 received a background survey within 24 h of settlement at the recruit training site, including their general personal information, vaccination history, mental status and clinical symptoms. Then, nasopharyngeal swabs of these recruits were collected to detect common respiratory pathogens [influenza virus type A, influenza virus type B, adenovirus(Adv), human respiratory syncytial virus, human bocavirus and human metapneumovirus] by PCR. In addition, fasting venous blood was collected in the morning for Adv Ig G antibody detection. During the three months of training, the recruits were monitored for symptoms of respiratory infection, and nasopharyngeal swabs were collected from those with an axillary temperature ≥38℃ and other respiratory symptoms within 4 h of symptom onset. Samples were further examined by PCR.Results: Among the 795 effective nasopharyngeal swab samples collected during survey, two cases of group C type 1 Adv were identified by PCR. During the 3 months of training, fever and respiratory symptoms occurred in 39 recruits(incidence rate of 4.9%) and 5 cases of Adv were detected(positive rate of 12.8%). Genotyping showed 3 cases of type 4 Adv and 2 of type 3 Adv. No type 7, 14 or 55 Adv was detected. The Adv-Ig G positive rate of recruits was 48.2%. Among the 5 Adv positive cases with fever and respiratory symptoms, 4 were Adv-Ig G positive.Conclusion: The pathogen carrier rate in recruits was low, and only group C Adv, which causes mild infection in humans, was detected. No respiratory outbreak was observed at the recruit training site, and sporadic cases were mainly caused by type 3 and type 4 Adv.

A prognostic four-gene signature and a therapeutic strategy for hepatocellular carcinoma:Construction and analysis of a circRNA-mediated competing endogenous RNA network

Background:Hepatocellular carcinoma(HCC)has a poor long-term prognosis.The competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC prognosis.Based on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is feasible.Methods:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC.Gene function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory network.In the proteinprotein interaction network,hub genes were identified and subjected to regression analysis,producing an optimized four-gene signature for prognostic risk stratification in HCC patients.Anti-HCC drugs were excavated by assessing the DEGs between the low-and high-risk groups.A circRNA-microRNA-hub gene subnetwork was constructed,in which three hallmark genes,KIF4A,CCNA2,and PBK,were subjected to functional enrichment analysis.Results:A four-gene signature(KIF4A,CCNA2,PBK,and ZWINT)that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas(TCGA)cohort and International Cancer Genome Consortium(ICGC)cohort was developed.CDK inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC patients.Subsequent analysis has revealed that PBK,CCNA2,and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion,regulating microsatellite instability(MSI),and exerting an impact on HCC progression.Conclusions:The present study highlights the role of the circRNA-related regulatory network,identifies a four-gene prognostic signature and biomarkers,and further identifies novel therapy for HCC.

Current status of liver transplantation for human immunodeficiency virus-infected patients in China's Mainland

According to the report from the Chinese Center for Disease Control and Prevention,the prevalence of human immunodeficiency virus(HIV)infection exceeded 1.2 million individuals by the year 2022,with an annual increase of about 80000 cases.The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%,almost twice the rate of the general population in China.In addition to the well-documented susceptibility to opportunistic infections and new malignancies,HIV infected patients frequently experience liver-related organ damage,with the liver and kidneys being the most commonly affected.This often leads to the development of end-stage liver and kidney diseases.Therefore,organ transplantation has emerged as an important part of active treatment for HIV infected patients.However,the curative effect is not satisfactory.HIV infection has been considered a contraindication for organ transplantation.Until the emergence of highly active anti-retroviral therapy in 1996,the once intractable replication of retrovirus was effectively inhibited.With prolonged survival,the failure of important organs has become the main cause of death among HIV patients.Therefore,transplant centers worldwide have resu-med exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion.This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation(LT)in main-land China.To date,our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV,and all but one,who died two months postoperatively due to sepsis and progressive multi-organ failure,have survived.Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions,cytomegalovirus infection,bacteremia,pulmonary infections,acute kidney injury,new-onset cancers,or vascular and biliary complications.

Dynamic changes and clinical value of lipocalin 2 in liver diseases caused by microbial infections

Lipocalin 2(LCN2)plays a pivotal role in iron metabolism,particularly in the context of microbial infection resistance(e.g.,viruses,bacteria,parasites,etc.).LCN2 combats microbial infection by directly assisting the body in competing with microorganisms for iron,inducing immune cells to secrete various cytokines to enhance systemic immune responses,or recruiting neutrophils to infectious sites.The liver serves as the primary organ for LCN2 secretion during microbial infections.This review encapsulates recent advances in dynamic changes,clinical values,and the effects of LCN2 in infectious liver diseases caused by various microbial microorganisms.

Message from Editor-in-Chief:Write a New Chapter of Infectious Diseases&Immunity in Concerted Efforts

Infectious Diseases&Immunity(IDI)is with you to welcome in the New Year.We extend our heartfelt gratitude to all the experts,editorial board members,and reviewers whose dedicated efforts have contributed to the development of IDI.We also express our appreciation to every reader and author who has shown interest in the progress of IDI.Our best wishes for the New Year to all!IDI was inaugurated in April 2021 and has successfully published 11 consecutive issues.

An Update on the Efficacy and Functionality of Probiotics for the Treatment of Non-Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease(NAFLD),which has a global prevalence of 20%–33%,has become the main cause of chronic liver disease.Except for lifestyle medication,no definitive medical treatment has been established so far,making it urgent to find effective strategies for the treatment of NAFLD.With the identification of the significant role played by the gut microbiota in the pathogenesis of NAFLD,studies on probiotics for the prevention and treatment of NAFLD are increasing in number.Bacteria from the Bifidobacterium and Lactobacillus genera constitute the most widely used traditional probiotics.More recently,emerging next-generation probiotics(NGPs)such as Akkermansia muciniphila and Faecalibacterium prausnitzii have also gained attention due to their potential as therapeutic options for the treatment of NAFLD.This review provides an overview of the effects of oral administration of traditional probiotics and NGPs on the development and progress of NAFLD.The mechanisms by which probiotics directly or indirectly affect the disease are illustrated,based on the most recent animal and clinical studies.Although numerous studies have been published on this topic,further research is required to comprehensively understand the specific underlying mechanisms among probiotics,gut microbiota,and NAFLD,and additional large-scale clinical trials are required to evaluate the therapeutic efficacy of probiotics for the treatment of NAFLD,as well as the safety of probiotics in the human body.

Outcomes of ABO-incompatible liver transplantation in end-stage liver disease patients co-infected with hepatitis B and human immunodeficiency virus

BACKGROUND Human immunodeficiency virus(HIV)-positive patients coinfected with hepatitis B virus(HBV)are eligible for liver transplantation(LT)in Africa and Southeast Asia,particularly China.However,the outcome of HIV-HBV coinfected patients referred for ABO-incompatible LT(ABOi-LT)is unknown.AIM To clarify the outcome of ABOi-LT for HIV-HBV coinfected patients with endstage liver disease(ESLD).METHODS We report on two Chinese HIV-HBV coinfected patients with ESLD who underwent A to O brain-dead donor LT and reviewed the literature on HIV-HBV coinfected patients treated with ABO-compatible LT.The pretransplantation HIV viral load was undetectable,with no active opportunistic infections.Induction therapy consisted of two sessions of plasmapheresis and a single dose of rituximab in two split doses,followed by an intraoperative regimen of intravenous immunoglobulin,methylprednisolone,and basiliximab.Post-transplant maintenance immunosuppressive agents consisted of tacrolimus and mycophenolate mofetil,and prednisone.RESULTS At the intermediate-term follow-up,patients showed undetectable HIV viral load,CD4(+)T cell counts greater than 150 cells/μL,no HBV recurrence,and stable liver function.A liver allograft biopsy showed no evidence of acute cellular rejection.Both patients survived at 36-42 mo of follow-up.CONCLUSION This is the first report of ABOi-LT in HIV-HBV recipients with good intermediate-term outcomes,suggesting that ABOi-LT may be feasible and safe for HIV-HBV coinfected patients with ESLD.

Development and Validation of a Prognostic Risk Score System for COVID-19 Inpatients:A Multi-Center Retrospective Study in China

Coronavirus disease 2019(COVID-19)has become a worldwide pandemic.Hospitalized patients of COVID-19 suffer from a high mortality rate,motivating the development of convenient and practical methods that allow clinicians to promptly identify high-risk patients.Here,we have developed a risk score using clinical data from 1479 inpatients admitted to Tongji Hospital,Wuhan,China(development cohort)and externally validated with data from two other centers:141 inpatients from Jinyintan Hospital,Wuhan,China(validation cohort 1)and 432 inpatients from The Third People’s Hospital of Shenzhen,Shenzhen,China(validation cohort 2).The risk score is based on three biomarkers that are readily available in routine blood samples and can easily be translated into a probability of death.The risk score can predict the mortality of individual patients more than 12 d in advance with more than 90%accuracy across all cohorts.Moreover,the Kaplan-Meier score shows that patients can be clearly differentiated upon admission as low,intermediate,or high risk,with an area under the curve(AUC)score of 0.9551.In summary,a simple risk score has been validated to predict death in patients infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2);it has also been validated in independent cohorts.

A new prognostic model for drug-induced liver injury especially suitable for Chinese population

Drug-induced liver injury(DILI)is a rare side effect of drugs caused by all kinds of prescription or over-the-counter chemi-cals,biological agents,traditional Chinese medicine(TCM),natu-ral medicine(NM),health products,dietary supplements and their metabolites,and even excipients,which can lead to jaundice,liver failure,or even death.Although it is rare in term of single drug,the occurrence of DILI in all liver injuries is not low due to the wide range of drugs and foods involved.Moreover,there was an increasing trend of incidence of DILI since 2010 worldwide,with Asian regions showing the highest incidence[1].

MSC-derived exosomes attenuate hepatic fibrosis in primary sclerosing cholangitis through inhibition of Th17 differentiation

Primary sclerosing cholangitis(PSC)is an autoimmune cholangiopathy characterized by chronic inflammation of the biliary epithelium and periductal fibrosis,with no curative treatment available,and liver transplantation is inevitable for end-stage patients.Human placentalmesenchymal stem cell(hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis,inhibit collagen production and possess immunomodulatory properties in autoimmune liver disease.Here,we prepared hpMSC-derived exosomes(Exo^(MSC))and further investigated the anti-fibrotic effects and detailed mechanism on PSC based on Mdr2^(−/−)mice and multicellular organoids established from PSC patients.The results showed that Exo^(MSC) ameliorated liver fibrosis in Mdr2^(−/−)mice with significant collagen reduction in the preductal area where Th17 differentiation was inhibited as demonstrated by RNAseq analysis,and the percentage of CD4+IL-17A+T cells was reduced both in Exo^(MSC)-treated Mdr2^(−/−)mice(Mdr2^(−/−)-Exo)in vivo and Exo^(MSC)-treated Th17 differentiation progressed in vitro.Furthermore,Exo^(MSC) improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular organoids.Thus,our data demonstrate the antifibrosis effect of Exo^(MSC) in PSC disease by inhibiting Th17 differentiation,and ameliorating the Th17-induced microenvironment,indicating the promising potential therapeutic role of Exo^(MSC) in liver fibrosis of PSC or Th17-related diseases.

Relationship between Phenotypic Changes of Dendritic Cell Subsets and the Onset of Plateau Phase during Intermittent Interferon Therapy in Patients with CHB

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86.Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer.Results In total,143 patients were enrolled(NH group,n=49;NA group,n=47;P group,n=47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001.Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Mitochondrial dysfunction: A promising therapeutic target for liver diseases

The liver is an important metabolic and detoxification organ and hence demands a large amount of energy,which is mainly produced by the mitochondria.Liver tissues of pa-tients with alcohol-related or non-alcohol-related liver diseases contain ultrastructural mito-chondrial lesions,mitochondrial DNA damage,disturbed mitochondrial dynamics,and compromised ATP production.Overproduction of mitochondrial reactive oxygen species in-duces oxidative damage to mitochondrial proteins and mitochondrial DNA,decreases mito-chondrial membrane potential,triggers hepatocyte inflammation,and promotes programmed cell death,all of which impair liver function.Mitochondrial DNA may be a poten-tial novel non-invasive biomarker of the risk of progression to liver cirrhosis and hepatocellular carcinoma in patients infected with the hepatitis B virus.We herein present a review of the mechanisms of mitochondrial dysfunction in the development of acute liver injury and chronic liver diseases,such as hepatocellular carcinoma,viral hepatitis,drug-induced liver injury,alcoholic liver disease,and non-alcoholic fatty liver disease.This review also discusses mito-chondrion-centric therapies for treating liver diseases.

Plasma Metabonomics of Human Adenovirus-infected Patients with Pneumonia and Upper Respiratory Tract Infection

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains unclear.In the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were explored.Methods In total,35 patients were enrolled in the study following an outbreak of HAdV-7 in the army,of whom 14 had pneumonia and 21 had URTI.Blood samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted metabolomics.Results Over 90% of the differential metabolites identified between the pneumonia patients and URTI patients were lipids and lipid-like molecules,including glycerophospholipids,fatty acyls,and sphingolipids.The metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid metabolism.The sphingolipid metabolism was identified as a significantly differential pathway between the pneumonia patients and URTI patients and between the acute and recovery stages for the pneumonia patients,but not between the acute and recovery stages for the URTI patients.Ceramide and lactosylceramide,involved in sphingolipid metabolism,were significantly higher in the pneumonia patients than in the URTI patients with good discrimination abilities[area under curve(AUC)0.742 and 0.716,respectively;combination AUC 0.801].Conclusion Our results suggested that HAdV modulated lipid metabolism for both the patients with URTI and pneumonia,especially the sphingolipid metabolism involving ceramide and lactosylceramide,which might thus be a potential intervention target in the treatment of HAdV infection.

Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain unclear.Consequently,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of PCa.Methods:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at Zhongnan Hospital of Wuhan University.The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa.The expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques.To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa.The Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical significance.Results:ASPA was identified as a novel inhibitor of PCa progression.The expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,migration,and invasion,respectively.The inhibitory role of ASPA in PCa was further confirmed using orthotopic and tumor-bearing mouse models.Mechanistically,ASPA was shown to directly interact with the LYN and inhibit the phosphorylation of LYN as well as its downstream targets,JNK1/2 and C-Jun,in both PCa cells and mouse models,in an enzyme-independent manner.Importantly,the inhibition of LYN activation by bafetinib abrogated the promoting effect of ASPA knockdown on PCa progression in both in vitro and in vivo models.Moreover,we observed an inverse relationship between ASPA expression and LYN activity in clinical PCa samples,suggesting a potential regulatory role of ASPA in modulating LYN signaling.Conclusions:Our findings provide novel insights into the tumor-suppressive function of ASPA in PCa and highlight its potential as a prognostic biomarker and therapeutic target for the management of this malignancy.

Prognostic value of ultrasound in early arterial complications post liver transplant

Liver transplantation is the primary therapeutic intervention for end-stage liver disease.However,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.The clinical manifestations associated with early arterial complications following liver transplantation are often non-specific.Without timely intervention,these complications can result in graft fai-lure or patient mortality.Therefore,early diagnosis and the formulation of an op-timal treatment plan are imperative.Ultrasound examination remains the pre-dominant imaging modality for detecting complications post liver transplan-tation.This article comprehensively reviews common causes and clinical present-ations of early hepatic artery complications in the post-transplantation period and delineates abnormal sonographic findings for accurate diagnosis of these con-ditions.Overall,ultrasound offers the advantages of convenience,safety,effect-iveness,and non-invasiveness.It enables real-time,dynamic,and precise evalua-tion,making it the preferred diagnostic method for post-liver transplantation assessments.INTRODUCTION Liver transplantation stands as the primary therapeutic approach for end-stage liver disease.Continuous advancements in surgical techniques and the application of novel immunosuppressive agents contribute to ongoing improvements in the success rate and overall survival in patients undergoing liver transplantation procedures.Despite these advan-cements,vascular complications,particularly those involving the hepatic artery,pose significant risks to patients.During the early stages following liver transplantation(within the first 30 d),proper hepatic artery function is crucial for hepatic arterial blood flow.During later stages,collateral circulation,including arteries such as the phrenic artery,right gastric artery,and gastroduodenal artery,becomes important for maintaining hepatic blood supply.It is now understood that the establishment of effective collateral circulation is pivotal for determining the prognosis of hepatic artery complic-ations.The clinical manifestations of these complications are closely linked to factors such as timing,severity,and the specific type of onset.Insufficient hepatic arterial blood flow can lead to abnormal liver function,hepatic infarction,and the formation of hepatic abscesses.Additionally,since the hepatic artery is the sole blood supply to the biliary tract,hepatic artery-related ischemia may result in biliary stricture,obstruction,and the formation of bile ducts.Ultrasound examination remains the primary imaging modality for diagnosing complications post liver transplantation.This article comprehensively reviews common causes and clinical presentations of early hepatic artery complications in the post-transplantation period and outlines abnormal sonographic findings for accurately diagnosing these conditions.NORMAL HEPATIC ARTERY During the intraoperative phase,an ultrasound examination is typically conducted to evaluate the hepatic artery anas-tomosis.The normal internal diameter of the hepatic artery typically ranges from 2 to 5 mm.Two strong echo points are typically identified near the anastomosis.To assess blood flow dynamics,peak systolic velocity,end-diastolic velocity,and resistance index are measured at the donor and recipient sides of the anastomosis following angle correction.Anastomotic stenosis presence and severity can be evaluated by comparing the velocity at the anastomotic site with that at the recipient side.Postoperatively,direct visualization of the anastomosis site through gray ultrasound scans is often challenging.The surgical approach has a significant impact on the proper hepatic artery’s position,resulting in a lower overall success rate of continuous visualization.Color Doppler ultrasound is primarily employed to trace the artery’s path,and spectral measurements are taken at the brightest position of the Color Doppler blood flow signal,primarily used to identify the presence of high-speed turbulence.Hepatic artery spectrum examination plays a crucial role,as a favorable arterial spectral waveform and appropriate hepatic artery flow velocity typically indicate a successful anastomosis,even in cases where the hepatic artery anastomosis cannot be directly visualized by ultrasound.The hepatic artery runs alongside the portal vein,often selected as a reference due to its larger inner diameter.A normal hepatic artery spectrum displays a regular pulsation pattern with a rapid rise in systole and a slow decline in diastole.Parameters for assessing hepatic artery resistance include a resistance index between 0.5 to 0.8 and an artery systolic acceleration of less than 80 ms.Instantaneous increases in the resistance index(RI>0.8)often occur within 2 d after surgery,followed by a subsequent return to normal hepatic arterial parameters.It has been established that the maximum blood flow velocity during systole in the hepatic artery should not exceed 200 cm/s[1].

儿童慢性乙型肝炎防治专家共识

为了规范儿童慢性乙型肝炎的预防、诊断和抗病毒治疗,实现世界卫生组织提出的“2030年消除病毒性肝炎公共卫生危害”目标,由中华医学会感染病学分会、肝病学分会、儿科学分会感染学组和国家感染性疾病临床医学研究中心组织有关专家,以国内外慢性乙型肝炎防治指南及近年来儿童乙型肝炎抗病毒治疗的临床研究进展为依据,结合我国诊疗实际情况及经验,制定了《儿童慢性乙型肝炎防治专家共识》。以期为临床医师做出合理的治疗决策提供更多的参考和依据。

Liver diseases in COVID-19:Etiology,treatment and prognosis

In December 2019,a novel coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was identified in Wuhan,China causing coronavirus disease-2019(COVID-19).Numerous studies have shown varying degrees of liver damage in patients infected with SARS-CoV-2.However,in previous case studies of COVID-19,the exact cause of liver injury has not been clearly elucidated,nor is there clear evidence of the interaction between liver injury and COVID-19.This study will analyze the causes of liver injury in COVID-19 and the influence of liver-related complications on the treatment and prognosis of COVID-19.

Role of bile acids in liver diseases mediated by the gut microbiome

The intensive crosstalk between the liver and the intestine performs many essential functions.This crosstalk is important for natural immune surveillance,adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial metabolites.The interaction between the gut microbiome and bile acids is bidirectional.The gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via enzymes.Similarly,bile acids also shape the composition of the gut microbiome by modulating the host’s natural antibacterial defense and the intestinal immune system.The interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases,especially liver diseases.As essential mediators of the gut-liver crosstalk,bile acids regulate specific host metabolic pathways and modulate the inflammatory responses through farnesoid X-activated receptor and G protein-coupled bile acid receptor 1.Several clinical trials have demonstrated the signaling effects of bile acids in the context of liver diseases.We hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.

Diagnostic sensitivity of imaging modalities for hepatocellular carcinoma smaller than 2 cm

AIM:To compare the imaging results with histology and to evaluate the diagnostic sensitivity of imaging modalities for hepatocellular carcinoma(HCC)smaller than 2 cm.METHODS:Nodules smaller than 2 cm(n=34)revealed by ultrasonography(US)in 29 patients with liver cirrhosis were analyzed.Histological diagnosis of HCC was performed by ultrasonographic guidance:moderately-differentiated HCC(n=24);well-differentiated HCC(n=10).The patterns disclosed by the four imaging modalities defined the conclusive diagnosis of HCC:(1)contrast-enhanced computed tomography(CECT),hypervascularity in the arterial phase and washout in the equilibrium phase;(2)Sonazoid contrast-enhanced US(CEUS),hypervascularity in the early vascular phase and defect in the Kupffer phase;(3)gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid(Gd-EOBDTPA)-enhanced magnetic resonance imaging(MRI),hypervascularity in the arterial phase and/or defect in the hepatobiliary phase;and(4)CT arterioportal angiography:hypervascularity by CT during arteriography and/ or perfusion defect by CT during arterial portography.RESULTS:Overall,the sensitivity of diagnosing HCC smaller than 2 cm was 52.9%(18/34)(95%CI:35.170.2)by CECT;67.6%(23/34)(95%CI:49.5-82.6)by Sonazoid CEUS;76.5%(26/34)(95%CI:58.8-89.3) by Gd-EOB-DTPA MRI;and 88.2%(30/34)(95%CI: 72.5-96.7)by CT arterioportal angiography.The diagnostic sensitivity of detecting moderately-differentiated HCC by CECT,Sonazoid CEUS,Gd-EOB-DTPA MRI and CT arterioportal angiography was 62.5%(15/24)(95%CI: 40.6-81.2),79.2%(19/24)(95%CI:57.8-92.9),75.0% (18/24)(95%CI:53.3-90.2)and 95.8%(23/24)(95% CI:78.9-99.9),respectively.A significant difference(P< 0.05)was observed between CECT and CT arterioportal angiography in all nodules.There was no difference between Sonazoid CEUS,Gd-EOB-DTPA MRI,and CT arterioportal angiography.The combined sensitivity of Sonazoid CEUS and Gd-EOB-DTPA MRI was 94.1%(32/34).CONCLUSION:Changing the main diagnostic modality for HCC smaller than 2 cm from CT arterioportal angiography to Sonazoid CEUS and Gd-EOB-DTPA MRI is recommended.

Progress in hepatitis B virus-related acute-on-chronic liver failure treatment in China:A large,multicenter,retrospective cohort study using a propensity score matching analysis

Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.