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Frontiers of Medicine 2022年第5期16卷 667-685页

作者： Yuqiu Han Lanjuan Li Baohong Wang 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 Research Units of Infectious disease and Microecology Chinese Academy of Medical SciencesHangzhou 310003China Jinan Microecological Biomedicine Shandong Laboratory Jinan 250117China

Nonalcoholic fatty liver disease(NAFLD)is a hepatic manifestation of metabolic syndrome and a common cause of liver cirrhosis and cancer.Akkermansia muciniphila(A.muciniphila)is a next-generation probiotic that has been reported to improve metabolic disorders.Emerging evidence indicates the therapeutic potential of A.muciniphila for NAFLD,especially in the inflammatory stage,nonalcoholic steatohepatitis.Here,the current knowledge on the role of A.muciniphila in the progression of NAFLD was summarized.A.muciniphila abundancy is decreased in animals and humans with NAFLD.The recovery of A.muciniphila presented benefits in preventing hepatic fat accumulation and inflammation in NAFLD.The details of how microbes regulate hepatic immunity and lipid accumulation in NAFLD were further discussed.The modulation mechanisms by which A.muciniphila acts to improve hepatic inflammation are mainly attributed to the alleviation of inflammatory cytokines and LPS signals and the downregulation of microbiota-related innate immune cells(such as macrophages).This review provides insights into the roles of A.muciniphila in NAFLD,thereby providing a blueprint to facilitate clinical therapeutic applications.

关键词： Akkermansia muciniphila NAFLD NASH steatosis inflammation

The Development of Early Life Microbiota in Human Health and Disease

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Engineering 2022年第5期8卷 101-114页

作者： Hanying Lv Lijiang Zhang Yuqiu Han Li Wu Baohong Wang 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 310003China Center of Safety Evaluation Hangzhou Medical College(Zhejiang Academy of Medical Sciences)Hangzhou 310053China Research Units of Infectious Disease and Microecology Chinese Academy of Medical SciencesHangzhou 310003China

The colonization of the human microbiota in early life has long-lasting health implications.The status of the initial intestinal microbiota determines human growth and development from infancy to adulthood,and thus represents a crucial window in our long-term development.This review aims to summarize the latest findings on the symbiotic gut microbiota early in life and its vital role in metabolic-,allergic-,and auto-immune-disorder-related diseases,including obesity,diabetes,allergy,autism,inflammatory bowel disease,and stunting.It discusses the development process and various factors shaping the gut micro-biota,as well as the crosstalk between the gut microbiota and the host’s physiological systems(especially intestinal immune development and homeostasis,and the central nervous system in the course of neu-rodevelopment),during the early life establishment of the gut microbiota,in order to decipher the mech-anisms of diseases associated with the intestinal microbiome of early life.In addition,it examines microbiota-targeted therapeutic methods that show promising effects in treating these diseases.The true process of gut microbiome maturation,which depends on genetics,nutrition,and environmental factors,must be scrutinized in order to monitor healthy gut microbiome development and potentially correct unwanted courses by means of intervention via methods such as novel probiotics or fecal microbiota transplantation.

关键词： Microbiota Pediatric diseases Probiotics Neurodevelopment Intestinal immune development

Epidemiology and Mechanisms of Ceftazidime-Avibactam Resistance in Gram-Negative Bacteria

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Engineering 2022年第4期8卷 138-145页

作者： Tingting Xu Yuqi Guo Yang Ji Baohong Wang Kai Zhou Shenzhen Institute of Respiratory Diseases Shenzhen People’s Hospital&2nd Clinical Medical College of Jinan University&1st Affiliated Hospital of Southern University of Science and TechnologyShenzhen 518020China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases Collaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003China

Carbapenem resistance presents a major challenge for the global public health network, as clinical infections caused by carbapenem-resistant organisms(CRO) are frequently associated with significant morbidity and mortality. Ceftazidime–avibactam(CAZ–AVI) is a novel cephalosporin/β-lactamase inhibitor combination offering an important advance in the treatment of CRO infections. CAZ–AVI has been reported to inhibit the activities of Ambler classes A, C, and some class D enzymes. However, bacterial resistance has been emerging shortly after the introduction of this combination in clinical use, with an increasing trend. Understanding these resistance mechanisms is crucial for guiding the development of novel treatments and aiding in the prediction of underlying resistance mechanisms. This review aims to systematically summarize the epidemiology of CAZ–AVI-resistant strains and recently identified resistance mechanisms of CAZ–AVI, with a focus on the production of β-lactamase variants, the hyperexpression of β-lactamases, reduced permeability, and overexpressed efflux pumps. The various mechanisms of CAZ–AVI resistance that have emerged within a short timescale emphasize the need to optimize the use of current agents, as well as the necessity for the surveillance of CAZ–AVI-resistant pathogens.

关键词： Ceftazidime-avibactam Resistance mechanism Carbapenem-resistant b-lactam/b-lactamase inhibitor

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肝脏移植术后糖尿病患者肠道微生物组的变化

Engineering 2023年第12期31卷 98-111页

作者： Qi Ling Yuqiu Han Yue Ma Xiaosen wang Zheng Zhu Jingyu wang Jiaying Cao Lin Xiaohan Jun wang Baohong Wang 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 Jinan Microecological Biomedicine Shandong Laboratory Jinan 250117China Department of Surgery the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Key Lab of Combined Multi-Organ Transplantation Ministry of Public HealthHangzhou 310003China CAS Key Laboratory for Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100101China Shandong First Medical University&Shandong Academy of Medical Sciences Jinan 250117China Research Units of Infectious Disease and Microecology Chinese Academy of Medical SciencesHangzhou 310003China

Post-transplant diabetes mellitus(PTDM)increases the risk of graft failure and death in liver transplant(LT)recipients.Experimental studies have indicated that enteric dysbiosis mediated by immunosuppressive tacrolimus(TAC)could contribute to glucose disorders,but no data on human recipients with PTDM have been reported.Here,by combining high-throughput shotgun metagenomics sequencing and metabolomics profiling,we characterized the intestinal microbiome(IM)in LT recipient cohort with or without PTDM and deciphered the potential relationship among IM,TAC dosage,and diabetes.By comparing with both non-PTDM and classical type 2 diabetes mellitus(T2DM),we identified microbial signatures of PTDM,which was characterized by the enriched Proteobacteria and decreased Bacteroidetes.Additionally,the altered microbes,as well as the microbial metabolomics,correlated with the dosage of TAC.Specifically,the levels of beneficial microbes associated with PTDM were lowered in recipients with the high TAC trough concentrations(>5 ng·mL^(-1))than those with low ones(<5 ng·mL^(-1)),which was accompanied by reduced faecal metabolites involved in the biosynthesis of a-linolenic acid and arachidonic acid-lowering factors of developing T2DM.Moreover,these microbial signatures linked with the extent of glucose disorders in LT recipients.In summary,the faecal microbiome and metabolome differed between PTDM and non-PTDM patients,which were linked with TAC dosage.This study was the first to explore taxonomic alterations and bacterial gene functions to better understand the contribution of the IM to PTDM.

关键词： Post-transplant diabetes mellitus Tacrolimus Metagenomics Metabolomics

The Human Microbiota in Health and Disease

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Engineering 2017年第1期3卷 71-82页

作者： Baohong Wang Mingfei Yao Longxian Lv Zongxin Ling Lanjuan Li National Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases State Key Laboratory for Diagnosis and Treatment of Infectious Diseases The First Affiliated Hospital School of Medidne Zhejiang University Hangzhou 310003 China

Trillions of microbes have evolved with and continue to live on and within human beings. A variety of environmental factors can affect intestinal microbial imbalance, which has a close relationship with human health and disease. Here, we focus on the interactions between the human microbiota and the host in order to provide an overview of the microbial role in basic biological processes and in the development and progression of major human diseases such as infectious diseases, liver diseases, gastrointestinal cancers, metabolic diseases, respiratory diseases, mental or psychological diseases, and autoimmune diseases. We also review important advances in techniques associated with microbial research, such as DNA sequencing, metabonomics, and proteomics combined with computation-based bioinformatics.Current research on the human microbiota has become much more sophisticated and more comprehensive.Therefore, we propose that research should focus on the host-microbe interaction and on causeeffect mechanisms, which could pave the way to an understanding of the role of gut microbiota in health and disease, and provide new therapeutic targets and treatment approaches in clinical practice.

关键词：微生物健康传染病肝病胃肠道恶性肿瘤代谢紊乱微生物技术益生菌

Unusual global outbreak of monkeypox:what should we do?

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Frontiers of Medicine 2022年第4期16卷 507-517页

作者： Miaojin Zhu Jia Ji Danrong Shi Xiangyun Lu Baohong Wang Nanping Wu Jie Wu Hangping Yao Lanjuan 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 HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China Jinan Microecological Biomedicine Shandong Laboratory Jinan 250117China

Recently,monkeypox has become a global concern amid the ongoing COVID-19 pandemic.Monkeypox is an acute rash zoonosis caused by the monkeypox virus,which was previously concentrated in Africa.The re-emergence of this pathogen seems unusual on account of outbreaks in multiple nonendemic countries and the incline to spread from person to person.We need to revisit this virus to prevent the epidemic from getting worse.In this review,we comprehensively summarize studies on monkeypox,including its epidemiology,biological characteristics,pathogenesis,and clinical characteristics,as well as therapeutics and vaccines,highlighting its unusual outbreak attributed to the transformation of transmission.We also analyze the present situation and put forward countermeasures from both clinical and scientific research to address it.

关键词： monkeypox poxviruses vaccine infectious diseases

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

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Engineering 2021年第5期7卷 679-686页

作者： Mingfei Yao Lingling Qv Yanmeng Lu Baohong Wang Björn Berglund Lanjuan Li State Key Laboratory for Diagnosis and Treatment of Infectious Disease National Clinical Research Center for Infectious DiseaseCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003China Department of Clinical and Experimental Medicine Linköping UniversityLinköping SE 58183Sweden

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.

关键词： Non-alcoholic fatty liver disease(NAFLD) Gut microbiota Probiotics Next-generation probiotics(NGPs)

Gut Microbiota-Controlled Tryptophan Metabolism Improves D-Gal/LPS-Induced Acute Liver Failure in C57BL/6 Mice

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Engineering 2022年第7期8卷 134-146页

作者： Zhipeng Zheng Li Wu Yuqiu Han Jun Chen Shuai Zhu Yuanyuan Yao Baohong Wang Lanjuan 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 310003China

Acute liver failure(ALF)has an abrupt onset with a frequently fatal outcome.Previous studies have found that oral antibiotics prevent drug-induced liver injury in animal experiments,indicating that the gut microbiota plays a critical role in the pathophysiological process.However,the underlying mechanism has not been fully understood.This study explored the comprehensive role of the gut microbiota in ALF using multi-omics.A cocktail of broad-spectrum antibiotics(Abx)pretreatment by gavage for four weeks improved the survival of D-(+)-galactosamine hydrochloride(D-Gal)/lipopolysaccharide(LPS)-induced ALF in C57BL/6 mice.RNA sequencing showed that inflammatory responses were inhibited and metabolic pathways were upregulated in the liver of Abx-treated ALF mice.The 16S rRNA gene sequencing revealed that Abx reshaped the composition and function of the gut microbiota,with an increased proportion of tryptophan(Trp)metabolism.In addition,global metabolic profiling by ultraperformance liquid chromatography–mass spectrometry(UPLC–MS)indicated that the gut microbiota post-Abx intervention reduced Trp excretion,liberated more Trp to the host,and enhanced the kynurenine(Kyn)pathway with increased production of Kyn.As an endogenous aryl hydrocarbon receptor(AhR)ligand,Kyn has anti-inflammatory and immunosuppressive effects.Furthermore,AhR-targeted treatments affected the outcome of ALF mice with or without Abx pretreatment,indicating that AhR directly regulated susceptibility to ALF,at least in part.This study demonstrates that the gut microbiota-dependent control of the Trp metabolism could regulate host susceptibility to ALF by modulating the activity of AhR,and thus provides a promising target for better management of ALF.

关键词： Gut microbiota Antibiotic Tryptophan Kynurenine Aryl hydrocarbon receptor Acute liver failure

Joint Limiting Control Strategy Based on Virtual Impedance Shaping for Suppressing DC Fault Current and Arm Current in MMC-HVDC Systems

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Journal of Modern Power Systems and Clean Energy 2023年第6期11卷 2003-2014页

作者： Qin Jiang Yan Tao baohong Li Tianqi Liu Zhe Chen Frede Blaabjerg Peng wang IEEE College of Electrical Engineering Sichuan UniversityChengdu 610065China Smart Grid Key Laboratory of Sichuan Province Chengdu610065China State Grid Jiangsu Electric Power Company Research Institute Nanjing 211103China Department of Energy Technology Aalborg UniversityAalborg 9920Denmark School of Electrical and Electronic Engineering Nanyang Technological UniversitySingapore 639798Singapore

This paper proposes a joint limiting control strategy for suppressing DC fault current and arm current in modular multilevel converter-based high-voltage direct current(MMC-HVDC) systems, which includes two target-oriented current limiting controls. To limit the DC fault current in the early fault stage, an equivalent modular multilevel converter(MMC) impedance is obtained, and its high-frequency part is reshaped by introducing virtual impedance, which is realized by adjusting the inserted submodules adaptively. Following the analysis of MMC control characteristics, the arm current limiting strategy is investigated, with results showing that the inner-loop control has significant effects on arm current and that a simple low-pass filter can reduce the arm current in the fault period. Finally, by combining the virtual impedance shaping and innerloop control, the fault currents of DC lines and MMC arms can be suppressed simultaneously, which can not only alleviate the interrupting pressure of the DC circuit breaker, but also prevent the MMC from being blocked by the arm overcurrent. Theoretical analysis conclusions and the proposed strategy are verified offline by a digital time-domain simulation on Power Systems Computer Aided Design/Electromagnetic Transients including DC platform, and experiment on a real-time digital simulator platform.

关键词： Modular multilevel converter(MMC) highvoltage direct current(HVDC)transmission direct current fault fault current limitation arm current suppression virtual impedance direct current circuit breaker

Temporal and spatial distribution characteristics of nutrients in Clarion-Clipperton Fracture Zone in the Pacific in 2017

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Acta Oceanologica Sinica 2022年第1期41卷 1-10页

作者： baohong Chen Kaiwen Zhou Kang wang Jigang wang Sumin wang Xiuwu Sun Jinmin Chen Cai Lin Hui Lin Third Institute of Oceanography Ministry of Natural ResourceXiamen 361005China Institute for Advanced Ocean Study Ocean University of ChinaQingdao 266003China

This research investigated eight stations in Clarion-Clipperton Fracture Zone(CCFZ)in the eastern tropical Pacific in 2017 to study the spatial distribution characteristics of nutrients and chlorophyll a(Chi a)concentration,and compared nutrient concentrations and molar ratios with those of other investigations 20 years ago in the same area.The study found that dissolved inorganic nutrient(N,P and Si)concentrations were lowest in the upper layer,and increased from surface to some depths,then they decreased a little to the bottom.N was the limited nutrient factor for the growth of phytoplankton community.Although nutrient concentrations and molar ratios have no obvious changes in 2017 comparing those in 1998-2003,supplemented from the equatorial Pacific,nutrient concentrations in the study area were higher than those in seamounts in the North Pacific and Station ALOHA.Furthermore,this study used Generalized Additive Models(GAMs)to infer the underlying bottom-up factors controlling phytoplankton abundance(Chi a concentration),showing that depth,salinity and PO^-P concentration were major factors controlling the growth of phytoplankton community.Furthermore,this study can provide basic data and theoretical support for the development of polymetallic nodule area and its long-term impact assessment on the environment.

关键词： nutrients Chla GAMs CCFZ Pacific