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Comparative study on the anti-tuberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiao He extract and JieHeWan

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Military Medical Research 2022年第2期9卷 164-183页

作者： Li-Yao Duan Yan Liang Wen-Ping Gong Yong Xue Jie Mi Jie Wang Lan Wang Zai-Xing Jia Hong Lei Yu-Mei Liang Jun Liu Yue Zheng Xue-Qiong Wu tuberculosis Prevention and Control Key laboratory Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and TreatmentTuberculosis Research Institutethe 8th Medical CenterChinese PLA General HospitalBeijing 100091China Hebei North University Zhangjiakou 075000HebeiChina Clinical laboratory the 8th Medical CenterChinese PLA General HospitalBeijing 100091China Pathology Department the 8th Medical CenterChinese PLA General HospitalBeijing 100091China Guangdong Qifang Pharmaceutical Co. LtdGuangzhou 510075China

Background:The traditional Chinese medicine NiuBeiXiaoHe(NBXH)extract and Chinese medicine preparation JieHeWan(JHW)exhibit anti-tuberculosis(TB)*** anti-TB effect of NBXH was compared with that of JHW to elucidate the mechanism of action of ***:BALB/c mice aged 6-8 weeks were randomly divided into a normal control group,TB model group,JHW treatment group,and NBXH treatment *** 3 and 13 weeks of treatment,the therapeutic effect in each group was evaluated by comparing lung histopathology,lung and liver colony counts,the number of spots representing effector T cells secreting IFN-γin an enzyme-linked immunospot assay(ELISPOT),and the levels of Th1,Th2,and Th17 cytokines,which were measured by a cytometric bead array(CBA).Mouse RNA samples were subjected to transcriptome ***:After 13 weeks of treatment,the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group(Pgroup,the lung colony counts in the JHW and NBXH groups were significantly decreased(Pgroup were significantly increased(Ptuberculosis(***)*** to GO and KEGG analyses,the changes in biological process(BP),cell composition(CC)and molecular function(MF)terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent,but they were mainly related to the immune response and inflammatory response in the mouse TB ***:NBXH had therapeutic effects similar to those of JHW in improving lung histopathology,reducing lung colony counts,and regulating the levels of *** restored significant changes in gene expression and repaired cell damage caused by *** infection by regulating immune-related pathways,which clarified the mechanism of action of NBXH.

关键词： Traditional Chinese medicine tuberculosis NiuBeiXiaoHe extract JieHeWan Therapeutic effect

First-Line Drug Resistance Patterns of Mycobacterium tuberculosis Complex Isolates from Re-Treatment Patients from Sudan

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Journal of tuberculosis Research 2016年第3期4卷 98-104页

作者： Muatsim Ahmed Mohammed Adam Hamdan Mustafa Hamdan Ali Eltahir Awad Gasim Khalil National tuberculosis Reference laboratory National Public Health Laboratory Federal Ministry of Health Khartoum Sudan National tuberculosis Control Program Federal Ministry of Health Khartoum Sudan tuberculosis Research group/Institute of Endemic Diseases University of Khartoum Khartoum Sudan

Drug susceptibility testing (DST) plays a pivotal role in TB patients’ management leading to the selection of most effective drugs. This study aimed to determine resistance patterns to first line anti-TB drugs in Mycobacterium tuberculosis isolates from re-treated patients from Sudan. A total of 239 sputum specimens were collected from smear positive re-treatment TB patients during the period from July 2009 to July 2010. Specimens were pre-treated according to Petroff method. The recovered isolates were tested for sensitivity to first line anti-TB drugs by the 1% proportion method. One hundred and forty three (143/239, 59.8%) mycobacterial isolates were successfully recovered. The majority (98.6%, 141/143) of the isolates were Mycobacterium tuberculosis complex strains. Two strains (2/143, 1.4%) were identified as RIF/INH-resistant MOTT, while fifty four isolates (38.3%, 54/141) were MDR. Multi- drug resistant Mycobacterium tuberculosis complex (MDR-TB) among re-treatment patients from national referral centers for tuberculosis diagnosis and management was considerably high in the study isolates.

关键词： MDR Sudan TB Re-Treatment DST

Evaluation of the Xpert MTB/RIF assay for diagnosis of tuberculosis and rifampin resistance in county-level laboratories in Hunan province, China

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Chinese Medical Journal 2014年第21期127卷 3744-3750页

作者： Hu Peilei Bai Liqiong Liu Fengping Ou Xichao Zhang Zhiying Yi Songlin Chen Zhongnan Gong Daofang Liu Binbin Guo Jingwei Tan Yunhong Hunan Provincial tuberculosis Reference laboratory Hunan Provincial Institute for Tuberculosis Control and Prevention Changsha Hunan 410013 China National tuberculosis Reference laboratory Chinese Center for Disease Control and Prevention Beijing 102206 China tuberculosis Program Office Program for Appropriate Technology in Health B eijing 100022 China

Background The Xpert MTB/RIF showed high sensitivity and specificity in previous studies carried out in different epidemiological and geographical settings and patient populations in high-burden tuberculosis （TB） ***,there were little data obtained by validation or demonstration study of the assay in *** this study,the performance of Xpert MTB/RIF was investigated in two county-level laboratories in Hunan Province,*** Consecutive patients with suspected pulmonary tuberculosis （PTB） and suspicion for multidrug-resistant tuberculosis （MDR-TB） were *** each patient suspected to have PTB,three sputum specimens （one spot sputum,one night sputum,and one morning sputum） were collected and each sputum was tested with smear microscopy,L（o）wenstein-Jensen （LJ） culture,and Xpert MTB/RIF *** comparison across subgroups and testing methods,95％ confidence intervals were *** analyses were done with SPSS 16.0,and P ＜0.05 was regarded as *** For case detection,the sensitivity of Xpert MTB/RIF was 100％ for smear-and culture-positive TB and 88.6％ for smear-negative and culture-positive TB; the overall sensitivity was 94.5％ for all culture-positive *** specificity was 99.8％.The sensitivity of Xpert MTB/RIF assay was 22.0％ in clinical TB patients and the specificity reached 100.0％ in the group of patients who are infected with nontuberculous *** the detection of rifampin resistance,the sensitivity of MTB/RIF RIF-resistance detection was 92.9％,and the specificity was 98.7％.Of the 26 Xpert MTB/RIF-positive and RIF-resistant patients confirmed by LJ proportion tests,20 （76.9％） patients were infected by *** The Xpert MTB/RIF assay is a highly sensitive and specific method for diagnosis of TB and RIF resistance,which will enable it to have the potential to be used in county-level laboratories and lead to the reduction of the infectious pool and improvements in TB control in ***

关键词： pulmonary tuberculosis Xpert MTB/RIF diagnosis rifampin resistance

Immunogenicity and protective efficacy study using combination of four tuberculosis DNA vaccines

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Science China Life Sciences 2003年第5期46卷 495-502+562页

作者：蔡宏田霞呼西旦潘怡李国利庄玉辉朱玉贤 China Peking University tuberculosis Research laboratory 309 Hospital of PLA Institute of Veterinary Xinjiang Academy of Animal Science Beijing 100091 Peking University Beijing 100871 College of Life Science National laboratory of Protein Engineering and Plant Genetic Engineering Urumqi 830000

Immune response and protective efficacy for the combination of four tuberculosis DNA vaccines were evaluated in this study. We obtained 1︰200 antibody titers against Ag85B 21d after mice were vaccinated for the first time by four recombinant eukaryotic expression vectors containing coding sequences for Ag85B, MPT-64, MPT-63 and ESAT-6. The titers of Ag85B were elevated to 1︰102400 after the second injection and decreased to 1︰12800 after the third injection. Antibody titers for MPT-64 and MPT-63 reached 1︰25600 21 d after the first vaccination, and were then decreased following the second and third injections. No antigen-specific antibody titer against ESAT-6 was detected in sera harvested from immunized mice at any time. These DNA vaccines evoked specific IFN-g responses in the spleens of vaccinated mice as well. When challenged with M. tuberculosis H37Rv, we found that the lungs of the vaccinated mice produced 99.8% less bacterial counts than that of the empty-vector control group and the bacterial counts were also significantly less than that of the BCG group. Histopathological analyses showed that the lungs of vaccinated mice produced no obvious caseation while over 50%—70% of the pulmonary parenchyma tissue produced central caseation in the vector control group. Our results indicated that the combination of four tuberculosis DNA vaccines may generate high levels of immune responses and result in better animal protection.

关键词： Mycobacterium tuberculosis secreted proteins combination DNA vaccines immunogenicity protective efficacy.

Detection of SARS-CoV-2 Antibodies in Oral Fluid Using a Magnetic Particle-Based Chemiluminescence Immunoassay-Beijing Municipality,China,2021

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China CDC weekly 2022年第40期4卷 890-894页

作者： Naiying Mao Mei Dong Zhen Zhu Qi Huang Xiali Yu Hui Xie Jianping Dong Jingyi Sun Fang Huang Wenbo Xu NHC Key laboratory of Medical Virology and Viral Diseases WHO WPRO Regional Reference Laboratory of Measles and RubellaMeasles Laboratory in National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijingChina Institute for Immunization and Prevention Beijing Center for Disease Control and PreventionBeijing Academy for Preventive MedicineBeijing Institute of Tuberculosis Control Research and PreventionBeijingChina Department of Infectious Diseases Beijing Haidian HospitalBeijing Haidian Section of Peking University Third HospitalBeijingChina

Introduction:Oral fluids(OFs)have been broadly used as non-invasive samples for evaluating protective IgG antibodies from natural infection or vaccination,especially in pediatric ***:Paired OF and serum were collected from both individuals who received a booster dose of the inactive coronavirus disease 2019(COVID-19)vaccine as well as those who did not have a history of COVID-19 vaccination and infection(as the control group).The total human IgG antibody(HIgG)content was evaluated as a marker of OF sampling *** in-house adapted magnetic particle-based chemiluminescence immunoassay was used for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)IgG antibody detection in the *** SARS-CoV-2 IgG antibody in the serum samples was detected using a commercial ***:In total,579 paired OF and serum samples were *** additional 172 OF samples were collected from preschool *** results indicated that the HIgG concentration in qualified OF samples should be higher than 0.3μg/*** to the serum assay,the in-house OF immunoassay for detecting IgG antibodies against SARS-CoV-2 had 95.06%accuracy,95.03%sensitivity,and 100%***:Overall,the in-house immunoassay for detecting SARS-CoV-2 IgG antibodies in OF showed high potential for application towards serological surveillance and immunization effect assessment after large-scale,inactive COVID-19 vaccination in China.

关键词： vaccination protective specificity

Coupling effects of temperature,confining pressure,and pore pressure on permeability and average pore size of Longmaxi shale

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Deep Underground Science and Engineering 2023年第4期2卷 359-370页

作者： Xiaoyan Zhang Hongsen Li Xue Tan Guoliang Li Hua Jiang School of Mechanics and Civil Engineering China University of Mining and TechnologyBeijingChina Beijing Urban Construction group Co. LtdBeijingChina BGI Engineering consultants Ltd BeijingChina Key laboratory of Shale Gas and Geoengineering Institute of Geology and GeophysicsChinese Academy of SciencesBeijingChina

The evolution due to temperature and pressure of shale reservoir permeability affects the productivity evaluation and development decision of shale gas reservoirs,which is very important for the exploration and development of unconventional gas *** study analyzed the coupling effects of temperature(25,50,and 75°C),effective stress(15 and 30 MPa),and pore pressure(0.5,2.0,4.0,and 8.0 MPa)on the permeability of the shale sample in the Longmaxi *** the temperature and pressure increased,the apparent permeability exhibited a downward trend,and the absolute permeability decreased with the rise of temperature or effective *** in‐depth analysis of the gas slippage factors under the conditions of different temperature and pressure was conducted to evaluate the trend of the average pore width with temperature and *** results were then veriﬁed by scanning electron microscopy(SEM).The results provide new insights into evaluating the permeability of the Longmaxi shale and can be used to enhance the gas recovery rate of deep shale gas reservoirs.

关键词： absolute permeability apparent permeability gas slippage factors pore width shale

Interferon-Gamma Release Assay is Not Appropriate for the Diagnosis of Active tuberculosis in High-Burden tuberculosis Settings： A Retrospective Multicenter Investigation

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Chinese Medical Journal 2018年第3期131卷 268-275页

作者： Wan-Li Kang Gui-Rong Wang Mei-Ying Wu Kun-Yun Yang Er-Tai A Shu-Cai Wu Shu-Jun Geng Zhi-Hui Li Ming-Wu Li Liang Li Shen-Jie Tang Epidemiology Research Department Beijing Chest Hospital Capital Medical University Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing 101149 China tuberculosis Clinical laboratory Beijing Chest Hospital Capital Medical University Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing 101149 China Department of tuberculosis Souzhou 5th People's Hospital Souzhou Jiangsu 215007 China Department of tuberculosis Hunan Chest Hospital Changsha Hunan 410013 China Department of tuberculosis Chest Hospital of Xinjiang Uygur Autonomous Region Urumqi Xinjiang 830049 China Department of tuberculosis Hebei Chest Hospital Shijiazhuang Hebei 050041 China Department of tuberculosis Kunming 3rd People's Hospital Kunming Yunnan 650041 China Department of tuberculosis Beijing Chest Hospital Capital Medical University Beijing Tuberculosis and Thoracic Tumor Research Institute Beijing 101149China

Background：Interferon-gamma release assay （IGRA） has been used in latent tuberculosis （TB） infection and TB diagnosis,but the results from different high TB-endemic countries are *** aim of this study was to investigate the value of IGRA in the diagnosis of active pulmonary TB （PTB） in ***：We conducted a large-scale retrospective multicenter investigation to further evaluate the role of IGRA in the diagnosis of active PTB in high TB-epidemic populations and the factors affecting the performance of the *** patients who underwent valid *** assays from December 2012 to November 2015 in six large-scale specialized TB hospitals in China and met the study criteria were retrospectively *** were divided into three groups：group 1,sputum culture-positive PTB patients,confirmed by positive Mycobacterium tuberculosis sputum culture;group 2,sputum culture-negative PTB patients;and group 3,non-TB respiratory *** medical records of all patients were ***-square tests and Fisher＇s exact test were used to compare categorical *** logistic analyses were performed to evaluate the relationship between the results of T-SPOT in TB patients and other ***：A total of 3082 patients for whom complete information was available were included in the investigation,including 905 sputum culture-positive PTB cases,914 sputum cultmre-negative PTB cases,and 1263 non-TB respiratory disease *** positive rate of *** was 93.3% in the culture-positive PTB group and 86.1% in the culture-negative PTB *** the non-PTB group,the positive rate of *** was 43.6%.The positive rate of *** in the culture-positive PTB group was significantly higher than that in the culture-negative PTB group （x2 =25.118,P 〈 0.01）,which in turn was significantly higher than that in the non-TB group （x2 =566.l 16,P 〈 0.01）.The overall results were as follows：sensitivity,89.7%;specificity,56.37%;positive predictive valu

关键词： Active tuberculosis Diagnosis Interferon-Gamma Release Assay

Synthesis and antimycobacterial screening of new N-(4-(5-aryl-3-(5-methyl-1,3,4-oxadiazol-2-yl)-1H-pyrazol-1-yl)phenyl)-4-amide derivatives

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Chinese Chemical Letters 2016年第3期27卷 365-369页

作者： Nagabhushana Nayak Jurupula Ramprasad Udayakumar Dalimba Perumal Yogeeswari Dharmarajan Sriram Organic Chemistry laboratory Department of ChemistryNational Institute of Technology Karnataka Medicinal Chemistry and Drug Discovery Research laboratory Pharmacy GroupBirla Institute of Technology and Science-PilaniHyderabad Campus

This article demonstrates the synthesis, characterization and the study of in vitro antitubercular activities of twenty four new N-（4-（5-aryl-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）-4-amide derivatives（8a–x）. The antitubercular activity of the compounds against Mycobacterium tuberculosis H37Rv（MTB） revealed that 2-chloro-N-（4-（5-（4-chlorophenyl）-3-（5-methyl-1,3,4-oxadiazol-2-yl）-1H-pyrazol-1-yl）phenyl）benzamide（8n） is the most promising lead molecule with a MIC of1.56 mg/m L, while the corresponding unsubstituted benzamide derivative（8o） is the next most active molecule with a MIC of 3.13 mg/m L. Interestingly, the pyrazole intermediate 5b containing chlorophenyl and N-acylcarbohydrazide substituents also showed significant activity（MIC = 3.13 mg/m L）. Further, the active molecules did not show toxicity against a normal NIH 3T3 cell line, signifying their suitability for further drug development.

关键词： Pyrazole-oxadiazole hybrids Antitubercular activity SC-XRD analysis In vitro cytotoxicity

Profiling B and T cell immune responses to co-infection of Mycobacterium tuberculosis and hookworm in humans

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Infectious Diseases of Poverty 2015年第1期4卷 133-142页

作者： Xin-Xu Li Jia-Xu Chen Li-Xia Wang Jun Sun Shao-Hong Chen Jun-Hu Chen Xiao-Yan Zhang Xiao-Nong Zhou National Institute of Parasitic Diseases Chinese Center for Disease Control and PreventionKey Laboratory of Parasite and Vector BiologyMinistry of HealthWHO Collaborating Centre for MalariaSchistosomiasis and Filariasis207 Rui Jin Er RoadHuangpu DistrictShanghai 200025PR China(PRC) National Center for tuberculosis Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206PR China Shanghai Public Health Clinical Center Key Laboratory of Medical Molecular Virology of Ministry of EducationInstitutes of Biomedical SciencesFudan UniversityShanghai 201508PR China

Background:Humoral and cellular immune responses play protective roles against Mycobacterium tuberculosis(MTB)***,hookworm infection decreases the immune response to hookworm and bystander ***,immune responses to co-infection of MTB and hookworm are still unknown,although co-infection has been one of the public health problems in co-endemic areas of pulmonary tuberculosis(PTB)and hookworm ***,it is essential to evaluate B and T cell immune responses to the ***:Seventeen PTB cases co-infected with hookworm,26 PTB cases,15 patients with hookworm infection,and 24 healthy controls without PTB or hookworm infection were enrolled in the *** of CD3,CD4,CD8,CD10,CD19,CD20,CD21,CD25,CD27,CD38,FoxP3,and PD-1 were assessed on B and T cell subsets using multicolor flow ***:For the B cell(CD19+)subsets,naïve B cells(CD10−CD27−CD21+CD20+),plasma cells(CD10−CD27+CD21−CD20−),and tissue-like memory B cells(CD10−CD27−CD21−CD20+)had higher proportions,whilst resting memory B cells(CD10−CD27+CD21+CD20+)had lower proportions in the group co-infected with MTB and hookworm as compared to other *** of activated memory B cells(CD10−CD27+CD21−CD20+)did not differ among the four *** the T cell(CD3+)subsets,frequencies of regulatory T cells(CD4+CD25+Foxp3+)and exhausted CD4+and CD8+T cells(CD4+PD-1+and CD8+PD-1+)were higher,and frequencies of activated CD4+and CD8+T cells(CD4+CD38+and CD8+CD38+)were lower in the co-infected group as compared to the other ***:The change patterns of the cell profile of circulating lymphocytes were indentified in human co-infection of MTB and hookworm,which might indicate that the humoral and cellular immune responses are more suppressed.

关键词： Co-infection Mycobacterium tuberculosis Hookworm Immune response