Table of Content

10 April 2025, Volume 47 Issue 4

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Guideline·Standard·Consensus

Evidence-based guidelines for application of digital adherence technology in tuberculosis medication management in China

Tuberculosis Control Branch of Chinese Antituberculosis Association, The Youth Branch of Chinese Antituberculosis Association, Editorial Board of Chinese Journal of Antituberculosis

Chinese Journal of Antituberculosis. 2025, 47(4):  385-397.  doi:10.19982/j.issn.1000-6621.20250042

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Timely identification of active tuberculosis (TB) patients and individuals with latent tuberculosis infection (LTBI), followed by targeted treatment, constitutes a critical strategy for TB epidemic control. Digital adherence technology (DAT) utilizes digital tools to assist healthcare providers in monitoring and promoting medication compliance among TB patients and those undergoing preventive treatment, thereby enhancing therapeutic adherence. This guideline systematically summarized the characteristics and practical evidence of DAT currently implemented in China’s TB prevention and control efforts, including video-observed therapy, electronic medication monitors, mobile applications, and SMS reminders. It further proposes recommendations for the application of DAT in supporting anti-TB treatment and TB preventive therapy, aiming to offer evidence-based guidance for the optimization and refinement of TB medication management strategies using DAT across various regions.

Original Articles

Investigation on the willingness of tuberculosis health-care workers to implement tuberculosis preventive treatment and analysis of influencing factors

Li Jinhao, Hu Dongmei, Xu Caihong

Chinese Journal of Antituberculosis. 2025, 47(4):  398-407.  doi:10.19982/j.issn.1000-6621.20240427

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Objective: To investigate the willingness of tuberculosis health-care workers (TB-HCWs) to implement tuberculosis preventive treatment (TPT) and analyze influencing factors, providing reference for scaling up TPT in China. Methods: A cross-sectional survey was conducted across 11 provinces in China, targeting TB-HCWs from general hospitals, chronic disease hospitals, TB-specialized hospitals, TB control institutes, centers for disease control (CDC) and prevention and primary healthcare institutions. A self-designed questionnaire was used to assess TB-HCWs’ willingness to implement TPT, screening method and treatment method. Multivariate logistic regression models were applied to identify influencing factors. Results: Among 14291 participants, 92.20% (13176/14291) expressed willingness to implement TPT. Multivariate analysis revealed that higher willingness among TB-HCWs with high school or lower education, college diplomas, and bachelor’s degrees compared to those with postgraduate degrees (OR=1.782, 95%CI: 1.196-2.626, P=0.004; OR=1.866, 95%CI: 1.291-2.657, P=0.001; OR=1.841,95%CI: 1.295-2.577, P<0.001). Staff in primary healthcare institutions and other institutions showed higher willingness than CDC personnel (OR=1.542, 95%CI: 1.140-2.077, P=0.005;OR=2.745, 95%CI: 1.699-4.589, P<0.001). Notably, TB-HCWs in TB-designated medical institutions demonstrated greater willingness than those in non-designated facilities (OR=1.217, 95%CI: 1.043-1.423, P=0.013). The primary motivations for willingness included reducing TB incidence (97.24% (12813/13176)), protecting high-risk populations (81.32% (10715/13176)), and availability of professional guidance (71.33% (9398/13176)), whereas concerns about drug resistance (75.41% (138/183)), adverse reactions (72.68% (133/183)), and efficacy uncertainty (65.03% (119/183)) were predominant barriers. 52.25% (6885/13176) of willing TB-HCWs had previously participated in TPT. Among them, TB-HCWs using tuberculin skin test (PPD), TBST, and IGRAs as screening methods accounted for 94.89% (6533/6885), 62.02% (4270/6885), and 57.60% (3966/6885), respectively. TB-HCWs adopting 3HR, 6-9H, immunoprophylaxis, 3HP, and 4R as treatment regimens accounted for 74.09% (5101/6885), 64.71% (4455/6885), 59.23% (4078/6885), 57.47% (3957/6885), and 49.75% (3425/6885), respectively. Conclusion: TB-HCWs in China currently exhibit high willingness to implement TPT, yet disparities exist across educational backgrounds, institutional levels, and facility types. Targeted training and policy support are critical to accelerate TPT implementation and reduce tuberculosis burden.

Analysis of the treatment outcomes and influencing factors of rifampicin-resistant pulmonary tuberculosis patients aged 65 and above in China from 2015 to 2021

Li Yuhong, Mei Jinzhou, Su Wei, Ruan Yunzhou, Liu Yushu, Zhao Yanlin, Liu Xiaoqiu

Chinese Journal of Antituberculosis. 2025, 47(4):  408-415.  doi:10.19982/j.issn.1000-6621.20240456

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Objective: To analyse the treatment outcomes and influencing factors of patients with rifampicin-resistant pulmonary tuberculosis (RR-PTB) aged 65 years and above in China from 2015 to 2021. Methods: The medical records of patients aged 65 years and older diagnosed with RR-PTB and treated nationwide from January 1, 2015, to December 31, 2021, were retrieved from the “Drug-Resistant Case Management” section of the “Surveillance Report Management” module within the “China Information System for Disease Control and Prevention”. Descriptive analysis was performed on the patients’ demographic characteristics, diagnostic and treatment details, and treatment outcomes. Univariate and multivariate logistic regression analysis were used to analyse the factors influencing treatment outcomes. Results: From 2015 to 2021, a total of 13806 RR-PTB patients aged 65 and above were registered nationwide, with an incidence rate of 1.16 per 100000 (13806/1191.33 million). The rate increased from 0.50 per 100000 (726/145.24 million) in 2015 to 1.37 per 100000 (2743/200.56 million) in 2021. The proportion of elderly RR-PTB patients among all RR-PTB patients was 16.15% (13806/85494), increasing from 13.24% (726/5484) in 2015 to 19.12% (2743/14348) in 2021. The treatment rate of registered patients was 80.18% (11070/13806), increasing from 58.13% (422/726) in 2015 to 90.01% (2469/2743) in 2021. The treatment success rate was 46.37% (5133/11070), increasing from 37.20% (157/422) in 2015 to 48.85% (1206/2469) in 2021, showing a significant upward trend ($χ^{2}_{trend}$ values were 96.329, 272.135, 919.021, and 30.029, with P-values all <0.001). Multivariate logistic regression analysis revealed that, relative to individuals aged 65-69, females, homemakers, and unemployed individuals, eastern region, primary treatment, and rifampicin monoresistance, those in older age groups (70-74, 75-79, and 80+), males, individuals engaged in agriculture, pastoralism, or fishing, residents of central and western regions, retreatment, with multidrug-resistant, pre-extensively drug-resistant, or extensively drug-resistant pulmonary tuberculosis exhibited significantly higher risks of treatment failure (OR=1.156, 95%CI: 1.055-1.268; OR=1.415, 95%CI: 1.269-1.578; OR=1.887, 95%CI: 1.655-2.154; OR=1.202, 95%CI: 1.101-1.312; OR=1.152, 95%CI: 1.037-1.279; OR=1.655, 95%CI: 1.503-1.823; OR=1.657, 95%CI: 1.494-1.837; OR=1.109, 95%CI: 1.028-1.197; OR=1.243, 95%CI: 1.147-1.346; OR=1.331, 95%CI: 1.015-1.752). Conclusion: The registration rate and proportion of elderly RR-PTB patients aged 65 and above in China have exhibited an upward trend. Although the treatment initiation rate among registered patients is relatively high, the treatment success rate remains suboptimal. Particular attention should be directed towards male patients, those aged 70 and above, individuals engaged in agriculture, pastoralism, or fishing, residents of central and western regions, patients with prior treatment history, as well as those diagnosed with multidrug-resistant tuberculosis, pre-extensively drug-resistant tuberculosis, or extensively drug-resistant tuberculosis.

Status and influencing factors of diagnosis and treatment delay of rifampicin resistant pulmonary tuberculosis patients, Jilin Province, 2020—2023

Jiang Xue, Bai Yunlong, Ma Jianjun, An Yuan, Yang Fan, Zhao Qinglong

Chinese Journal of Antituberculosis. 2025, 47(4):  416-424.  doi:10.19982/j.issn.1000-6621.20240530

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Objective: To analyze diagnosis and treatment delay and their related influencing factors among rifampicin-resistant tuberculosis (RR-TB) patients in Jilin Province, aiming to provide a reference basis for developing prevention and control measures in Jilin Province. Methods: Medical records on RR-TB patients from 2020 to 2023 were extracted from the Tuberculosis Management Information System, a subsystem of the China Disease Prevention and Control Information System. Trends of diagnosis and treatment delay rates over time were analyzed using trend chi-square test, and logistic regression model was used to examine the related influencing factors. Results: Among 1931 RR-TB patients, their health-care seeking delay rate, definitive diagnosis delay rate and treatment delay rate were 50.7% (979/1931), 12.7% (245/1931) and 25.4% (491/1931), respectively. From 2020 to 2023, the rate of definitive diagnosis delay increased ($χ^{2}_{trend}$=12.353,P<0.001), while the rate of treatment delay decreased ($χ^{2}_{trend}$=33.459,P<0.001). Logistic regression model showed that patients being detected by primary care units recommending to TB designated hospital (OR=0.443, 95%CI:0.241-0.817) and patients being relapse (OR=0.818, 95%CI:0.680-0.984) were protective factors for health-care seeking delay, comorbidity (OR=1.312, 95%CI:1.080-1.721) and multi-drug resistance (OR=1.252, 95%CI:1.035-1.515) were risk factors for health-care seeking delay. Patients were detected through general hospital referring to TB designated hospital (OR=2.184, 95%CI:1.568-3.042) and TB designated hospital tracing (OR=1.946, 95%CI:1.390-2.724) were risk factors for definitive diagnosis delay, molecular biological rapid testing (OR=0.140, 95%CI:0.072-0.273)and diagnosed in provincial or municipal medical institutions (OR=0.072, 95%CI:0.049-0.107) were protective factors for definitive diagnosis delay. Molecular biological rapid detection (OR=0.420, 95%CI:0.136-0.501) was a protective factor for treatment delay, relapse patients (OR=1.259, 95%CI:1.019-1.555) and floating population (OR=1.907, 95%CI:1.275-2.852) were risk factors for treatment delay. Conclusion: The risks of diagnosis and treatment delays in Jilin Province were relatively high. In order to further reduce these delay, corresponding prevention and control measures for high-risk factors should be taken.

Analysis of factors influencing the treatment outcomes of patients with pulmonary tuberculosis and diabetes mellitus in Henan Province (2019—2023)

Wu Xuan, Zhang Yanqiu, Xu Jiying, Meng Dan, Sun Dingyong

Chinese Journal of Antituberculosis. 2025, 47(4):  425-431.  doi:10.19982/j.issn.1000-6621.20240460

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Objective: To identify the determinants of adverse treatment outcomes among patients with pulmonary tuberculosis and diabetes mellitus (PTB-DM) who have rifampicin-sensitive or unknown drug resistance status in Henan Province. Methods: Medical records of patients diagnosed with pulmonary tuberculosis and diabetes mellitus (PTB-DM) in Henan Province between January 1, 2019, and December 31, 2023, were retrieved from the Tuberculosis Management Information System, a subsystem of the China Disease Prevention and Control Information System. Patients with documented drug-resistant tuberculosis, as well as those with severe comorbidities or complications, were excluded. A total of 7354 eligible patients were included in the final analysis. The cumulative treatment success rate was estimated using the Kaplan-Meier method, while the Cox proportional hazards regression model was employed to identify risk factors associated with unsuccessful treatment outcomes. Results: Among the 7354 patients included in the study, 86.1% (6329/7354) achieved successful tuberculosis treatment, while 13.9% (1025/7354) experienced adverse treatment outcomes. The cumulative treatment success rate, as estimated using the Kaplan-Meier method, was 80.7%. Multivariate Cox proportional hazards regression analysis identified several protective factors for successful anti-tuberculosis treatment in PTB-DM patients, including sputum smear negativity at the end of the second month of treatment (HR=0.388, 95%CI: 0.281-0.535), an unavailable sputum smear result (HR=0.251, 95%CI: 0.165-0.380), and the use of a six-month treatment regimen (HR=0.129, 95%CI: 0.094-0.176). Conversely, risk factors associated with adverse treatment outcomes included older age (≥65 years; HR=1.137, 95%CI: 1.002-1.290), local household registration in Henan Province (HR=1.517, 95%CI: 1.072-2.148), positive bacteriological findings (HR=1.277, 95%CI: 1.105-1.476), and delayed diagnosis (HR=1.137, 95%CI: 1.005-1.287). Conclusion: Optimizing early sputum monitoring and implementing a standardized six-month short-course anti-tuberculosis treatment regimen for PTB-DM patients can significantly reduce the risk of adverse treatment outcomes. Meanwhile, heightened vigilance is required for older adults (≥65 years), patients with positive bacteriological findings, those experiencing delays in seeking medical care, and individuals with local household registration in Henan Province, as they remain at increased risk of unfavorable treatment outcomes.

Analysis of treatment outcomes and influencing factors of patients with pulmonary tuberculosis complicated with diabetes mellitus in Jilin Province,2018—2022

An Yuan, Bai Yunlong, Zhao Qinglong, Ma Jianjun, Jiang Xue, Pan Yan, Gao Ying, Gao Zhihui

Chinese Journal of Antituberculosis. 2025, 47(4):  432-438.  doi:10.19982/j.issn.1000-6621.20240529

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Objective: To analyze treatment outcomes and influencing factors of patients with pulmonary tuberculosis complicated with diabetes mellitus (PTB-DM) in Jilin Province from 2018 to 2022, and to provide a basis for improving PTB-DM prevention and control strategy. Methods: Data of PTB patients in Jilin Province from 2018 to 2022 were collected through the Tuberculosis Management Information System of the China Disease Control and Prevention Information System. Characteristics and treatment outcomes of PTB-DM patients were analyzed using descriptive methods. Binary logistic regression model was used to analyze influencing factors of treatment outcomes. Results: From 2018 to 2022, a total of 2640 PTB-DM patients were registered in Jilin Province, accounting for 5.67% (2640/46594) of the total population of PTB patients, which increased from 3.45% (468/13569) in 2018 to 9.10% (573/6296) in 2022, showing a yearly increasing trend ($χ^{2}_{trend}$=302.583, P<0.05). PTB-DM patients were mainly male (79.02%, 2086/2640), 45 to 64 years old (61.36%, 1620/2640), etiologically positive (77.61%, 2049/2640). The treatment success rate of PTB-DM patients in the province was 89.37% (2119/2371), and the adverse outcome incidence was 10.63% (252/2371).Multivariable logistic regression analysis showed that age group of ≥65 years (OR=1.573, 95%CI:1.009-2.452), etiologically positive (OR=1.471, 95%CI:1.029-2.104), receiving retreatment(OR=2.311, 95%CI:1.565-3.412), floating population(OR=4.745, 95%CI: 3.359-6.704) were risk factors for adverse outcomes in PTB-DM patients. Conclusion: The treatment outcomes of PTB-DM patients in Jilin Province are generally poor, so more attention should be paid to PTB-DM patients over 65 years old, etiologically positive, receiving retreatment, and floating population.

Analysis of under-reporting before arrival of pulmonary tuberculosis patients registered and managed by Tuberculosis Prevention and Control Institutions in Xicheng District, Beijing from 2018 to 2023

Feng Wei, Zheng Hailun, Meng Weili, Luo Ping

Chinese Journal of Antituberculosis. 2025, 47(4):  439-443.  doi:10.19982/j.issn.1000-6621.20240491

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Objective: To analyze the under-reporting situation of network infectious disease reports (hereinafter referred to as “network reporting”) of pulmonary tuberculosis patients before registration and management in the tuberculosis prevention and control (referred to as “tuberculosis prevention”) institutions in Xicheng District, Beijing, and to provide a scientific basis for further improvement of patient detection. Methods: The data was from the “Tuberculosis Information Management System”, a subsystem of the “China Information System for Disease Control and Prevention”, and the medical records of the outpatient department of Xicheng tuberculosis prevention institution from 2018 to 2023. A total of 1233 patients who needed network reporting before arrival were divided into 693 cases of symptom-based consultations and 540 cases of health check-ups according to the source of the patients. The under-reporting situation before arrival was analyzed, and the imaging and disease conditions of the patients at the time of arrival were comparatively analyzed. Results: Among the 1233 patients, 887 were reported before arrival, and 346 were not reported. There were 135 under-reported cases among the symptom-based consultation patients, with an under-reporting rate of 19.48% (135/693), and 211 under-reported cases among the health check-up patients, with an under-reporting rate of 39.07% (211/540). The under-reporting rate of symptom-based consultation patients was lower than that of health check-up patients, and the difference was statistically significant (χ²=57.719, P<0.001). Comparing the image and symptoms of patients at the time of arrival for symptom-based consultations and health check-ups, the proportions were as follows: the lesion involved 1-3 sites, 76.91% (533/693) and 90.37% (488/540); cavities, 38.67% (268/693) and 22.22% (120/540); cough and expectoration, 72.15% (500/693) and 18.15% (98/540); hemoptysis, 12.84% (89/693) and 0.93% (5/540); other symptoms, 51.08% (354/693) and 9.26% (50/540). All the differences were statistically significant (χ²=38.611, 38.084, 354.351, 61.201, 240.982, all Ps<0.001). Conclusion: The under-reporting rate before arrival of health check-up patients in the tuberculosis prevention institutions in Xicheng District, Beijing was significantly higher than that of symptom-based consultation patients. However, the condition of symptom-based consultation patients was more serious. It suggests that it is necessary to further improve the existing supervision and inspection methods of tuberculosis prevention institutions and to establish a network reporting mechanism for pulmonary tuberculosis in independent physical examination institutions to further improve the detection of pulmonary tuberculosis patients.

Experimental study on the role of Mce4C in the uptake and utilization of cholesterol by Mycobacterium tuberculosis

Hu Yifan, Du Boping, Wu Yadong, Zhu Chuanzhi, Zhang Lanyue, Jia Hongyan, Sun Qi, Pan Liping, Zhang Zongde, Li Zihui

Chinese Journal of Antituberculosis. 2025, 47(4):  444-453.  doi:10.19982/j.issn.1000-6621.20240579

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Objective: To investigate whether Mce4C protein is involved in the uptake and utilization of cholesterol by Mycobacterium tuberculosis (MTB). Methods: The impact of different cholesterol concentrations (cholesterol-free group, 0.01% cholesterol group, and 0.1% cholesterol group) on the expression of MTB mce4C gene was analyzed by quantitative polymerase chain reaction. Growth curves plotted by measuring A₆₀₀ value of cultured bacterial solutions with an ultraviolet-visible spectrophotometer and supplemented by scanning electron microscopy, were used to analyze the differences in growth rate and morphology among the wild-type MTB H37Rv reference strain (WT), mce4C knockout strain (Δmce4C), and its complemented strain (Δmce4C+mce4C). To determine whether Mce4C was involved in the uptake of cholesterol by MTB, the changes of cholesterol levels in bacteria, bacterial medium and lysates of infected cells were measured either by using testing kits to quantitatively measure cholesterol content or by determining the fluorescence value of NBD-cholesterol. The subcellular localization of the Mce4C protein was determined through immunoblotting experiments on separation and combination of different MTB components. Results: The expression level of mce4C gene increased with elevation of cholesterol concentration in Sauton medium. After one week’s culture, the mce4C relative expression levels were 1.000±0.588, 1.390±0.162, and 3.622±1.031 respectively for cholesterol-free group, 0.01% cholesterol group, and 0.1% cholesterol group, with statistically significant difference (F=28.200, P=0.001). As the culture time in cholesterol-containing Sauton medium extended (20, 40, 60, 70, 80 days), the decrease of A₆₀₀ value of Δmce4C became increasingly more pronounced compared to WT and Δmce4C+mce4C. By the 80th day, the A₆₀₀ value of Δmce4C (0.913±0.017) was significantly lower than that of WT (1.245±0.011) and Δmce4C+mce4C (1.246±0.029), with all differences being statistically significant (t=28.182, P<0.001; t=17.140, P<0.001). When the three strains were cultured in cholesterol-containing Sauton medium, the cholesterol content in Δmce4C bacteria was lower than that in WT and Δmce4C+mce4C, while the cholesterol content in its culture supernatant was higher. By the 21st day, the total cholesterol content in Δmce4C bacteria ((1.058±0.012) μg/ml) was significantly lower than that in WT ((1.347±0.087) μg/ml) and Δmce4C+mce4C ((1.505±0.021) μg/ml), and the cholesterol content in the culture supernatant ((16.371±0.753) μg/ml) was significantly higher than that in WT ((7.740±0.422) μg/ml) and Δmce4C+mce4C ((7.274±0.131) μg/ml). All these differences were statistically significant (t=4.621, P=0.044; t=25.679, P=0.002; t=-14.135, P=0.005; t=-16.827, P=0.004). At different time points (4, 24, 48, 72 h) after infecting THP-1 cells, the cholesterol content in the lysates of cells infected with Δmce4C was significantly higher than that in cells infected with WT and Δmce4C+mce4C. Even at the lowest point at 4 h post-infection, the cholesterol content in the lysates of cells infected with Δmce4C ((7.749±0.017) μg/ml) was higher than that in cells infected with WT ((7.180±0.173) μg/ml) and Δmce4C+mce4C ((6.725±0.288) μg/ml), and the differences were statistically significant (t=-6.556, P=0.001; t=-7.106, P<0.001). Conclusion: The expression of mce4C gene increases with increasing cholesterol concentration in the culture medium. Knockout of mce4C gene reduces the growth rate of MTB in cholesterol-containing Sauton medium and the cholesterol content of MTB bacteria, increases the cholesterol content of the culture medium and lysates of infected cells, indicating that Mce4c is involved in the uptake and utilization of cholesterol by MTB from the external environment. Deletion of its coding gene can cause MTB to grow significantly defectively when cholesterol is the only carbon source, which may be an important factor for MTB to survive in human body for long time and be pathogenic.

Study on the mechanism of IL-22 and p38 MAPK signaling pathways in inhibiting bone destruction in bone and joint tuberculosis

Sheng Jie, Hong Kaifeng, Mierzhati Aisha, Tang Wei, Dilixiati Abulizi

Chinese Journal of Antituberculosis. 2025, 47(4):  454-459.  doi:10.19982/j.issn.1000-6621.20240568

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Objective: o elucidate the mechanistic role of interleukin-22 (IL-22) in mediating bone destruction in bone and joint tuberculosis via the p38 mitogen-activated protein kinase (MAPK) signaling pathway. Methods: (1) A total of 58 patients diagnosed with bone and joint tuberculosis who underwent surgical intervention at the Department of Orthopedics, Xinjiang Uygur Autonomous Region Infectious Disease Hospital between January and December 2021 were enrolled as the case group. A control group comprising 51 patients with fractures who underwent surgical treatment at the same institution during the same period was also established. Peripheral blood serum samples were collected from all participants, and IL-22 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Additionally, bone tissue specimens were obtained for protein expression analysis. The expression levels of p38 MAPK, phosphorylated p38 (p-p38), cathepsin K (CatK), and matrix metalloproteinase-9 (MMP9) were determined via Western blotting. (2) Mouse monocyte-macrophage leukemia cells (RAW264.7) were differentiated into osteoclast-like cells and subsequently divided into six experimental groups: osteoclast group, osteoclast+H37Rv group, osteoclast+H37Rv+negative control group, osteoclast+H37Rv+IL-22-shRNA group, osteoclast+H37Rv+p38 inhibitor group, and osteoclast+H37Rv+p38 inhibitor+IL-22-shRNA group. The osteoclastogenic activity was assessed using tartrate-resistant acid phosphatase (TRAP) staining, while gene and protein expression levels of p38 MAPK, CatK, and MMP9 were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Results: (1) Clinical findings: The serum IL-22 levels in the control group (median (quartiles): 34.61 (28.29, 76.92) pg/ml) were significantly lower than those in the case group (102.74 (56.12, 132.78) pg/ml), with a statistically significant difference (Z=-3.840, P=0.001). The protein expression levels of p38, p-p38, CatK, and MMP9 in the case group were 0.649±0.043, 0.856±0.062, and 0.506±0.072, respectively, all of which were significantly higher than those in the control group (0.346±0.078, 0.708±0.094, and 0.366±0.046, respectively), with statistically significant differences (t=-8.368, -3.203, -4.025; all P<0.05). (2) Cellular experiment findings: The number of TRAP-positive osteoclasts per microscopic field (×100) was highest in the osteoclast+H37Rv group (51.333±12.858), significantly exceeding that of all other groups (F=26.270, P<0.001). The expression levels of p-p38, CatK, and MMP9 proteins were markedly upregulated in the osteoclast+H37Rv group but were significantly downregulated following intervention with IL-22 short hairpin RNA (shRNA) and a p38 MAPK inhibitor. Conclusion: Silencing IL-22 expression and inhibiting the p38 MAPK signaling pathway significantly mitigates bone destruction associated with bone and joint tuberculosis. These findings suggest that IL-22 and p38 MAPK play pivotal roles in osteoclastic activity and bone resorption in the pathogenesis of bone and joint tuberculosis, highlighting their potential as therapeutic targets for preventing disease-associated bone loss.

Profile analysis of circRNA expression and identification of diagnostic markers in peripheral blood mononuclear cells of tuberculosis patients

Wang Yingchao, Liu Weiyi, Ji Xiuxiu, Shang Xuetian, Jia Hongyan, Zhang Lanyue, Sun Qi, Du Boping, Zhu Chuanzhi, Pan Liping, Zhang Zongde

Chinese Journal of Antituberculosis. 2025, 47(4):  460-470.  doi:10.19982/j.issn.1000-6621.20250043

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Objective: This study aims to uncover the expression profile of circular RNAs (circRNAs) in peripheral blood mononuclear cells (PBMCs) from tuberculosis (TB) patients, and identify potential circRNAs as diagnostic biomarkers for TB. Methods: Microarray chip was used to get the circRNA expression profiles of PBMCs from TB patients and healthy controls (HCs). Weighted gene co-expression network analysis (WGCNA) was employed to identify critical gene modules strongly associated with TB. The functions of genes within these key modules were further explored through gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and immune infiltration analysis. Subsequently, the circRNAs derived from the key modules and had significant differences between TB and HCs, were validated by real-time fluorescent quantitative PCR (qPCR) in an independent validation sample set, to verify the microarray results. The receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance of these candidate circRNAs. Additionally, Pearson correlation analysis was conducted for the candidate circRNAs and clinical features. Results: Through WGCNA analysis, a total of 16 gene modules were identified, with the brown module being the most strongly associated with TB. Functional enrichment analysis revealed that genes in the brown module were primarily enriched in T cell receptor signaling pathway, mitogen-activated protein kinase signaling pathway, mitochondrial autophagy in animal cells, ferroptosis, ubiquitin-mediated proteolysis and other functional pathways. Immune infiltration analysis based on the genes in the brown module indicated significant differences in the proportion of CD8⁺ T cells (P<0.001), resting memory CD4⁺ T cells (P<0.0001) and monocytes (P<0.001) between the TB and HCs group. In the brown module, nine TB-specific circRNAs were identified based on the selection criteria (P<0.05, fold change >4 or <0.25, and the mean expression value >10 in at least one group). Among them, hsa_circ_0052124’s expression level was significantly downregulated in the TB group (Z=―6.328, P<0.0001), its area under the ROC curve (AUC) was 0.976 (95%CI: 0.940-1.000, P<0.0001), with a sensitivity of 90.0% (95%CI: 73.5%-97.9%) and a specificity of 100.0% (95%CI: 88.4%-100.0%), which meant it could effectively distinguish TB patient from HC individuals. Pearson correlation analysis showed a positive correlation between hsa_circ_0052124 expression level and other clinical features (P<0.01), including apolipoprotein B (r=0.715), lipoprotein(a)(r=0.598), and glucose (r=0.575) level in the peripheral blood. Conclusion: Our study uncovered the circRNA expression profile of TB patients, identified a key gene module significantly associated with TB, and discovered a circRNA (hsa_circ_0052124) with a significant difference between TB patients and HCs.

Diagnostic value of urine lipoarabinomannan antigen detection in extrapulmonary tuberculosis

Zhu Mingzhi, Shao Yanqin, Fan Dapeng, Liu Libin, Mei Bin, Dai Lingshan, Cai Long

Chinese Journal of Antituberculosis. 2025, 47(4):  471-476.  doi:10.19982/j.issn.1000-6621.20240383

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Objective: To explore the diagnostic value of urinary lipoarabinomannan (LAM) antigen detection in patients with extrapulmonary tuberculosis. Methods: Urine samples of 92 suspected patients with extra pulmonary tuberculosis treated in Hangzhou Red Cross Hospital from April 2023 to June 2024 were continuously collected for LAM antigen detection, and GeneXpert MTB/RIF (Xpert) test detection was performed on the corresponding lesion site samples. Taking the clinical comprehensive diagnosis as the reference standard, the diagnostic efficiency of the two methods alone and in combination for extrapulmonary tuberculosis was compared. Results: Based on the comprehensive clinical diagnosis results, the sensitivity, specificity and area under curve (AUC) of urine LAM antigen and Xpert for the test of extrapulmonary tuberculosis were 49.3% (95%CI: 36.8%-61.8%), 92.0% (95%CI: 74.0%-99.0%), 0.706 (95%CI: 0.602-0.797) and 49.3% (95%CI: 36.8%-61.8%), 100.0% (95%CI: 86.3%-100.0%), 0.746 (95%CI: 0.645-0.831), respectively. The sensitivity of urine LAM antigen combined with Xpert to detect extrapulmonary tuberculosis was 73.1% (95%CI: 60.9%-83.2%), which was higher than that of urine LAM antigen (χ²=27.672, P<0.001) and Xpert (χ²=17.576, P<0.001). The AUC was 0.826 (95%CI: 0.733-0.897), which was higher than that of urine LAM antigen and Xpert detection; and the differences were statistically significant (Z=1.602, P<0.001; Z=4.175, P=0.037). Conclusion: Urine LAM antigen detection has a certain application prospect in the diagnosis of extrapulmonary tuberculosis, and the combination with Xpert can improve the sensitivity of detection and enhance the application value in the diagnosis of extrapulmonary tuberculosis.

Effectiveness of a continuity of care model in patients with tuberculous meningitis

Hao Mingxiao, Mi Jie, Xu Zongyi

Chinese Journal of Antituberculosis. 2025, 47(4):  477-481.  doi:10.19982/j.issn.1000-6621.20240477

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Objective: To evaluate the effectiveness of a continuity of care model in managing patients with tuberculous meningitis (TBM). Methods: A total of 60 patients diagnosed with TBM and admitted to The Eighth Medical Center of the General Hospital of the Chinese People’s Liberation Army between April 2015 and October 2022 were included in the study. Among them, 30 patients admitted between April 2015 and December 2018 were assigned to the control group, while 30 patients admitted between January 2019 and October 2022 comprised the observation group. The control group received routine nursing care, whereas the observation group underwent an integrated nursing intervention combining routine nursing care with a continuity of care model. The quality of life and prognostic outcomes of both groups were assessed before and after the intervention, along with treatment adherence and self-efficacy levels measured at 1, 3, 6, and 12 months post-intervention. Results: The treatment adherence scores in the observation group at 1, 3, 6, and 12 months following the continuity of care model intervention were 75.24±4.02, 80.36±4.45, 86.74±5.62, and 90.61±6.02, respectively, which were significantly higher than those in the control group (67.00±4.58, 73.99±4.70, 78.10±5.50, and 80.55±5.98, respectively). The differences were statistically significant (t=7.406, P=0.000; t=5.391, P=0.000; t=6.018, P=0.000; t=6.494, P=0.000). Similarly, self-efficacy scores in the observation group at 1, 3, 6, and 12 months post-intervention were 24.82±3.98, 26.56±4.02, 29.44±3.45, and 33.21±3.77, respectively, all of which were significantly higher than those in the control group (22.02±3.32, 22.01±3.69, 25.17±3.51, and 26.38±3.46, respectively). These differences were also statistically significant (t=2.959, P=0.004; t=4.567, P=0.000; t=4.752, P=0.000; t=7.311, P=0.000). Post-intervention quality of life scores were higher in the observation group compared to the control group. The favorable prognosis rate in the observation group (80.0%, 24/30) was significantly higher than that in the control group (50.0%, 15/30). Additionally, the mortality rate (0) and recurrence rate (6.7%, 2/30) in the observation group were significantly lower than those in the control group (13.3%, 4/30, and 30.0%, 9/30, respectively). These differences were statistically significant (χ²=5.934, P=0.015; χ²=4.286, P=0.038; χ²=5.455, P=0.020). Conclusion: The integration of a continuity of care model into routine nursing care significantly enhances treatment adherence in TBM patients, improves self-efficacy, optimizes prognosis, and reduces the risks of disability and disease recurrence.

Bibliometric analysis of global research status and hotspots in the basic research of Traditional Chinese Medicine for tuberculosis

Shang Xiyu, Zhang Huifang, Cao Yuqing, Xiong Yibai, Ji Xinyu, Tian Yaxin, Li Jiajia, Wang Ni, Ma Yan

Chinese Journal of Antituberculosis. 2025, 47(4):  482-497.  doi:10.19982/j.issn.1000-6621.20240567

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Objective: To explore the global research status and trends in basic research on Traditional Chinese Medicine (TCM) for prevention and treatment of tuberculosis (TB). Methods: We conducted a comprehensive literature review of Chinese and English publications related to basic TCM research against TB using Chinese national knowledge infrastructure, Wanfang database, PubMed and Web of Science database with a cutoff date of June 30, 2024. Bibliometric analysis was performed using CiteSpace and VOSviewer software to visualize publication metrics, author and institution networks, keywords clusters and the frequency of TCM interventions in both Chinese and English literature. Results: A total of 140 articles were included, contributed by 546 authors from 190 institutions, including 102 Chinese articles (72.86%) and 38 English articles (27.14%). The first publication appeared in 1961, with a noticeable increase in research output observed since 1993. In terms of journal distribution, the journal with the most Chinese publications was Chinese Journal of Antituberculosis (6.86%, 7/102), and the journal with the most English publications was Journal of Ethnopharmacology (10.53%, 4/38). Regarding author collaboration networks, the Chinese literature formed two research terms centered around “Wang Lixin and Wang Yi”, “Pan Jianhua, Shi Guomin, Xiang Yangen, Yu Rong”, respectively, while the English literature formed research teams centered around “Jiang Xin, Sun Jinxia, Zheng Yuejuan”. The institution collaboration network centered around “Shanghai University of Traditional Chinese Medicine” and “Changzhi Medical College.” Keyword clustering analysis in both Chinese and English literature revealed 16 distinct clusters, with research hotspots primarily concentrating on antibacterial effects and immunomodulation. Additionally, Prunella vulgaris, Radix Ranunculi Ternati, Radix stemonae, Rhubarb, Garlic were the most concerned single herb; baicalin, Radix Ranuncoli Ternati extracts, Allicin and Curcumin were the most TCM ingredients or extracts; while the combination of Bletilla striata (Thunb. ex A. Murray) Rchb. f. and Stemona japonica (Blume) Miq. (Bai Ji-Bai Bu) as the most strongly correlated herbal pair in TCM formulations. Conclusion: Basic research on TCM against TB has gained significant traction globally in recent years. The antibacterial effects and immune regulation mechanisms of TCM may become the future focus of development. Future investigations should enhance cross-sector and interdisciplinary collaborations to further elucidate the mechanisms underpinnings and optimize therapeutic patterns of TCM in TB prevention and treatment.

Review Articles

Advances in the clinical diagnosis and treatment of post-tuberculosis chronic pulmonary aspergillosis

Qin Lili, Yang Chengqing, Mai Hongzhen, Xu Qifeng, Xue Xinying, Lu Xiwei

Chinese Journal of Antituberculosis. 2025, 47(4):  498-504.  doi:10.19982/j.issn.1000-6621.20240527

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Tuberculosis (TB) remains the leading cause of death from infectious diseases globally. Increasing recognition has been given to the long-term consequences of post-tuberculosis lung disease (PTLD), which profoundly affect patients’ physical health, psychological well-being, and socioeconomic stability. Among these sequelae, post-tuberculosis chronic pulmonary aspergillosis (PTLD-CPA) is a persistent Aspergillus infection that arises during or after TB treatment. The substantial overlap in clinical manifestations and radiological features between CPA and TB frequently leads to misdiagnosis and inappropriate treatment, further exacerbating disease progression and associated morbidity. This underscores the critical need for early screening and timely intervention for Aspergillus infection. This review consolidates current evidence on the epidemiology, clinical characteristics, diagnostic modalities, treatment strategies, and screening protocols for PTLD-CPA. By delineating key priorities for prevention and disease management, we propose a comprehensive, life-cycle-based health management framework for TB, integrating early detection, targeted therapeutic interventions, and long-term surveillance to mitigate the enduring burden of PTLD-CPA.

Progress in bronchoscopic diagnosis and treatment of lymph node fistula tracheobronchial tuberculosis

Luo Li, Luo Linzi, Yin Quhua, Zhou Lei, Lu Zhibin, Ding Yan, Xiao Yangbao

Chinese Journal of Antituberculosis. 2025, 47(4):  505-512.  doi:10.19982/j.issn.1000-6621.20240438

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Lymph node fistula tracheobronchial tuberculosis (TBTB) lacks clinical specific manifestations and can only be diagnosed through bronchoscopy, which is prone to misdiagnosis and missed diagnosis. In recent years, with the popularization and development of bronchoscopy and bronchial intervention techniques, the detection and cure rates of lymph node fistula TBTB have significantly increased. On the basis of systemic anti-tuberculosis drug therapy, other treatment techniques, such as local drug infusion under bronchoscopy, freezing, thermal ablation, and balloon dilation etc., are becoming increasingly diverse. Choosing an appropriate comprehensive intervention therapy based on different bronchoscopic manifestations of lymph node fistula TBTB has become an effective auxiliary means for clinical treatment of TBTB. This article is a review about the bronchoscopic interventional treatment strategies for lymph node fistula TBTB by reviewing the characteristics of bronchoscopic manifestations and the efficacy of interventional treatment methods for lymph node fistula TBTB, as well as the research progress of new bronchoscopic therapies in recent years. It is hopefully to provide some help on choosing a fast and effective endoscopic treatment with personalized care for patients with lymph node fistula TBTB.

Research progresses on the role and mechanism of calcium-binding protein S100A12 and neutrophil extracellular trap formation in lung injury of severe pulmonary tuberculosis patients

Song Yunlin, Buzukela Abuduaini, Wang Guirong, Zhang Jiyuan, Lu Xiaobo

Chinese Journal of Antituberculosis. 2025, 47(4):  513-519.  doi:10.19982/j.issn.1000-6621.20240445

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The incidence and mortality rates of severe pulmonary tuberculosis remain persistently high. However, the disease face significant diagnostic challenges due to the lack of specificity in clinical signs and symptoms during the early stages of the disease. Furthermore, the therapeutic of severe tuberculosis has become being complicated due to multiple factors, such as drug-drug interactions, drug-disease interactions, and adverse drug reactions, all of which together pose new challenges for tuberculosis prevention and control. The pathogenesis of severe tuberculosis involves a complex interaction between the host and Mycobacterium tuberculosis, yet the mechanism of pathogenesis remains incompletely understood. Recent studies indicate that calcium-binding protein S100A12 (hereafter “S100A12”) and neutrophil extracellular traps (NETs) are essential in developing severe tuberculosis. S100A12 drives the formation of NETs, and serve as a key protein mediating the physiopathological effects of NETs. S100A12 contributes to the mechanism of lung function injury in severe tuberculosis patients through regulation the release of immune cells, inflammatory cytokine release, and their interaction. Nevertheless, the regulatory mechanisms of S100A12 and NETs in severe tuberculosis pathogenesis has not been fully elucidated. Given this, this review aims to comprehensively summarize the research progress on S100A12 and NETs in severe tuberculosis and their potential molecular mechanisms to provide a new scientific basis and innovative insights for exploring therapeutic strategies for severe tuberculosis.

Association between pulmonary tuberculosis and the gut microbiota: treatment strategies

Li Min, Yao Yushan, Qiao Haixia, Lei Hong

Chinese Journal of Antituberculosis. 2025, 47(4):  520-526.  doi:10.19982/j.issn.1000-6621.20240547

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Tuberculosis (TB) remains a prevalent respiratory infectious disease worldwide. In recent years, accumulating evidence has highlighted a strong association between the gut microbiota and TB pathogenesis. The gut microbiota plays a critical role in modulating TB immunity through the gut-lung axis, while TB infection itself can induce significant dysbiosis in the intestinal microbial ecosystem. This review explores the bidirectional interplay between Mycobacterium tuberculosis (MTB) infection and the gut microbiota, elucidates the immunological mechanisms underlying their interaction, and discusses the therapeutic potential of microbiome-based interventions for TB. These insights may contribute to the development of novel treatment strategies for TB management.