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Table of Content

    10 November 2019, Volume 41 Issue 11
    • Retrospect and Prospect
      Historic review of anti-tuberculosis chemotherapy during seventy years of the People’s Republic of China
      FAN Lin,XIONG Kun-long,XIAO He-ping
      Chinese Journal of Antituberculosis. 2019, 41(11):  1145-1148.  doi:10.3969/j.issn.1000-6621.2019.11.001
      Abstract ( 921 )   HTML ( 24 )   PDF (1062KB) ( 581 )   Save
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      Tuberculosis (TB) is an ancient disease. The historical process of chemotherapy of tuberculosis is worth reviewing and summing up due to its occurrence and development accompanied with human long term and arduous struggle against TB. With the founding of the People’s Republic of China and the development of various aspects of our country in the past 70 years, and from the advent of the first generation of anti-tuberculosis chemotherapy drugs and chemotherapy regimen in the early 1950s, to the research and development of new anti-tuberculosis drugs, as well as the exploration, improvement and perfection of chemotherapy regimen including preventive treatment, the progress of chemotherapy for tuberculosis in the 70 years since the founding of the People’s Republic of China confirms the course of complete control of tuberculosis in human history.

      Retrospect and prospect on biological products for immunological prevention, therapy and diagnosis of tuberculosis in China
      ZHAO Ai-hua,WANG Guo-zhi,XU Miao
      Chinese Journal of Antituberculosis. 2019, 41(11):  1149-1154.  doi:10.3969/j.issn.1000-6621.2019.11.002
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      Immunological prevention, treatment and diagnosis of tuberculosis is one of the most necessary measures to control tuberculosis. This paper summarizes the development, research status and future development direction of tuberculosis-related biological products in China, and then prospects the organic use of various biological products under the framework of the established tuberculosis immune prevention system to reduce the rate of tuberculosis infection and incidence, as well as the possibility of changing the status quo of high burden of tuberculosis in China.

      Original Articles
      Antibacterial effect of sulfur heteroarotinoid A2 on Mycobacterium tuberculosis in vitro and in vivo
      QIU Qian,YANG Song,CHEN Yong,XU Xiao-ming,YANG Zai-xing
      Chinese Journal of Antituberculosis. 2019, 41(11):  1155-1159.  doi:10.3969/j.issn.1000-6621.2019.11.003
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      Objective To evaluate the antibacterial effect of sulfur heteroarotinoid A2 (SHetA2) on Mycobacterium tuberculosis (MTB) in vitro and in vivo.Methods (1) SHetA2 with different doses (2.5 μg/ml, 5.0 μg/ml, 10.0 μg/ml, and 20.0 μg/ml) was added to Sutong medium in test tube, followed by the addition of the equal volume of MTB standard strain H37RV solution (1 mg/ml, 0.1 ml/each inoculation, containing 10 6 CFU). After cultured at 37℃ for 2 weeks, the minimum inhibitory concentration (MIC) of SHetA2 was determined. (2) Seventy-six specific pathogen free Kunming mice were inoculated with nebulizer inhalation device to establish tuberculosis infection model. Sixty mice were modeled successfully and randomly divided into control group, isoniazid group, and SHetA2 group in equal numbers (n=20), accordingly, the mice were treated with saline, isoniazid, and SHetA2, respectively, in different groups. After 45 days of treatment, the changes in physical signs, body weight, lung tissue bacterial load, and histopathology were observed. Results (1) In vitro results showed that MIC of SHetA2 against standard strain MTB H37RV was 10 μg/ml. (2) In vivo anti-tuberculosis experiments showed that after 45 days of treatment, the body weight of the control group was (27.21±2.85) g, which was significantly lower than those of isoniazid group ((37.98±3.09) g) and SHetA2 group ((38.28±3.43) g), with statistically significant difference (F=4.05, P=0.023). The difference of body weight between the isoniazid group and SHetA2 group (q=0.10, P=0.998) was not statistically significant. In the control group, the ratio of severe lung lesions (80.0%, 16/20) was significantly higher than those of isoniazid group (15.0%, 3/20) and SHetA2 group (10.0%, 2/20), with statistically significant difference (χ 2=32.18, P<0.01). Lung bacterial load (lg10 CFU/ml) of control group was 7.01±1.23, which was obviously higher than those of isoniazid group (2.59±0.87) and SHetA2 group (2.25±0.94), with statistically significant difference (F=6.71, P=0.002); while no statistically significant difference was found between the isoniazid group and SHetA2 group (q=0.33, P=0.970). Conclusion SHetA2 has a considerable antibacterial effect on MTB both in vivo and in vitro, which may be a candidate for new anti-tuberculosis drugs.

      Preliminary study on the action mechanism of TBI-166 against drug-resistant Mycobacterium tuberculosis
      ZHANG Ye,LI Yuan-yuan,XU Jian,CHEN Xi,WANG Bin,FU Lei,LU Yu
      Chinese Journal of Antituberculosis. 2019, 41(11):  1160-1166.  doi:10.3969/j.issn.1000-6621.2019.11.004
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      Objective To explore the mechanism of TBI-166 against drug-resistant Mycobacterium tuberculosis (MTB) by determining the reactive oxygen content and catalase activity of MTB.Methods H37Rv standard strains were treated with clofazimine (CFZ) or TBI-166 at 1, 2, 4, 8 times the minimal inhibitory concentration (MIC) for 24 hours. The levels of reactive oxygen species (ROS) in bacteria were determined with fluorescent probe 2',7'-dichloro fluorescent yellow diacetate ROS detection kit, and the changes of ROS levels in bacteria were compared before and after the medication of CFZ or TBI-166 with different concentrations. The catalase activities of 5 strains resistant to both CFZ and TBI-166, 3 strains resistant to CFZ but sensitive to TBI-166, 1 strain (13385) sensitive to both CFZ and TBI-166, and H37Rv standard strain were determined by the catalase activity detection kit. The difference in catalase activity between drug-resistant strains and sensitive strains to both CFZ and TBI-166 was compared. SPSS 19.0 software was used for statistical analysis. Spearman correlation analysis and linear regression analysis were performed upon the concentrations of TBI-166 and the fluorescence values. The significance level was 0.05.Results The ROS results showed that after 24 h of treatments with different concentrations CFZ and TBI-166, the rank order of the fluorescence value of samples were 1 MIC (6668.5) >8 MIC (2751.5) >2 MIC (2572.0) >4 MIC (2015.0), and 8 MIC (2637.5) >4 MIC (2297.0) >2 MIC (2085.5) >1 MIC (1896.0), respectively. The amount of ROS accumulated in the bacteria was at least 2 times higher than that in the negative control samples without drug (H37Rv standard strain+DCFH-DA, 878.5). Moreover, in the strains treated with different concentrations of TBI-166, the fluorescence values were positively correlated with the drug concentration (Spearman correlation analysis, r=0.976, P<0.001). The regression equation test results showed that the regression model was significant (F=92.576, P=0.011). The catalase activity results showed that the average catalase activity of the CFZ-resistant strains (0.87 U/10 4 cell) was nearly twice that of the CFZ-sensitive strains (0.48 U/10 4 cell). The average catalase activity of the TBI-166-resistant strains (0.88 U/10 4 cell) was slightly higher than that of the TBI-166-sensitive strains (0.71 U/10 4 cell), and was similar to that of CFZ-resistant strains. Conclusion Both CFZ and TBI-166 can induce the accumulation of intracellular ROS in MTB, and the two drugs may have similar mechanisms of action. Increased catalase activity may be associated with the drug resistance to CFZ and TBI-166 in MTB.

      The value of serum CXC chemokine receptor 3 ligands in the diagnosis of active pulmonary tuberculosis
      WEI Lan,JIA Xin-zhuan,QIN Xue-bo,FENG Jun-peng,LI Yu-zhuo,DUAN Xiao-liang
      Chinese Journal of Antituberculosis. 2019, 41(11):  1167-1172.  doi:10.3969/j.issn.1000-6621.2019.11.005
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      Objective To evaluate the value of CXCR3 ligand in the diagnosis of active pulmonary tuberculosis.Methods 106 patients with active pulmonary tuberculosis (PTB)(including 31 patients with sputum smear acid-fast staining negative, 39 patients with sputum smear acid-fast staining +~++, 36 patients with sputum smear acid-fast staining +++~++++), 89 patients with lung malignant tumors (PMT)(12 cases of small cell lung cancer, 37 cases of adenocarcinoma, 35 cases of squamous cell carcinoma, 3 cases of large cell carcinoma and 2 cases of neuroendocrine carcinoma), 82 patients with other pulmonary benign disease (PBD)(36 cases of secondary infection of bronchiectasis, 13 cases of lung abscess, 15 cases of fungal infection, 12 cases of mycoplasma infection, 6 cases of hamartoma), and 90 healthy controls (HC) were selected in Hebei Provincial Chest Hospital from March 2018 to December 2018. Serum interferon-γ (IFN-γ) and CXCR3 ligands (IFN-γ induced mononuclear factor (CXCL9),IFN-γ-inducible protein 10 (CXCL10), and IFN-inducible T-cell α chemoattractant (CXCL11)) were determined by ELISA.Results The contents of CXCL9, CXCL10 and CXCL11 in PTB group were (650.28 (220.00,881.21) pg/ml, 390.00 (200.05,500.29) pg/ml, 150.33 (80.12,320.00) pg/ml) which had statistical significance when compared with those (120.21 (33.50, 244.28) pg/ml, 58.00 (30.25, 85.56) pg/ml, 35.52 (20.27, 44.50) pg/ml) in PMT group (χ 2 values were 124.21, 155.03, 118.68; P values were 0.000), and compared with those (45.52 (15.25, 86.55) pg/ml, 55.56 (26.75, 86.28) pg/ml, 31.53 (20.50, 45.25) pg/ml) in PBD group (χ 2 values were 194.93, 159.84, 124.71; P values were 0.000), and compared with those (50.11 (28.32, 81.22) pg/ml, 50.28 (32.27, 70.62) pg/ml, 11.46 (5.28, 30.39) pg/ml) in HC group (χ 2 values were 184.68, 183.53, 208.18; P values were 0.000). IFN-γ in PTB group (13.00 (8.50, 18.25) pg/ml) had no statistical significance when compared with those (15.11 (8.50,18.00) pg/ml) in PMT group (χ 2=10.05, P=0.509), and compared with those (13.02 (9.90, 18.28) pg/ml) in PBD group (χ 2=1.17, P=0.940). IFN-γ in PTB group had statistical significance compared with those (10.86 (7.01, 12.00) pg/ml) in HC group (χ 2=80.19, P=0.000). The area under curves (AUC) of CXCL9, CXCL10 and CXCL11 were 0.700, 0.680 and 0.778 in PTB group respectively. Conclusion Serum CXCR3 ligands may be helpful in the diagnosis of active pulmonary tuberculosis, especially CXCL11 and CXCL9 are more prominent than CXCL10.

      Detection value analysis of three laboratory techniques for diagnosing tuberculosis and drug resistance in smear-positive patients
      SHI Lian,REN Yi-jie,XI Ying,SHI Lei,GUO Chen,GUAN Jian
      Chinese Journal of Antituberculosis. 2019, 41(11):  1173-1178.  doi:10.3969/j.issn.1000-6621.2019.11.006
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      Objective To evaluate the detection and application value of BACTEC MGIT 960 mycobacterial liquid culture (referred to as “MGIT 960 culture”), GeneXpert MTB/RIF (GeneXpert) and fluorescent PCR melting curve analysis in smear-positive pulmonary tuberculosis (PTB) patients.Methods We retrospective analysized of total 411 smear-positive patients who were admitted to Shenyang Chest Hospital from Oct. 2016 to Feb. 2018. Through Mycobacterium tuberculosis antigen detection (MPB64 test) and met the clinical diagnostic criteria, 392 patients were diagnosed with tuberculosis, 19 patients with negative MPB64 and identified as non-tuberculous mycobacteria by gene chip strain. The detection efficiency of MGIT 960 culture, GeneXpert and fluorescent PCR melting curve technique in smear-positive PTB patients was compared. Based on the proportional drug sensitivity test, the detection efficiencies of drug resistance phenotypes and drug resistance genes were compared.Results In clinical confirmed 392 smear-positive PTB patients, the sensitivity of MGIT 960 culture, GeneXpert and fluorescent PCR melting curve technique to sputum samples were 96.17% (377/392), 99.74% (391/392) and 92.09% (361/392), respectively; the specificity were all 100.00% (19/19). Based on the proportional drug sensitivity test, the sensitivity of GeneXpert and PCR melting curve technique in RFP resistance test were both 94.44% (119/126). The sensitivity of PCR melting curve technique in INH, Lfx, Am resistance tests were 74.84% (116/155), 83.33% (75/90) and 44.00% (22/50). The sensitivity of MGIT 960 culture to RFP, INH, Lfx and Am resistance tests were 96.03% (121/126),98.06% (152/155), 100.00% (50/50) and 96.67% (87/90).Conclusion The GeneXpert method is easy, fast and safe, and can quickly diagnose tuberculosis and detect RFP resistance. Fluorescence PCR melting curve technology can detect four kinds drug resistance, with short detection time, rapid diagnosis of multidrug resistant tuberculosis/extensive drug-resistant tuberculosis, and guiding clinical medication. The MGIT 960 liquid susceptibility is extremely consistent with modified Roche culture technology. It is a common method for rapid diagnosis of tuberculosis and first-line drug-resistant tuberculosis which can significantly shorten the time of phenotypic drug susceptibility test.

      Analysis of identification results of 106 strains of non-tuberculous mycobacteria in Shaoxing area in 2017
      JIN Fa-xiang,TAO Xue-fang,WANG Hua-jun,XU Wen-fang,CHEN Xue-fang
      Chinese Journal of Antituberculosis. 2019, 41(11):  1179-1183.  doi:10.3969/j.issn.1000-6621.2019.11.007
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      Objective Analyze the prevalence of non-tuberculous mycobacteria (NTM) in Shaoxing and provide a scientific basis for NTM diagnosis and treatment.Methods In the Shaoxing area, 972 strains of mycobacteria were isolated in 2017, and the preliminary strain identification of Mycobacterium tuberculosis complex and NTM was carried out by using the colloidal gold method of Mycobacterium tuberculosis antigen detection. 106 strains were NTM, accounting for mycobacterial culture-positive strains 10.91% (106/972), for the initial identification of NTM strains using DNA microarray method for NTM strain identification.Results One hundred and six strains of NTM were identified by DNA microarray method. There were 14 species of bacteria. The top 3 strains were 55 strains of Mycobacteria intracellulare (51.89%), 19 strains of Mycobacterium avium (17.92%) and 13 strains of Mycobacterium kansasii (12.26%). The remaining ones were: 4 strains of Mycobacteria chelonae-abscessus (3.77%), 3 strains of Mycobacterium scrofulaceum (2.83%), 3 strains of Mycobacterium gordonae (2.83%), and 2 strains of Mycobacterium terrae (1.89%), the other 7 strains (6.60%).Conclusion In 2017, the clinical isolation rate of NTM in Shaoxing accounted for 10.91% of the positive strains of mycobacterial culture, and there were many NTM species. Mycobacterium intracellulare, Mycobacterium avium and Mycobacterium kansasii were the main epidemic strains of NTM in Shaoxing.

      Detection value of the second-generation linear probe technique for drug resistance in Mycobacterium tuberculosis culture-positive isolates
      JIANG Li-na,MU Cheng,SUN Rui,WANG Zhi-rui,DAI Wen-xi,WANG Chun-hua
      Chinese Journal of Antituberculosis. 2019, 41(11):  1184-1190.  doi:10.3969/j.issn.1000-6621.2019.11.008
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      Objective To evaluate the clinical application value of second-generation linear probe technique (GenoType MTBDRplus VER 2.0, called “GenoType 2.0”) for rapid detection of resistance to isoniazid (INH) and rifampicin (RFP) in clinical isolates of Mycobacterium tuberculosis (MTB). Methods A total of 6315 sputum specimens from suspected tuberculosis patients in the reference laboratory of Tianjin Tuberculosis Control Center from April 2017 to April 2019 were collected, and 349 strains identified as MTB by smear positive, culture positive and flora positive were served as the research objects. Conventional drug susceptibility testing (DST) and GenoType 2.0 assay were, respectively, used to detect resistance to RFP and INH of culturing-positive specimens. Based on DST as the reference standard, the detection efficiency of GenoType 2.0 assay were evaluated. Results The detection rates of RFP-sensitive, single resistance to RFP and multi-drug resistance to RFP and INH were 86.53% (302/349), 87.97% (307/349) and 86.25% (301/349) in GenoType 2.0; 2.58% (9/349), 2.29% (8/349) and 2.29% (8/349) in DST; and 10.89% (38/349), 9.74% (34/349) and 11.46% (40/349) in GenoType 2.0+DST, respectively, all the comparisons between GenoType 2.0 and DST, GenoType 2.0+DST and GenoType 2.0 or GenoType 2.0+DST and DST did not assign statistical significance (χ2=0.322, P=0.851; χ2=0.112, P=0.946; χ2=0.546, P=0.761). The detection rates of INH-sensitive, single resistance to INH and multidrug resistance to RFP and INH were 79.94% (279/349), 80.23% (280/349) and 79.65% (278/349) in GenoType 2.0; 9.17% (32/349), 9.46% (33/349) and 9.46% (33/349) in DST; and 10.89% (38/349), 10.32% (36/349) and 10.89% (38/349) in GenoType 2.0+DST, respectively, all the comparisons between GenoType 2.0 and DST, GenoType 2.0+DST and GenoType 2.0 or GenoType 2.0+DST and DST did not assign statistical significance (χ2=0.071, P=0.965; χ2=0.017, P=0.991; χ2= 0.061, P=0.970). Compared with DST, the sensitivity, specificity, coincidence rate, Kappa value of GenoType 2.0 to RFP and INH resistance tests were 91.67% (44/48) and 95.89% (70/73), 99.00% (298/301) and 100.00% (276/276), 97.99% (342/349) and 99.14% (346/349), 0.91 and 0.97, respectively. Conclusion The GenoType 2.0 assay has high sensitivity and specificity as well as shorter detection period for the detection of RFP and INH resistance, and thus it can meet the needs of clinical early diagnosis and timely treatment of tuberculosis.

      Analysis of catastrophic health expenditure and its influencing factors in patients with rifampicin-resistant pulmonary tuberculosis
      YANG Tian-chi,CHEN Qin,CHEN Tong,YU Mei,LIN Xiang
      Chinese Journal of Antituberculosis. 2019, 41(11):  1191-1196.  doi:10.3969/j.issn.1000-6621.2019.11.009
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      Objective To understand the incidence of catastrophic health expenditure (CHE) and its influencing factors in patients with rifampicin-resistant tuberculosis (TB).Methods Ninety-two patients (confirmed by sputum culture of Mycobacterium tuberculosis, rifampicin and isoniazid susceptbility test of clinical isolates) who were registered from 2016 to 2017 in the drug-resistant TB designated hospital in Ningbo and treated for at least 12 months were selected to participant in a questionnaire survey on the economic burden of TB, 85 participants completed the survey with an effective rate of 92.4%. According to recommendation given by World Health Organization, CHE was defined as health expenditure exceeding 40% of the family’s capacity to pay, incidence of household CHE were then calculated. Chi-square test was conducted to screen out suspicious factors with α=0.10, then multivariate logistic regression was conducted to identify influencing factors of CHE with the suspicious factors as independent variables and α=0.05.Results 71.8% (61/85) of those families surveyed had CHE due to TB. Multivariate logistic regression analysis showed that families with high annual per capita income (“RMB 25000 yuan-”:OR=0.179, 95%CI=0.035-0.906, P=0.038; “≥RMB 40000 yuan”:OR=0.118, 95%CI=0.023-0.605, P=0.010) had a lower risk of CHE comparing with those with low annual per capita income (“<RMB 15000 yuan”), and families with patients hospitalized for TB (OR=5.623, 95%CI=1.739-18.178, P=0.004) had a higher risk of CHE.Conclusion The incidence of CHE in patients with rifampicin-resistant TB is high. Hospitalization for TB is a risk factor of CHE, high annual per capita income of the family is a protective factor.

      Application of closed-loop management in safe drug administration among elderly tuberculosis patients
      ZHANG Ning,MA Yun,WANG Rong,CUI Bei,LIU Li
      Chinese Journal of Antituberculosis. 2019, 41(11):  1197-1202.  doi:10.3969/j.issn.1000-6621.2019.11.010
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      Objective To analyze the application effect of using closed-loop management for safe drug administration among elderly tuberculosis patients.Methods Three hundred and two elderly patients with pulmonary tuberculosis treated in Shaanxi Provincial Tuberculosis Hospital from January 1, 2017 to December 30, 2017 were enrolled as control group, for whom situation of medication non-compliance in the course of treatment were investigated. 295 elderly patients with pulmonary tuberculosis treated from January 1, 2018 to December 30, 2018 were enrolled as observation group. Closed-loop management was implemented on the observation group to correct those medication non-compliances found in the control group which included establishing drug safety management protocol and implementing management, evaluating the effect of the implementation, analyzing problems existing during the safe medication management process, and rectifying and tracking problems found. The compliance of taking medicine, the incidence and detection rate of adverse drug reactions were compared between those two groups.Results In observation group, 95.60% (282/295) patients took medicine timely, and the detection rate of adverse drug reactions was 92.11% (105/114), both of them were higher than that in control group (medicine taking correctness 74.83%(226/302), detection rate 76.74% (99/129)).Those differences were statistically significant (χ 2=50.694,10.599, P=0.000, 0.001). The difference of the incidence of adverse drug reactions rate in two group was not statistically significant (observation group 38.64% (114/295), control group 42.72% (129/302), χ 2=1.025,P=0.311).Conclusion Closed-loop management can improve the compliance of medicine taking. It has no effect on the incidence of adverse drug reactions but can improve the detection rate, and increase the safety of medication among elderly patients with pulmonary tuberculosis.

      Analysis of influencing factors for prognosis of tuberculous meningitis patients with consciousness disorder
      WANG Man-zhi,CHEN Fang,WEI Song-qing,ZHOU Hai-yi,HU Jin-yue,XIE He-bin,ZHANG Xiao-fo,LI Jia,SHI Jia-yun,WU Lei
      Chinese Journal of Antituberculosis. 2019, 41(11):  1203-1210.  doi:10.3969/j.issn.1000-6621.2019.11.011
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      Objective To analyze influencing factors for prognosis of tuberculous meningitis (TBM) with disturbance of consciousness.Methods Clinical data of 112 patients with consciousness disorder and TBM in Changsha Central Hospital from January 2013 to January 2019 was retrospectively analyzed. 21 (18.8%) patients were definite TBM cases while 84 (75.0%) were probable TBM cases, and 7 (6.2%) were possible TBM cases. According to their scores of modified Rankin scale (mRS) assessed at discharge from hospital, patients were divided into 48 (42.9%) patients with good prognosis and 64 (57.1%) patients with poor prognosis. There were 24 males with good prognosis. The median age was 18.50 (5.31, 3.75) years and the median duration of disease was 20.00 (11.25, 30.00) days. There were 20 males in the poor prognosis group, with a median age of 27.00 (3.06, 49.75) years and a duration of 15.00 (10.00, 20.00) days. Logistic regression analysis was used to analyze influencing factors of poor prognosis of patients.Results Univariate analysis showed that hospital stay (Z=-1.982, P=0.048), sex (χ 2=4.043, P=0.044), disease stage (χ 2=17.733, P=0.000), convulsion (χ 2=8.054, P=0.005), hyponatremia (χ 2=9.481, P=0.002), brain edema (χ 2=4.386, P=0.036), hydrocephalus (χ 2=5.992, P=0.014) were influencing factors for poor prognosis among TBM patients with impaired consciousness. Multivariate analysis showed that hyponatremia (P=0.043, OR=2.784, 95%CI:1.034-7.495), stage Ⅲ of consciousness disturbance (P=0.002, OR=6.855, 95%CI:2.001-23.480), encephaledema (P=0.030, OR=3.491, 95%CI:1.132-10.768) were risk factors for poor prognosis. Conclusion Hyponatremia, stage Ⅲ of disease and brain edema are the main influencing factors for poor prognosis for TBM patients with disturbance of consciousness.

      A randomized controlled clinical study of different interventional techniques in the treatment of inflammatory infiltrative type endobronchial tuberculosis
      GUO Chun-hui,ZHANG Ying,SU Yan-ju,WANG Xiao-rui,CAI Ying-bo,SHAO Ming-hui,JIN Li-li,LIN Hong,JI Bin-ying
      Chinese Journal of Antituberculosis. 2019, 41(11):  1211-1216.  doi:10.3969/j.issn.1000-6621.2019.11.012
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      Objective To analyze the earlier clinical efficacy for inflammatory infiltrative type endobronchial tuberculosis with three interventional techniques which was intra-airway administration, cryotherapy and cryotherapy combined with intra-airway administration.Methods One hundred and eighty patients with inflammatory infiltrative type endobronchial tuberculosis admitted in Harbin Chest Hospital were randomly divided into three groups which were drug perfusion group, cryotherapy group and combined treatment group during November, 2015 to June, 2017. There were 60 patients in each group. All patients were received chemotherapy with 2H-R-Z-E/10H-R-E and interventional treatment under bronchoscopy once one week. Isoniazid with 0.3 gram was injected in local site of bronchial under bronchoscopy in drug perfusion group. The freezing alone was performed in the cryotherapy group, and the cryotherapy combination with injection of INH with 0.3 gram was conducted in the combined treatment group under bronchoscopy. The improvement of clinical symptoms (cough, expectoration), the absorption of lesions under bronchoscopy, the negative conversion of sputum bacteria, the absorption of obstructive pneumonia in the lungs and the occurrence of adverse reactions were observed and recorded after 1, 2 and 6 months of treatment, and the results were compared and analyzed.Results The median number of treatment times (M(Q1,Q3)) was 4 (3, 5) in the cryotherapy group and in the combined treatment group each other, which were significantly lower than those in the drug perfusion group 6 (4, 7) times) (χ 2=28.62, P<0.01). One month after treatment, in the cryotherapy group and combined treatment group, the sputum negative conversion rate (88.3% (53/60) and 90.0% (54/60)), the effective absorption rate under bronchoscopy (71.7% (43/60) and 73.3% (44/60)), the improvement rate of clinical symptoms (cough, expectoration) (95.0% (57/60) and 96.7% (58/60)) and showed that the absorption rate of obstructive pneumonia showed in pulmonary CT imaging (77.3% (17/22) and 78.9% (15/19)) were significantly higher than those (70.0% (42/60), 51.7% (31/60), 66.7% (40/60), and 40.0% (8/20)) of drug perfusion group with the significant differences statistically (χ 2 values were 10.37, 7.73, 28.52, 8.63 in each, and P were 0.006, 0.021, <0.01, 0.013, respectively). At the end of 2 months after treatment, in the cryotherapy group and combined treatment group, the sputum negative conversion rate (100.0% (60/60) and 100.0% (60/60)) and the effective absorption rate under bronchoscopy (96.7% (58/60) and 96.7% (58/60)) were significantly higher than those (90.0% (54/60) and 85.0% (51/60)) in drug perfusion group with the significant differences statistically (χ 2 were 12.41 and 8.12, respectively, and P were 0.002 and 0.017, respectively). The effective absorption of obstructive pneumonia in the drug perfusion group, cryotherapy group and combined treatment group was 80.0% (16/20), 90.9% (20/22) and 89.5% (17/19), respectively, with no significant difference (χ 2=1.26, P=0.534), and the clinical symptoms (cough, expectoration) disappeared. After 6 months of treatment, all sputum bacteria in the three groups were negative conversion, and the lesions, clinical symptoms (cough, expectoration) and obstructive pneumonia disappeared in the three groups. Conclusion Cryotherapy can promote quickly sputum negative conversion of inflammatory infiltrative type endobronchial tuberculosis, focus absorption, effective improvement of the clinical symptoms, recovering bronchial patency, and no obvious adverse reactions. It is a safe and effective treatment technique.

      Technical Communication
      Screening and identification of serological diagnostic antigens for tuberculosis
      YANG Shuang,GUO Jing-wei,HU Yi-min,TAN Yun-hong,TAN Xiao,YUAN Shi-shan
      Chinese Journal of Antituberculosis. 2019, 41(11):  1217-1222.  doi:10.3969/j.issn.1000-6621.2019.11.013
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      Objective To screen and identify the antigens of Mycobacteria tuberculosis (MTB) that can be specifically recognized by serum of tuberculosis patients.Methods The standard strain H37Rv of MTB was cultured in L-J medium for four weeks, and then collected to extract MTB antigens using ice bath ultrasound. The serum of 30 newly treated tuberculosis patients admitted to Hunan Provincial Institute of Tuberculosis Prevention and Control for the first time from February to July 2013 was collected. Meanwhile, the serum of 20 health examinees received by the clinical laboratory of Hunan Provincial People’s Hospital in July 2013 was collected. Next, the IgG of 20 tuberculosis patients was extracted by saturated ammonium sulfate precipitation. The serological antigens were screened from the crude antigens of MTB by co-immunoprecipitation and verified in the remaining 10 tuberculosis patients by Western blot. The positive protein band was cut from sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gel and identified by the tandem mass spectrometry.Results One protein band in 16 kDa specifically recognized by serum of tuberculosis patients was screened from the crude antigens of MTB by co-immunoprecipitation. Based on the tandem mass spectrometry analysis, 3 protein antigens were achieved as heat shock protein 16.3 (Hsp16.3), glycosyltransferase and iron-regulated Lsr2 protein precursor.Conclusion Three serological antigens were obtained from the crude antigens of MTB by co-immunoprecipitation and the tandem mass spectrometry, which may provide further evidence for the selection of serological diagnostic antigens for tuberculosis.

      Review Articles
      Progress on the application of matrix-assisted laser desorption ionization-time of flight mass spectrometry in the field of tuberculosis research
      MU Cheng,WANG Chun-hua
      Chinese Journal of Antituberculosis. 2019, 41(11):  1223-1226.  doi:10.3969/j.issn.1000-6621.2019.11.014
      Abstract ( 563 )   HTML ( 7 )   PDF (819KB) ( 273 )   Save
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      Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has the advantages of high throughput, high speed, automation, etc., has become an important tool for bio-macromolecular research. It has made remarkable progress on clinical research and has become increasingly prominent in the field of tuberculosis research. This review mainly introduced the application of MALDI-TOF MS in the identification of mycobacterium, research of drug-resistance tuberculosis, screening of tuberculosis serum markers, detection of tuberculosis susceptibility gene polymorphisms and research of anti-tuberculosis drug metabolism in order to strengthen the understanding to MALDI-TOF MS in the field of tuberculosis research.

      Clinical features of erythema nodosum and its diagnostic value for tuberculosis
      YANG Song,YAN Xiao-feng
      Chinese Journal of Antituberculosis. 2019, 41(11):  1227-1230.  doi:10.3969/j.issn.1000-6621.2019.11.015
      Abstract ( 553 )   HTML ( 7 )   PDF (767KB) ( 489 )   Save
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      Erythema nodosum (EN) is a common sign in department of dermatology and can be seen in systemic multiple system diseases. The purpose of this article is to explore the clinical features of erythema nodosum and to evaluate its diagnostic value for active tuberculosis (TB). Clinically, erythema nodosum presents with a sudden onset of red, painful, subcutaneous soft nodules and plaques, mainly localized to the extension of calf. EN may be associated with a variety of conditions such as infection, medications, sarcoidosis, pregnancy, inflammatory bowel disease, oral contraceptive, autoimmune disease, antibiotics, hormone response, lymphoma and other malignancy causes. The causes are unclear in around 50% of cases. It is well known that EN is a delayed hypersensitivity reaction induced by various stimulants. The clinical diagnosis for the atypical cases mainly depend on the biopsy or diagnostic treatment. Because of the complex etiology of EN, systemic diseases such as skin tuberculosis, leprosy, sarcoidosis and nodular arteritis need to be excluded. In the TB epidemic area, Mycobacterium tuberculosis infection (MTI) and active tuberculosis are closely related to EN. It is helpful to improve the EN symptoms, prevent EN relapse and control the active TB conditions through anti-tuberculous treatment in the patients who have active TB combined with EN and MTI with EN. EN can be associated with systemic multisystem diseases including tuberculosis, but further studies need to be done to reveal the underlying causes of EN. EN may be an early symptom of TB. It can be helpful for early diagnosis and treatment of the patients who have MTI with EN or TB with EN by the combination of tuberculin skin test (TST), acid-fast bacillus (AFB) detection and imaging techniques or diagnostic anti-tuberculosis treatment.

Monthly, Established in Novembar 1934
ISSN 1000-6621
CN 11-2761/R

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