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Human Placental Mesenchymal Stem Cells Relieve Primary Sclerosing Cholangitis via Upregulation of TGR5 in Mdr2^(-/-)Mice and Human Intrahepatic Cholangiocyte Organoid Models

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Research 2024年第2期2023卷 355-372页

作者： Qigu Yao Wenyi Chen Yingduo Yu Feiqiong Gao Jiahang Zhou Jian Wu Qiaoling Pan Jinfeng Yang Lingling Zhou Jiong Yu Hongcui Cao Lanjuan Li State key laboratory for the diagnosis and treatment of Infectious diseases Cllaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affliated HospitalZhejang University School of Medicine79 Qingchun Rd.Hangzhou 310003China National Clinical Research Center for Infectious diseases HangzhouChina key laboratory of diagnosis and treatment of Aging and Physic-chemical Injury diseases of Zhejiang Province 79 Qingchun Rd.Hangzhou 310003China Jjinan Microecological Biomedicine Shandong laboratory Jinan 250117China

Primary sclerosing cholangitis(PSC)is a biliary disease accompanied by chronic inflammation of the liver and biliary *** stem cells(MSCs)are used to treat liver diseases because of their immune regulation and regeneration-promoting *** study was performed to explore the therapeutic potential of human placental MSCs(hP-MSCs)in PSC through the Takeda G protein-coupled receptor 5(TGR5)receptor *** tissues were collected from patients with PSC and healthy donors(n=4)for RNA sequencing and intrahepatic cholangiocyte organoid ***-MSCs were injected via the tail vein into Mdr2^(-/-),bile duct ligation(BDL),and 3,5-diethoxycarbonyl-1,4-dihydrocollidine(DDC)mouse models or co-cultured with organoids to confirm their therapeutic effect on biliary *** in bile acid metabolic profile were analyzed by liquid chromatography/tandem mass spectrometry(LC-MS/MS).Compared with healthy controls,liver tissues and intrahepatic cholangiocyte organoids from PSC patients were characterized by inflammation and cholestasis,and marked downregulation of bile acid receptor TGR5 ***-MSC treatment apparently reduced the inflammation,cholestasis,and fibrosis in Mdr2^(-/-),BDL,and DDC model *** activating the phosphatidylinositol 3 kinase/extracellular signal-regulated protein kinase pathway,hP-MSC treatment promoted the proliferation of cholangiocytes,and affected the transcription of downstream nuclear factorκB through regulation of the binding of TGR5 and Pellino3,thereby affecting the cholangiocyte inflammatory phenotype.

关键词： inflammation TGR5 Human

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Impact of short-term ambient air pollution exposure on the risk of severe COVID-19

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Journal of Environmental Sciences 2024年第1期135卷 610-618页

作者： Baihuan Feng Jiangshan Lian Fei Yu Dan Zhang Weizhen Chen QiWang Yifei Shen Guoliang Xie Ruonan Wang Yun Teng Bin Lou Shufa Zheng Yida Yang Yu Chen Department of laboratory Medicine The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China key laboratory of Clinical In Vitro Diagnostic Techniques of Zhejiang Province Hangzhou 310000China Institute of laboratory Medicine Zhejiang UniversityHangzhou 310000China Department of Infectious diseases The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310000China 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 310000China

Ecological studies suggested a link between air pollution and severe COVID-19 outcomes,while studies accounting for individual-level characteristics are *** the present study,we aimed to investigate the impact of short-term ambient air pollution exposure on disease severity among a cohort of 569 laboratory confirmed COVID-19 patients admitted to designated hospitals in Zhejiang province,China,from January 17 to March 3,2020,and elucidate the possible biological processes involved using *** with mild cases,severe cases had higher proportion of medical conditions as well as unfavorable results in most of the laboratory tests,and manifested higher air pollution exposure *** exposure to air pollutants was associated with increased risk of severe COVID-19 with odds ratio(OR)of 1.89(95%confidence interval(CI):1.01,3.53),2.35(95%CI:1.20,4.61),2.87(95%CI:1.68,4.91),and 2.01(95%CI:1.10,3.69)for PM_(2.5),PM_(10),NO_(2)and CO,*** for NO_(2)remained significant in two-pollutant models after adjusting for other *** analysis showed 884 differentially expressed genes which mainly were enriched in virus clearance related biological processes between patients with high and low NO_(2)exposure levels,indicating that compromised immune response might be a potential underlying mechanistic *** findings highlight the impact of shortterm air pollution exposure,particularly for NO_(2),on COVID-19 severity,and emphasize the significance in mitigating the COVID-19 burden of commitments to improve air quality.

关键词： Air pollution COVID-19 Severity Transcriptomics immune response

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Efficacy of substances containing 3 types of active ingredients-saponins, flavones, and alkaloids in regulation of cytokines in autoimmune diseases a systematic review and Meta-analysis based on animal studies

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Journal of Traditional Chinese Medicine 2024年第3期44卷 417-426页

作者： ZHU Ruifang ZHANG Jun LYU Yaru CHEN Yulu HAN Shifan WANG Hongwei key laboratory for Molecular diagnosis and treatment of Hematologic diseases Second Hospital of Shanxi Medical University Editorial Office First Hospital of Shanxi Medical University School of Nursing Shanxi Medical University

OBJECTIVE: To investigate the efficacy of substances containing 3 types of active ingredients-saponins,flavones, and alkaloids on experimental animals with autoimmune diseases(AIDs).METHODS: The protocol for this systematic review and Meta-analysis was prospectively registered with PROSPERO(CRD42023395741). Searches were conducted in the China National Knowledge Infrastructure, Wanfang, Chinese Science and Technology Journals, China Biomedical, Pub Med,Cochrane Library, and Embase databases to screen for animal studies investigating the therapeutic effects of saponins, flavones, or alkaloids on autoimmune diseases;consequently, corresponding data extraction tables were prepared. Systematic Review Centre for laboratory Animal Experimentation was used to assess the risk of methodological bias in the included literature. RevMan 5.4 was used for the Meta-analysis on the 8 serum ***: A total of 31 studies were included, all of which were randomized controlled studies. Meta-analysis indicated that substances rich in saponins, flavones, and alkaloids reduced serum levels of interleukin(IL)-1β[standardized mean difference(SMD) =-1.94, 95%confidence interval(CI)(-2.99,-0.90), P = 0.0003], IL-6 [SMD =-1.65, 95% CI(-2.33,-0.97,) P immunerelated cytokines, it may be a novel dietary substance to relieve and control autoimmune diseases in the future.

关键词： Meta-analysis alkaloids autoimmune diseases flavones saponins system evaluation

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

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Hepatobiliary & Pancreatic diseases International 2024年第3期23卷 272-287页

作者： Hai-Yan Zhang Jia-Jie Zhu Zong-Ming Liu Yu-Xuan Zhang Jia-Jia Chen Ke-Da Chen Zhejiang Chinese Medical University Hangzhou 310053China Shulan International Medical College Zhejiang Shuren UniversityHangzhou 310015China 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 310009China

Background:Hepatocellular carcinoma(HCC)has a poor long-term *** competition of circular RNAs(circRNAs)with endogenous RNA is a novel tool for predicting HCC *** on the alterations of circRNA regulatory networks,the analysis of gene modules related to HCC is ***:Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in *** function,pathway,and protein interaction analyses were performed for the differentially expressed genes(DEGs)in this regulatory *** 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 ***-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 ***: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 *** inhibitors,PI3K inhibitors,HDAC inhibitors,and EGFR inhibitors were predicted as four potential mechanisms of drug action(MOA)in high-risk HCC *** 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 ***: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.

关键词： Hepatocellular carcinoma circRNA-related ceRNA network Biomarker Least absolute shrinkage and selection operator Bioinformatics

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

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World Journal of Hepatology 2024年第2期16卷 177-185页

作者： Feng Chen Shan-Shan Wu Chao Chen Cheng Zhou 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 HospitalCollege of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvinceChina

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 *** liver serves as the primary organ for LCN2 secretion during microbial *** review encapsulates recent advances in dynamic changes,clinical values,and the effects of LCN2 in infectious liver diseases caused by various microbial microorganisms.

关键词： Lipocalin 2 Microbial infection Immunity Liver diseases

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Correlation of Oral Microbiota With Different immune Responses to Antiretroviral Therapy in People Living With HIV

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Infectious Microbes & diseases 2024年第2期6卷 85-92页

作者： Jingying Pan Xiaodi Zhang Danrong Shi Xuebin Tian Lijun Xu Xiangyun Lu Mingqing Dong Peng Yao Zhaoyi Pan Nanping Wu Hangping Yao 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 HospitalSchool of MedicineZhejiang UniversityHangzhouChina Department of Infectious Disease Zhejiang Qingchun HospitalZhejiang UniversityHangzhouChina Jinan Microecological Biomedicine Shandong laboratory JinanChina

Both HIV infection and antiretroviral therapy(ART)affect the oral *** successful treatment with ART in people living with HIV(PLWH),which leads to a significant decline in viral loads and immune reconstitution,is associated with changes in or recovery of the oral microbiome remains ***,we performed a cross-sectional study of 118 PLWH receiving regular ART and 40 healthy controls(HCs).Among the 118 PLWH,18 immunological nonresponders(INRs;immune cell counts were *** INR group showed lower alpha diversity than the IR and HC groups,which displayed similar alpha *** genera Alloprevotella,Prevotella and Neisseria were more abundant in PLWH than in HCs,whereas the genera Rothia,Streptococcus and Fusobacterium were more abundant in HCs than in *** genus Rothia was more abundant in the INR group,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus were more abundant in the IR *** genera Rothia and Alloprevotella were negatively and positively associated with CD4^(+)T cell counts,***,an increased abundance of Rothia in the oral microbiome is associated with unfavorable outcomes regarding immune reconstitution in PLWH receiving regular ART,whereas Prevotella,Alloprevotella,Porphyromonas and Haemophilus are associated with favorable outcomes.

关键词： HIV oral microbiome antiretroviral therapy immunological nonresponders immunological responders

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Human pluripotent stem cell-derived kidney organoids:Current progress and challenges

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World Journal of Stem Cells 2024年第2期16卷 114-125页

作者： Hong-Yan Long Zu-Ping Qian Qin Lan Yong-Jie Xu Jing-Jing Da Fu-Xun Yu Yan Zha Graduate School Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina Department of laboratory Medicine Guizhou Provincial People’s HospitalGuiyang 550002Guizhou ProvinceChina Department of Nephrology Guizhou Provincial People’s HospitalGuiyang 550002Guizhou ProvinceChina key laboratory of diagnosis and treatment of pulmonary immune diseases National Health CommissionGuizhou Provincial People’s HospitalGuiyang 550002Guizhou ProvinceChina

Human pluripotent stem cell(hPSC)-derived kidney organoids share similarities with the fetal ***,the current hPSC-derived kidney organoids have some limitations,including the inability to perform nephrogenesis and lack of a corticomedullary definition,uniform vascular system,and coordinated exit path-way for urinary ***,further studies are required to produce hPSC-derived kidney organoids that accurately mimic human kidneys to facilitate research on kidney development,regeneration,disease modeling,and drug *** this review,we discussed recent advances in the generation of hPSC-derived kidney organoids,how these organoids contribute to the understanding of human kidney development and research in disease ***,the limitations,future research focus,and applications of hPSC-derived kidney organoids were highlighted.

关键词： Kidney Organoids Human pluripotent stem cell Development Vascular system Disease modeling

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Granulomatosis with polyangiitis presented as multiple cutaneous abscesses after hysterectomy

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Chinese Medical Journal 2024年第6期137卷 755-756页

作者： Xiaoting Song Mengrui Li Yinggai Song Ping Tu Hang Li Yang Wang Rong Xu Min Chen Xiaojuan Yu Suxia Wang Fude Zhou Minghui Zhao Ruoyu Li Xiaoyu Jia Xiaowen Wang Department of Dermatology and Venereology Peking University First HospitalBeijing 100034China Beijing key laboratory of Molecular diagnosis on Dermatoses Beijing 100034China National Clinical Research Center for Skin and immune diseases Beijing 100034China Renal Division Department of MedicinePeking University First HospitalBeijing 100034China Institute of Nephrology Peking UniversityBeijing 100034China key laboratory of Renal Disease Ministry of Health of ChinaBeijing 100034China Research Units of diagnosis and treatment of immune-mediated Kidney diseases Chinese Academy of Medical SciencesBeijing 100034China

To the Editor:A 62-year-old woman presented to the dermatology department with a 5-month history of multiple painless cutaneous abscesses and ulcers[Figure 1A],occurring 1 month after a transvaginal hysterectomy due to uterine *** general condition was good before and after the surgery,with no abnormal physical signs apart from *** reported no fever,night sweat,cough,or abdominal pain,but 10 kg *** has no history of diabetes,autoimmune diseases,or chronic infectious *** was no similar illness in her family.

关键词： hysterectomy pain surgery

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FGF4 protects the liver from immune-mediated injury by activating CaMKKβ-PINK1 signal pathway to inhibit hepatocellular apoptosis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 1605-1623页

作者： Zhifeng Huang Tongtong Pan Liang Xu Lu Shi Xiong Ma Liya Zhou Luyao Wang Jiaojiao Wang Guoqing Zhu Dazhi Chen Lingtao Song Xiaomin Pan Xiaodong Wang Xiaokun Li Yongde Luo Yongping Chen Hepatology diagnosis and treatment Center Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseasesthe First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035China Oujiang laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)&School of Pharmaceutical SciencesWenzhou Medical UniversityWenzhou 325035China School of laboratory Medicine and Life Sciences Wenzhou Medical University&Key Laboratory of Laboratory MedicineMinistry of EducationWenzhou Medical UniversityWenzhou 325035China Division of Gastroenterology and Hepatology Key Laboratory of Gastroenterology and HepatologyMinistry of HealthState Key Laboratory for Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China Hangzhou Medical College Hangzhou 311300China

immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine;however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca^(2+)/calmodulin-dependent protein kinasekinase 2 (CaMKKβ) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.

关键词： Fibroblast growthfactor 4 Fibroblast growth factor receptor 4 immune liver injury Ca^(2+)/Calmodulin dependent protein

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Successful extracorporeal membrane oxygenation-assisted treatment for a kidney transplant recipient infected with severe COVID-19

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World Journal of Emergency Medicine 2024年第5期15卷 416-418页

作者： Dongdong Li Ping Wang Yuanqiang Lu Department of Emergency Medicine the First Affi liated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China key laboratory for diagnosis and treatment of Physicochemical and Aging Injury diseases of Zhejiang Province Hangzhou 310003China

Clinical practice has shown that kidney transplant recipients infected with COVID-19 are prone to developing critical illness and have a higher mortality rate.[1]Kidney transplant recipients require long-term oral anti-rejection drugs to suppress the immune *** result may be related to the strong immunosuppression in kidney transplant recipients compared to the general population.[2]Therefore,the treatment of kidney transplant recipients infected with severe COVID-19 is a difficult ***,we report the use of extracorporeal membrane oxygenation(ECMO)-assisted treatment for a kidney transplant recipient who was infected with severe COVID-19.

关键词： kidney infected Kidney

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