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International Journal of Clinical Medicine 2011年第1期2卷 18-22页

作者： Takashi Saito Tatsuo Ichinohe Junya Kanda Miki Nagao Shunji Takakura Yutaka Ito Yoshitsugu Iinuma Kouhei Yamashita Tadakazu Kondo Takayuki Ishikawa Takashi Uchiyama Satoshi Ichiyama Department of Infection Control and Prevention Kyoto University Hospital department of Hematology and Oncology Kyoto University Hospital Department of Infection Control and Prevention Shiga Medical Center for Adults

We retrospectively evaluated the efficacy and safety of the combination drug piperacillin/tazobactam (PIPC/TAZ) in comparison with those of fourth-generation cephalosporins (4th Cephs) as initial empirical treatment in hematological malignancies patients with febrile neutropenia (FN). Among 200 patients assessed in this study, 49 had received PIPC/TAZ and 151 4th Cephs. Patient background characteristics were comparable between the two treatment groups. The overall efficacy rate in those receiving 4th Cephs and PIPC/TAZ was 57.0% (86/151 patients) and 59.2% (29/49 patients), respectively, with no significant difference detected between the two treatment regimens (P = 0.78). Treat-ment did not need to be discontinued or interrupted due to development of adverse drug reactions in any of the patients. Therefore in this study the efficacy and safety of PIPC/TAZ as initial antimicrobial treatment for FN in patients with hematological malignancies were not inferior to those of 4th Cephs. Based on the preliminary data obtained in this study, we propose to conduct a multicenter, prospective, controlled study to compare PIPC/TAZ versus CFPM given as empirical antimicrobial treatment against FN in patients with hematological malignancies.

关键词： Febrile Neutropenia Piperacillin/Tazobactam Fourth-Generation Cephalosporins Safety Efficacy

Schistosoma japonicum attenuates dextran sodium sulfateinduced colitis in mice via reduction of endoplasmic reticulum stress

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World Journal of Gastroenterology 2017年第31期23卷 5700-5712页

作者： Ya Liu Qing Ye Yu-Lan Liu Jian Kang Yan Chen Wei-Guo Dong department of Gastroenterology Key Laboratory of Hubei Province for Digestive System DiseaseRenmin Hospital of Wuhan University department of Hospital infection Renmin Hospital of Wuhan University departments of Critical Care Medicine Renmin Hospital of Wuhan University

AIM To elucidate the impact of Schistosoma(S.) japonicum infection on inflammatory bowel disease by studying the effects of exposure to S. japonicum cercariae on dextran sodium sulfate(DSS)-induced colitis. METHODS infection was percutaneously established with 20 ± 2 cercariae of S. japonicum, and colitis was induced by administration of 3% DSS at 4 wk post infection. Weight change, colon length, histological score(HS) and disease activity index(DAI) were evaluated. Inflammatory cytokines, such as IL-2, IL-10 and IFN-γ, were tested by a cytometric bead array and real-time quantitative polymerase chain reaction(RT-PCR). Protein and m RNA levels of IRE1α, IRE1β, GRP78, CHOP, P65, P-P65, P-IκBα and IκBα in colon tissues were examined by Western blot and RT-PCR, respectively. Terminal deoxynucleotidyl transferase-mediated d UTP nick-end labeling positive cells, cleaved-caspase 3 expression and Bcl2/Bax were investigated to assess the apoptosis in colon tissues.RESULTS Mice infected with S. japonicum cercariae were less susceptible to DSS. Mice infected with S. japonicum cercariae and treated with DSS showed decreased weight loss, longer colon, and lower HS and DAI compared with mice treated with DSS alone. A substantial decrease in Th1/Th2/Th17 response was observed after infection with S. japonicum. Endoplasmic reticulum(ER) stress and the nuclear factor-kappa B(NF-κB) pathway were reduced in mice infected with S. japonicum cercariae and treated with DSS, along with ameliorated celluar apoptosis, in contrast to mice treated with DSS alone. CONCLUSION Exposure to S. japonicum attenuated inflammatory response in a DSS-induced colitis model. In addition to the Th1/Th2/Th17 pathway and NF-κB pathway, ER stress was shown to be involved in mitigating inflammation and decreasing apoptosis. Thus, ER stress is a new aspect in elucidating the relationship between helminth infection and inflammatory bowel disease(IBD), which may offer new therapeutic methods for IBD.

关键词： Endoplasmic reticulum stress Schistosoma japonicum Colitis

Recent advances in understanding T cell activation and exhaustion during HBV infection

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Virologica Sinica 2023年第6期38卷 851-859页

作者： Lu Wang Xiaoqing Zeng Zida Wang Ling Fang Jia Liu department of Infectious Diseases Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China Joint International Laboratory of infection and Immunity Huazhong University of Science and TechnologyWuhan430022China Central Sterile Supply department Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430022China

Chronic hepatitis B virus(HBV)infection remains a major public health concern globally,and T cell responses are widely believed to play a pivotal role in mediating HBV clearance.Accordingly,research on the characteristics of HBV-specific T cell responses,from activation to exhaustion,has advanced rapidly.Here,we summarize recent developments in characterizing T cell immunity in HBV infection by reviewing basic and clinical research published in the last five years.We provide a comprehensive summary of the mechanisms that induce effective anti-HBV T cell immunity,as well as the latest developments in understanding T cell dysfunction in chronic HBV infection.Furthermore,we briefly discuss current novel treatment strategies aimed at restoring anti-HBV T cell responses.

关键词： Hepatitis B virus(HBV) T cell Immune therapy

Simvastatin inhibits apoptosis of endothelial cells induced by sepsis through upregulating the expression of Bcl-2 and downregulating Bax

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World Journal of Emergency Medicine 2014年第4期5卷 291-297页

作者： Hui Fu Qiao-sheng Wang Qiong Luo Si Tan Hua Su Shi-lin Tang Zheng-liang Zhao Li-ping Huang department of Critical Care Medicine First Affi liated Hospital of University of South China Department of Infection Third Hospital of Hengyang City

BACKGROUND: Many studies have showed that apoptosis of endothelial cells plays a curial role in the progress of sepsis. But the role of simvastatin in apoptosis of endothelial cells induced by sepsis is not clear. The present study aimed to investigate the role of simvastatin in apoptosis of endothelial cells induced by sepsis and its mechanism.METHODS: Human umbilical vein endothelial cells(HUVECs) were randomly divided into three groups: control group, sepsis serum intervention group(sepsis group) and simvastatin+sepsis serum intervention group(simvastatin group). After 24-hour incubation with corresponding culture medium, the relative growth rate of HUVECS in different groups was detected by MTT assay; the apoptosis of HUVECs was detected by Hoechst33258 assay and fl ow cytometry; and the expression of the Bcl-2 and Bax genes of HUVECs was detected by PCR.RESULTS: Compared with the sepsis group, HUVECs in the simvastatin group had a higher relative growth rate. Apoptotic HUVECs decreased significantly in the simvastatin group in comparison with the sepsis group. Expression of the Bcl-2 gene in HUVECs decreased obviously, but the expression of the Bax gene increased obviously after 24-hour incubation with sepsis serum; however, the expression of the Bcl-2 and Bax genes was just the opposite in the simvastatin group.CONCLUSIONS: Our study suggests that simvastatin can inhibit apoptosis of endothelial cells induced by sepsis through upregulating the expression of Bcl-2 and downregulating Bax. It may be one of the mechanisms for simvastatin to treat sepsis.

关键词： Simvastatin Sepsis Endothelial cells Apoptosis Bcl-2 gene Bax gene

Dickkopf-1 has an Inhibitory Effect on Mesenchymal Stem Cells to Fibroblast Differentiation

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Chinese Medical Journal 2016年第10期129卷 1200-1207页

作者： Yan Li Sang-Sang Qiu Yan Shao Hong-Huan Song Gu-Li Li Wei Lu Li-Mei Zhu department of Chronic Communicable Disease Jianqsu Provincial Center for Disease Prevention and Control Nanjing Jiangsu 210009 China Department of Infection Management Affiliated Wuxi People's Hospital to Nanjing Medical University Wuxi Jiangsu 214023 China

Background： Mesenchymal stem cells （MSCs） are bone marrow stem cells which play an important role in tissue repair. The treatment with MSCs will be likely to aggravate the degree of fibrosis. The Wnt/β-catenin signaling pathway is involved in developmental and physiological processes, such as fibrosis. Dickkopfs （DKKs） are considered as an antagonist to block Wnt/β-catenin signaling pathway by binding the receptor of receptor-related protein （LRP5/6）. DKK1 was chosen in attempt to inhibit fibrosis of MSCs by lowering activity of Wnt/β-catenin signaling pathway. Methods： Stable MSCs were randomly divided into four groups： MSCs control, MSCs ＋ transforming growth factor-β （TGF-β）, MSCs ＋ DKK1, and MSCs ＋ TGF-β ＋ DKK1. Flow cytometry was used to identify MSCs. Cell viability was evaluated by 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide test. lmmunofluorescence was used to detect protein expression in the Wnt/β-catenin signaling pathways. Western blotting analysis was employed to test expression of fibroblast surface markers and, finally, real-time reverse transcription polymerase chain reaction was employed to test mRNA expression offibroblast surface markers and Wnt/β-catenin signaling proteins. Results： Cultivated MSCs were found to conform to the characteristics of standard MSCs： expression of cluster of differentiation （CD） 73, 90, and 105, not expression of 34, 45, and 79. We found that DKK1 could maintain the normal cell morphology of MSCs. Western blotting analysis showed that fibroblast surface markers were expressed in high quantities in the group MSCs ＋ TGF-β. However, the expression was lower in the MSCs ＋ TGF-β ＋ DKK1. Immunofluorescence showed high expression of all Wnt/β-catnin molecules in the MSCs ＋ TGF-β group but expressed in lower quantities in MSCs ＋ TGF-β ＋ DKK1 group. Finally, mRNA expression of fibroblast markers vimentin, α-smooth muscle actin and Wnt/β-catenin signaling proteins β-catenin, T-cell factor, and glycogen synthase kinase-3β was significantly increased in MSCs

关键词： Dickkopfs-1 Fibrosis Mesenchymal Stem Cells Wnt/β-catenin Signaling Pathway

Does Hospital Ownership Influence Hand Hygiene Compliance?

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2017年第5期37卷 787-794页

作者：叶丽萍张新平赖晓全 School of Medicine and Health Management Tongji Medical College Huazhong University of Science and Technology department of Nosocomial infection Tongji Hospital Tongji Medical College Huazhong University of Science and Technology

The issue as to whether hospital ownership has an impact on the quality of care has long been a serious concern. Hand hygiene（HH） compliance is regarded as an important indicator of the quality of care in the control of hospital-acquired infections. However, little information is available on whether hospital ownership influences HH compliance. In this study, of 229 hospitals selected from Hubei province in China, 152 were public and 77 were private hospitals. A total of 23 652 healthcare workers（HCWs） were surveyed, using a convenience sampling. HH compliance, the WHO＇s ＂My Five Moments for hand hygiene＂（5 MHH）, among HCWs, together with the factors of hospital ownership, training frequency, bed occupancy rates, etc. were collected. Univariate analysis and ordinal logistic regression analysis were used to analyze factors affecting HH compliance. Overall, HH compliance rates were 67% and 79% for public and private hospitals, respectively. The HH compliance rates of HCWs and 5 MHH were between 55% and 95%, and influenced by hospital ownership（P〈0.05）, excluding compliance rate at the moment after body fluid exposure, and other influence factors included training frequency and bed occupancy rate（P〈0.05）. HH compliance is better in private than in public hospitals. Hospital ownership is a significant factor affecting HH compliance, in addition to training frequency and bed occupancy rate.

关键词： hospital ownership hand hygiene compliance influence factors ordinal logistic regression analysis

An unprecedented outbreak investigation for nosocomial and community-acquired legionellosis in Hong Kong

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Chinese Medical Journal 2012年第23期125卷 4283-4290页

作者： CHENG Vincent Chi-chung WONG Samson Sai-yin CHEN Jonathan Hon-kwan CHAN Jasper Fuk-woo TO Kelvin Kai-wang POON Rosana Wing-shan WONG Sally Cheuk-ying CHAN Kwok-hung TAI Josepha Wai-ming HO Pak-leung TSANG Thomas Ho-fai YUEN Kwok-yung department of Microbiology Queen Mary Hospital Hong Kong China infection Control Team Queen Mary Hospital Hong Kong China Centre for Health Protection Department of Health Hong Kong China

Background The environmental sources associated with community-acquired or nosocomial legionellosis were not always detectable in the mainland of China and Hong Kong, China. The objective of this study was to illustrate the control measures implemented for nosocomial and community outbreaks of legionellosis, and to understand the environmental distribution of legionella in the water system in Hong Kong, China. Methods We investigated the environmental sources of two cases of legionellosis acquired in the hospital and the community by extensive outbreak investigation and sampling of the potable water system using culture and genetic testing at the respective premises. Results The diagnosis of nosocomial legionellosis was suspected in a patient presenting with nosocomial pneumonia not responsive to multiple beta-lactam antibiotics with subsequent confirmation by Legionella pneumophila serogroup 1 antigenuria. High counts of Legionella pneumophila were detected in the potable water supply of the 70-year-old hospital building. Another patient on continuous ambulatory peritoneal dialysis presenting with acute community-acquired pneumonia and severe diarrhoea was positive for Legionella pneumophila serogroup 1 by polymerase chain reaction （PCR） testing on both sputum and nasopharyngeal aspirate despite negative antigenuria. Paradoxically the source of the second case was traced to the water system of a newly commissioned office building complex. No further cases were detected after shock hyperchlorination with or without superheating of the water systems. Subsequent legionella counts were drastically reduced. Point-of-care infection control by off-boiled or sterile water for mouth care and installation of water filter for showers in the hospital wards for immunocompromised patients was instituted. Territory wide investigation of the community potable water supply showed that 22.1% of the household water supply was positive at a mean legionella count of 108.56 CFU/ml （range 0.10 to 639.30 CFU/ml）. Conclusions Potable wa

关键词： outbreak nosocomial legionellosis community-acquired legionellosis

Spontaneous modulation of a dynamic balance between bacterial genomic stability and mutability: roles and molecular mechanisms of the genetic switch

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Science China(Life Sciences) 2014年第3期57卷 275-279页

作者： TANG Le LIU RuoWei JIN Gang ZHAO ErYing LIU GuiRong LIU ShuLin Genomics Research Center Harbin Medical University department of Biopharmaceutics Harbin Medical University HMU-UCFM Center for infection and Genomics Harbin Medical University department of Microbiology and Infectious Diseases University of Calgary

Bacteria need a high degree of genetic stability to maintain their species identities over long evolutionary times while retaining some mutability to adapt to the changing environment.It is a long unanswered question that how bacteria reconcile these seemingly contradictory biological properties.We hypothesized that certain mechanisms must maintain a dynamic balance between genetic stability and mutability for the survival and evolution of bacterial species.To identify such mechanisms,we analyzed bacterial genomes,focusing on the Salmonella mismatch repair(MMR)system.We found that the MMR gene mutL functions as a genetic switch through a slipped-strand mispairing mechanism,modulating and maintaining a dynamic balance between genetic stability and mutability during bacterial evolution.This mechanism allows bacteria to maintain their phylogenetic status,while also adapting to changing environments by acquiring novel traits.In this review,we outline the history of research into this genetic switch,from its discovery to the latest findings,and discuss its potential roles in the genomic evolution of bacteria.

关键词：细菌基因组遗传稳定性分子机制基因开关可变性平衡系统发育地位错配修复

Human umbilical cord-derived mesenchymal stem cell therapy in patients with COVID-19:a phase 1 clinical trial

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1010-1016页

作者： Fanping Meng Ruonan Xu Siyu Wang Zhe Xu Chao Zhang Yuanyuan Li Tao Yang Lei Shi Junliang Fu Tianjun Jiang Lei Huang Peng Zhao Xin Yuan Xing Fan Ji-Yuan Zhang Jinwen Song Dawei Zhang Yanmei Jiao Limin Liu Chunbao Zhou Markus Maeurer Alimuddin Zumla Ming Shi Fu-Sheng Wang department of Infectious Diseases Fifth Medical Center of Chinese PLA General HospitalNational Clinical Research Center for Infectious DiseasesBeijingChina Immunotherapy Programme Champalimaud Centre for the UnknownLisbonPortugal I Med Clinic University of MainzMainzGermany Department of Infection Division of Infection and ImmunityUniversity College LondonLondonUK National Institute for Health Research Biomedical Research Centre University College London Hospitals NHS Foundation TrustLondonUK

No effective drug treatments are available for coronavirus disease 2019(COVID-19).Host-directed therapies targeting the underlying aberrant immune responses leading to pulmonary tissue damage,death,or long-term functional disability in survivors require clinical evaluation.We performed a parallel assigned controlled,non-randomized,phase 1 clinical trial to evaluate the safety of human umbilical cord-derived mesenchymal stem cells(UC-MSCs)infusions in the treatment of patients with moderate and severe COVID-19 pulmonary disease.The study enrolled 18 hospitalized patients with COVID-19(n=9 for each group).The treatment group received three cycles of intravenous infusion of UC-MSCs(3×107 cells per infusion)on days 0,3,and 6.Both groups received standard COVID-treatment regimens.Adverse events,duration of clinical symptoms,laboratory parameters,length of hospitalization,serial chest computed tomography(CT)images,the PaO2/FiO2 ratio,dynamics of cytokines,and IgG and IgM anti-SARS-CoV-2 antibodies were analyzed.No serious UC-MSCs infusion-associated adverse events were observed.Two patients receiving UC-MSCs developed transient facial flushing and fever,and one patient developed transient hypoxia at 12 h post UC-MSCs transfusion.Mechanical ventilation was required in one patient in the treatment group compared with four in the control group.All patients recovered and were discharged.Our data show that intravenous UC-MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated.Phase 2/3 randomized,controlled,double-blinded trials with long-term follow-up are needed to evaluate the therapeutic use of UC-MSCs to reduce deaths and improve long-term treatment outcomes in patients with serious COVID-19.

关键词： patients infusion clinical