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Voice from China:nomenclature of the novel coronavirus and related diseases

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Chinese Medical Journal 2020年第9期133卷 1012-1014页

作者： Gui-Zhen Wu jian-Wei Wang xu jian-qing Asian-Pacific Biosafety Association Chinese Center for Disease Control and Prevention Research Center in National Institute for Viral Disease Control and Prevention Chinese Academy of Mediw cal Sciences and Peking Union Medical College Christophe Merieux Laboratory Institutes of Biomedical Sciences and Shanghai Public Health Clinical Center Fudan University Shanghai Institute of Emerging and Reemerging Infectious School of Translational Medicines at Shanghai Public Health Clinical Center Fudan University

Since early December 2019,the novel coronavirus has caused an outbreak of pneumonia that has claimed over 2000 lives,with more than 77,000 confirmed cases of infection by February 23,2020 in China.[1]The World Health Organization(WHO)recently named the disease caused by this new coronavirus as"coronavirus disease 2019(COVID-19)".The International Committee on Taxonomy of Viruses(ICTV)has named the new virus"severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)".[2]However,questions have been raised by different academic and professional bodies regarding whether the nomenclature is appropriate.

关键词： acute diseases respiratory

CD4^+ T cell-mediated presentation of non-infectious HIV-1 virion antigens to HIV-specific CD8^+ T cells

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Chinese Medical Journal 2006年第19期119卷 1629-1638页

作者： xu jian-qing Franco Lori Julianna Lisziewicz State Key Laboratory for Infectious Diseases Prevention and Control National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 100050 China Research Institute for Genetic and Human Therapy Washington DC 20007 USA

Background The mechanism of chronic immune activation and impairment of HIV-specific immune responses during chronic infection is not fully understood. However, it is known that high immune activation leads to more rapid progression to AIDS. We hypothesize that CD4^＋ T cell-mediated viral antigen presentation contributes to this pathologic immune activation in HIV-infected individuals. Methods HIV-specific T cells, responding to noninfectious HIV-1 virions as antigen, were measured by flow cytometric assays. These experimental conditions reflect the in vivo condition where noninfectious HIV-1 represents more than 99% of the antigens. Results CD4^＋ T cells purified from HIV-infected individuals were capable of cross presenting exogenous noninfectious HIV-1 virions to HIV-1-specific CD8^＋ T cells. Cross presentation required the entry of HIV-1 to CD4^＋ T cells and antigen translocation from endoplasmic reticulum to the Golgi complex. Blocking CD4^＋ mediated activation of HIV-specific CD8^＋ T cells and redirecting the viral antigens to antigen presenting cells improved HIV-specific T cell responses. Contusions One possible cause of chronic immune activation and impairment of HIV-1 specific T cell responses is represented by HIV-1 harboring CD4^＋ T cells cross presenting HIV-1 antigen to activate CD8^＋ T cells. This new mechanism provides the first evidence that cross presentation of noninfectious HIV-1 virions play a role in the immunopathogenesis of HIV-1 infection.

关键词： HIV antigen presenting CD4^+ T cell CD8+ T cell immune pathogenesis

HIV/AIDS vaccine development： are we walking out from the dark？

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Chinese Medical Journal 2010年第23期123卷 3489-3494页

作者： WAN Yan-min WANG You-chun xu jian-qing Department of Scientific Research Shanghai Public HealthClinical Center Institutes of Biomedical Sciences Key Laboratoryof Medical Molecular Virology of Shanghai Medical College andInstitute of Medical Microbiology Fudan University Shanghai201508 China National Institute for the Control of-Pharmaceutical and BiologicalProducts Beijing 100050 China State Key Kaboratory for Infectious Disease Prevention andControl Chinese Center for Disease Control and PreventionBeijing 102206 China

The need for AIDS vaccine has been emphasized by the increase of HIV-1 prevalence in sexual transmission which bridges the spreading of HIV-1 from high-risk population to other populations. After more than two-decade intensive effort on the AIDS vaccine development, it remains elusive whether and how an effective vaccine will be achieved. Recent data released from a phase Ⅲ trial in Thailand showed a partial protection might be accomplishable by（R）the ＂prime-boost＂combination of two vaccines： ALVAC（R） HIV vaccine （the prime）, and AIDSVAX（R） B/E vaccine （the boost）.1 This unprecedented large clinical trial observed that the prime-boost combination lowered the rate of HIV infection by 31.2% compared to placebo based on the modified intent-to-treat population （n=51 vs. n=74,respectively; P=0.04）. However, debating on the efficacy interpretation of this trial arose among field ***, how to improve the efficacy will become the most important question to be tackled. Here we reviewed the recent publications and summarized the major progress achieved.

关键词： human immunodeficiency virus 1 vaccine innate immunity cross-reactive

HLA-DR expression on regulatory T cells is closely associated with the global immune activation in HIV-1 infected subjects naive to antiretroviral therapy

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Chinese Medical Journal 2011年第15期124卷 2340-2346页

作者： XIAO jian QIAN Ke-lei CAO qing-hua QIU Chen-li QIU Cao xuE Yi-le ZHANG Xiao-yan ZHONG Ping xu jian-qing LI Ming-yuan WANG Ying Department of Microbiology West China School of preclimcal and Forensic Medicine Sichuan University Chengdu Sichuan 610041 China Department of AIDS/STD Shanghai Municipal Center for Disease Control and Prevention Shanghai 200336 China Shanghai Public Health Clinical Center Institutes of Biomedical Sciences Key Laboratory of Medical Molecular Virology of Ministry of Education/Health Shanghai Medical College Fudan University Shanghai 201508 China

Background The frequencies of regulatory T cells （Tregs） increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs. Methods Tregs were defined as CD4＋CD25＋CD127lo/-T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer. Results Compared to HIV-1 seronegative donors, the levels of HLA-DR on CD4＋CD25＋CD127lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads （r=0.3163, P=-0.004） and negatively with CD4 T-cell counts （r=-0.4153, P 〈0.0001）. In addition, significant associations between HLA-DR expression on CD4＋CD25＋CD127lo/- Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4＋ and CD8＋ T cells were also identified. Conclusion HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.

关键词： human immunodeficiency virus type 1 T-lymphocytes, regulatory HLA-DR antigens immune activation

A mouse model based on replication-competent Tiantan vaccinia expressing luciferase/HIV-1 Gag fusion protein for the evaluation of protective efficacy of HIV vaccine

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Chinese Medical Journal 2009年第14期122卷 1655-1659页

作者： HUANG Yang QIU Chao LIU Lian-xing FENG Yan-meng ZHU Ting xu jian-qing State Key Laboratory for Infectious Diseases Prevention and Control National Center for AIDS/STD Control and Prevention Chinese Center of Disease Control and Prevention Beijing 100050 China Shanghai Public Health Clinical Center Institutes of Biomedical Sciences Fudan University Shanghai 201508 China

Background Developing an effective vaccine against human immunodeficiency virus type 1 （HIV-1） remains a grand challenge after more than two decades of intensive effort. It is partially due to the lack of suitable animal models for screening and prioritizing vaccine candidates. In this study, we aim to develop a mice model to test HIV-1 vaccine efficacy. Methods We constructed a recombinant vaccinia expressing firefly luciferase and HIV-1 Gag fusion protein based on Tiantan strain, an attenuated but replication-competent poxvirus （rTTV-lucgag）. By quantifying the luciferase activity as its read out, we defined the biodistribution of Tiantan strain poxvirus in mice inoculated intraperitoneally and attempted to apply this model to evaluate the HIV-1 vaccine efficacy. Results Our data demonstrated that the rTTV-lucgag was able to express high level of luciferase （〈106 relative luciferase units （RLU）/mg protein） and HIV-1 Gag （〉3 folds increase comparing to the control）. After intraperitoneal inoculation, this virus had dominant replication in the ovary, uterus, and cervix of mice and the luciferase activities in those organs are significantly correlated with viral titers （r^2=0.71, P 〈0.01）. Pre-immunization with an HIV gag DNA vaccine reduced the luciferase activity in ovary from （6006±3141） RLU/mg protein in control group to （1538±463） RLU/mg protein in vaccine group （P=0.1969）. Conclusions The luciferase activity in ovary could represent viral replication in vivo; this rTTV-lucgag/mice model may be suitable to assess the protective efficacy of cytotoxic T-cell responses to HIV Gag with less tedious work and high through-put.

关键词： human immunodeficiency virus type 1 vaccine mice model luciferase

Chloramphenicol improved expression of recombinant cholera toxin B subunit in Escherichia coli and its adjuvanticity

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Chinese Medical Journal 2011年第17期124卷 2751-2755页

作者： XIE Xiao-yan WAN Yan-min ZHU Zhao-qin ZHANG Huan-xiang xu jian-qing Shanghai Public Health Clinical Center Institutes of Biomedical Sciences Key Laboratory of Medical Molecular Virology of Ministry of Education Shanghai Medical College Fudan University Shanghai 201508 China Department of Cell Biology Medical College of Soochow University jiangsu Province Key Laboratory of Stem Cell Research Suzhou Jiangsu 215123 China

Background Cholera toxin B subunit （CTB） was shown to be a potent adjuvant for protein immunogen, especially when inoculated through mucosal route. We aimed to optimize the expression approach for CTB and thereafter to determine the adjuvant effect on DNA vaccine. Methods Wild type CTB coding gene was amplified and cloned into prokaryotic expression vector pET-30a, and the recombinant CTB was expressed in the presence of different concentration of chloramphenicol and isopropyl β-D-thiogalactoside. Purified recombinant CTB was mixed with HIV-1 AE2f tat-rev-integrase-vif-nef fusion gene DNA vaccine and female BALB/c mice were vaccinated with a DNA priming-recombinant vaccinia vectored vaccine boosting regimen through intramuscular injection. Interferon γ （IFN-γ） enzyme-linked immunospot （Elispot） assay was used to read out the specific T-cell immunity. Results Chloramphenicol was essential for the efficient expression of recombinant CTB （rCTB） in pET-30a/BL21 （DE3） system and could be optimized at the concentration of 0.625 μg/ml in the presence of chloramphenicol. The purified rCTB could bind with GM1 efficiently. INF-γ Elispot data showed the T-cell response induced in CTB adjuvanted group （（734±240） spot forming cells/106 splenocytes） was higher than that induced by non-adjuvanted （（520±150） spot forming cells/10e splenocytes）, all responses against different antigens were enhanced in parallel. Conclusion CTB could be efficiently expressed in the presence of chloramphenicol and purified CTB is functional and capable of enhancincl the specific T cell responses elicited by DNA vaccine, the mechanism needs to be explored in the future.

关键词： HIV-1 DNA vaccine cholera toxin B subunit expression efficacy adjuvant

Immunization with HBsAg-Fc fusion protein induces a predominant production of Thl cytokines and reduces HBsAg level in transgenic mice

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Chinese Medical Journal 2012年第18期125卷 3266-3272页

作者： MENG Zhe-feng WANG Hua-jing YAO Xin WANG xuan-yi WEN Yu-mei DAI jian-xin XIE You-hua xu jian-qing Shanghai Public Hlealth Clinical Center Key Lab of MedicalMolecular Virology Shanghai Medical College Institutes ofBiomedical Sciences Fudan University China Shanghai 200433 Intern-ational Joint Cancer Institute & Chinese People's LiberationArmy General Hospital Cancer Center Second Military MedicalUniversity China Shanghai 200433

Background The Fc receptor associated pathway might improve the immune responses against hepatitis B virus （HBV） as previously described by us. In addition, the Fit3 ligand （FL） has been reported to potentiate antigen presenting cells in vivo and may act as a potential adjuvant to boost antigen-specific immune responses. In this study, the immune efficacies of a set of fusion proteins of HBsAg and Fc and/or FL were evaluated in HBsAg transgenic mice. Methods The fusion proteins composed of HBsAg and the Fc domain of murine IgG1 （HBsAg-Fc） and/or the Fit3 ligand, and yeast-derived recombinant HBsAg were used as immunogen to immunize HBsAg transgenic mice, respectively. Serum and liver HBsAg levels, serum anti-HBsAg and cytokine profile, and the activities of alanine aminotransferase （ALT）/AST were investigated after immunization. Results After six injections, the most pronounced decrease in serum and liver HBsAg levels was observed in the HBsAg-Fc immunized group. In addition, serum Thl cytokines and ALT/AST activities were highest in this group, indicating an effective induction of a favorable cellular immune response. Interestingly, the fusion protein containing HBsAg-Fc and the Fit3 ligand stimulated an alternative Thl-type immune response featured with high level productions of tumor necrosis factor a （TNF-a） and monocyte chemoabstractant protein 1 （MCP-1）, causing a more severe cytotoxicity in hepatocytes while showed less effective in reducing serum HBsAg level. Conclusion HBsAg-Fc is effective in eliciting both the humeral and cellular immune responses against HBsAg in HBsAg transgenic mice, which makes it a potential immunogen for the immunotherapy of chronic hepatitis B.

关键词： Fc receptor hepatitis B surface antigen transgenic mice hepatitis B virus therapeutic vaccine

Used car price prediction based on XGBoost and retention rate

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The Journal of China Universities of Posts and Telecommunications 2024年第3期31卷 72-79页

作者： Shen Yutian Chen jian Dai Min Zhang Sirui xu Jing Wang qing College of Mechanical Engineering Yangzhou UniversityYangzhou 225127China College of Economics and Management Southeast University Chengxian CollegeNanjing 210088China Shandong Shuncheng Automobile Trade Co. LtdJinan 250000China

In order to improve the accuracy of used car price prediction,a machine learning prediction model based on the retention rate is proposed in this ***,a random forest algorithm is used to filter the variables in the *** main characteristic variables that affect used car prices,such as new car price,service time,mileage and so on,are filtered ***,the linear regression classification method is introduced to classify the test data into high and low retention rate *** that,the extreme gradient boosting(XGBoost)regression model is built for the two datasets *** prediction results show that the comprehensive evaluation index of the proposed model is 0.548,which is significantly improved compared to 0.488 of the original XGBoost ***,compared with other representative machine learning algorithms,this model shows certain advantages in terms of mean absolute percentage error(MAPE),5%accuracy rate and comprehensive evaluation *** a result,the retention rate-based machine learning model established in this paper has significant advantages in terms of the accuracy of used car price prediction.

关键词： random forest data dimensionality reduction extreme gradient boosting(XGBoost) retention rate price prediction

A new approach for sequencing virion genome of Chinese HIV-1 strains subtype B and BC from plasma

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Chinese Medical Journal 2011年第2期124卷 304-308页

作者： MENG Zhe-feng ZHANG Xiao-yan XIN Ruo-lei XING Hui HE Xiang xu jian-qing SHAO Yi-ming Shanghai Public Health Clinical Center Key Laboratory of Medical Molecular Virology of Ministry of Health Shanghai Medical College Institutes of Biomedical Sciences Fudan University Shanghai 200433 China Key Laboratory of Infectious Disease Prevention and Control National Center for AIDS/STD Control and Prevention Chinese Center for Disease Control and Prevention Beijing 100050 China

Background Although it was widely accepted that full-length HIV genome sequences is important in studying virus genetic evolution and variation as well as developing vaccine candidate,to directly sequencing HIV-1 genome of virion RNA remains as a challenge *** to date,no published genomic sequences from virion RNA are available for Chinese prevalent HIV-1 strains due to the absence of specialized protocol and appropriate lab *** this study we developed a straightforward approach for amplifying and sequencing HIV virion RNA from plasma by modifying published protocols and further confirmed it is suitable to process Chinese *** The methods for viral RNA extraction and gene amplification was modified and optimized as could be widely used in most Chinese *** alignment of Chinese HIV-1 strains was employed for designing specialized primer sets for Thai-B and BC recombinant *** on comprehensively consideration of high variable gene region and recombinant breakpoints in BC recombinant strains,a three-amplicon strategy （including 4.3-kb gag-pol,2.9-kb pol-env and 2.7-kb env-ne） was *** addition,one amplicon （9 kb near full-length genome） was also used in 32 samples with varied viral *** amplicons were directly sequenced by DNA automated *** Twenty-five percent（8/32） amplification efficiency was achieved by the one-amplicon strategy and 65.6%（21/32） by three-amplicon *** one amplicon strategy,none of complete near full-length genome sequences was obtained by DNA *** three-amplicon strategy,75% sequences were achieved in DNA *** efficiency but not sequencing efficiency was closely associated with viral *** Three-amplicon strategy covering all encoding regions of HIV-1 is suitable for Thai-B and BC recombinant strains and could be potentially employed in less-well equipped Chinese labs.

关键词： human immunodeficiency virus 1 RNA full-genome amplification