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World Journal of Clinical Cases 2021年第7期9卷 1705-1713页

作者： Juan Lu Zhong-Yang Xie Dan-Hua Zhu Lan-Juan Li 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 UniversityHangzhou 310003Zhejiang ProvinceChina

BACKGROUND The coronavirus disease 2019(COVID-19)caused by novel coronavirus 2019 in December 2019 has spread all around the globe and has caused a *** is still no current effective guidance on the clinical management of *** stem cell therapy has been shown to be one of the therapeutic approaches to alleviate pneumonia and symptoms through their immunomodulatory effect in COVID-19 *** SUMMARY We describe the first confirmed case of COVID-19 in Hangzhou to explore the role of human menstrual blood-derived stem cells(MenSCs)in the treatment of ***,we review the immunomodulation effect including nonspecific and specific immune functions of MenSCs for the therapy of *** MenSCs can be helpful to find a promising therapeutic approach for COVID-19.

关键词： COVID-19 Human menstrual blood-derived stem cells Immunoregulatory therapy Inflammatory response Cytokine storm Case report

Multifunctional role of microRNAs in mesenchymal stem cell-derived exosomes in treatment of diseases

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World Journal of Stem Cells 2020年第11期12卷 1276-1294页

作者： Hui-Kang Xu Li-Jun Chen Si-Ning Zhou Yi-Fei Li Charlie Xiang 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 UniversityHangzhou 310003Zhejiang ProvinceChina

Mesenchymal stem cells can be replaced by exosomes for the treatment of inflammatory diseases,injury repair,degenerative diseases,and *** are small vesicles rich in a variety of nucleic acids[including messenger RNA,Long non-coding RNA,microRNA(miRNA),and circular RNA],proteins,and *** can be secreted by most cells in the human body and are known to play a key role in the communication of information and material transport between *** exosomes,miRNAs were neglected before their role in various activities of organisms was *** studies have confirmed that miRNAs play a vital role within *** review focuses on the specific role of miRNAs in MSC-derived exosomes(MSC-exosomes)and the methods commonly used by researchers to study miRNAs in *** together,miRNAs from MSC-exosomes display immense potential and practical value,both in basic medicine and future clinical applications,in treating several diseases.

关键词： MicroRNA Mesenchymal stem cells Exosomes Modulation of mesenchymal stem cells Inflammatory diseases Injury repair

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

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World Journal of Gastroenterology 2021年第22期27卷 3010-3021页

作者： Jun-Wei Shao Tian-Tian Ge Sen-Zhong Chen Gang Wang Qin Yang Chun-Hong Huang Li-Chen Xu Zhi Chen 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 UniversityHangzhou 310003Zhejiang ProvinceChina

The intensive crosstalk between the liver and the intestine performs many essential *** crosstalk is important for natural immune surveillance,adaptive immune response regulation and nutrient metabolism and elimination of toxic bacterial *** interaction between the gut microbiome and bile acids is *** gut microbiome regulates the synthesis of bile acids and their biological signaling activity and circulation via ***,bile acids also shape the composition of the gut microbiome by modulating the host’s natural antibacterial defense and the intestinal immune *** interaction between bile acids and the gut microbiome has been implicated in the pathophysiology of many intestinal and extra intestinal diseases,especially liver *** 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 *** clinical trials have demonstrated the signaling effects of bile acids in the context of liver *** hypothesize the existence of a gut microbiome-bile acids-liver triangle and explore the potential therapeutic strategies for liver diseases targeting the triangle.

关键词： Bile acids Gut microbiome Liver diseases Farnesoid X-activated receptor G protein-coupled bile acid receptor 1 Immune response

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

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Hepatobiliary & Pancreatic diseases International 2023年第6期22卷 551-553页

作者： Yan-Fei Chen Lan-Juan Li 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 HospitalZhejiang University School of MedicineHangzhou 310003China

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 *** 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 ***,there was an increasing trend of incidence of DILI since 2010 worldwide,with Asian regions showing the highest incidence[1].

关键词： drugs injuries liver

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

Efficacy of telbivudine in HBeAg-positive chronic hepatitis B patients with high baseline ALT levels

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World Journal of Gastroenterology 2010年第32期16卷 4095-4099页

作者： Guo-Cai Lv Wen-Jiang Ma Lin-Jung Ying Xi Jin Lin Zheng Yi-Da Yang state key laboratory for diagnosis and treatment of infectious diseases Department of infectious diseases First Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310003 Zhejiang ProvinceChina

AIM:To evaluate the efficacy and safety of telbivudine(LDT) in hepatitis B e antigen(HBeAg)-positive chronic hepatitis B(CHB) patients who have high baseline alanine aminotransferase(ALT) levels between 10 and 20 times the upper limit of ***:Forty HBeAg-positive CHB patients with high baseline ALT levels between 10 and 20 times the upper limit of normal were enrolled and received LDT monotherapy for 52 *** forty patients with baseline ALT levels between 2 and 10 times the upper limit of normal were included as *** compared the virological,biochemical,serological and side effect profiles between the two groups at 52 ***:By week 52,the mean decrease in hepatitis B virus(HBV) DNA level compared with baseline was 7.03 log10 copies/mL in the high baseline ALT group and 6.17 log10 copies/mL in the control group,respectively(P treatment.

关键词： Chronic hepatitis B Hepatitis B e antigen Serum alanine aminotransferase level Telbivudine

Hepatitis C virus infection and biological falsepositive syphilis test:a single-center experience

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Hepatobiliary & Pancreatic diseases International 2011年第4期10卷 399-402页

作者： Wei-Fang Zhu,Shui-Ying Lei and Lan-Juan Li state key laboratory for diagnosis and treatment of infectious diseases key laboratory of infectious diseases,Zhejiang Province Department of infectious diseases,First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310003,China state key laboratory for diagnosis and treatment of infectious diseases key laboratory of infectious diseases Zhejiang Province Department of infectious diseases First Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310003 China

BACKGROUND:Rapid plasma regain positive and/or treponema pallidum hemagglutination negative [RPR(+)/TPHA(-)] results were designated as biologic false-positive (BFP).There are limited data about BFP reactions against syphilis in patients with hepatitis C virus (HCV) *** study aimed to determine the prevalence of BFP reactions for syphilis in patients with HCV infection in a large sample and assess the relationship between BFP reactions and HCV ***:A total of 2656 patients with positive anti-HCV and 5600 healthy control subjects were enrolled in this *** C serology was determined by a second generation ELISA test for HCV *** serology was determined by the RPR *** subjects with reactive RPR positive underwent the TPHA *** and laboratory data were collected by trained ***:Among 2656 patients,111 (4.2%) had a reactive RPR *** the 111 patients who were subjected to reactive RPR test,30 (27.0%) showed HCV(+)/RPR(+).Of 5600 healthy controls,80 (1.4%) had a reactive RPR *** (17.5%) controls with HCV(-)/RPR(+) had a non-reactive TPHA *** represented 1.1% of all HCV-positive and 0.3% of all HCV-negative subjects (P0.05).CONCLUSIONS:The data of this study demonstrate that HCV infection is associated with a false-positive RPR *** this study BFPs were significantly more common in HCV positive patients compared to HCV-negative *** abnormality can be considered as a predictor for *** BFPs must be considered in assessing the frequency of syphilis in a

关键词： hepatitis C virus biological false-positive syphilis

Review of the pharmacological effects of astragalosideⅣand its autophagic mechanism in association with inflammation

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World Journal of Clinical Cases 2022年第28期10卷 10004-10016页

作者： Ying Yang Meng Hong Wen-Wen Lian Zhi Chen 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 DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

Astragalus membranaceus Bunge,known as Huangqi,has been used to treat various diseases for a long ***Ⅳ(AS-Ⅳ)is one of the primary active ingredients of the aqueous Huangqi *** experimental models have shown that AS-Ⅳexerts broad beneficial effects on cardiovascular disease,nervous system diseases,lung disease,diabetes,organ injury,kidney disease,and gynaecological *** review demonstrates and summarizes the structure,solubility,pharmacokinetics,toxicity,pharmacological effects,and autophagic mechanism of AS-Ⅳ.The autophagic effects are associated with multiple signalling pathways in experimental models,including the PI3KI/Akt/m TOR,PI3KⅢ/Beclin-1/Bcl-2,PI3K/Akt,AMPK/m TOR,PI3K/Akt/m TOR,SIRT1–NF-κB,PI3K/AKT/AS160,and TGF-β/Smad signalling *** on this evidence,AS-Ⅳcould be used as a replacement therapy for treating the multiple diseases referenced above.

关键词： AstragalosideⅣ Pharmacological effect Autophagy Inflammation

Go-Ichi-Ni-San 2:A potential biomarker and therapeutic target in human cancers

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World Journal of Gastrointestinal Oncology 2022年第10期14卷 1892-1902页

作者： Dan-Dan Shan Qiu-Xian Zheng Zhi Chen 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 DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina

Cancer incidence and mortality are increasing globally,leading to its rising status as a leading cause of *** Go-Ichi-Ni-San(GINS)complex plays a crucial role in DNA replication and the cell *** GINS complex consists of four subunits encoded by the GINS1,GINS2,GINS3,and GINS4 *** findings have shown that GINS2 expression is upregulated in many diseases,particularly *** example,increased GINS2 expression has been found in cervical cancer,gastric adenocarcinoma,glioma,non-small cell lung cancer,and pancreatic *** correlates with the clinicopathological characteristics of the *** addition,high GINS2 expression plays a pro-carcinogenic role in tumor development by promoting tumor cell proliferation and migration,inhibiting tumor cell apoptosis,and blocking the cell *** review describes the upregulation of GINS2 expression in most human tumors and the pathway of GINS2 in tumor ***2 may serve as a new marker for tumor diagnosis and a new biological target for therapy.

关键词： Go-Ichi-Ni-San Go-Ichi-Ni-San 2 Cancer Biomarker Clinicopathological characteristics Molecular mechanism

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

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Asian Journal of Pharmaceutical Sciences 2024年第1期19卷 119-134页

作者： Wenyi Chen Feiyan Lin Xudong Feng Qigu Yao Yingduo Yu Feiqiong Gao Jiahang Zhou Qiaoling Pan Jian Wu Jinfeng Yang Jiong Yu Hongcui Cao Lanjuan Li state key laboratory for the diagnosis and treatment of infectious diseases National Clinical Research Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesNational Medical Center for Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Jinan Microecological Biomedicine Shandong laboratory Jinan 250117China key laboratory of diagnosis and treatment of Aging and Physic-chemical Injury diseases of Zhejiang Province Hangzhou 310003China

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 *** placentalmesenchymal stem cell(hpMSC)-derived exosomes have demonstrated the ability to prevent fibrosis,inhibit collagen production and possess immunomodulatory properties in autoimmune liver ***,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 *** 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 ***,Exo^(MSC) improved the hypersecretory phenotype and intercellular interactions in the hepatic Th17 microenvironment by regulating PERK/CHOP signaling as supported by multicellular ***,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.

关键词： Mesenchymal stem cell Exosomes Primary sclerosing cholangitis Fibrosis Organoids Th17