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Longitudinal gut fungal alterations and potential fungal biomarkers for the progression of primary liver disease

Science China(Life Sciences) 2024年第6期67卷 1183-1198页

作者： Shiman Jiang Lvwan Xu Yanfei Chen Zheyue Shu Longxian Lv Yuxi Zhao Kefan Bi Sisi Yang Qiangqiang Wang Lanjuan Li 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 310003China division of Hepatobiliary and Pancreatic Surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Liver disease,a major health concern worldwide,is a serious and progressive ***,we not only established a mouse model of DEN+CCl4-induced primary liver disease but also collected clinical human samples to investigate longitudinal alterations in the gut *** liver disease advanced,gut integrity was disrupted,and the mycobiota was disturbed in the mouse *** metabolites associated with hepatocellular carcinoma(HCC)differed from those associated with the cirrhotic phase as follows:levels of stercobilin and aflatoxin B1 dialcohol were reduced,while levels of triterpenoids,bafilomycin A1,and DHEA were increased in the HCC *** abundance of the phylum Chytridiomycota increased as the chronic liver disease progressed and was then replaced by the phylum Ascomycota in *** on the results from clinical human samples,the genus Candida(Ascomycota)(in humans)and the genus Kazachstania(Ascomycota)(in mice)occupied a dominant position in the HCC group,while other fungi were *** increased abundance of *** and depletion of *** may be hallmarks of the progression of liver cirrhosis to early ***,the administration of *** and *** in the LC-HCC progression could accelerate or retard the progression of ***,gut fungi have the potential to serve as a noninvasive clinical biomarker and even a treatment method.

关键词： gut mycobiome liver disease longitudinal studies hepatocarcinogenesis fungal biomarker

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

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Biomedical and Environmental Sciences 2024年第3期37卷 303-314页

作者： YANG Liu WANG Shi Yu JIANG Ting Ting DENG Wen CHANG Min WU Shu Ling CAO Wei Hua LU Yao SHEN Ge LIU Ru Yu GAO Yuan Jiao XU Meng Jiao HU Lei Ping ZHANG Lu XIE Yao LI Ming Hui Department of Hepatology division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Center for infectious diseases Second Affiliated Hospital of Air Force Medical UniversityXi'an 710038ShaanxiChina Department of Hepatology division 2 Peking University Ditan Teaching HospitalBeijing 100015China

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 *** 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 *** 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<*** 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.

关键词： CHB Dendritic Cells Intermittent Interferon Therapy Plateau Phase

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

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Current Medical Science 2024年第1期44卷 121-133页

作者： Ting-ting WEI Wen XU Bo TU Wan-xue ZHANG Xin-xin YANG Yiguo ZHOU Shan-shan ZHANG Jun-lian YANG Ming-zhu XIE Juan DU Wei-wei CHEN Qing-bin LU Department of epidemiology and Biostatistics School of Public HealthPeking UniversityBeijing 100191China Department of infectious Disease The Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijing 100039China Department of Laboratorial Science and Technology&Vaccine Research Center School of Public HealthPeking UniversityBeijing 100191China Department of Health Policy and Management School of Public HealthPeking UniversityBeijing 100191China Global Center for infectious Disease and Policy Research&Global Health and infectious diseases Group Peking UniversityBeijing 100191China Key Laboratory of epidemiology of Major diseases(Peking University) Ministry of EducationBeijing 100191China

Objective Human adenovirus(HAdV)infection is common and can develop to serious conditions with high mortality,yet the mechanism of HAdV infection remains *** the present study,the serum metabolite profiles of HAdV-7-infected patients with pneumonia or upper respiratory tract infection(URTI)were *** 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 *** samples were collected at the acute stage and at the recovery stage and were analyzed by untargeted *** 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 *** metabolic pathways that were significantly enriched were primarily the lipid metabolism pathways,including sphingolipid metabolism,glycerophospholipid metabolism,and linoleic acid *** 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 *** 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.

关键词： human adenovirus metabonomic lipids pneumonia upper respiratory tract infection

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Antibodies Targeting a Conserved Surface Polysaccharide Are Protective Against a Wide Range of Microbial Pathogens Producing b-1-6-Linked Poly-N-Acetylglucosamine(PNAG)

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Engineering 2024年第7期38卷 69-76页

作者： Xi Lu Guoqing Li Jing Pang Xinyi Yang Colette Cywes-Bentley Xuefu You Gerald B.Pier Beijing Key Laboratory of Antimicrobial Agents Institute of Medicinal BiotechnologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China division of infectious diseases Department of MedicineBrigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115USA

The b-1-6-linked poly-N-acetylglucosamine(PNAG)polymer is a conserved surface polysaccharide produced by many bacteria,fungi,and protozoan(and even filarial)*** wide-ranging expression makes PNAG an attractive target for vaccine development,as it potentially encompasses a broad range of *** progress has been made in discovering important properties of the biology of PNAG expression in recent *** molecular characterization and regulation of operons for the production of PNAG biosynthetic proteins and enzymes have been studied in many *** addition,the physiological function of PNAG has been further ***-based vaccines and PNAG-targeting antibodies have shown great efficacy in preclinical ***,clinical tests for both vaccines and antibodies have been carried out in humans and economically important animals,and the results are *** it is not destined to be a smooth road,we are optimistic about new vaccines and immunotherapeutics targeting PNAG becoming validated and eventually licensed for clinical use against multiple infectious agents.

关键词： Poly-N-acetylglucosamine Conjugate vaccine Monoclonal antibody

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STAT3-Dependent Effects of Polymeric Immunoglobulin Receptor in Regulating Interleukin-17 Signaling and Preventing Autoimmune Hepatitis

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Engineering 2024年第5期36卷 209-222页

作者： Ting Li Tongtong Pan Nannan Zheng Xiong Ma Xiaodong Wang Fang Yan Huimian Jiang Yuxin Wang Hongwei Lin Jing Lin Huadong Zhang Jia Huang Lingming Kong Anmin Huang Qingxiu Liu Yongping Chen Dazhi Chen Hepatology Diagnosis and Treatment Center The First Affiliated Hospital of Wenzhou Medical University&Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver DiseasesWenzhou 325035China Department of Clinical Medicine Hangzhou Medical CollegeHangzhou 310053China State Key Laboratory for Oncogenes and Related Genes Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200001China Wenzhou Medical University Wenzhou 325035China division of infectious diseases Lishui People’s HospitalLishui 323000China

One-third of patients with autoimmune hepatitis(AIH)have cirrhosis at the time of *** relevance of these variables,although unknown,is believed to be critical in AIH because of suspected interactions between the gut microbiome and genetic *** of the gut flora and elevated polymeric immunoglobulin receptor(pIgR)levels have been observed in both patients and mouse ***,there is a direct relationship between pIgR expression and transaminase levels in patients with *** this study,we aimed to explore how pIgR influences the secretion of regenerating islet-derived 3 beta(Reg3b)and the flora composition in AIH using in vivo experiments involving patients with AIH and a concanavalin A-induced mouse model of ***3b expression was reduced in pIgR gene(Pigr)-knockout mice compared to that in wild-type mice,leading to increased microbiota ***,exogenous pIgR supplementation increased Reg3b expression and maintained microbiota *** sequencing revealed the participation of the interleukin(IL)-17 signaling pathway in the regulation of Reg3b through ***,the introduction of external pIgR could not restore the imbalance in gut microbiota in AIH,and the decrease in Reg3b expression was not apparent following the inhibition of signal transducer and activator of transcription 3(STAT3).In this study,pIgR facilitated the upregulation of Reg3b via the STAT3 pathway,which plays a crucial role in preserving the balance of the intestinal microbiota in *** this research,we discovered new molecular targets that can be used for the diagnosis and treatment of AIH.

关键词： Autoimmune hepatitis Polymeric immunoglobulin receptor Regenerating islet-derived 3 beta Intestinal microbiota Signal transducer and activator of transcription 3

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Pulmonary Bacterial Infection and Liver Cirrhosis: Current Status and Treatment

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infectious Microbes & diseases 2024年第1期6卷 5-10页

作者： Yingying Zhao Song Yang Huichun Xing Center of Liver diseases division 3 Beijing Ditan HospitalCapital Medical UniversityBeijingChina

Liver cirrhosis has a higher incidence rate and mortality when complicated with bacterial *** bacterial infections,especially bacterial pneumonia,increase the susceptibility of cirrhotic patients to decompensation,with a higher likelihood of *** pneu-monia is often overlooked in patients with liver cirrhosis,although it can impact the clinical progress and *** diagnosis and inappropriate antibiotic treatments are associated with poor prognosis and increased *** understanding of mechanisms and appropriate antibiotic treatments for cirrhosis-related bacterial pneumonia remain ***,we reviewed the epidemiology,clinical characteristics and treatment of pulmonary bacterial infections in cirrhotic patients to provide suggestions for clinical practice.

关键词： bacterial pneumonia liver cirrhosis epidemiology characteristics treatment

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Advances in technology for the laboratory diagnosis of individuals with HIV/AIDS coinfected with Mycobacterium tuberculosis

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Biosafety and Health 2024年第3期6卷 133-142页

作者： Jin Sun Xiaoxu Han Hongxia Yan Xin Zhang Taiyi Jiang Tong Zhang Hao Wu Grigory Kaminskiy Yingmin Ma Eduard Karamov Bin Su Beijing Key Laboratory for HIV/AIDS Research Clinical and Research Center for Infectious DiseasesBeijing Youan HospitalCapital Medical UniversityBeijing 100069China State Health Organization Tula Regional Center for Control and Prevention of AIDS and infectious diseases Tula 300002Russia Department of Respiratory and Critical Care Medicine Beijing Youan HospitalCapital Medical UniversityBeijing 100069China Gamaleya National Research Centre for epidemiology and Microbiology of the Ministry of Health of the Russian Federation Moscow 123098Russia

The high morbidity and mortality rate of individuals with human immunodeficiency virus(HIV)/acquired immunodeficiency syndrome(AIDS)coinfected with Mycobacterium tuberculosis(MTB)is a tough challenge for current global tuberculosis prevention and control ***/MTB coinfection is more complex than a single infection,and the interaction between the two diseases aggravates the deterioration caused by the disease,resulting in increased hospitalizations and *** screening and early diagnosis facilitate the timely initiation of anti-tuberculosis treatment in HIV/MTB coinfected individuals,thereby reducing transmission and the incidence of adverse *** date,pathogenic detection has remained the gold standard for diagnosing tuberculosis,but its sensitivity and specificity are greatly affected by the body's immune status,which limits its application in the diagnosis of HIV/MTB ***,immunology and molecular detection technology has developed *** detection technologies,such as interferon-γ release assays,interferon-gamma inducible protein 10,and GeneXpert MTB/RIF assay have overcome the limitations of traditional detection methods,significantly improved the sensitivity and specificity of tuberculosis diagnosis,and brought new hope to the detection of HIV/MTB *** this article,the principle,scope of application,and latest research progress of relevant detection methods are reviewed to provide a reference for the early diagnosis of HIV/MTB coinfection.

关键词： Human immunodeficiency virus(HIV) Mycobacterium tuberculosis(MTB)coinfection Mycobacterium tuberculosis(MTB) Early diagnosis

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Real-world utility of serological tests in patients with suspected scrub typhus in the Republic of Korea:A single-center,retrospective,observational study

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Asian Pacific Journal of Tropical Medicine 2024年第6期17卷 273-280,I0004,I0005页

作者： Seulki Kim A Reum Kim Seungjin Lim Su Jin Lee Moonsuk Bae division of infectious diseases Department of Internal MedicinePusan National University Yangsan HospitalYangsanRepublic of Korea Research Institute for Convergence of Biomedical Science and Technology Pusan National University Yangsan HospitalYangsanRepublic of Korea Department of Internal Medicine Pusan National University School of MedicineBusanRepublic of Korea

Objective:Serological tests are widely used for scrub typhus diagnosis;however,their limitations are *** study aims to assess their practical value in clinical ***:We analyzed the data of adult patients with suspected scrub typhus who visited a tertiary care hospital in the Republic of Korea from September to December from 2019 to *** included patients had an acute fever and at least one of the following ten secondary findings:myalgia,skin rash,eschar,headache,thrombocytopenia,increased liver enzyme levels,lymphadenopathy,hepatomegaly,splenomegaly,and pleural *** diagnoses were grouped as scrub typhus or other diseases by two infectious disease ***:Among 136 patients who met the eligibility criteria,109 had scrub typhus and 27 had different *** and paired total antibodies using immunofluorescence assay(IFA),and total antibodies using immunochromatography-based rapid diagnostic testing(ICT)were measured in 98%,22%,and 75%of all patients,*** using paired samples for scrub typhus was established at a median of 11[interquartile range(IQR)10-16]days following the first *** the 82 admitted patients,the median admission time was 9(IQR 7-13)*** to IFA,58(55%)patients with scrub typhus had total immunoglobulin titers≥1:320,while 23(85%)patients with other disease had titersdiseases showed negative ICT ***:Serological testing for scrub typhus is currently insufficient for decision-making in clinical practice.

关键词： Scrub typhus Serological test Immunofluorescence assay Immunochromatography Rapid detecting test

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infectious causes of fever of unknown origin in developing countries: An international ID-IRI study

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Journal of Intensive Medicine 2024年第1期4卷 94-100页

作者： Hakan Erdem Jaffar AAl-Tawfiq Maha Abid Wissal Ben Yahia George Akafity Manar Ezzelarab Ramadan Fatma Amer Amani El-Kholy Atousa Hakamifard Bilal Ahmad Rahimi Farouq Dayyab Hulya Caskurlu Reham Khedr Muhammad Tahir Lysien Zambrano Mumtaz Ali Khan Aun Raza Nagwa Mostafa El-Sayed Magdalena Baymakova Aysun Yalci Yasemin Cag Umran Elbahr Aamer Ikram Department of infectious diseases&Clinical Microbiology Gulhane School of MedicineTurkish Health Sciences UniversityAnkaraTurkey Specialty Internal Medicine and Quality and Patient Safety Department Johns Hopkins Aramco HealthcareDhahranSaudi Arabia division of infectious diseases Indiana University School of MedicineIndianapolisINUSA Department of infectious diseases Farhat Hached University HospitalIbn El Jazzar Medical SchoolUniversity of SousseSousseTunisia Internal Medicine Department Farhat Hached University HospitalIbn El Jazzar Medical SchoolUniversity of SousseSousseTunisia Cape Coast Teaching hospital Cape CoastGhana Medical Parasitology Faculty of MedicineSuez UniversitySuezEgypt Department of Medical Microbiology and Immunology Faculty of MedicineZagazig UniversityZagazigEgypt Department of Clinical Pathology Faculty of MedicineCairo UniversityGizaEgypt Department of infectious diseases School of MedicineIsfahan University of Medical SciencesIsfahanIran Department of infectious diseases Kandahar University Medical FacultyTeaching HospitalKandaharAfghanistan Department of infectious diseases Mohammed Bn Khalifa Bn Salman Alkhalifa Specialist Cardiac CenterAwaliBahrain Department of infectious diseases and Clinical Microbiology Faculty of MedicineIstanbul Medeniyet UniversityIstanbulTurkey Department of Pediatric Oncology National Cancer Institute–Cairo UniversityChildren Cancer Hospital EgyptCairoEgypt Department of Medicine Federal General HospitalIslamabadPakistan Institute for Research in Medical Sciences and Right to Health(ICIMEDES) Scientific Research Unit(UIC)Faculty of Medical Sciences(FCM)National Autonomous University of Honduras(UNAH)TegucigalpaHonduras National Institute of Health IslamabadPakistan Shaukat Khanum Memorial Cancer hospital and Research Center LahorePakistan Medical Parasitology Department Research Institute of OphthalmologyGizaEgypt Department of infectious diseases Military Medical AcademySofiaBulgaria Department of Infecti

Background:Fever of unknown origin(FUO)in developing countries is an important dilemma and further research is needed to elucidate the infectious causes of ***:A multi-center study for infectious causes of FUO in lower middle-income countries(LMIC)and lowincome countries(LIC)was conducted between January 1,2018 and January 1,*** total,15 participating centers from seven different countries provided the data,which were collected through the infectious diseasesInternational Research Initiative *** adult patients with confirmed infection as the cause of FUO were included in the *** severity parameters were quick Sequential Organ Failure Assessment(qSOFA)≥2,intensive care unit(ICU)admission,vasopressor use,and invasive mechanical ventilation(IMV).Results:A total of 160 patients with infectious FUO were included in the ***,148(92.5%)patients had community-acquired infections and 12(7.5%)had hospital-acquired *** most common infectious syndromes were tuberculosis(TB)(n=27,16.9%),infective endocarditis(n=25,15.6%),malaria(n=21,13.1%),brucellosis(n=15,9.4%),and typhoid fever(n=9,5.6%).Plasmodium falciparum,Mycobacterium tuberculosis,Brucellae,Staphylococcus aureus,Salmonella typhi,and Rickettsiae were the leading infectious agents in this study.A total of 56(35.0%)cases had invasive procedures for *** mean qSOFA score was 0.76±0.94{median(interquartile range[IQR]):0(0–1)}.ICU admission(n=26,16.2%),vasopressor use(n=14,8.8%),and IMV(n=10,6.3%)were not ***,38(23.8%)patients had at least one of the severity *** mortality rate was 15(9.4%),and the mortality was attributable to the infection causing FUO in 12(7.5%)***:In LMIC and LIC,tuberculosis and cardiac infections were the most severe and the leading infections causing FUO.

关键词： Developing countries Fever of unknown origin Infection

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Antimicrobial stewardship and targeted therapies in the changing landscape of maternal sepsis

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Journal of Intensive Medicine 2024年第1期4卷 46-61页

作者： Nishel M Shah Esmita Charani Damien Ming Fook-Choe Cheah Mark R Johnson Department of Metabolism Digestion and ReproductionImperial College LondonChelsea and Westminster HospitalLondonUK Health Protection Research Unit in Healthcare Associated Infection and Antimicrobial Resistance Imperial College LondonLondonUK division of infectious diseases and HIV Medicine Department of MedicineGroote Schuur HospitalUniversity of Cape TownCape TownSouth Africa Department of infectious diseases Imperial College LondonChelsea and Westminster HospitalLondonUK Department of Paediatrics Faculty of MedicineUniversiti Kebangsaan Malaysia Medical CentreKuala LumpurMalaysia

Pregnant and postnatal women are a high-risk population particularly prone to rapid progression to sepsis with significant morbidity and mortality ***,severe maternal infections can have a serious detrimental impact on neonates with almost 1 million neonatal deaths annually attributed to maternal infection or *** this review we discuss the susceptibility of pregnant women and their specific physiological and immunological adaptations that contribute to their vulnerability to sepsis,the implications for the neonate,as well as the issues with antimicrobial stewardship and the challenges this poses when attempting to reach a balance between clinical care and urgent ***,we review advancements in the development of pregnancy-specific diagnostic and therapeutic approaches and how these can be used to optimize the care of pregnant women and neonates.

关键词： Sepsis Pregnancy Immunology Cardiovascular Personalised medicine Antibiotic stewardship

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