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The Relationship between Viral Replication and the Severity of Hepatic Necroinflammatory Damage Changed before HBeAg Loss in Patients with Chronic Hepatitis B Virus Infection

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Journal of Clinical and Translational Hepatology 2024年第4期12卷 381-388页

作者： Leijie Wang Jian Wang Kunyu Zhao Lina Jiang Xinxin Zhang Jingming Zhao Jie Li Fengmin Lu department of microbiology and Immunology College of Basic Medical SciencesZhengzhou UniversityZhengzhouHenanChina department of microbiology&infectious Disease Center School of Basic Medical SciencesPeking UniversityBeijingChina department of infectious Diseases Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsuChina department of Pathology and Hepatology The Fifth Medical Center of PLA General HospitalBeijingChina department of infectious Diseases Rui Jin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina

Background and Aims:Disease progression of chronic hepatitis B virus(HBV)infection is driven by the interactions between viral replication and the host immune response against the *** study aimed to clarify the relationship between HBV replication and hepatic inflammation during disease ***:Two cross-sectional,one validation cohort,and meta-analyses were used to explore the relationship between HBV replication and liver *** analysis,multiple linear regression,and logistic regression were used to explore the relationship between ***:In the cross-sectional cohorts A and B including 1,350 chronic hepatitis B patients,Spearman analysis revealed a negative relationship between HBV replication(such as HBV DNA)and liver inflammation(such as ALT)in HBeAg-positive patients with higher HBV DNA>2×10^(6) IU/mL(rho=0.278 and 0.260)and HBeAg-negative patients(rho=0.450 and 0.363).After adjustment for sex,age,and anti-HBe,results from logistic regression and multiple linear regression showed the opposite relationship still existed in HBeAg-positive patients with different DNA levels;the opposite relationship in HBeAg-positive patients with different DNA levels was validated in a third cohort;the opposite relationship in patients with different HBeAg status was partially confirmed by meta-analysis(overall R:-0.004 vs 0.481).Conclusions:These results suggested a negative relationship between viral replication and liver inflammation in HBeAgpositive patients with high HBV DNA,which changed to a positive relationship for those HBeAg-positive patients with DNA less than 2×10^(6) IU/mL and HBeAg-negative patients.

关键词： Chronic hepatitis B HBeAg HBV DNA ALT.

AGK2 pre-treatment protects against thioacetamide-induced acute liver failure via regulating the MFN2-PERK axis and ferroptosis signaling pathway

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 43-51页

作者： Qing-Qi Zhang Qian Chen Pan Cao Chun-Xia Shi Lu-Yi Zhang Lu-Wen Wang Zuo-Jiong Gong department of infectious Diseases Renmin Hospital of Wuhan UniversityWuhan 430060China

Background:Acute liver failure(ALF)is an unpredictable and life-threatening critical *** pathological characteristic of ALF is massive necrosis of hepatocytes and lots of inflammatory cells infiltration which may lead to multiple organ ***:Animals were divided into 3 groups,normal,thioacetamide(TAA,ALF model)and TAA+*** L02 cells were divided into 5 groups,normal,TAA,TAA+mitofusin 2(MFN2)-siRNA,TAA+AGK2,and TAA+AGK2+MFN2-siRNA *** liver histology was evaluated with hematoxylin and eosin staining,inositol-requiring enzyme 1(IRE1),activating transcription factor 6β(ATF6β),protein kinase R(PKR)-like endoplasmic reticulum kinase(PERK)and phosphorylated-PERK(p-PERK).C/EBP homologous protein(CHOP),reactive oxygen species(ROS),MFN2 and glutathione peroxidase 4(GPX4)were measured with Western blotting,and cell viability and liver chemistry were also *** endoplasmic reticulum membranes(MAMs)were measured by ***:The liver tissue in the ALF group had massive inflammatory cell infiltration and hepatocytes necrosis,which were reduced by AGK2 *** comparison to the normal group,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+in the TAA-induced ALF model group were significantly increased,which were decreased by AGK2 *** levels of MFN2 and GPX4 were decreased in TAA-induced mice compared with the normal group,which were enhanced by AGK2 *** with the TAA-induced L02 cell,apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+were further increased and levels of MFN2 and GPX4 were decreased in the MFN2-siRNA ***2 pre-treatment decreased the apoptosis rate and levels of IRE1,ATF6β,p-PERK,CHOP,ROS and Fe2+and enhanced the protein expression of MFN2 and GPX4 in MFN2-siRNA treated L02 *** observation showed that level of MAMs was promoted in the AGK2 pre-treatment group when compared with the TAA-induced gr

关键词： SIRT2 inhibitor AGK2 Acute liver failure MFN2 Ferroptosis

Advances in the Treatment of Autoimmune Hepatitis

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Journal of Clinical and Translational Hepatology 2024年第10期12卷 878-885页

作者： Zelu Meng Yida Yang State Key Laboratory for Diagnosis and Treatment of infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesDepartment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina

Autoimmune hepatitis(AIH)is a chronic,progressive inflammatory liver disease caused by autoimmune reactions,with an unknown *** left untreated,it can progress to cirrhosis,liver failure,or even *** most patients respond well to first-line treatments,a significant number experience poor responses or intolerance,requiring the use of second-or third-line *** research into the pathogenesis of AIH is leading to the development of novel therapeutic *** review summarized recent advancements in the treatment of AIH both domestically and internationally.

关键词： Hepatitis,Autoimmune Immunosuppression Treatment Management Update Remission Induction Long-term Prognosis

A statistical approach to enhance the productivity of Streptomyces baarensis MH-133 for bioactive compounds

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Synthetic and Systems Biotechnology 2024年第2期9卷 196-208页

作者： Mohamed H.Kalaba Gamal M.El-Sherbiny Osama M.Darwesh Saad A.Moghannem Botany and microbiology department Faculty of Science(Boys)Al-Azhar UniversityCairo 11884Egypt Agricultural microbiology department National Research CentreDokkiCairoEgypt

The goal of this study was to use statistical optimization to change the nutritional and environmental conditions so that Streptomyces baarensis MH-133 could make more active *** trials were used to screen for critical variables influencing productivity using the Placket-Burman Design *** MH-133 is significantly influenced by elicitation,yeast extract,inoculum size,and incubation period in terms of antibacterial activity.A total of 27 experimental trials with various combinations of these factors were used to carry out the response surface technique using the Box-Behnken *** analyses revealed that the model was highly significant(p<0.001),with a lack-of-fit of 0.212 and a coefficient determination(R2)of ***,the model predicted that the response as inhibition zone diameter would reach a value of 27 *** optimal conditions,*** MH-133 produced 18.0 g of crude extract to each 35L and was purified with column *** active fraction exhibiting antibacterial activity was characterized using spectroscopic *** MIC and MBC values varied between 37.5 and 300μg/ml and 75 and 300μg/ml,*** conclusion,the biostatistical optimization of the active fraction critical variables,including environmental and nutritional conditions,enhances the production of bioactive molecules by Streptomyces species.

关键词： S.baarensis MH-133 Placket-Burman designBox-Behnken design ESKAPE Antibacterial activity

Eliciting CD4-mimicking broadly neutralizing antibodies:new avenues towards the rational design of an HIV vaccine

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Signal Transduction and Targeted Therapy 2024年第3期9卷 836-838页

作者： Frauke Muecksch Oliver T.Fackler department of infectious Diseases Heidelberg UniversityMedical Faculty HeidelbergVirologyCenter for Integrative Infectious Disease Research(CIID)HeidelbergGermany Chica and Heinz Schaller(CHS)Research Group Department of Infectious DiseasesVirologyUniversity Hospital HeidelbergHeidelbergGermany department of infectious Diseases Heidelberg UniversityMedical Faculty HeidelbergIntegrative VirologyCenter for Integrative Infectious Disease Research(CIID)HeidelbergGermany German Centre for Infection Research(DZIF) Partner Site HeidelbergHeidelbergGermany

In a study recently published in Cell,Saunders et *** that a new anti-HIV vaccine triggers antibody responses resembling CD4-binding site broadly neutralizing antibody precursors in rhesus macaques.1 This study provid... 详细信息

关键词： al. vaccine rational

Mitochondrial dysfunction: A promising therapeutic target for liver diseases

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Genes & Diseases 2024年第3期11卷 324-337页

作者： Ping Chen Lichao Yao Mengqin Yuan Zheng Wang Qiuling Zhang Yingan Jiang Lanjuan Li department of infectious Diseases Renmin Hospital of Wuhan UniversityWuhanHubei 430060China State Key Laboratory for Diagnosis and Treatment of infectious Diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouZhejiang 310003China

The liver is an important metabolic and detoxification organ and hence demands a large amount of energy,which is mainly produced by the *** 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 *** 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 *** 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 *** 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 *** review also discusses mito-chondrion-centric therapies for treating liver diseases.

关键词： Chronic diseases Liverdamage Mesenchymalstem cell Mitochondrial dysfunction Oxidativestress

A real-world study of the differences in Traditional Chinese Medicine diagnosis and treatment rules for coronavirus disease 2019 between Northern and Southern China

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Journal of Traditional Chinese Medicine 2024年第4期44卷 822-829页

作者： SU Rui SU Youzhu WANG Shuo FAN Jie LIU Qingquan LIU Mifeng department of infectious diseases Capital Medical University Beijing Hospital of Traditional Chinese MedicineBeijing 100010China

OBJECTIVE:To explore the differences in Traditional Chinese Medicine(TCM)diagnosis and treatment rules for coronavirus disease 2019(COVID-19)between Northern and Southern China based on the real-world data from 982 COVID-19 ***:All consecutive cases of COVID-19 admitted to the TCM department of designated COVID-19 hospitals in eight provinces and cities were retrospectively *** were divided into a Northern and a Southern group according to the location of the admitting *** symptoms,syndrome elements,syndrome distribution and herbal treatments were *** core prescriptions were extracted using the multiscale backbone-based network comparison algorithm(msbNC).RESULTS:The distribution of syndrome elements showed that dampness was common in Northern and Southern China,wind and heat were more often present in the South,while fire toxin and spleen deficiency were more often encountered in the *** distribution of syndromes showed that the South was dominated by heat dampness accumulating in the lung(55.69%),while the North was dominated by dampness-toxin stagnating in the lung(44.90%).The results of core prescription mining showed that dispelling dampness,dispersing wind,clearing heat and strengthening spleen were the common treatment methods in Northern and Southern *** mild cases,Jinyinhua(Flos Lonicerae)and Lianqiao(Fructus Forsythiae Suspensae)were often used in the South to clear heat and relieve exterior symptoms,while Chaihu(Radix Bupleuri Chinensis)and Huangqin(Radix Scutellariae Baicalensis)were often used in the North to relieve muscles by expelling *** moderate cases,Chaihu(Radix Bupleuri Chinensis),Qinghao(Herba Artemisiae Annuae),and Shigao(Gypsum Fibrosum)were often used to clear heat of Tri-jiao Channel and stomach in the South,while Fuling(Poria),Chenpi(Pericarpium Citri Reticulatae),and Dangshen(Radix Codonopsis)were often used to invigorate spleen and remove dampness in the *** severe cases

关键词： COVID-19 medicine,Chinese traditional North-South difference core prescription syndrome retrospective studies

Metabolic Dysregulation and Metabolite Imbalances in Acuteon-chronic Liver Failure:Impact on Immune Status

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Journal of Clinical and Translational Hepatology 2024年第10期12卷 865-877页

作者： Danmei Zhang Chunxia Shi Yukun Wang Jin Guo Zuojiong Gong department of infectious Diseases Renmin Hospital of Wuhan UniversityWuhanHubeiChina

Liver failure encompasses a range of severe clinical syndromes resulting from the deterioration of liver function,triggered by factors both within and outside the *** the definition of acute-on-chronic liver failure(ACLF)may vary by region,it is universally recognized for its association with multiorgan failure,a robust inflammatory response,and high short-term mortality *** advances in metabolomics have provided insights into energy metabolism and metabolite alterations specific to ***,immunometabolism is increasingly acknowledged as a pivotal mechanism in regulating immune cell ***,understanding the energy metabolism pathways involved in ACLF and investigating how metabolite imbalances affect immune cell functionality are crucial for developing effective treatment strategies for *** review methodically examined the immune and metabolic states of ACLF patients and elucidated how alterations in metabolites impact immune functions,offering novel perspectives for immune regulation and therapeutic management of liver failure.

关键词： Acute-on-chronic liver failure Immunometabolism Metabolism Metabolic reprogramming Metabolomics Microenvironment

Epidemic management in a measles outbreak in 2023,the return of vaccine-preventable diseases:A single center,retrospective observational study

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Asian Pacific Journal of Tropical Medicine 2024年第3期17卷 110-118页

作者： Sevgi Aslan Tuncay Gulsen Akkoc Seyhan Yilmaz Burcu Parlak Pinar Canizci Erdemli Aylin Dizi Isik Didem Buyuktas Aytac Meryem Cagla Abaci Capar Eda Kepenekli Kadayifci Marmara University Faculty of Medicine Department of Pediatric Infectious DiseaseIstanbulTurkey

Objective:To investigate the importance of immunization in preventing measles infection and to determine the most useful laboratory tests for confirmation of ***:This study included pediatric cases evaluated with a presumed diagnosis of measles between December 2022 and June 2023,at Marmara University Pendik Training and Research *** effects of vaccination status and underlying disease on the clinical course,treatments,and complications were ***:In total,117 patients were enrolled in the study with a median age of 80 months(IQR:32.5-125.0).Twelve patients with contact history were asymptomatic and had an underlying disorder,and intravenous immunoglobulin was given to them for post-exposure ***-one patients had confirmed measles *** treatment was given to three patients(a newborn,a girl with rhabdomyosarcoma,and a healthy boy)with respiratory ***-eight percent of confirmed measles cases were unvaccinated,and all hospitalized cases were unvaccinated or *** full-vaccinated children had confirmed measles *** PCR from nasopharyngeal swabs was negative in all of them,and their diagnosis was established with anti-measles IgM ***:The measles vaccine is the most effective way to protect from measles and measles-related *** measles can also occur in fully vaccinated patients,the disease is milder than in unvaccinated *** ELISA and RT-PCR tests together may be beneficial in patients with high clinical suspicion for early diagnosis.

关键词： Measles Outbreak Vaccination Vitamin A Ribavirin