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TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization

Neuroscience Bulletin 2024年第1期40卷 17-34页

作者： Siying Qu Shengfeng Hu Huiting Xu Yongjian Wu Siqi Ming Xiaoxia Zhan Cheng Wang Xi Huang Center for Infection and Immunity and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000China The State Key Laboratory of Respiratory Disease Guangdong Provincial Key Laboratory of Allergy and Clinical ImmunologyThe Second Affiliated HospitalGuangzhou Medical UniversityGuangzhou 510260China Department of Laboratory Medicine The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Division of Nephrology Department of Medicinethe Fifth Affliated Hospital of Sun Yat-sen UniversityZhuhai 519000China

Multiple sclerosis(MS)is a neuroinflammatory demyelinating disease,mediated by pathogenic T helper 17(Th17)***,the therapeutic effect is accompa-nied by the fluctuation of the proportion and function of Th17 cells,which prompted us to find the key regulator of Th17 differentiation in ***,we demonstrated that the triggering receptor expressed on myeloid cells 2(TREM-2),a modulator of pattern recognition receptors on innate immune cells,was highly expressed on pathogenic CD4-positive T lymphocyte(CD4^(+)T)cells in both patients with MS and experimental autoimmune encephalomyelitis(EAE)mouse *** knockout of Trem-2 in CD4^(+)T cells significantly alleviated the disease activity and reduced Th17 cell infiltration,activation,differentiation,and inflammatory cytokine production and secretion in EAE ***,with Trem-2 knockout in vivo experiments and in vitro inhibitor assays,the TREM-2/zeta-chain associated protein kinase 70(ZAP70)/signal transducer and activator of transcription 3(STAT3)signal axis was essential for Th17 activation and differentiation in EAE *** conclusion,TREM-2 is a key regulator of pathogenic Th17 in EAE mice,and this sheds new light on the potential of this therapeutic target for MS.

关键词： Multiple sclerosis Experimental autoimmune encephalomyelitis T helper 17 Triggering receptor expressed on myeloid cells 2

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Cost-Effectiveness Analysis of Combined Chemotherapy Regimen Containing Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis in china

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Biomedical and Environmental Sciences 2023年第6期36卷 501-509页

作者： XU Cai Hong QIU Ying Peng HE Zi Long HU Dong Mei YUE Xiao CHEN Zhong Dan XU Yuan Yuan ZHAO Yan Lin national Center for Tuberculosis Control and Prevention China CDCBeijing 100226China china national Health Development Research Center Beijing 100226China The University of Sheffield S102TNSheffieldThe United Kingdom The Central South University Changsha 410083HunanChina World Health Organization Representative Office for china Beijing 100600China

Objective This study aims to estimate the cost-effectiveness of the combined chemotherapy regimen containing Bedaquiline(BR)and the conventional treatment regimen(CR,not containing Bedaquiline)for the treatment of adults with multidrug-resistant tuberculosis(MDR-TB)in *** A combination of a decision tree and a Markov model was developed to estimate the cost and effects of MDR patients in BR and CR within ten *** model parameter data were synthesized from the literature,the national TB surveillance information system,and consultation with *** incremental cost-effectiveness ratio(ICER)of BR *** was *** BR(***)had a higher sputum culture conversion rate and cure rate and prevented many premature deaths(decreased by 12.8%),thereby obtaining more quality-adjusted life years(QALYs)(increased by 2.31 years).The per capita cost in BR was as high as 138,000 yuan,roughly double that of *** ICER for BR was 33,700 yuan/QALY,which was lower than china's 1×per capita Gross Domestic Product(GDP)in 2020(72,400 yuan).Conclusion BR is shown to be cost *** the unit price of Bedaquiline reaches or falls below57.21 yuan per unit,BR is expected to be the dominant strategy in china over CR.

关键词： Bedaquiline Cost-effectiveness Multidrug-resistant tuberculosis china

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Early assessment of the safety and immunogenicity of a third dose(booster)of COVID-19 immunization in Chinese adults

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Frontiers of Medicine 2022年第1期16卷 93-101页

作者： Yuntao Zhang Yunkai Yang Niu Qiao Xuewei Wang Ling Ding Xiujuan Zhu Yu Liang Zibo Han Feng Liu Xinxin Zhang Xiaoming Yang china national Biotec Group Company Limited Beijing 100024China Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Beijing Institute of Biological Products China National Biotec Group Company LimitedBeijing 100176China national Vaccine and Serum Institute China National Biotec Group Company LimitedBeijing 101111China Department of infectious diseases Research Laboratory of Clinical VirologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China

Inducing durable and effective immunity against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)via vaccination is essential to combat the current pandemic of coronavirus disease 2019(COVID-19).It has been noticed that the strength of anti-COVID-19 vaccination-induced immunity fades over time,which calls for an additional vaccination regime,as known as booster immunization,to restore immunity among previously vaccinated *** we report a pilot open-label trial of a third dose of BBIBP-CorV,an inactivated SARS-CoV-2 vaccine(Vero cell),on 136 participants aged between 18 to 63 *** and immunogenicity in terms of neutralizing antibody titers and cytokine/chemokine responses were analyzed as the main endpoint until day *** systemic reactogenicity was either absent or mild,SARS-CoV-2-specific neutralizing antibody titers rapidly arose in all participants within 4 weeks,surpassing the peak antibody titers elicited by the initial two-dose immunization *** increases of cellular immunity-associated cytokines and chemokines were also detected in the majority of participants after the third ***,in an exploratory study,a newly developed recombinant protein vaccine,NVSI-06-08(CHO Cells),was found to be safe and even more effective than BBIBP-CorV in eliciting humoral immune responses in BBIBP-CorV-primed ***,these results indicate that a third immunization schedule with either homologous or heterologous vaccine showed favorable safety profiles and restored potent SARS-CoV-2-specific immunity,providing support for further trials of booster vaccination in larger populations.

关键词： COVID-19 SARS-CoV-2 vaccine immunization booster immunization

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miR-146a negatively regulates NK cell functions via STAT1 signaling

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Cellular & Molecular Immunology 2017年第8期14卷 712-720页

作者： Dongqing Xu Qiuju Han Zhaohua Hou Cai Zhang Jian Zhang Institute of Immunopharmaceutical Sciences School of Pharmaceutical SciencesShandong UniversityJinan 250012China

It is known that natural killer(NK)cell function is downregulated in chronic hepatitis B(CHB)-infected patients and in hepatic carcinoma(HCC)patients,but the mechanisms underlying this functional downregulation are largely *** this study,microRNA(miR)-146a expression increased in NK cells from CHB and HCC patients compared with NK cells from healthy donors,and miR-146a levels were negatively correlated to NK cell *** of miR-146a reduced NK cell-mediated cytotoxicity and the production of interferon(IFN)-γand tumor necrosis factor-α,which were reversed upon inhibition of *** NK cells,miR-146a expression was induced by interleukin(IL)-10 and transforming growth factor-β,but reduced after treatment with interleukin-12,IFN-αand IFN-β.We further revealed that miR-146a regulated NK cell functions by targeting *** together,upregulated miR-146a expression,at least partially,attributes to NK cell dysfunction in CHB and HCC ***,miR-146a may become a therapeutic target with great potential to ameliorate NK cell functions in liver disease.

关键词： CHB HCC miR-146a natural killer cells STAT1

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Soluble interleukin-6 receptor is elevated during influenza A virus infection and mediates the IL-6 and IL-32 inflammatory cytokine burst

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Cellular & Molecular Immunology 2015年第5期12卷 633-644页

作者： Jun Wang Qing Wang Tao Han Yong-Kui Li Sheng-Li Zhu Fang Ao Jian Feng Ming-Zhen Jing Li Wang Lin-Bai Ye Ying Zhu The State Key Laboratory of Virology College of Life Sciences Wuhan University Wuhan China

Influenza A virus （IAV） infection is a major worldwide public health problem. However, the factors involved in mediating the inflammatory response to this infection and their relationships remain poorly understood. Here, we show that IAV infection stimulates the expression of the soluble IL-6 receptor （slL-6R）, a multifunctional protein involved in IL-6 signaling. Interestingly, slL-6R expression upregulated the levels of its own ligand, IL-6 and those of the pro-inflammatory cytokine IL-32. shRNA-mediated knockdown of slL-6R suppressed I L-6 and IL-32, indicating that this regulation is dependent on slL-6R during IAV infection. Furthermore, our results demonstrate that IL-32 participates in a negative feedback loop that inhibits slL-6R while upregulating IL-6 expression during IAV infection. Therefore, we show that slL-6R is a critical cellular factor involved in the acute inflammatory response to viral infection.

关键词： IL-32 IL-6 inflammation network influenza A virus soluble IL-6 receptor

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Prevalence,Incidence,and Characteristics of Tuberculosis Among Known Diabetes Patients—A Prospective Cohort Study in 10 Sites,2013–2015

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china CDC weekly 2022年第3期4卷 41-46页

作者： Jun Cheng Yanling Yu Qiongjin Ma Zhijian Wang Qingrong Zhou Guolong Zhang Shuangyi Hou Lin Zhou Feiying Liu Lan Xia Lin Xu Canyou Zhang Yinyin Xia Hui Chen Hui Zhang Lixia Wang national Center for Tuberculosis Control and Prevention China CDCBeijingChina Heilongjiang Provincial Center for Disease Control and Prevention HarbinHeilongjiangChina Minhang District Center for Disease Control and Prevention ShanghaiChina Center for Disease Control and Prevention of Danyang County DanyangJiangsuChina Center for Disease Control and Prevention of Jiangshan city JiangshanZhejiangChina Henan Provincial Center for Disease control and prevention ZhengzhouHenanChina Hubei Provincial Center for Disease Control and Prevention WuhanHubeiChina Center for Tuberculosis Control of Guangdong Province GuangzhouGuangdongChina Guangxi Center for Disease Prevention and Control NanningGuangxi Zhuang Autonomous RegionChina Sichuan Provincial Center for Disease Control and Prevention ChengduSichuanChina Yunnan Provincial Center for Disease Control and Prevention KunmingYunnanChina

Summary What is already known about this topic?The association of diabetes mellitus(DM)with both increased risk of tuberculosis(TB)and unfavorable treatment outcomes has been identified by many studies(1).However,epidemic data for TB cases in DM patients is absent in *** is added by this report?This current population-based prospective cohort study,conducted in ten counties located in eastern,central,and western china during 2013–2015,revealed a high prevalence and incidence of TB in known DM *** TB cases were captured by active case-finding and a much higher presence of being asymptomatic among TB/DM patients was *** are the implications for public health practice?Active case-finding should be carried out in DM patients and populations at high risk for developing TB.A TB symptom screening-based case-finding strategy is not enough;chest radiography check should be done once a year for these patients.

关键词： finding Diabetes Patients

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Knowledge and Use of Personal Protective Measures for Mitigating Acute Respiratory Infections in Children 6-16 Years of Age in Rural Communities of Macheng City,Hubei,china

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Biomedical and Environmental Sciences 2022年第10期35卷 968-975页

作者： CHEN Yue ZHAN Jian Bo DONG Shao Bo LU Jian GUO Jun Feng FAN Jin Song GE Jing LIN Xiao Jing LAN Yu QIN Kun HU Bing ZHOU Jian Fang XU Cui Ling Chinese national Influenza Center National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionKey Laboratory for Medical VirologyKey Laboratory for Medical VirologyNational Health and Family Planning CommissionBeijing 102206China Hubei Provincial Center for Disease Control and Prevention Wuhan 430079HubeiChina Macheng City Center for Disease Control and Prevention Macheng 438399HubeiChina

Acute respiratory infections are the most common illnesses experienced by people of all ages *** epidemiologic studies have shown that viruses cause most of these acute respiratory illnesses[1].

关键词： Acute respiratory acute

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Hepatocellular carcinoma: Mechanisms of progression and immunotherapy

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World Journal of Gastroenterology 2019年第25期25卷 3151-3167页

作者： Yu Jiang Qiu-Ju Han Jian Zhang Institute of Immunopharmaceutical Sciences School of Pharmaceutical SciencesShandong University

Liver cancer is one of the most common malignancies,and various pathogenic factors can lead to its occurrence and *** all primary liver cancers,hepatocellular carcinoma(HCC)is the most *** extensive studies,an increasing number of molecular mechanisms that promote HCC are being *** resection is still the most effective treatment for patients with early ***,early detection and treatment are difficult for most HCC patients,and the postoperative recurrence rate is high,resulting in poor clinical prognosis of *** immunotherapy takes longer than conventional chemotherapy to produce therapeutic effects,it persists for *** recent years,the emergence of many new immunotherapies,such as immune checkpoint blockade and chimeric antigen receptor T cell therapies,has given new hope for the treatment of HCC.

关键词： Hepatocellular carcinoma Mechanisms Immunotherapy

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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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The substitution V379I in PA protein attenuates the pathogenicity of influenza A(H1N1)pdm09 viruses in mice

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Science china(Life Sciences) 2017年第9期60卷 1044-1046页

作者： Yongkun Chen Wenfei Zhu Tian Bai Xiaohui Zou Siyu Zhang Yan Sun Xiyan Li XingyYu Xiang Qinglong Zhao Chaoyang Huang Tao Chen Dayan Wang Yuelong Shu national Institute for Viral Disease Control and Prevention Collaboration Innovation Center for Diagnosis and Treatment of Infectious DiseasesChinese Center for Disease Control and PreventionKey Laboratory for Medical VirologyNational Health and Family Planning CommissionBeifing 102206China Hunan Provincial Center for Disease Control and Prevention Changsha 410005China Changsha Central Hospital Changsha 410004China Jilin Provincial Center for Disease Control and Prevention Changchun 130062China

Dear Editor,Since August 2010,the world was in the post-pandemic period and the influenza A（H1N1）pdm09（pdmH1N1）virus co-circulated with H3N2 and B virus seasonally（WHO,2010）.The continuous surveillance on the pdmH1N1 virus in the post-pandemic period was recommended by *** order to detect unusual events that might indicate a shift in severity disease,or emergence of a new virus,we collected a total of 312 throat swabs of laboratory-confirmed pdmHlNl patients from Hunan and Jilin provinces in china during January to March, 2016. Amongst them, 212 were influenza-like illness （ILI） outpatients while the remaining 100 were hospitalized patients.

关键词： B病毒流感甲型致病性 A蛋白小鼠流行季节住院病人

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