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    Interpretation of WHO consolidated guidelines on tuberculosis: Module 3: diagnosis: tests for tuberculosis infection
    Xin Henan, Gao Lei
    Chinese Journal of Antituberculosis    2023, 45 (7): 639-643.   DOI: 10.19982/j.issn.1000-6621.20230128
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    On September 30, 2022, the World Health Organization (WHO) published the WHO consolidated guidelines on tuberculosis: Module 3: diagnosis: tests for tuberculosis infection. The medical evidence-based guideline systematically evaluated the performance of different tests and recommended using of Mycobacterium tuberculosis antigen-based skin tests for the diagnosis of tuberculosis infection for the first time. The author now introduces the development of the new guideline and interprets the three key recommendations hoping to provide evidence-based reference for tuberculosis infection test and control.

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    Interpretation of WHO consolidated guidelines on tuberculosis: Module 1: prevention: tuberculosis preventive treatment
    Guo Tonglei, Xin Henan, Gao Lei
    Chinese Journal of Antituberculosis    2023, 45 (8): 723-727.   DOI: 10.19982/j.issn.1000-6621.20230199
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    World Health Organization (WHO) published the WHO consolidated guidelines on tuberculosis: Module 1: prevention: tuberculosis preventive treatment (2020 version guideline) on February 25, 2020, and guided the implementation of the 2020 version guideline through the implementation manual which contains the details of the implementation of guidance recommendations. The 2020 version guideline integrates the latest research since the WHO released Latent tuberculosis infection: updated and consolidated guidelines for programmatic management in 2018, and updates some recommendations. The author introduces the 2020 version guideline and interprets its key recommendations, hoping to provide a reference for the implementation of tuberculosis preventive treatment in China.

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    Expert consensus on clinical monitoring and management of QTc interval prolongation caused by anti-tuberculous drugs
    Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis, Beijing Chest Hospital, Capital Medical University
    Chinese Journal of Antituberculosis    2024, 46 (1): 8-17.   DOI: 10.19982/j.issn.1000-6621.20230271
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    Bedaquiline, delamanid, clofazimine and fluoroquinolones such as levofloxacin and moxifloxacin are essential to improve the global cure rate of multidrug resistant and extensively drug-resistant tuberculosis. However, these drugs may lead to the prolongation of QTc interval corrected by electrocardiograph, which may cause serious adverse effects. Clinicians need to timely find, properly deal with and prevent adverse effects. This article aims at the common problems in clinical monitoring and management of QTc interval prolongation caused by anti-tuberculous drugs. According to the published research data and the application experience of participating experts, it was formed through discussion among many experts. Professional advice was given on the discovery, treatment and prevention of QTc interval prolongation caused by anti-tuberculous drugs, aiming at timely and standardized prevention and treatment of adverse reactions in the process of anti-tuberculous treatment.

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    Expert consensus on the diagnosis and treatment of superficial lymph node tuberculosis
    Senior Department of Tuberculosis, the th Medical Center of Chinese PLA General Hospital, Editorial Board of Chinese Journal of Antituberculosis, Tuberculosis Control Branch of China Intrnational Exchange and Promotive Association for Medical and Health Care
    Chinese Journal of Antituberculosis    2023, 45 (6): 531-542.   DOI: 10.19982/j.issn.1000-6621.20230120
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    Superficial lymph node tuberculosis is the most common extrapulmonary tuberculosis. Due to the lack of specificity in its clinical symptoms, it is hard to differentiate it from non-tuberculous lymphadenitis, lymphoma, lymph node metastatic cancer, and other diseases. At present, there are many treatment methods for superficial lymphoid tuberculosis, mainly including systemic chemotherapy, local treatment, and integrated treatment with traditional Chinese and western medicine, while local treatment includes local injection of anti-tuberculosis drugs, ultrasonic drug penetration, and focal clearance and resection. Due to the advantages and disadvantages of each treatment scheme, it is better to choose appropriate treatment methods for specific types. How to select a reasonable treatment plan still lacks relevant guidance documents. Therefore, to standardize the diagnosis and treatment of superficial lymph node tuberculosis, and improve the level of clinicians to enable the patients to recover early and reduce recurrence, the Eighth Medical Center of Chinese PLA General Hospital, the Editorial Board of the Chinese Journal of Antituberculosis, and the Basic and Clinical Speciality Committees of the Tuberculosis Control Branch of China International Exchange and Promotive Association for Medical and Health Care jointly organized experts to combine the experience and methods of diagnosis and treatment of superficial lymph node tuberculosis in China, as well as research results related to diagnosis and treatment abroad, to formulate Expert consensus on the diagnosis and treatment of superficial lymph node tuberculosis. This consensus outlines the epidemiology, pathogenesis, pathophysiological characteristics and main clinical manifestations of superficial lymph node tuberculosis. It also introduces common examination methods, puts forward the diagnostic criteria, differential diagnosis, and prognosis, and gives treatment suggestions according to different clinical stages and pathological types, so that the clinicians can accurately diagnose and reasonably treat the patients with superficial lymph node tuberculosis.

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    Expert consensus on the clinical application of nucleic acid MALDI-TOF MS technique in the diagnosis of tuberculosis and non-tuberculosis mycobacteriosis
    Senior Department of Tuberculosis, the th Medical Center of Chinese PLA General Hospital, Editorial Board of Chinese Journal of Antituberculosis, Tuberculosis Control Branch of China Intrnational Exchange and Promotive Association for Medical and Health Care
    Chinese Journal of Antituberculosis    2023, 45 (6): 543-558.   DOI: 10.19982/j.issn.1000-6621.20230113
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    Nucleic acid matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) technique has been increasingly applied in the etiology and drug resistance diagnosis of tuberculosis and non-tuberculous mycobacteriosis, providing a rapid and accurate basis for early diagnosis, differential diagnosis, and drug resistance identification. However, it needs to be normalized that the clinician’s understanding and grasp of sample selection, retention, submitting time and precautions, and interpretation of report results. This consensus summarizes the clinical indications and specimen collection precautions of nucleic acid MALDI-TOF MS detection technique for the diagnosis of tuberculosis and non-tuberculous mycobacteriosis, and introduces how to correctly interpret the reported results of nucleic acid MALDI-TOF MS technique used to mycobacterial species and drug resistance. It has important significance to further standardize the clinical application of nucleic acid MALDI-TOF MS technique in the diagnosis of tuberculosis and non-tuberculous mycobacteriosis, improve the level of clinical diagnosis, and guide the early accurate and effective clinical treatment.

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    Study on the detection of rifampicin resistance of Mycobacterium tuberculosis in sputum samples using fluorescence PCR probe melting curve technique
    Wang Nenhan, Tian Lili, Chen Shuangshuang, Zhao Yanfeng, Fan Ruifang, Chen Hao, Ren Yixuan, Zhang Jie, Yi Junli, Yang Xinyu, Yu Lan, Ding Beichuan, Li Chuanyou, Dai Xiaowei
    Chinese Journal of Antituberculosis    2023, 45 (6): 583-588.   DOI: 10.19982/j.issn.1000-6621.20230086
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    Objective: To evaluate the application value of the fluorescence PCR probe melting curve (MeltPro) technique in the detection of rifampicin-resistance of Mycobacterium tuberculosis (MTB) in sputum samples. Methods: Sputum samples of primary treated pulmonary tuberculosis (PTB) with positive GeneXpert MTB/RIF from Beijing Center for Disease Control and Prevention between May 2021 and May 2022 were collected. These sputum samples were tested using smear, mycobacterium isolation, and rifampicin-resistance by MeltPro technique. Drug sensitivity test (DST) of rifampicin was used for culturing positive strains, the differences in the detection rate of rifampicin resistance using DST, GeneXpert MTB/RIF, and MeltPro technique were compared. The proportional DST results of rifampicin were used as a standard to evaluate the drug-resistance detection efficiency of MeltPro technique. Results: A total of 158 qualified positive MTB sputum samples were collected, after mycobacterium culture, 130 strains were got. The success rate of the detection by MeltPro technique for rifampicin in sputum samples was 79.1% (125/158). As the grade of sputum smear results increased, the success rate of MeltPro technique increased from 59.3% (32/54, negative) to 100.0% (18/18, positive, grade +++); the success rate also increased with the increase of MTB grade detected by GeneXpert MTB/RIF, from 64.5% (20/31, extremely low) to 92.9% (26/28, high), the differences between each grade were statistically significant (H=22.271, P=0.001; H=15.637, P=0.001). The detection rates of rifampicin resistance using MeltPro technique, GeneXpert MTB/RIF method and proportional DST were 17.6% (22/125), 12.7% (20/158) and 13.1% (17/130), respectively. There was no statistically significant difference between the three methods (χ2=1.537, P=0.464). Based on the results of proportional DST, the sensitivity, specificity, positive predictive value, negative predictive value, Kappa of MeltPro technique in the detection of rifampicin were 100.0% (17/17), 94.6% (88/93), 77.3% (17/22), 100.0% (88/88), 0.845, respectively, and were 100.0% (17/17), 97.3% (110/113), 85.0% (17/20), 100.0% (110/110), 0.906, respectively of GeneXpert MTB/RIF in the detection of rifampicin. Conclusion: The MeltPro technique has high sensitivity and specificity in detecting rifampicin resistance of MTB in sputum samples of PTB, and can quickly and accurately screen the rifampicin resistance; attention should be paid to the quality of sputum samples when promoting the application in grassroots laboratories.

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    Progress on economic burden of patients with drug-resistant tuberculosis
    Wang Boning, Li Tao, Chen Wei
    Chinese Journal of Antituberculosis    2023, 45 (6): 607-612.   DOI: 10.19982/j.issn.1000-6621.20230018
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    While the global tuberculosis epidemic has shown a decline trend in recent years, the economic burden induced by drug-resistant tuberculosis has increased. The reason is that the treatment of drug-resistant tuberculosis is expensive, the course of the disease is prolonged, and the side effects of treatment are serious. The authors reviewed the economic burden of drug-resistant tuberculosis and revealed the current research status of the economic burden of drug-resistant tuberculosis and its influencing factors to provide a reference for subsequent researches and medical insurance policy formulation.

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    Development process of setting of critical concentrations for phenotypic drug susceptibility testing of Mycobacterium tuberculosis
    Song Yuanyuan, Xia Hui, Zhao Yanlin
    Chinese Journal of Antituberculosis    2023, 45 (7): 631-638.   DOI: 10.19982/j.issn.1000-6621.20230153
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    Phenotypic drug susceptibility testing of Mycobacterium tuberculosis remains a crucial method for detecting drug resistance. However, the accuracy and reproducibility of certain drugs are sub-optimal with critical concentration being one of the key factors affecting results. This article provides a systematic summary and introduction on establishing and revising critical concentrations for anti-tuberculosis drug susceptibility testing, and offered valuable guidance to laboratory technicians and clinicians for accurately interpreting drug susceptibility testing methods and results, as well as to facilitate critical concentration research.

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    Application of ARIMA, ARIMAX, and NGO-LSTM models in forecasting the incidence of tuberculosis cases in Liaocheng City, Shandong Province
    Sun Minghao, Duan Yuqi, Zheng Liang, Yu Shengnan, Cheng Chuanlong, Zuo Hui, Chen Ming, Li Xiujun
    Chinese Journal of Antituberculosis    2023, 45 (12): 1177-1185.   DOI: 10.19982/j.issn.1000-6621.20230253
    Abstract344)   HTML15)    PDF(pc) (2008KB)(114)       Save

    Objective: The purpose of this study was to determine the optimal model for predicting tuberculosis incidence in Liaocheng City, Shandong Province by comparing the Autoregressive Integrated Moving Average (ARIMA) model, the Autoregressive Integrated Moving Average with Exogenous Regressors (ARIMAX) model, and the Long Short-Term Memory (LSTM) model combined with the Northern Goshawk Optimization (NGO) algorithm. Methods: Monthly tuberculosis case data from January 2011 to December 2018 were collected. We constructed ARIMA model, ARIMAX model, and NGO-LSTM model based on data from January 2011 to December 2017, respectively, and evaluate the performance of the three models in predicting the number of tuberculosis cases in 2018. Results: The mean absolute percentage errors (MAPE) for the ARIMA model, the multivariate ARIMAX model considering the monthly average relative humidity (lagged by 1 month) and the minimum temperature (lagged by 2 months), and the NGO-LSTM model for predicting tuberculosis incidence in 2018 were 9.293%, 8.419%, and 5.820%, respectively. The mean absolute errors (MAE) were 19.282, 16.997, and 13.119, respectively, and the root mean square errors (RMSE) were 23.773, 22.191, and 16.297, respectively. Conclusion: Among the three models, the NGO-LSTM model had the best predictive performance for monthly tuberculosis incidence in Liaocheng City, providing a new idea for the establishment of a tuberculosis alerting system and scientific basis for relevant departments to make decisions on tuberculosis prevention and control policy.

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    Recent advances in the source and biological function of bacterial DNA in extracellular vesicles
    Liu Dingyi, Sun Hong, Sheng Gang, Sun Zhaogang
    Chinese Journal of Antituberculosis    2023, 45 (7): 693-698.   DOI: 10.19982/j.issn.1000-6621.20230060
    Abstract340)   HTML18)    PDF(pc) (736KB)(195)       Save

    Cells can release their own substances or metabolites outside the cell through extracellular vesicles, which is also known as EV (exosomes). As research progressed, it is discovered that bacteria can also produce exosomes that encapsulate many macromolecules (including proteins, lipids, DNA and RNA) and that bacterial exosomes are closely linked to a variety of biological activities, including bacterial survival and development, as well as bacterial-mediated intra- and inter-species interactions. Researchers have also found that both Gram-negative and Gram-positive bacteria can produce exosomes containing DNA, and that bacterial exosomes DNA can perform biological functions such as mediating horizontal gene transfer, assisting in biofilm formation, and stimulating immunomodulatory mechanisms. In this paper, the production mode and biological functions of bacterial extracellular DNA have been elucidated, so that readers can have deeper understanding of bacterial exosomes DNA and promote further research and development of bacterial exosome DNA.

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    Analysis of the incidence and risk factors of activepulmonary tuberculosis among close contacts in Kashgar, Xinjiang Uygur Autonomous Region
    Peng Xiaowang, Fan Xiaolei, Xiang Yang, Maiwulajiang·Yimamu , Hu Pengyuan, Wang Yanjie, Teng Zihao
    Chinese Journal of Antituberculosis    2023, 45 (6): 601-606.   DOI: 10.19982/j.issn.1000-6621.20230010
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    Objective: To analyze the incidence and influencing factors of close contacts of active pulmonary tuberculosis patients in Kashgar, Xinjiang Uygur Autonomous Region, and to provide a scientific basis for the development of close contact screening strategies. Methods: Data of 11411 active pulmonary tuberculosis (TB) patients registered and reported in Kashgar, Xinjiang Uygur Autonomous Region were collected, excluding 58 deaths, no close contacts, and incomplete information, 11353 active TB patients were actually included as indicated cases, from January to June 2018 reported in the “Tuberculosis Management Information System”, a subsystem of the “China Disease Prevention and Control Information System”. Close contacts were identified through household interviews and face-to-face questionnaires, cohorts were established, general demographic information were obtained, and screening for suspicious symptoms of TB, chest X-ray and sputum smear, etc.. The comprehensive diagnosis was made by a team of experts from the designated TB medical institution, and close contacts not diagnosed with active TB were followed up for three years (once a year). Multifactorial logistic regression was used to analyze the risk factors of the occurrence of active TB in close contacts. Results: A total of 25577 close contacts were identified in 11353 indicated cases, with an average of approximately 2.25 close contacts traced per indicated case. Active TB was detected in 2106 cases during the 3-year follow-up period, with an incidence rate of 8.26%. Multifactorial logistic regression analysis showed that male (OR (95%CI): 1.396 (1.260-1.546)), primary treatment (OR (95%CI): 1.605 (1.413-1.824)), and age 15-34 years (OR (95%CI): 1.318 (1.033-1.682)) or 35-54 years (OR (95%CI): 3.054 (2.717-3.432)) were independent risk factors for the development of active TB in the close contacts. Close contacts with a history of previous TB disease (OR (95%CI): 22.447 (18.570-27.134)), age ≤14 years (OR (95%CI): 2.792 (2.224-3.507)) and ≥55 years (OR (95%CI): 2.089 (1.777-2.457)), and social relationships with the indicated case’s were parents (OR (95%CI): 6.521 (4.284-9.926)), spouse (OR (95%CI): 6.311 (4.478-8.894)), children (OR (95%CI): 6.708 (4.739-9.495)), grandchildren (OR (95%CI): 10.003 (6.702-14.930)), siblings (OR (95%CI): 4.851 (3.171-7.422)), grandparents (OR (95%CI)=9.976 (4.083-24.375)), relatives (OR (95%CI)=2.456 (1.363-4.428)), and village doctors (OR (95%CI): 7.166 (2.110-16.339)), were all independent risk factors for the development of active TB among them. Conclusion: The incidence of active TB is high among close contacts in Kashgar. In patient management and health education, emphasis should be focused on male, newly treated, and middle-aged and young patients; meanwhile, screening and follow-up should be focused on close contacts with a previous history of TB, the elderly, the young and those who with close social relations with the patients.

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    Interpretation of the World Health Organization's Use of targeted next-generation sequencing to detect drug-resistant tuberculosis Rapid communication, 2023
    Huang Hairong
    Chinese Journal of Antituberculosis    2023, 45 (10): 921-924.   DOI: 10.19982/j.issn.1000-6621.20230311
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    The World Health Organization released “Use of targeted next-generation sequencing to detect drug-resistant tuberculosis Rapid communication,2023” recently, in order to timely share the important data and opinions formed accordingly on drug resistance detection by the targeted next-generation sequencing technique. Therefore, facilitate the understanding of this new technique and accelerate its promotion. This note interpreted the key data and the opinions in the rapid communication, so as to help the reader to recognize the value of the targeted next-generation sequencing technique in the diagnosis of drug resistant tuberculosis.

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    Analysis of drug resistance characteristics of pulmonary tuberculosis in children in Guangdong, 2014—2020
    Zhuo Wenji, Zhang Chenchen, Chen Xunxun, Wei Wenjing, Yu Meiling, Peng Kehao, Xu Liuyue, Chen Yanmei
    Chinese Journal of Antituberculosis    2023, 45 (7): 687-692.   DOI: 10.19982/j.issn.1000-6621.20230109
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    Objective: To investigate the drug resistance characteristics of Mycobacterium tuberculosis (MTB) isolates from children with pulmonary tuberculosis (PTB) in Guangdong Province from 2014 to 2020. Methods: According to the enrollment standard, 1274 (3.3%) MTB isolates from children aged 0 to 18 were collected from 32 sentinel sites of PTB resistance surveillance (39046 MTB isolates) in Guangdong Province from January 1, 2014 to December 30, 2020. Analysed the data of drug resistance of MTB isolates for first- and second-line of anti-TB drugs (including isoniazid (INH), streptomycin (Sm), ethambutol (EMB), rifampicin (RFP), kanamycin (Km), propylthioisoniacin (Pto), capreomycin (Cm), ofloxacin (Ofx), and sodium p-aminosalicylate (PAS)) and summarized the drug resistance characteristics. Results: The proportion of PTB children was dropped from 4.3% (123/2856) in 2014 to 3.1% (177/5760) in 2020, showing a downward trend of year by year ($X_{trend}^{2}$=25.864, P<0.001). The resistance rates of the isolates to anti-TB drugs from high to low were Sm (14.8% (189/1274))>INH (7.7% (98/1274))>RFP (6.3% (80/1274))>EMB (6.0% (77/1274))>Ofx (3.5% (44/1274))=PAS (3.5% (44/1274))>Pto (2.9% (37/1274))>Km (2.5% (32/1274))>Cm (2.2% (28/1274)), and the drug resistance rate, mono-resistance rate, poly-resistance rate, multidrug-resistance rate (MDR) and extensively drug resistance rate (XDR) of MTB of the 1274 isolates was 26.0% (331/1274), 15.4% (196/1274), 4.2% (54/1274), 3.1% (39/1274), and 0.8% (10/1274), respectively. The XDR of MTB in children aged 0 to 12 was significantly higher than that in children aged 13 to 18 (3.0% (3/100) vs. 0.6% (7/1174); χ2=6.837, P=0.038). In addition, the XDR of MTB in boys was significantly higher than that in girls (1.3% (10/749) vs. 0.0% (0/525); χ2=10.679, P=0.007), and the resistance rate of MTB in the Pearl River Delta was significantly higher than that in eastern and northwestern Guangdong (28.1% (213/758) vs. 22.9% (118/516); χ2=4.370, P=0.037). Conclusion: The prevalence of PTB in children in Guangdong Province is serious. The drug resistance in PTB children aged 0-12 years, who were boys, and who lived in Pearl River Delta should be paid special attention.

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    Research progress of subclinical tuberculosis
    Wang Hanfei, Zhao Yanlin, Xu Caihong
    Chinese Journal of Antituberculosis    2023, 45 (8): 808-813.   DOI: 10.19982/j.issn.1000-6621.20230159
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    Subclinical tuberculosis is a disease state between latent tuberculosis infection and active tuberculosis. Early detection and intervention of subclinical tuberculosis patients can reduce the risk of developing into active tuberculosis, improve the prognosis, and block the transmission of tuberculosis. This article reviewed domestic and international research progress of subclinical tuberculosis, including the definition, clinical characteristics, transmissibility, pathogenesis, biomarkers, screening and diagnostic methods, in order to identify the current research progress and challenges of subclinical tuberculosis, and provide novel research ideas to accelerate the research on subclinical tuberculosis and exploring more effective tuberculosis prevention and control strategies in China.

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    Chinese Journal of Antituberculosis    2023, 45 (7): 714-717.   DOI: 10.19982/j.issn.1000-6621.20230144
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    Application of regression discontinuity in public health
    Yu Shengnan, Gao Qi, Zheng Liang, Shi Yuan, Chen Yijin, Li Xiujun
    Chinese Journal of Antituberculosis    2023, 45 (7): 644-650.   DOI: 10.19982/j.issn.1000-6621.20230130
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    Regression discontinuity (RD) is a kind of statistical method for making causal inferences based on counterfactuals composed of both sides of the cutoff. In recent years, the application of RD has gradually increased in public health, especially in the fields of factors influencing air quality and the effects of related policy interventions, as well as vaccine effectiveness. Since the outbreak of the COVID-19, RD has also been increasingly applied to investigate the impact of the epidemic on public health and individual behavior. The application conditions of RD are relatively simple, and RD can reduce the effect of confounding and reflect the causal relationship between variables more realistically. In this study, based on the introduction of the idea and application of RD, the current status of its application in public health is reviewed.

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    Analysis of risk factors for extensive lung focus and cavities in type 2 diabetes mellitus patients complicated with newly treated pulmonary tuberculosis
    Wang Min, Yuan Yuan, Tan Shouyong, Yang Zilong, Feng Zhiyu, Zhang Hong, Wu Di, Chen Zeying, Huang Xianlin, Kuang Haobin
    Chinese Journal of Antituberculosis    2023, 45 (8): 761-767.   DOI: 10.19982/j.issn.1000-6621.20230147
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    Objective: To explored the risk factors of extensive lung focus and cavities in type 2 diabetes mellitus (T2DM) patients complicated with newly treated pulmonary tuberculosis (PTB), to provide reference for clinical treatment strategies. Methods: Through electronic medical records and hospital information system, 955 T2DM patients complicated with newly diagnosed positive PTB who were hospitalized in Guangzhou Chest Hospital for the first time from January 2013 to January 2018 were collected for a conducted retrospective study. Univariate and multivariate logistic regression analysis was conducted with extensive lung focus (imaging lung lesions ≥3 lung fields) and cavity as dependent variables, and age, gender, diabetes course, glycosylated hemoglobin, lymphocyte (LY), neutrophil ratio (NLR), and whether metformin was used in recent three months as independent variables. Results: Among the 955 patients, 753 (78.8%) had extensive focus and 659 (69.0%) had cavities. The multivariate logistic regression analysis showed that the history of usage of metformin (OR=0.656, 95%CI: 0.449-0.957) and the high level of LY (OR=0.608,95%CI: 0.404-0.915) were protective factors for the extensive focus of both diseases. The occurrence of cavities (OR=2.094, 95%CI: 1.498-2.926) and the high level of NLR (OR=2.681, 95%CI: 1.860-3.864) were risk factors for the extensive focus of both diseases. The extensive focus (OR=1.945, 95%CI: 1.390-2.719) and high level of glycosylated hemoglobin (OR=1.206, 95%CI: 1.078-1.350), the high level of NLR (OR=1.390, 95%CI: 1.012-1.991) were the risk factors for cavitation. Conclusion: When T2DM complicated with PTB, the extensive focus and cavities were common, and both were risk factors for each other. Treatment that includes metformin should be the first choice for T2DM patients, and active monitoring and management of glycated hemoglobin, lymphocyte and NLR indicators should be carried out to alleviate the disease condition when complicated with tuberculosis.

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    Value of DNA real-time fluorescence isothermal amplification method and combined testing in early diagnosis of tuberculous pleurisy
    Zhao Guolian, Lei Qian, Wang Pei, Ren Yunxia, Guan Jing
    Chinese Journal of Antituberculosis    2023, 45 (7): 681-686.   DOI: 10.19982/j.issn.1000-6621.20230055
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    Objective: To investigate the value of DNA real-time fluorescence isothermal amplification method (abbreviated as “constant temperature amplification method”), combined with adenosine deaminase (ADA) and peripheral blood tuberculosis infection T cell spot test (T-SPOT. TB) detection in the early diagnosis of tuberculous pleurisy. Methods: Using retrospective research method, 427 patients with pleural effusion of unknown causes admitted to Xi’an Chest Hospital from January 2020 to December 2021 were selected as the research objects. All patients underwent pleural effusion isothermal amplification, ADA, Mycobacterium tuberculosis culture, and peripheral blood T-SPOT.TB testing. Based on clinical comprehensive diagnostic criteria as a reference, the early diagnostic value of pleural effusion DNA constant temperature amplification combined with ADA and peripheral blood T-SPOT.TB for tuberculous pleurisy was analyzed. Results: Among 427 subjects, 279 cases (65.3%) were diagnosed as tuberculous pleurisy (tuberculous pleurisy group) and 148 cases were diagnosed as non-tuberculous pleurisy (non-tuberculous pleurisy group). The optimal threshold of ADA was 19.5 U/L. Among the single detection methods, the specificity and sensitivity of the constant temperature amplification method were 100.00% and 31.54%, which were similar to those of Mycobacterium tuberculosis culture (100.00% and 30.11%, respectively). The sensitivity of ADA and T-SPOT.TB in peripheral blood was 74.91% and 84.95%,respectively, and the specificity was 87.16% and 74.91%, respectively. ADA+T-SPOT.TB could obtain high sensitivity (94.27%) and specificity (99.32%) in parallel and series, respectively. The parallel detection efficiency of isothermal amplification method, ADA and T-SPOT.TB got the same value as that with the Mycobacterium tuberculosis culture method in parallel. Among the joint detection methods, ADA+T-SPOT.TB detection in series had the highest cost-effectiveness, with a cost effectiveness ratio (C/E) of 669.23. Conclusion: The constant temperature amplification method with rapid detection protocols such as ADA and peripheral blood T-SPOT.TB could provide strong evidence for the early diagnosis and treatment of tuberculous pleurisy patients.

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    Research progress on the correlation between intestinal microbiota short chain fatty acids and pulmonary tuberculosis
    Zhang Xiaomeng, Li Min, Chai Yinghui, Zhou Jing, Lei Hong
    Chinese Journal of Antituberculosis    2023, 45 (7): 699-706.   DOI: 10.19982/j.issn.1000-6621.20230079
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    Short chain fatty acids (SCFA) are the main metabolites of the gut microbiota, mainly including formic acid, acetic acid, propionic acid, butyric acid and their branched chain fatty acids, and some salts. Research has shown that there is a significant direct correlation between SCFA and the occurrence and development of pulmonary tuberculosis. Pulmonary tuberculosis leads to imbalance of gut microbiota, thereby reducing the abundance of SCFA, which affects the host immune system and the response of inflammatory factors; the disorder of host immune system and inflammatory factor will promote the occurrence and development of pulmonary tuberculosis.The author reviewed the correlation between SCFA and pulmonary tuberculosis, the possible regulatory mechanism between them, and whether it was possible to improve the abundance of SCFA in the body by regulating intestinal flora to achieve the purpose of treatment or adjuvant treatment of pulmonary tuberculosis.

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    Effect of microcard combined with vitamin D on the balance of CD4+ T cell subsets in initially treated patients with smear positive pulmonary tuberculosis
    Shang Yaomin, Zhou Xiaolei, Xue Yunling, Leng Xia
    Chinese Journal of Antituberculosis    2023, 45 (6): 575-582.   DOI: 10.19982/j.issn.1000-6621.20230078
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    Objective: To evaluate the effect of the combination of microcard (Mycobacterium vaccae vaccine) and vitamin D adjuvant therapy on the balance of CD4+ T cell subsets in initially treated patients with smear positive pulmonary tuberculosis (PTB), and to analyze its clinical efficacy. Methods: A prospective study was designed. According to the inclusion criteria and patient’s willing, the initially treated patients with smear positive PTB (PTB group) admitted to Henan Chest Hospital from June 2019 to June 2022 were enrolled into conventional anti-tuberculosis treatment group (control group), conventional anti-tuberculosis with microcard treatment group (microcard group) and conventional anti-tuberculosis combined with microcard and vitamin D adjuvant therapy group (combined group). Excluding those who could not complete the 6-month treatment course due to various reasons, 74 cases in each group were included (222 patients). The proportion of Th1, Th2, Th17, Treg cells and the levels of IFN-γ, IL-4, IL-17, IL-10 in peripheral blood of patients/healthy subjects were detected in each group before treatment and after 6-month treatment, and the sputum negative conversion rate, lesion and pulmonary cavities and comprehensive efficacy were evaluated by the end of 6-month treatment. Results: After six months treatment, the Th1/Th2, Treg/Th17 ratios and IFN-γ levels in the combined group (2.32±0.39, 0.45±0.03 and (16.13±2.67) pg/ml) were significantly higher than those in the microcard group (2.19±0.25, 0.34±0.03 and (14.16±3.45) pg/ml; t=2.414, P=0.017; t=22.303, P=0.000; t=3.885, P=0.000) and control group (2.08±0.37, 0.26±0.02 and (12.34±1.73) pg/ml; t=3.840, P=0.000; t=45.331, P=0.000; t=10.248, P=0.000). The levels of IL-4, IL-17 and IL-10 ((36.54±2.01) pg/ml, (27.10±3.58) pg/ml and (35.46±3.84) pg/ml) in the combined group were significantly lower than those in the microcard group ((37.23±1.78) pg/ml, (28.43±2.16) pg/ml and (43.58±4.06) pg/ml; t=2.211, P=0.029; t=2.736, P=0.007; t=12.499, P=0.000) and control group ((38.89±2.16) pg/ml, (29.40±3.27) pg/ml and (50.24±4.22) pg/ml; t=6.851, P=0.000; t=4.732, P=0.000; t=22.284, P=0.000); the negative conversion rate of sputum smear (97.30% (72/74)) and the total effective rate (91.89% (68/74)) were significantly higher than those in the microgram group (83.78% (62/74) and 79.73% (59/74); χ2=7.889, P=0.005; χ2=4.495, P=0.034) and control group (78.38% (58/74) and 77.03% (57/74); χ2=12.397, P=0.000; χ2=6.229, P=0.013). Conclusion: Conventional anti-tuberculosis combined with microcard and vitamin D adjuvant therapy can significantly promote the balance restoration of T lymphocyte subsets Th1/Th2 and Th17/Treg, and effectively improve cytokines levels of IFN-γ, IL-4, IL-17 and IL-10, and it has a significant clinical benefit.

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    Analysis of death related factors in tuberculosis destroyed lung patients undergoing invasive mechanical ventilation
    Cheng Yao, Chen Hongde, Wu Guihui, Lai Min, Luo Haixia, Cui Kunping, Li Yuke
    Chinese Journal of Antituberculosis    2023, 45 (7): 651-657.   DOI: 10.19982/j.issn.1000-6621.20230054
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    Objective: To explore the clinical characteristics and death-related factors of patients with tuberculosis-destroyed lung (TDL) undergoing invasive mechanical ventilation (IMV). Methods: A retrospective study was conducted in 107 TDL-IMV patients admitted to the intensive care unit of Chengdu Public Health Clinical Center from January 2017 to December 2021.The epidemiological data, complications, comorbidities, acute physiology and chronic health status scores (APACHE Ⅱ score), sequential organ failure scores (SOFA score), causes of IMV, laboratory test results, and clinical outcomes, etc., of the patients were collected. The above indicators in patients with different clinical outcomes were compared and analyzed, and unconditional multivariate logistic regression was used to analyze the influencing factors of death in TDL-IMV patients. Results: Of the 107 subjects, 42 (39.3%) died and 65 (60.7%) survived. Univariate analysis showed that 52.4% (22/42) of the patients in the death group were complicated with chronic obstructive pulmonary disease, which was significantly higher than that in the survival group (20.0%, 13/65, χ2=12.154, P=0.000); IMV for acute respiratory failure accounted for 52.4% (22/42), which was significantly higher than that of survival group (23.1%, 15/65, χ2=9.685, P=0.002); the albumin level ((25.34±4.22) g/L) was significantly lower than that in the survival group ((28.71±6.26) g/L, t=3.065, P=0.002); N-terminal pro-B-type natriuretic peptide level (median (quartile): 993.45 (869.32, 1096.61) ng/L) was significantly higher than that of survival group (649.26 (528.40, 789.82) ng/L, U=-7.085, P=0.000). Further multivariate logistic regression analysis showed that comorbidities with chronic obstructive pulmonary disease (OR=4.999, 95%CI: 1.253-19.937), IMV treatment for acute respiratory failure (OR=8.548, 95%CI: 2.045-35.729), hypoproteinemia (OR=13.069, 95%CI: 2.662-64.156) and high levels of N-terminal pro-B-type natriuretic peptide (OR=11.354, 95%CI: 2.809-45.888) were independent risk factors for the death of patients with TDL-IMV. Conclusion: Patients with TDL-IMV have a high risk of death, especially those who complicated with chronic obstructive pulmonary disease, undergoing IMV treatment due to acute respiratory failure, hypoproteinemia and high level of N-terminal pro-B-type natriuretic peptide.

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    An analysis of the epidemic characteristics and treatment outcomes of tuberculosis patients aged ≥65 years old in Ningxia Hui Autonomous Region from 2019 to 2022
    Tian Xiaomei, Sha Xiaolan, Liu Ye, Liu Guangtian, Lei Juan
    Chinese Journal of Antituberculosis    2023, 45 (9): 857-863.   DOI: 10.19982/j.issn.1000-6621.20230166
    Abstract256)   HTML14)    PDF(pc) (751KB)(144)       Save

    Objective: To analyze the epidemic characteristics and treatment outcomes of pulmonary tuberculosis patients aged ≥65 years old in Ningxia from 2019 to 2022 and to provide epidemiological basis for further prevention and control in the elderly tuberculosis cases. Methods: The number of whole population and that of population aged ≥65 years, number of pulmonary tuberculosis cases, age, sex, diagnosis category, treatment category, case finding ways, residence location, occupation, and treatment outcome in Ningxia in 2019-2022, were retrospectively extracted from the statistical analysis of tuberculosis module in the “Infectious Disease Surveillance System” subsystem of the “China Disease Prevention and Control Information System” and the integrated management of disease prevention and control module and the characteristics of the epidemic situation and the treatment outcome were analyzed. Results: From 2019 to 2022, the average notification rates of pulmonary tuberculosis and the pathogenic positive patients among the population aged ≥65 years old were 114.59/100000 (3155/2753300) and 74.42/100000 (2049/2753300), respectively. The notification rates decreased from 137.87/100000 (864/626700) and 86.64/100000 (543/626700) in 2019 to 99.53/100000 (757/760600) and 62.32/100000 (474/760600) in 2022, showing an annually decline trend ($\chi_{\text {trend}}^{2}$=47.824, P=0.000; $\chi_{\text {trend}}^{2}$=28.020, P=0.000). However, the notification rates of pulmonary tuberculosis and the pathogenic positive patients with ≥65 years accounted for 40.84% (3155/7725) and 45.90% (2049/4464) of the total tuberculosis patients, respectively, which increased from 36.06% (864/2396) and 41.45% (543/1310) in 2019 to 45.49% (757/1664) and 50.64% (474/936) in 2022, respectively, indicating an annualy increasing trend ($\chi_{\text {trend}}^{2}$=56.440, P=0.000; $\chi_{\text {trend}}^{2}$=23.053, P=0.000). From the clinical features perspective, the proportion of female, etiological positive, retreatment category and referral among elderly patients ≥65 years old were 53.44% (1686/3155), 64.94% (2049/3155), 6.59% (208/3155) and 76.89% (2426/3155), respectively, which were higher than those of patients <65 years old, respectively, accounting for 40.02% (1829/4570), 52.84% (2415/4570), 5.08% (232/4570) and 74.00% (3382/4570) (χ2=135.495, P=0.000; χ2=138.402, P=0.000; χ2=7.987, P=0.005; χ2=99.856, P=0.000). From the regional distribution, the proportion pulmonary tuberculosis with ≥65 years old with was higher in Zhongwei, Wuzhong and Shizuishan (47.78% (731/1530), 46.55% (783/1682) and 44.16% (367/831), respectively). In Shizuishan, the proportion increased from 37.55% (95/253) in 2019 to 52.02% (90/173) in 2022 with an annually increasing trend ($\chi_{\text {trend}}^{2}$=10.210, P=0.017). The proportions of elderly patients in Yinchuan and Guyuan were relatively lower (36.02% (857/2379) and 32.00% (417/1303), respectively). However, the proportions increased from 29.65% (223/752) and 26.21% (103/393) in 2019 to 41.30% (204/494) and 39.67% (119/300) in 2022, respectively, showing an increasing trend ($\chi_{\text {trend}}^{2}$=26.113, P=0.000; $\chi_{\text {trend}}^{2}$=17.234, P=0.001). From the perspective of occupational distribution, the proportion of farmer was higher (73.38% (2315/3155)), but decreased from 79.05% (683/864) in 2019 to 68.83% (521/757) in 2022. This was followed by household workers or unemployed and retirees (14.17% (447/3155) and 11.92% (376/3155), respectively). However, their share increased from 9.95% (86/864) and 10.42% (90/864) in 2019 to 17.57% (133/757) and 13.21% (100/757) in 2022. In terms of treatment outcome, the successful treatment rate of elderly tuberculosis patients (90.60% (2102/2320)) was statistically lower than that of patients <65 years (95.99% (3396/3538)) (χ2=70.394, P=0.000). The successful treatment rate of elderly patients increased from 88.28% (738/836) in 2019 to 92.31% (720/780) in 2021, showing an increasing trend ($\chi_{\text {trend}}^{2}$=8.605, P=0.014). Conclusion: From 2019 to 2022, the incidence of pulmonary tuberculosis in elderly patients aged ≥65 years old in Ningxia showed a decline trend, the proportion of elderly tuberculosis cases among whole tuberculosis cases showed an increasing trend. Therefore, health education and active screening of tuberculosis in spepcific populations, such as elderly women, etiological positive, retreatment, referral and follow-up, household worker, unemployed and retired people, and elderly patients in Shizuishan City, Yinchuan City and Guyuan City should be focused on to effectively reduce the tuberculosis epidemic in Ningxia.

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    Nutritional status of drug-resistant pulmonary tuberculosis patients and the influencing factors: a multi-center, large-sample study
    Ding Qin, Zhang Shengkang, Ren Fei, Chen Xiaohong, Hu Chunmei, Chen Wei, Fan Lin
    Chinese Journal of Antituberculosis    2023, 45 (9): 826-832.   DOI: 10.19982/j.issn.1000-6621.20230047
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    Objective: To investigate the nutritional status of drug-resistant pulmonary tuberculosis patients and analyze the influencing factors. Methods: A retrospective study was conducted in 1766 drug-resistant pulmonary tuberculosis patients from 29 tuberculosis specialized hospitals in 17 provinces and 2 municipalities of China from January 1, 2020 to December 31, 2021. The age range of the patients was 18 to 90 years with the average age of (45.88±16.43) years, and the average body mass index (BMI) was 20.03±3.25. Among them, 1255 were male (71.06%) and 511 were female (28.94%). Demography information and clinical characteristics of the subjects were collected. The Nutritional Risk Screening-2002 (NRS-2002) was used to assess whether the subjects were at nutritional risk. Further assessment and diagnosis of malnutrition were conducted in accordance with the Global Leadership Initiative on Malnutrition (GLIM) standards. Multivariate logistic regression analysis was used to investigate the influencing factors of nutritional risk in drug-resistant pulmonary tuberculosis patients. Results: The NRS-2002 score of 1766 subjects fluctuated from 1 to 5, and the median score (Quartile) was 3 (1 to 4) points. A total of 1103 cases (62.46%) of the subjects had nutritional risks (NRS-2002 score ≥3 points). In the NRS-2002 score ≥3 group, 70.56% (254/360) of the patients aged 60-79 years old, 83.33% (25/30) aged ≥80 years old, and BMI of all the patients (100.0% (602/602)) <18.5, which were significantly higher than those in the NRS-2002 score <3 group (accounted for 29.44% (106/360), 16.67% (5/30), and 0, respectively)(χ2 values were 6.256 and 1345.000, respectively; P values were 0.012 and <0.01). Multivariate logistic regression analysis showed that older age (with 18-39 years old group as reference, 60-79 years old group: OR (95%CI)=2.130 (1.194-3.803); ≥80 years old group: OR (95%CI)=12.400 (3.114-49.369)) and lower BMI (with BMI ≥20.5 as reference, BMI <18.5: OR (95%CI)=56.937 (26.537-122.161)) were risk factors for nutritional risk in drug-resistant pulmonary tuberculosis patients. The incidence of malnutrition among the study subjects was 52.55% (928/1766). Among 1103 individuals at risk for nutrition, the incidence of malnutrition was 84.13% (928/1103). Conclusion: Drug-resistant pulmonary tuberculosis patients have a higher nutritional risk and a higher incidence of malnutrition. Therefore, it is necessary to conduct standardized nutritional risk screening and diagnosis of malnutrition for such patients as early as possible, with special attention paid to elder and low BMI patients.

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    Current status and progress of imaging evaluation methods for detecting pulmonary tuberculosis combined with lung cancer
    Wen Limin, Hou Dailun
    Chinese Journal of Antituberculosis    2023, 45 (6): 620-624.   DOI: 10.19982/j.issn.1000-6621.20230045
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    Tuberculosis ranks second of the leading causes of communicable disease induced deaths worldwide. Lung cancer ranks first in both morbidity and mortality of malignant tumors in China. Because pulmonary tuberculosis and lung cancer can coexist, their differentiation is a clinical challenge. With the rapid development of imaging technology, the early identification of pulmonary tuberculosis and lung cancer using image evaluation provides great guide for diagnostic process of these two diseases. This paper mainly reviews the classic imaging evaluation methods and the latest research progress of novel methods for detecting pulmonary tuberculosis and lung cancer comorbidity, and analyzes the challenges of existing imaging evaluation methods and the future development direction.

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    Clinical practice guidelines for early detection of pulmonary tuberculosis in general medical facilities
    National Center of Medical Quality Control for Respiratory Diseases , Tuberculosis Branch of Chinese Medical Association , Tuberculosis Control Branch of Chinese Antituberculosis Association , China-Japan Friendship Hospital
    Chinese Journal of Antituberculosis    2024, 46 (2): 127-140.   DOI: 10.19982/j.issn.1000-6621.20230428
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    The diagnosis delay of pulmonary tuberculosis not only results in aggravation and treatment challenges for patients but also leads to the continuously group spreading of tuberculosis. Early detection in general medical facilities, the main primary diagnosis healthcare contact for pulmonary tuberculosis patients, plays a crucial role in achieving the goal of “End tuberculosis strategy”. The National Center of Medical Quality Control for Respiratory Diseases, Tuberculosis Branch of Chinese Medical Association, Tuberculosis Control Branch of Chinese Antituberculosis Association, and China-Japan Friendship Hospital jointly organized experts to formulate the Clinical practice guidelines for early detection of pulmonary tuberculosis in general medical facilities based on the results of China’s tuberculosis prevention practice and the relevant guidelines of the World Health Organization and supplement relevant research evidence at home and abroad. This guide systematically summarizes the characteristics of different diagnostic techniques for pulmonary tuberculosis and proposes tuberculosis screening strategies for different target populations seeking treatment in comprehensive medical institutions, providing evidence for improving and optimizing early detection of pulmonary tuberculosis in national and regional comprehensive medical institutions.

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    Analysis of epidemiological characteristics and treatment outcomes of pulmonary tuberculosis patients in floating population in Tongzhou District of Beijing, 2012—2021
    Yang Chao, Wang Jing, Tang Guilin, Geng Yang
    Chinese Journal of Antituberculosis    2023, 45 (6): 594-600.   DOI: 10.19982/j.issn.1000-6621.20220502
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    Objective: To analyze the characteristics and treatment outcomes of pulmonary tuberculosis (PTB) in floating population in Tongzhou District of Beijing, so as to provide reference for formulating TB prevention and control strategies. Methods: Data of 3202 PTB cases of floating population in Tongzhou District of Beijing from 2012 to 2021 was collected through Tuberculosis Management Information System of China Information System for Disease Control and Prevention, which included gender, age, occupation, case source, treatment classification, treatment outcomes and so on. Descriptive statistics was used to analyze the patients’ characteristics, treatment and outcomes. The seasonal effect of time series was analyzed by using seasonal index. Results: From 2012 to 2021, a total of 4996 cases of PTB patients were registered in Tongzhou District of Beijing, among which 3202 cases were from floating population, accounting for 64.09% of total cases. The incidence of PTB patients of floating population increased from 34.48/100000 in 2012 to 62.36/100000 in 2016 ( χ t r e n d 2=32.913,P<0.001), and then decreased to 37.80/100000 in 2021 ( χ t r e n d 2=15.061,P<0.001). The male-female ratio of patients was 1.75∶1. The main age group was 15-44 years old (79.17% (2535/3202)). The main occupation was housekeepers/unemployed people (41.41% (1326/3202)). The main source of patients was people refered from general hospitals (65.46% (2096/3202)), and the patients were generally delayed for health care visit (37.76% (1209/3202)). Most patients came from Hebei Province (22.49% (720/3202)) and Heilongjiang Province (9.81% (314/3202)). All patients received full-course supervision and management. The overall treatment success rate was 94.38% (3022/3202), while 85 cases (2.65%) defaulted, 12 cases (0.37%) died, and 36 cases (1.12%) developed multidrug-resistant TB. Conclusion: The epidemic of PTB among the floating population in Tongzhou District of Beijing were mainly male, young adults, housekeepers/unemployed and had high visit delay rates and differenciated regional distribution, thus corresponding prevention and control strategies should be formulated according to these epidemic characteristics.

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    Meta-analysis of effectiveness and safety of the cycloserine-containing treatment for multidrug-resistant pulmonary tuberculosis in China
    Zheng Rui, Zhao Mingrui, Yang Yuanzheng
    Chinese Journal of Antituberculosis    2023, 45 (7): 658-668.   DOI: 10.19982/j.issn.1000-6621.20230057
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    Objective: The purpose of this study was to provide evidence for clinical treatment of multidrug-resistant pulmonary tuberculosis (MDR-PTB) by assessing the effectiveness and safety of using cycloserine (Cs)-containing anti-tuberculosis regimens in China. Methods: A search for “cycloserine”“multi-drug resistant pulmonary tuberculosis”“treatment effect” and “adverse effects” was conducted in database of China National Knowledge Infrastructure, Wanfang Data, VIP, China Biomedical Literature Service System, PubMed, Embase, and Cochrane Library for literature published from January 2011 to September 2022. Randomized controlled trials (RCT) of Cs-containing anti-tuberculosis regimens for the treatment of MDR-PTB in China were targeted. The literature was screened by two researchers and the Cochrane 5.1.0 bias risk assessment tool was used to evaluate the methodological quality of the included studies. Stata 17.0 MP software was used to analyze the outcome indicators. Results: A total of 35 included literature was divided into: Cs+conventional treatment compared with conventional treatment group, 1128 cases; thymosin+Cs+conventional treatment group compared with the conventional treatment group, 791 cases; Cs+conventional treatment group compared with para aminosalicylic acid+conventional treatment group, 433 cases; Cs+conventional treatment compared with ethambutol+conventional treatment, 419 cases. The results of Meta-analysis indicated that compared with conventional anti-tuberculosis treatment, Cs-containing regimens showed superior effectiveness in treating MDR-PTB (RR=2.191, 95%CI: 1.847-2.599), including the rate of sputum conversion (RR=2.002, 95%CI: 1.696-2.364), lesion absorption (RR=2.259, 95%CI: 1.836-2.779), and cavity shrinkage (RR=1.812, 95%CI: 1.482-2.217). The incidence of adverse reactions in mental and nervous system was higher in Cs-containing regimens (RR=1.696, 95%CI: 1.493-1.927). Conclusion: The results suggested that the Cs-containing regimens were more effective in treating MDR-PTB, but caution should be taken for adverse reactions in the central nervous system.

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    Value of CRISPR-Cas13a detection in the diagnosis of pulmonary tuberculosis
    Zhang Zhiguo, Shang Yuanyuan, Zhang Xuxia, Liu Rongmei, Ma Liping, Qin Lin, Kong Zhongshun, Ren Weicong
    Chinese Journal of Antituberculosis    2023, 45 (6): 589-593.   DOI: 10.19982/j.issn.1000-6621.20230014
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    Objective: To assess the diagnostic value of CRISPR-Cas13a detection in pulmonary tuberculosis (TB) using clinical samples. Methods: A retrospective study was conducted at Beijing Chest Hospital Affiliated to Capital Medical University. The bronchoalveolar lavage fluid (BALF) specimens of 102 patients with pulmonary TB confirmed by GeneXpert MTB/RIF test (Xpert test) from September 2022 to December 2022 were enrolled as TB group, and the BALF specimens of 100 patients (including lung cancer, bacterial pneumonia, bronchiectasis, and chronic obstructive pulmonary disease) during the same period were recruited as non-TB group. The BALF samples of all patients were subjected to acid-fast bacilli smear microscopy, culture, Xpert test and CRISPR-Cas13a test. The diagnostic value of CRISPR-Cas13a in the detection of BALF for pulmonary TB was evaluated based on the results of Xpert test. Results: Among 102 specimens in the TB group, 99 (97.1%) were positive for CRISPR-Cas13a, 40 (39.2%) were positive for smear, and 68 (66.7%) were positive for culture. The positive detection rate of CRISPR-Cas13a was significantly higher than those of smear and culture (smear: χ2=58.141, P<0.001; culture: χ2=30.250, P<0.001). Compared with traditional methods, CRISPR-Cas13a was able to identify 28 clinically confirmed TB patients which would be otherwise missed by either smear or culture. The positive detection rate of Xpert was 100.0% in TB group, and the negative detection rate of Xpert was 100.0% in non-TB group. Taking the results of Xpert as a reference, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of CRISPR-Cas13a in detecting pulmonary TB were 97.1% (99/102), 96.0% (96/100), 96.5% (195/202), 96.1% (99/103) and 97.0% (96/99), respectively. Conclusion: Compared with traditional tests, CRISPR-Cas13a detection is simple and fast, with higher sensitivity and higher specificity in the detection of BALF for the diagnosis of pulmonary TB, and has a good application prospect.

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    Establishment of a cross primer isothermal amplification technique for rapid detection of Mycobacterium tuberculosis complex and nontuberculous mycobacteria
    Huang Wenbin, Chen Liping, Zhang Wang, Xiao Ting, Zhang Mane, Wu Dingchang
    Chinese Journal of Antituberculosis    2023, 45 (8): 734-743.   DOI: 10.19982/j.issn.1000-6621.20230088
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    Objective: To establish a molecular cross primer isothermal amplification (CPA) detection system for rapid detection of Mycobacterium tuberculosis complex (MTBC) and nontuberculous mycobacteria (NTM). Methods: Six sets of CPA primers and three probes were designed for 16S rRNA-a highly conservative gene sequence of mycobacterium. Using a plasmid containing 16S rRNA gene sequence (with a concentration of 1000 copies/μl) as a positive template, the optimal primer probe combination was selected, and the sensitivity, specificity, and inclusiveness of the established optimal reaction system were analyzed. Samples of 125 presumptive tuberculosis patients with signs or symptoms of tuberculosis from the Second Hospital of Longyan, Fujian Province from February 8, 2022 to March 14, 2023, were collected and then detected by the mycobacterium nucleic acid detection kit (PCR-fluorescence probe method) and the established CPA method. The consistency of the test results between the two methods was statistically analyzed, setting Kappa value ≥0.75 as having good consistency. Results: MTBC/NTM-16S-6 primer and MTBC/NTM-16S-LR-FAM-3 were selected as the best primer probe combinations for the mycobacterium detection system. The minimum detection limit of the detection system was 100 copies/μl, and the detection time was 40 minutes. It could detect MTBC and clinically common NTM, and show no cross reaction with other common respiratory tract bacteria. Compared with the real-time fluorescence quantitative PCR (RT-PCR) detection method, the positive prediction value of the established CPA system was 95.65% (66/69), the negative prediction value was 85.71% (48/56), the total consistency rate was 91.20% (114/125), and the Kappa value was 0.82. Conclusion: A rapid detection system of MTBC and NTM based on CPA technology was successfully established, which could provide a new detection method for the prevention and control of tuberculosis epidemic in primary hospitals.

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    Interpretation of WHO operational handbook on tuberculosis: module 1: prevention-infection prevention and control
    Sun Yuxian, Liu Yuhong
    Chinese Journal of Antituberculosis    2023, 45 (12): 1120-1124.   DOI: 10.19982/j.issn.1000-6621.20230365
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    In August 2023, World Health Organization (WHO) published WHO operational handbook on tuberculosis: module 1: prevention-infection prevention and control, as a supporting material for WHO consolidated guidelines on tuberculosis: module 1: prevention-infection prevention and control released in December 2022, to provide feasible suggestions for the implementation of the recommendations on tuberculosis infection prevention and control in clinical as well as prevention and control programme. The author interprets the key content of this manual for reference.

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    Survey on satisfaction of external quality assessment among tuberculosis laboratory network in China
    Song Yuanyuan, Xia Hui
    Chinese Journal of Antituberculosis    2023, 45 (6): 559-565.   DOI: 10.19982/j.issn.1000-6621.20230013
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    Objective: To identify the problems in the external quality assessment (EQA) of tuberculosis laboratories diagnosis and improve the quality through a satisfaction survey among tuberculosis laboratories network in China. Methods: The National Tuberculosis Reference Laboratory (NTRL) of Chinese Centre for Disease Control and Prevention designed and distributed online questionnaires to personnel involved in EQA in 2019, 2020 and 2021. The questionnaires were anonymously filled by personnel and then collected and analyzed by NTRL. The difference of satisfaction between 2019 and 2021 was analyzed, and the difference between personnel form different levels of institutes (provincial, prefecture, and county) in 2019 was also compared. Results: One thousand six hundred and fifteen, 30 and 314 personnel responded to the questionnaire in 2019, 2020 and 2021 respectively. Of the 25 questions in 2021, only psychological stress satisfaction (79.0%, 248/314) was less than 80%. Of the 26 questions in 2019, the satisfaction rate of four questions was below 80%, such as satisfaction of the impact on work load (69.3%, 1120/1615), satisfaction of the impact on economic burden (76.3%,1232/1615), satisfaction with psychological stress (66.1%, 1067/1615), and satisfaction of application for strains transportation permission (75.4%, 724/960). Among the 24 common questions in 2019 and 2021, the satisfaction rate of 22 questions in 2021 (79.0%-97.4%) was significantly higher than that in 2019 (66.1%-97.0%) except for the two questions related to results reporting time requirement that had no significant difference between 2019 and 2021. Conclusion: The satisfaction of respondents with most questions relevant with EQA is acceptable. Satisfactions with most questions has been improved after implementing of improvement measures. Some aspects, such as results reporting form and strain transportation still need further improvement, however.

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    Investigation of nutritional status and analysis of influencing factors in patients with extrapulmonary tuberculosis
    Ding Qin, Chen Wei, Zhang Shengkang, Ren Fei, Chen Xiaohong, Hu Chunmei, Chen Danping, Fan Lin
    Chinese Journal of Antituberculosis    2023, 45 (9): 839-844.   DOI: 10.19982/j.issn.1000-6621.20230221
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    Objective: To investigate the nutritional status of patients with extrapulmonary tuberculosis and analyze the related factors. Methods: A total of 3223 inpatients with extrapulmonary tuberculosis from 5 tuberculosis specialized hospitals from January 1, 2020 to December 31, 2021 were selected as research subjects, including 1852 males (57.46%) and 1371 females (42.54%); the median (quartile) age was 41 (28,58) years old. The general demography characteristics and clinical characteristics of the subjects were collected (including gender, age, height, body mass, clinical diagnosis, location of extrapulmonary tuberculosis, complications, immune status, previous tuberculosis treatment history, etc.), as well as the nutrition risk screening-2002 (NRS-2002) score. All the subjects had complete medical records and information, and were definitely diagnosed with extrapulmonary tuberculosis. Nutritional risk screening was conducted when they had not yet received effective anti-tuberculosis treatment or control. The occurrence of nutritional risk in the subjects was analyzed and the influencing factors of nutritional risk in patients with extrapulmonary tuberculosis were analyzed using a multivariate logistic regression model. Results: Among the 3223 study subjects, 86.91% (2801/3223) involved only one extrapulmonary site, and 13.09% (422/3223) involved two or more sites. The NRS-2002 score of subjects fluctuated from 1 to 5, and the median (quartile) score was 3 (1, 4). A total of 1814 cases (56.28%) had nutritional risk (NRS-2002 score ≥3). Of the 422 study subjects with involvement in two or more extrapulmonary sites, 63.74% (269/422) were at nutritional risk; of the 2801 studies involving a single extrapulmonary site, 55.16% (1545/2801) had nutritional risks. Multivariate logistic regression analysis showed that low body mass index (body mass index <18.5)(OR (95%CI)=20.641 (19.745-26.307)), concomitant immunosuppression (OR (95%CI)=1.182 (1.023-1.421)), and retreatment (OR (95%CI)=1.804 (1.549-2.177)) were risk factors for nutritional risk in patients with extrapulmonary nodules. Conclusion: The incidence of nutritional risk in patients with extrapulmonary tuberculosis is relatively high, and more attention should be paid to their nutritional status in clinical treatment, especially for patients with low body mass index, combined immunosuppression, and retreatment.

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    Prediction of the effectiveness and impact of the free healthcare policy for tuberculosis in China
    Zhou Wenyong, Wen Zexuan, Gao Mengxian, Li Tao, Zhang Hui, Wang Weibing
    Chinese Journal of Antituberculosis    2023, 45 (9): 845-856.   DOI: 10.19982/j.issn.1000-6621.20230143
    Abstract236)   HTML28)    PDF(pc) (2917KB)(181)       Save

    Objective: This study predicted the short-term and long-term epidemiological and economic impacts of the implementation of free tuberculosis (TB) healthcare policy in China, providing scientific evidence for the necessity and feasibility of free TB healthcare policy in China. Methods: Based on the natural history of TB, a TB dynamic model was developed, and two simulation scenarios were simulated to predict the impact of implementing free TB healthcare policy on the trend of TB epidemic, assuming a constant decline rate of annual incidence of TB and a gradually increasing decline rate of annual incidence of TB under other interventions, respectively. The cost-effectiveness, cost-utility, and cost-benefit analyses were conducted to evaluate the social benefits of the government’s investment on free TB healthcare policy. Results: With the free TB health care policy, when the decline rate is maintained at the current level, by 2035, 7584954 latent TB infections (LTBI) and 390333 TB cases can be avoided cumulatively, 195486 successfully treated drug-sensitive TB patients and 62251 drug-resistant TB patients can be increased cumulatively, and 2448501 disability-adjusted life years (DALY) and a social economic value of 273280420000 yuan can be saved. Every extra yuan invested by the government can generate a social economic value of 11.24 yuan. When the decline rate increases, by 2035, 5730438 LTBI and 273441 TB cases can be avoided cumulatively, 179592 successfully treated drug-sensitive TB patients and 49835 drug-resistant TB patients can be increased cumulatively, and 2179554 DALY and a social economic value of 233103460000 yuan can be saved. Every extra yuan invested by the government can generate a social economic value of 12.58 yuan. Conclusion: Implementing free TB healthcare policy can significantly reduce the transmission of TB and has a significant effect on saving social economic cost. These effects are more significant when the annual incidence of TB declines faster. It is recommended that the government shall implement free TB healthcare policy as soon as possible and other interventions to control the spread of TB.

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    Analysis of the public awareness rate of core knowledge of tuberculosis prevention and control in Shanxi
    Feng Miao, Huo Junfeng, Deng Junping, Wang Chunpu, Fan Yueling, Song Hong
    Chinese Journal of Antituberculosis    2023, 45 (8): 786-793.   DOI: 10.19982/j.issn.1000-6621.20230154
    Abstract233)   HTML20)    PDF(pc) (790KB)(216)       Save

    Objective: To investigate the awareness of core knowledge of tuberculosis prevention and control among residents in Shanxi, and provide scientific basis for strengthening health promotion and health education on tuberculosis control. Methods: From January to March 2021, a multi-stage stratified cluster random sampling method was applied to select 12 survey sites from each of the 11 cities in Shanxi. At least 100 participants were included in each survey site, resulting in a total of 132 survey sites (44 urban sites and 88 rural sites) and 13426 participants. A household survey was conducted using questionnaires to assess the participants’ awareness of core knowledge of tuberculosis prevention and control and the health education. A total of 13426 questionnaires were distributed, and 13426 valid questionnaires were collected with a response rate of 100.00%. Descriptive analysis and Chi-square tests were used to analyze the awareness of core knowledge of tuberculosis prevention and control. Results: The general awareness rate of all 5 key messages was 80.05% (53735/67130). The awareness rates of the five tuberculosis key messages were 71.80% (9640/13426), 88.99% (11948/13426), 89.65% (12037/13426), 80.73% (10839/13426), and 69.05% (9271/13426), respectively, which include “tuberculosis is a serious chronic infectious disease”, “tuberculosis is mainly transmitted through the respiratory tract”, “the suspicious symptoms of tuberculosis are cough and/or coughing with sputum for more than 2 weeks”, “the preventive measures of tuberculosis are mainly not spitting, covering the mouth and nose when coughing and sneezing, and wearing masks” and “the majority of pulmonary tuberculosis can be cured”. Among them, the total awareness rates of male participants, urban population, participants with younger age (15-19 years old), participants with a bachelor’s degree or above and participants from government institutions (80.30% (26091/32465), 82.30% (19020/23110), 84.43% (1372/1625), 84.18% (3405/4045) and 85.69% (3916/4570), respectively) were higher than those of female participants, rural population, aged 80 and above, illiterate or semiliterate population groups, and unemployed or self-employed individuals (79.75% (27644/34665), 78.86% (34712/44020), 69.45% (955/1375), 70.03% (2493/3560) and 77.68% (10269/13220), respectively). These differences were statistically significant (χ2=4.040, P=0.044; χ2=112.711, P<0.001; χ2=330.252, P<0.001; χ2=514.584, P<0.001; χ2=272.377, P<0.001, respectively). Furthermore, 78.69% (10565/13426) of the public population had received health education of tuberculosis. “Television” (55.88%, 5904/10565), “bulletin/wall newspapers/blackboard newspapers” (39.77%, 4202/10565), and “leaflets/folded pages/posters” (38.97%, 4117/10565) were the most common ways for receiving health education. “Radio/television/film/audiovisual materials” (62.75%, 8423/13423) remained the most popular way for the public population to acquire health knowledge. Conclusion: In recent years, the awareness of core knowledge of tuberculosis prevention and control among residents in Shanxi has increased significantly. However, it has not yet reached the national planning goals. Health education on tuberculosis control knowledge should be strengthened, especially for the populations with rural area, lower education, older ages, and unemployed or self-employed individuals.

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    Research progress on blood transcriptomic biomarkers in the diagnosis of tuberculosis
    Bei Cheng, Li Meng, Gao Qian
    Chinese Journal of Antituberculosis    2023, 45 (8): 801-807.   DOI: 10.19982/j.issn.1000-6621.20230182
    Abstract230)   HTML18)    PDF(pc) (803KB)(245)       Save

    Development of convenient, rapid and accurate tuberculosis (TB) diagnostic assays is an important part of ending TB. Current detection assays have drawbacks such as difficulties in sputum collection, which are expected to be overcome by methods based on blood transcripomic biomarkers. We conducted a review about the progress, limitations, and prospects of blood-based transcripomic biomarkers in the diagnosis of TB.

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    The mechanisms identification of the susceptibility discrepancy to isoniazid among clinical isolates of Mycobacterium kansasii
    Ren Ruyan, Xue Yi, Liang Qian, Huang Hairong
    Chinese Journal of Antituberculosis    2023, 45 (8): 728-733.   DOI: 10.19982/j.issn.1000-6621.20230129
    Abstract229)   HTML16)    PDF(pc) (773KB)(123)       Save

    Objective: To measure the susceptibility of clinical isolates of Mycobacterium kansasii (M.kansasii) to isoniazid (INH), and investigate the mechanism that causes the differences. Methods: The standard strain of Mycobacterium tuberculosis H37Rv (MTB, ATCC27294) and M.kansasii (ATCC12478), as well as 35 clinical strains of M.kansasii isolated from patients infected with nontuberculous mycobacteria, all of which come from Beijing Chest Hospital affiliated to Capital Medical University. The changes of minimum inhibitory concentration (MIC) of INH in vitro before and after the addition of effluvium pump inhibitors, including carbonyl cyanide 3-chlorophenzone, N, N'-dicyclohexylcarbodiimide, verapamil and reserpine, were measured by microplate method and their correlation was evaluated. Sequences of known genes associated with INH resistance were identified to understand the correlation between gene sequence polymorphisms and MIC values in clinical isolates. Catalase-peroxidase (KatG) of MTB and M.kansasii were overexpressed, the affinity of KatG proteins to INH was tested with the Biolayer Interferometry (BLI) technique, and the peroxide-peroxidase activity of KatG proteins was tested with enzyme-linked immunoassay. Results: 5.7% (2/35), 71.4% (25/35), 2.9% (1/35) and 20.0% (7/35) of the 35 clinical strains of M.kansasii had MIC to INH at 0.5 μg/ml, 1 μg/ml, 4 μg/ml and >32 μg/ml, respectively. After adding appropriate amounts of carbonyl cyanide 3-chlorophenzone, N, N'-dicyclohexylcarbodiimide, verapamil and reserpine, 5 (14.3%), 2 (5.7%), 9 (25.7%) and 0 strains showed more than 50% reduction in MIC values. The katG, inhA, kasA, ahpC and oxyR gene sequences of all clinical isolates were consistent with reference strain of M.kansasii. The dissociation constant between INH and KatG proteins derived from M.kansasii (KD=1.45×10-4 mol/L) was slightly lower than that from MTB (KD=7.44×10-4 mol/L), but the specific peroxidase activity of KatG proteins from MTB (318.69 U/mg) was higher than that from M.kansasii (87.62 U/mg). Conclusion: Clinical isolates M.kansasii showed variable INH susceptibility in vitro, but neither the known INH resistance-related gene polymorphisms nor the efflux pump was the main mechanism of this intra-specious difference in INH susceptibility. The higher susceptibility of MTB to INH than that of M.kansasii may be related to the stronger peroxidase activity of its KatG proteins.

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    Preliminary study on the gene function of Mycobacterium tuberculosis Rv2333c in macrophages
    He Ping, Wang Yiting, Song Zexuan, Xia Hui, Wang Shengfen, He Wencong, Zheng Yang, Zhao Yanlin
    Chinese Journal of Antituberculosis    2023, 45 (6): 566-574.   DOI: 10.19982/j.issn.1000-6621.20230059
    Abstract229)   HTML15)    PDF(pc) (2094KB)(128)       Save

    Objective: To explore the gene function of Mycobacterium tuberculosis (MTB) Rv2333c by overexpressing Rv2333c in Mycolicibacterium (M.) smegmatis in the process of infected macrophages. Methods: Overexpression of Rv2333c in M.smegmatis was achieved based on the construction of pSUM-MCS2-Rv2333c. Samples were collected at different time points after infecting macrophages with the empty strain (Ms_Vec) or the overexpression strain (Ms_Rv2333c). Then, the bacterial intracellular viability was assessed by counting colony-forming units (CFU) and the cytotoxicity of Rv2333c to the cell was detected by measuring the lactate dehydrogenase (LDH) activity in the cell media. Total RNA was extracted and the supernatant of culture media and cell lysates was collected to investigate Rv2333c effect on cytokines secretion and NF-κB/MAPK pathway in macrophages through reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and Western blotting experiments. Results: Rv2333c of MTB was successfully expressed in M.smegmatis. The cytotoxicity significantly decreased at the early stage (6 h) of macrophages infected with Ms_Rv2333c (LDH: Ms_Vec: (52.55±0.90) %, Ms_Rv2333c: (27.87±1.77) %; t=17.560, P<0.001), but the intracellular proliferation of Ms_Rv2333c was not affected (log10CFU: Ms_Vec: 7.45±0.05, Ms_Rv2333c: 7.35±0.16; t=1.069, P=0.345). RT-PCR revealed that IL-1β mRNA was downregulated at the early stage (6 h, Ms_Vec: 657.43±20.96, Ms_Rv2333c: 521.36±25.97; t=5.767, P=0.005), but upregulated at the late stage of macrophages infected with Ms_Rv2333c (48 h, Ms_Vec: 1548.53±125.17, Ms_Rv2333c: 2168.13±130.00; t=4.855, P=0.008). However, IL-6 mRNA was upregulated at the early (6 h) and late stage (48 h) of macrophages infected with Ms_Rv2333c (Ms_Vec: 2.46±0.49 & 776.41±15.38, Ms_Rv2333c: 6.02±0.37 & 1642.76±51.15; t=8.234 & 22.940, P=0.001 & <0.001, respectively). And the interferon-γ (IFN-γ) mRNA was also upregulated (Ms_Vec: 2.52±0.09 & 2.76±0.32, Ms_Rv2333c: 17.24±0.47 & 8.52±0.08; t=43.760 & 25.090, all P<0.001, respectively). The results of Western blotting showed that the expression of NF-κB and phosphorylation of ERK1/2 significantly increased in macrophages 3 hours after infecting with Ms_Rv2333c and maintained at high level even at 24 h (3 h, Ms_Vec: (1.00±0.14) % & (1.00±0.06) %, Ms_Rv2333c: (1.85±0.29) % & (1.74±0.03) %; t=3.765 & 15.040, P=0.020 & <0.001, respectively; 24 h, Ms_Vec: (1.00±0.14) % & (1.00±0.02) %, Ms_Rv2333c: (1.45±0.15) % & (1.17±0.04) %; t=3.041 & 5.538, P=0.038 & 0.005, respectively). Conclusion: Rv2333c plays an important role in the pathogenesis of MTB. Rv2333c inhibited apoptosis at the early stage of infection, which is helpful for the survival of bacteria in macrophages. In addition, Rv2333c can promote the expression of inflammatory factors at the middle and late stages of infection to induce inflammatory reaction in cells. It can also indirectly participate in transferring of NF-κB to the nucleus and regulating the activity of transcription factors by affecting the ERK1/2 phosphorylation capacity.

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    A cross-sectional study on the economic burden of pulmonary tuberculosis patients from western China
    Hao Dongqing, Li Tao, Huang Fei, Xu Caihong
    Chinese Journal of Antituberculosis    2023, 45 (11): 1021-1030.   DOI: 10.19982/j.issn.1000-6621.20230137
    Abstract228)   HTML24)    PDF(pc) (1032KB)(434)       Save

    Objective: To investigate the economic burden of patients with pulmonary tuberculosis (TB) in western China and provide reference for developing policies to reduce the economic burden of TB patients. Methods: This cross-sectional study employed cluster sampling to select 16 TB treatment facilities across 12 western provinces in China from October 2022 to December 2020. Face-to-face questionnaire surveys were conducted on drug-susceptive pulmonary TB patients who had undergone treatment for more than two weeks. These surveys encompassed their demographic characteristics, expenses and household income. Descriptive analysis was used to analyze the demographic characteristics, expenses and catastrophic expenditure of patients. Results: A total of 1030 patients with pulmonary TB were included in the study. The median (IQR) of the total cost for tuberculosis patients was 8703.30 (4046.00, 15715.59) yuan, comprising direct medical costs of 5823.85 (2341.01, 10852.23) yuan, direct non-medical costs of 1589.53 (675.14, 3163.45) yuan, and indirect costs of 12.03 (0.34, 720.27) yuan. A total of 52.82% (544/1030) of patients experienced household catastrophic expenditure for the treatment of pulmonary TB. Conclusion: The economic burden of pulmonary TB patients in western region of China is heavy. The total cost and direct medical cost of pulmonary TB patients are high, contributing to a heightened incidence of household catastrophic expenditure.

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    Chinese Journal of Antituberculosis    2023, 45 (6): 625-627.   DOI: 10.19982/j.issn.1000-6621.20230029
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    Progress of diagnosis of extrapulmonary tuberculosis with GeneXpert MTB/RIF Ultra
    Dong Yu, Zhang Fuzhen, Shang Yuanyuan, Pang Yu
    Chinese Journal of Antituberculosis    2023, 45 (12): 1193-1197.   DOI: 10.19982/j.issn.1000-6621.20230357
    Abstract227)   HTML17)    PDF(pc) (754KB)(147)       Save

    Extrapulmonary tuberculosis is a form of tuberculosis characterized by various infection routes and sites, complex clinical manifestations, and a lack of specific diagnosis. Currently, there are limitations in etiological and immunological diagnostic methods, and there is an urgent need for laboratory techniques that can quickly and accurately diagnose extrapulmonary tuberculosis to facilitate early detection and timely treatment. GeneXpert MTB/RIF Ultra (Xpert Ultra) is a novel molecular diagnostic tool that has revolutionized the rapid and precise diagnosis of extrapulmonary tuberculosis. The author examines the diagnostic effectiveness of Xpert Ultra in different types of extrapulmonary tuberculosis specimens, aiming to assess its clinical value and offer new insights into the diagnosis of extrapulmonary tuberculosis.

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    Chinese Journal of Antituberculosis    2023, 45 (8): 814-817.   DOI: 10.19982/j.issn.1000-6621.20230132
    Abstract225)   HTML10)    PDF(pc) (3192KB)(125)       Save
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    Chinese Journal of Antituberculosis    2023, 45 (9): 823-825.   DOI: 10.19982/j.issn.1000-6621.20230031
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    Application value of ultrasound guided percutaneous biopsy in the diagnosis of hip joint tuberculosis
    Cao Bingsheng, Zhang Gengchen, Fu Liyuan, Wang Jinshan
    Chinese Journal of Antituberculosis    2023, 45 (7): 669-672.   DOI: 10.19982/j.issn.1000-6621.20230101
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    Objective: To investigate the application value of ultrasound guided percutaneous biopsy in the diagnosis of hip joint tuberculosis. Methods: Forty-five patients with hip joint tuberculosis admitted to the Eighth Medical Centre of General Hospital of PLA from December 2012 to December 2022, were collected. Their hip ultrasound examination imaging data and ultrasound guided hip biopsy results were analyzed, and the ultrasound imaging characteristics of hip tuberculosis were summarized. The diagnostic rate of ultrasound guided puncture biopsy for hip joint tuberculosis and the impact of different ultrasound manifestations on the diagnostic rate of puncture biopsy for hip joint tuberculosis were analyzed. Results: Depending on the progression of the lesion, ultrasound manifestations of tuberculosis of hip joint can be divided into three categories. There were 10 patients of type Ⅰ, characterized by swollen synovial membrane or joint cavity accumulation, 22 patients of type Ⅱ, characterized by bone destruction on the joint surface and unevenness, and 13 patients of type Ⅲ, characterized by joint structure destruction and fusion into mixed echogenic masses. The success rate of ultrasound-guided puncture biopsy was 97.8% (44/45), and the overall diagnostic rate of puncture biopsy was 66.7% (30/45). Diagnostic rates of type Ⅰ, type Ⅱ and type Ⅲ were 30.0% (3/10), 72.7% (16/22) and 84.6% (11/13), respectively. Diagnostic rate of type Ⅰ was significantly lower than those of type Ⅱ and type Ⅲ (χ2=5.203, P=0.049; χ2=7.078, P=0.013). Conclusion: Conventional ultrasound can demonstrate the pathological morphologic change of hip joint tuberculosis and ultrasound guide biopsy has important value in the diagnosis of tuberculosis hip joint.

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    Focusing on the diagnosis of pulmonary tuberculosis in sputum-free patients and exploring the potential of tongue swab substitution
    Dong Yu, Pang Yu
    Chinese Journal of Antituberculosis    2023, 45 (12): 1131-1133.   DOI: 10.19982/j.issn.1000-6621.20230379
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    Tuberculosis is a global health threat. Pulmonary tuberculosis is the main form of tuberculosis, and sputum is the preferred diagnostic specimen. The bacteriological or molecular biological tests for sputum have become the gold standard, however, the difficulty of diagnosis in sputum-free patients is increasing. Although bronchial lavage fluid and gastric fluid can be used in the diagnosis of pulmonary tuberculosis, there are difficulties and inconveniences in the collection process. Tongue swab, as a simple and rapid specimen with low biosafety risk, may be an ideal replacement type of sputum specimen or a new means to assist in the diagnosis of tuberculosis. In this paper, the author emphasizes the importance of the diagnosis of patients with sputum-free pulmonary tuberculosis, and looks forward to the application of tongue swab in the diagnosis of pulmonary tuberculosis.

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    Investigation and analysis of awareness rate of core knowledge of tuberculosis prevention and control of newly diagnosed pathogenic positive pulmonary tuberculosis patients
    Jiang Xiaoying, Zhang Wen, Gao Mengqiu, Zhang Zhiguo, Mi Fengling
    Chinese Journal of Antituberculosis    2023, 45 (8): 794-800.   DOI: 10.19982/j.issn.1000-6621.20230090
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    Objective: To investigate the awareness of the core knowledge of tuberculosis prevention and control among newly diagnosed pathogenic positive pulmonary tuberculosis patients. Methods: Using the prospective cohort study method, 202 newly diagnosed pathogenic positive pulmonary tuberculosis patients who met the conditions of the “home treatment management model” and were included in three municipal tuberculosis prevention and control institutions (specialized hospitals), including the Beijing Chest Hospital affiliated to Capital Medical University, the Changping District Tuberculosis Prevention and Control Institute of Beijing, and the Daxing District Center for Disease Prevention and Control of Beijing, from January 2019 to January 2023, were investigated. A self-designed survey questionnaire was used to conduct a face-to-face inquiry survey on the survey subjects at their first visit, collecting their basic information, past medical history, and current diagnosis and treatment status. The respondents who reported that they knew tuberculosis related core knowledge were further investigated the awareness of tuberculosis prevention and control core knowledge. A total of 202 questionnaires were distributed and 202 valid questionnaires were collected, with a questionnaire effectiveness rate of 100%. The general situation of the respondents and the awareness of tuberculosis prevention and control core knowledge were statistically analyzed, and the factors affecting the awareness rate were further analyzed by logistic regression. Results: Of the 202 respondents, 191 (94.55%) reported that they knew about tuberculosis, and the total awareness rate of the 8 core knowledge of tuberculosis prevention and control was 70.42% (1076/1528). Univariate analysis showed that the total awareness rate was the highest in the 15-29 year old group (76.69%, 227/296), and the lowest in the 45-59 year old group (65.20%, 193/296), with a statistically significant difference (χ2=19.236, P<0.001). The total awareness rate of non local registered residence (74.20%, 558/752), those with bachelor’s degree or above (77.02%, 191/248), those who do not drink (73.15%, 673/920) and those who used to drink but now do not (70.09%, 342/488) was significantly higher than that of registered residence (67.52%, 524/776), middle school (71.56%, 750/1048), primary school and below (60.78%, 141/232) and current drinkers (55.83%, 67/120), respectively. The differences were statistically significant (χ2 values were 8.236, 16.213, 15.589, respectively, and P values were <0.005,<0.001, and <0.001, respectively). Multivariate logistic regression analysis showed that the probability of knowing tuberculosis prevention and control core knowledge of patients with chronic diseases and patients aged 45-59 years were 30.0% (95%CI: 9.1%-98.8%) and 18.5% (95%CI: 3.5%-99.4%) of patients without chronic diseases and patients aged 15-29 years, respectively. The information channel for respondents to obtain tuberculosis prevention and control knowledge was mainly media (such as network/television/radio/leaflets), with a selection rate of 53.93% (103/191). Conclusion: The total awareness rate of tuberculosis prevention and control core knowledge of newly diagnosed pathogenic positive pulmonary tuberculosis patients was low. Targeted measures should be taken for tuberculosis patients aged 45-59, with registered residence in the city, with secondary school and primary school education and below, and drinking now, and health education for tuberculosis prevention and control should be carried out through various information channels.

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    Analysis of correlation between apolipoprotein E gene polymorphisms and lipid levels with susceptibility to pulmonary tuberculosis
    Yu Zhikang, Xiong Nating, Wu Heming, Du Jingjin, Li Ling
    Chinese Journal of Antituberculosis    2023, 45 (8): 752-760.   DOI: 10.19982/j.issn.1000-6621.20230111
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    Objective: To explore the correlation between apolipoprotein E (ApoE) gene polymorphism and blood lipid levels with pulmonary tuberculosis. Methods: A retrospective study was conducted in 1118 patients diagnosed with pulmonary tuberculosis in Meizhou People’s Hospital from January 1, 2016 to December 12, 2020 (case group), and 582 healthy people in the hospital during the same period were selected as the control group. The general information (age, sex) and laboratory test indicators (blood routine test, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (Apo-A1), apolipoprotein B (Apo-B), and ApoE genotyping test results) of the subjects were collected. The distribution of ApoE genotypes, differences in blood lipid levels, and the correlation between ApoE genotypes and blood lipid levels between the case group and the control group were analyzed, and multivariate logistic regression was used to analyze the impact of ApoE genotypes and blood lipid levels on the incidence of pulmonary tuberculosis. Results: The levels of TG, TC, HDL-C, LDL-C, Apo-A1, and Apo-B in the case group were 1.23 (0.76, 1.47) mmol/L, (4.18±1.17) mmol/L, (1.14±0.38) mmol/L, (2.36±0.82) mmol/L, (0.94±0.32) g/L, and (0.79±0.26) g/L, respectively, and were all lower than those in the control group (1.64 (1.07, 2.06) mmol/L, (5.24±1.18) mmol/L, (1.36±0.34) mmol/L, (2.98±0.90) mmol/L, (1.31±0.33) g/L, (0.97±0.29) g/L, respectively), and the differences were statistically significant (U=-12.603, t=17.605, t=12.096, t=13.784, t=22.614, t=12.071, all P values <0.001). The TG, TC, HDL-C, LDL-C, Apo-A1, and Apo-B levels of individuals carrying the ApoE ε2/ε3 genotype in the case group were 1.21 (0.73, 1.38) mmol/L, (3.81±1.21) mmol/L, (1.17±0.36) mmol/L, (2.01±0.79) mmol/L, (0.96±0.32) g/L, and (0.67±0.22) g/L, respectively, lower than those in the control group (1.56 (0.96, 1.95) mmol/L, (4.78±1.03) mmol/L, (1.42±0.39) mmol/L, (2.50±0.81) mmol/L, (1.39±0.36) g/L, (0.83±0.28) g/L, respectively), and the differences were statistically significant (U=-3.805, t=5.009, t=3.968, t=3.666, t=7.755, t=3.491, all P values <0.001). The levels of TC, LDL-C, and Apo-B in patients carrying the ApoE ε2/ε3 genotype in the case group were (3.81±1.21) mmol/L, (2.01±0.79) mmol/L, and (0.67±0.22) g/L, respectively, which were lower than those carrying the ApoE ε3/ε3 genotype ((4.21±1.09) mmol/L, (2.40±0.76) mmol/L, and (0.81±0.25) g/L, respectively), with statistically significant differences (t values were 0.471, 5.595, and 5.681, respectively, all P values <0.001). The genotype frequency of ApoE ε2/ε3 genotype in the case group was 13.1% (146/1118),which was significantly higher than that in the control group (8.4% (49/582); χ 2=8.114, P=0.004). ε2 allele frequency in the case group (7.7% (174/2236)) was significantly higher than that of the control group (5.8% (67/1164); χ 2=4.770, P=0.029). Multivariate logistic regression analysis showed that carrying the ApoE ε2/ε3 genotypes (OR (95%CI)=1.763 (1.167-2.661))and ε2 allele gene (OR (95%CI)=1.630 (1.097-2.421)) were risk factors for pulmonary tuberculosis. Conclusion: Carrying ApoE ε2/ε3 genotype may lower the blood lipid levels in pulmonary tuberculosis patients, and carrying ApoE ε2/ε3 genotypes and ε2 allele population has a higher risk of developing pulmonary tuberculosis.

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    Estimation on direct medical costs of pulmonary tuberculosis in China
    Liu Yuhong, Gao Mengqiu, Zhang Lijie, Ma Liping, Nie Lihui, Jiang Guanglu, Ding Hongwan, Li Liang
    Chinese Journal of Antituberculosis    2023, 45 (12): 1134-1140.   DOI: 10.19982/j.issn.1000-6621.20230317
    Abstract220)   HTML40)    PDF(pc) (1317KB)(144)       Save

    Objective: To formulate clinical service packages required by different types of pulmonary tuberculosis and make estimation on direct medical costs accordingly. Results of estimation will be used to inform policy recommendations on optimized allocation of funds dedicated for tuberculosis prevention, promotion of multi-channel financing as well as further alleviation of financial burden of tuberculosis patients. Methods: According to China’s current tuberculosis prevention and control strategy, technical recommendations and clinical pathways, also in consideration of current capacity and clinical practices in tuberculosis designated hospitals at all levels, adoption and potential upgrade of new control strategy as well as application of new technologies and interventions in the future, this study had formulated different clinical service packages for different types of pulmonary tuberculosis patients and calculated the direct cost incurred by individual patient during diagnosis and treatment as well as total cost of these packages by multiplying the numbers of these different pulmonary tuberculosis patient groups in China. Results: Direct cost for a rifampicin-susceptible pulmonary tuberculosis patient was about 15370 Yuan, that of a rifampicin-resistant pulmonary tuberculosis patient was about 196585 Yuan. The annual budget required to cover the total direct medical cost of all pulmonary tuberculosis patients in China was about 14.69 billion Yuan with an average annual investment of 10 Yuan per capita, of which total medical cost for rifampicin-susceptible pulmonary tuberculosis patients accounts for 10.76 billion Yuan (73.2%, 10.76/14.69), that of rifampicin-resistant pulmonary tuberculosis patients was 3.93 billion Yuan (26.8%, 3.93/14.69). Of total medical cost, 8.31 billion Yuan (56.6%, 8.31/14.69) was incurred by outpatient cost; 6.38 billion Yuan (43.4%, 6.38/14.69) was inpatient cost. Conclusion: The estimates come out of this study have provided promotion of multi-channel financing, overall budgeting and allocation of funds dedicated for tuberculosis prevention and control, development of feasible medical cost alleviation and concession policy for tuberculosis patients with valuable references.

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    Interpretation of the Political Declaration of the Second High-level Meeting of the General Assembly of United Nations on the Fight Against Tuberculosis
    Zhang Lijie, Liu Yuhong
    Chinese Journal of Antituberculosis    2023, 45 (12): 1117-1119.   DOI: 10.19982/j.issn.1000-6621.20230380
    Abstract218)   HTML24)    PDF(pc) (1069KB)(146)       Save

    Tuberculosis is a major infectious disease that seriously endangers human health, and is also one of the major public health issues of global concern. The 78th General Assembly of United Nations held the second high-level meeting on the fight against tuberculosis in New York on September 23, 2023. Representatives of countries and international organizations expressed their support for the initiatives of United Nations initiative on the strategic goal of ending tuberculosis epidemic by 2030. Political Declaration of the High-level Meeting of General Assembly on the Fight Against Tuberculosis produced by the General Assembly was agreed by heads of state and government and senior representatives, which proposed the policy and measures to accelerate the achievement of the goal of ending tuberculosis epidemic by 2030.

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    Comparison of therapeutic effects between calcium sulfate incorporated with rifamycin sodium and autologous bone grafting in the treatment of thoraco-lumbar tuberculosis
    Wu Yunbiao, Pu Xingyu, Qi Yang, Kou Xianshuai, Xie Wendong, Luo Wenyuan, Liu Shengfen
    Chinese Journal of Antituberculosis    2023, 45 (7): 673-680.   DOI: 10.19982/j.issn.1000-6621.20230094
    Abstract218)   HTML14)    PDF(pc) (1991KB)(61)       Save

    Objective: To evaluate the efficacy and safety of calcium sulfate incorporated with rifamycin sodium in the treatment of thoraco-lumbar spinal tuberculosis through posterior approach lesion clearance and internal fixation surgery. Methods: A retrospective study was conducted in patients with thoraco-lumbar tuberculosis admitted to the Orthopedics, Cadre Ward of Gansu Provincial Hospital from June 2019 to August 2022. According to whether or not to implant rifamycin sodium calcium sulfate, the patients were divided into drug-loading group (simple posterior approach lesion removal combined with rifamycin sodium sulfate implantation) and bone graft group (simple posterior approach lesion removal combined with autologous bone implantation). Of the 54 cases initially included (26 cases in the drug-loading group and 28 cases in the bone graft group), 4 were lost to follow-up, and 50 cases were finally included (25 cases in the drug-loading group and 25 cases in the bone graft group). Lesion segments: 28 cases in the thoracic spine, 7 cases in the thoraco-lumbar spine, and 15 cases in the lumbar spine. The operation time, blood loss, hospital stay, postoperative complications, levels of ESR and CRP preoperative, 3 months postoperative and in the last follow-up were recorded, as well as the Cobb angles preoperative, 3 day, 3 months and 6 months postoperative and in the last follow-up. Results: All the 50 patients were followed up for 7-16 months. There was no significant difference in operation time ((168.04±17.22) min vs. (163.96±16.07) min, t=0.750, P=0.282), blood loss (911.20±93.38) ml vs. (904.40±90.74) ml, t=0.068, P=0.795) and hospital stay ((15.96±1.21) d vs. (15.28±1.31) d, t=3.651, P=0.062) between the two groups. The levels of ESR and CRP 3 months postoperative, in the drug-loaded group were significantly lower than those in the bone graft group ((26.48±2.76) mm/1 h vs. (28.64±3.03) mm/1 h, t=2.639, P=0.011; (3.45±0.79) mg/L vs. (4.41±1.15) mg/L, t=3.454, P=0.001). The Cobb angles in the bone graft group 6 months postoperative and in the last follow-up were significantly lower than those in the bone graft group ((12.32±0.68)° vs. (12.84±1.02)°, t=2.115, P=0.034; (12.43±0.76)° vs. (12.94±0.81)°, t=2.278, P=0.027). Conclusion: Simple posterior approach lesion removal combined with rifamycin sodium sulfate implantation for the treatment of thoraco-lumbar tuberculosis could achieve the goal of complete removal of lesions and reconstruction of spinal stability.

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    A longitudinal study on the characteristics of diagnosis and treatment service of multidrug-resistant/rifampicin resistant pulmonary tuberculosis from 2009 to 2020 in Nantong City, Jiangsu Province
    Che Beibei, Wang Xiaoping, Qiu Qing, Chen Cheng, Zheng Xubin, Zhao Qi, Xu Biao
    Chinese Journal of Antituberculosis    2023, 45 (9): 864-871.   DOI: 10.19982/j.issn.1000-6621.20230058
    Abstract217)   HTML14)    PDF(pc) (1505KB)(212)       Save

    Objective: To describe the longitudinal changes of case finding, clinical features and treatment for multidrug-resistant/rifampicin-resistant pulmonary tuberculosis (MDR/RR-PTB) in Nantong City, Jiangsu Province from 2009 to 2020, and to provide scientific guidance for optimizing the prevention and treatment policies for MDR/RR-PTB. Methods: Based on the Tuberculosis Information Management System, we collected the associated data of MDR/RR-PTB patients registered from 2009—2020 in Nantong City, Jiangsu Province. Longitudinal changes of detection rate, demographic characteristics, diagnostic delay, treatment coverage and treatment outcome for MDR/RR-PTB patients were depicted. Results: A total of 426 MDR/RR-PTB patients were detected in Nantong from 2009 to 2020. From 2014 to 2020, 4030 patients were screened, with an overall detection rate of 5.43% (219/4030). The detection rate fluctuated slightly over the years in response to different screening policy, from 16.83% (34/202) in 2014 to 2.85% (32/1123) in 2020, with a significantly decline trend (Ztrend=-11.541, P<0.001). During the past 12 years, the proportion of newly treated MDR/RR-PTB patients increased from 0 in 2009 to 53.12% (17/32) in 2020, and the proportion of patients aged ≥80 years decreased from 53.85% (7/13) in 2009 to 3.12% (1/32) in 2020. Overall, the diagnostic delay showed a decreasing trend since 2009, with the number of 97 (78, 207) days in 2009 and 0 (0, 0) day in 2020. As for treatment outcome among those received standardized treatment, the treatment success rate increased from 60.00% (6/10) in 2009 to 71.88% (23/32) in 2020, and the case fatality rate decreased from 20.00% (2/10) in 2009 to 9.38% (3/32) in 2020. Conclusion: This study showed that the detection rate of MDR/RR-PTB steadily decreased and maintained at a low level, while MDR/RR-PTB patients tended to be younger over time in Nantong City, and the proportion of newly treated patients increased annually. Diagnostic delay of MDR/RR-PTB patients tended to decrease. It is recommended to strengthen the standardized management of treatment in patients, especially for RR-PTB patients, to further decrease transmission.

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

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    China Association for Science and Technology
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