Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) infection, is currently the deadliest infectious disease in human that can evolve to severe forms. A comprehensive immune landscape for Mtb infection is critical for achieving TB cure, especially for severe TB patients. We performed single-cell RNA transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing of 213,358 cells from 27 samples, including 6 healthy donors and 21 active TB patients with varying severity (6 mild, 6 moderate and 9 severe cases). Two published profiles of latent TB infection were integrated for the analysis. We observed an obviously elevated proportion of inflammatory immune cells (e.g., monocytes), as well as a markedly decreased abundance of various lymphocytes (e.g., NK and γδT cells) in severe patients, revealing that lymphopenia might be a prominent feature of severe disease. Further analyses indicated that significant activation of cell apoptosis pathways, including perforin/granzyme-, TNF-, FAS- and XAF1-induced apoptosis, as well as cell migration pathways might confer this reduction. The immune landscape in severe patients was characterized by widespread immune exhaustion in Th1, CD8+T and NK cells as well as high cytotoxic state in CD8+T and NK cells. We also discovered that myeloid cells in severe TB patients may involve in the immune paralysis. Systemic upregulation of S100A12 and TNFSF13B, mainly by monocytes in the peripheral blood, may contribute to the inflammatory cytokine storms in severe patients. Our data offered a rich resource for understanding of TB immunopathogenesis and designing effective therapeutic strategies for TB, especially for severe patients.

Objective: To detect the cell-free DNA of Mycobacterium tuberculosis (Cf-TB) in the cerebrospinal fluid (CSF) of patients with tuberculous meningitis (TBM), and to assess the diagnostic value of this method for TBM. Methods: We prospectively included patients with suspected meningitis from the Department of Tuberculosis, Beijing Chest Hospital, Department of Neurology, Beijing Chaoyang Hospital and Department of Neurology, 263 Hospital of the People's Liberation Army from September 2019 to March 2022. A total of 189 patients were included in this study. Among them, 116 were male and 73 were female, aged from 7 to 85 years, with an average of (38.5±19.1) years. The CSF specimens of the patients were collected for Cf-TB, MTB culture and Xpert MTB/RIF. SPSS 20.0 was used for statistical analysis and the difference was statistically significant with P<0.05. Results: Among the 189 patients, there were 127 patients in the TBM group and 62 patients in the non-TBM group. The sensitivity of Cf-TB was 50.4% (95%CI 41.4%-59.3%), the specificity was 100% (95%CI 92.7%-100.0%), the positive predictive value was 100% (95%CI 92.9%-100.0%), and the negative predictive value was 49.6% (95%CI 40.6%-58.6%). Using clinical diagnosis as the gold standard, the sensitivity of Cf-TB was 50.4% (64/127), which was significantly higher than that of MTB culture (8.7%, 11/127) and Xpert MTB/RIF (15.7%,20/127) (all P<0.001). Using etiology as the gold standard, the sensitivity of Cf-TB was 72.7% (24/33), which was significantly higher than that of MTB culture [33.3%, 11/33, (χ2=10.28, P=0.001)] and was similar to Xpert MTB/RIF (60.6%, 20/33) (χ2=1.091, P=0.296). Conclusion: The sensitivity of the Cf-TB test was significantly higher than that of CSF MTB culture and Xpert MTB/RIF. Cf-TB may provide evidence for earlier diagnosis and treatment of TBM.

BackgroundTuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and remains a major health threat worldwide. However, a detailed understanding of the immune cells and inflammatory mediators in Mtb-infected tissues is still lacking. Tuberculous pleural effusion (TPE), which is characterized by an influx of immune cells to the pleural space, is thus a suitable platform for dissecting complex tissue responses to Mtb infection.MethodsWe employed singe-cell RNA sequencing to 10 pleural fluid (PF) samples from 6 patients with TPE and 4 non-TPEs including 2 samples from patients with TSPE (transudative pleural effusion) and 2 samples with MPE (malignant pleural effusion).ResultCompared to TSPE and MPE, TPE displayed obvious difference in the abundance of major cell types (e.g., NK, CD4+T, Macrophages), which showed notable associations with disease type. Further analyses revealed that the CD4 lymphocyte population in TPE favored a Th1 and Th17 response. Tumor necrosis factors (TNF)-, and XIAP related factor 1 (XAF1)-pathways induced T cell apoptosis in patients with TPE. Immune exhaustion in NK cells was an important feature in TPE. Myeloid cells in TPE displayed stronger functional capacity for phagocytosis, antigen presentation and IFN-γ response, than TSPE and MPE. Systemic elevation of inflammatory response genes and pro-inflammatory cytokines were mainly driven by macrophages in patients with TPE.ConclusionWe provide a tissue immune landscape of PF immune cells, and revealed a distinct local immune response in TPE and non-TPE (TSPE and MPE). These findings will improve our understanding of local TB immunopathogenesis and provide potential targets for TB therapy.

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis(Mtb), continues to be an important global health problem. Hence, gaining a comprehensive understanding of the immune characteristics in TB could aid the improvement of vaccines and therapeutics for TB, especially for severe TB.Methods: Single-cell RNA transcriptome and T-cell/B-cell receptor (TCR/BCR) sequencing were applied to dissect the peripheral immune responses of active TB and reveal the molecular mechanisms of TB pathogenesis. Single-cell transcriptional profiles were obtained from 6 healthy donors and 21 active TB patients with varying severity (6 mild, 6 moderate and 9 severe cases) and integrated with 2 published profiles of latent TB infection.Findings: We observed a decrease in multiple peripheral immune cells (e.g., NKs, DCs and MAIT), and an increase in monocytes and megakaryocytes in TB patients, particularly with severe disease. We also discovered a significant increase in monocytes resembling myeloid-derived suppressor cells in severe patients that may be involve in immune paralysis. The immune landscape in severe patients were characterized by widespread immune exhaustion in Th1, CD8+ T and NK cells, high cytotoxic state in CD8+ T and NK cells, and significant activation of cell apoptosis and migration pathways in T and NK cells. Systemic upregulation of pro-inflammatory cytokines and inflammatory response genes, mainly by monocytes, and similarly increased pro-inflammatory cytokine concentrations in the plasma may contribute to the inflammatory cytokine storms previously observed in severe patients.Interpretation: This comprehensive single-cell analysis of peripheral immune landscape will improve the understanding of TB immunopathogenesis, offering potential targets for therapies and vaccines for TB control.Funding Information: This work was supported by grants from National Key Research and Development Program of China (Grant Nos. 2021YFC2301101, 2021YFC2301102), Public service development and reform pilot project of Beijing Medical Research Institute (BMR2019-11), National natural science foundation of China (81970900, 82100011), Beijing Public Health Experts Project (2022-3-040), Beijing Social Science Foundation Project (19GLB033), Key Project of the Department of Science and Technology, Beijing, China (Grant Nos.D181100000418003, Z191100006619078).Declaration of Interests: The lead author and guarantor affirm that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned and registered have been explained.Ethics Approval Statement: The ethical approval for this study was obtained from the Beijing Chest Hospital ethics committee (ethical approval No. YNLX-2022-006). Written informed consent was acquired from each participant.

目的 分析目前初复治肺结核的耐药状况.方法 对2018年1—12月首都医科大学附属北京胸科医院结核科住院的310例耐药肺结核患者的药物敏感试验结果进行回顾性分析,与2010年本院160例耐药情况相比较,组间比较采用χ2检验.结果 与2010年相比,2018年利福平耐药结核病在耐药结核病中占比为10.6％(33/310),差异有显著性(P=0.007);复治耐药中利福平耐药结核病的比例明显升高(P=0.004);耐多药结核病患者在复治耐药中的比例明显升高[64.6％(128/198)],广泛耐药结核病患者的比例明显下降[14.6％(29/198)];在复治耐药结核病中89.2％对利福平耐药的结核病患者同时对异烟肼耐药.结论 利福平耐药结核病在耐药结核病中的比例升高,与XperMTB/RIF快速检测方法的广泛应用有关,利于耐多药结核病的早期发现.

We aimed to investigate the effect of interval between food intake and drug administration at fasting condition on the plasma concentrations of first-line anti- tuberculosis (TB) drugs in Chinese population. Newly diagnosed TB patients administered the anti-TB drugs under fasting conditions orally, and then had prepared breakfast at 30 minutes and 120 min after dosing, respectively. Blood sampling was also performed 120 minutes after dosing for the detection of Cmax purpose. Overall, twenty-five participants were included in our analysis. The Cmaxs of 30 minutes interval and 120 minutes interval were 21.8 ± 2.0 and 19.2 ± 2.0 μg/mL for rifampin, 1.6 ± 0.2 and 2.1 ± 0.2 μg/mL for isoniazid (INH), 1.5 ± 0.1and 1.5 ± 0.2 μg/mL for ethambutol (EMB), and 49.2 ± 3.7 and 41.5 ± 3.9 μg/mL for pyrazinamide, respectively. Statistical analysis revealed that there was no statistical difference between 2 groups. Additionally, 88.0% and 72.0% of the 25 participants at 2-hour interval group had peak concentrations less than the lower limit of the reference range for INH and EMB, respectively. The Cmaxs of INH were 0.9 ± 0.4 μg/ml for rapid acetylator, which was significantly lower than those of intermediate (1.4 ± 1.0 μg/mL), and slow acetylator (2.5 ± 1.0 μg/mL), respectively (P < .01). In conclusion, our data demonstrate that early food intake at 30 minutes after drug administration had no significant influence on the plasma concentrations. In addition, a high proportion of patients receiving first-line anti-TB regimen fail to achieve the expected plasma drug ranges of INH and EMB (P > .05).

Objective Moxifloxacin (MFX) shows good in vitro activity against Mycobacterium abscessus and can be a possible antibiotic therapy to treat M. abscessus infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against M. abscessus using zebrafish (ZF) model in vivo. Methods A formulation of M. abscessus labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared. Results Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference. Conclusion MFX showed limited efficacy against M . abscessus in vivo using ZF model. Its activity in vivo needs to be confirmed.

结核病是威胁人类健康的主要公共卫生问题,目前我国每年新发肺结核患者约90万例[1].结核病控制及治疗形式严峻,随着结核病诊断技术发展,临床医师对结核病、耐药结核及非结核分枝杆菌的认识有了很大提高.能够更早发现结核病及耐药结核病及非结核分枝杆菌病,将使患者得到及时诊治.但是结核病不是孤立的疾病,常常合并其他疾病,特别是影像学表现为多肺叶、多肺段、片状结节、空洞及纵膈淋巴结肿大的阴影,涉及多种疾病,给结核病诊断带来困难.结核病病理是以肉芽肿性炎及干酪坏死为主要表现疾病,结节病及曲霉菌感染病理也是肉芽肿性炎,临床表现相似,诊断困难,给临床医师带来困惑,本文结合1例疑似肺结核合并结节病及曲霉菌感染病例,了解诊治过程,并复习相关文献.

目的:研究肺结核患者治愈后复发危险因素以及耐药状况.方法:回顾性分析我院于2015年5月～2017年12月期间收治的1000例肺结核患者的临床资料.对所有患者均进行为期2年的随访观察,统计复发情况.将所有患者按照治愈后复发与否分成复发组58例以及无复发组942例,比较两组患者基线资料情况,包括年龄、性别、耐药、吸烟、职业类型、居住情况以及空洞,并对影响肺结核患者治愈后复发的因素作多因素Logistic回归分析,对所有治愈后复发患者的耐药情况进行检验,分析其耐单药、耐2药、耐3药、耐4药人数的占比情况.结果:1000例肺结核患者治愈后复发58例,复发率为5.80％.肺结核患者治愈后是否复发与性别、年龄、吸烟无关(P＞0.05),复发组耐药、体力型工作、流动人口、空洞患者的比例高于未复发组(P＜0.05).经多因素Logistic回归分析可得:耐药、体力型工作、流动人口、空洞均是肺结核患者治愈后复发的独立危险因素.58例患者中发生耐药例数27例,耐药率为46.55％;其中耐单药、耐2药、耐3药、耐4药人数分别为8、10、7、2例,相应占比为13.79％、17.24％、12.07％、3.45％.结论:肺结核患者治愈后复发的风险较高,尤其应注意耐药、体力型工作、流动人口、空洞的患者,以降低疾病复发,且肺结核复发患者的耐药情况不容乐观.

Tuberculosis (TB) patient serum cytokine levels may be predictive of anti-tuberculosis treatment progress. Here, serum levels of cytokines TNF-α, IL-4, sIL-2R and IFN-γ were measured then correlated to clinical TB manifestations, bacterial burden, chest imaging findings and clinical course. Study subjects included 67 newly diagnosed pulmonary TB (PTB) patients with active disease admitted to Beijing Chest Hospital for anti-TB chemotherapeutic treatment. Blood was drawn at 0 months (pre-treatment), 1–2 months (at any time between 1 and 2 month) and after 6 months completion of treatment and serum TNF-α, IL-4, sIL-2R and IFN-γ levels were measured in duplicate using enzyme-linked immunosorbent assays (ELISAs). Correlation analysis was conducted to evaluate sensitivity and specificity of cytokine levels as predictors of disease activity and treatment progress. The results indicated that the pre-treatment serum TNF-α level of the smear-negative group was lower than that of the smear 1+ group, while serum TNF-α after 6 months completion of treatment and IFN-γ levels at 1–2 months and after 6 months completion of treatment were significantly lower, respectively, than at 0 months (before treatment) (P < 0.05). Using a cut-off value of 845 pg/ml, serum TNF-α level was predictive of treatment progress, with a sensitivity of 51%, specificity of 60% and AUC of 0.594 (P = 0.013). Meanwhile, using a cut-off value of 393 pg/ml, serum IFN-γ provided superior monitoring efficacy, with a sensitivity of 60%, specificity of 64% and AUC of 0.651 (P = 0.017). In conclusion, both serum TNF-α and IFN-γ levels might be useful biomarkers for monitoring treatment progress.

BACKGROUND:The emergence of multidrug-resistant tuberculosis (MDR-TB) poses a serious obstacle to global TB control programs.METHODS:We carried out a prospective, randomized, multicenter study in China that was focused on the potential of a shorter regimen containing clofazimine (CFZ) for the treatment of MDR-TB. There were 135 MDR-TB cases that met eligibility requirements and were randomly stratified into either the control group or experimental group. Patients in the control group received an 18-month treatment regimen, whereas patients in the experimental group received a 12-month treatment regimen containing CFZ.RESULTS:At the completion of the treatment period, the difference in sputum-culture conversion rates between the experimental group and the control group was not significant. Notably, by the end of 3 months of treatment, 68.7% patients receiving the experimental regimen had sputum-culture conversion, as compared with 55.9% of those receiving the control regimen; this was a significant difference, suggesting an early sputum conversion (P = .04). There were 67 adverse events reported in 56 patients in this study, including 32 in the control group and 35 in the experimental group. No significant difference in the overall incidences of adverse events was observed between the 2 groups.CONCLUSIONS:The MDR-TB patients treated with the shorter regimen containing CFZ had a comparable successful outcome rate when compared to those with the standard regimen. The patients assigned to the experimental group achieved more rapid sputum-culture conversion, reflecting superior antimicrobial activity against MDR-TB.CLINICAL TRIALS REGISTRATION:Chinese Clinical Trial Registry ChiCTR 1800020391.

Background Our aim was to assess whether the use of cycloserine (CS) would bring additional benefit for multidrug-resistant tuberculosis (MDR-TB) patients, and to estimate the incidence and associated risk factors of adverse drug reactions (ADRs) from CS. Patients and methods In this study, we retrospectively reviewed the clinical outcomes and ADRs of MDR-TB patients treated with CS containing regimens between January 2012 and June 2015 in China. Results A total of 623 MDR-TB cases enrolled in this study received regimens containing CS. Of these cases, in 411 of the patients 374 (66.0%) were “cured” and 37 (5.9%) “complete treatment” by the end of the study. The elderly, patients with prolonged previous exposure to and history of anti-TB drugs, and pre-existing co-morbidity were more likely to be associated with adverse outcomes of MDR-TB patients (P<0.05). Hyperuricemia (22.8%, 142/623) was the most frequently observed ADR among these cases, while the most noted ADRs associated with the administration of CS was psychiatric symptoms, accounting for 4.3% (27/623) of study population. Nineteen (70.4%) out of 27 cases with psychiatric symptoms occurred before the 6-month timepoint, and were notably, the highest proportion of serious adverse, 29.6% (8/27) of which were noted after discontinuation of CS. Conclusion Our study demonstrates that a CS-containing regimen achieved a highly successful outcome in the treatment of MDR-TB and promising tolerance in Chinese population. The potential emergence of serious psychiatric symptoms highlights that patients need to be closely monitored for these conditions during treatment that includes CS.

AbstractMoxifloxacin (MFX) showed good activityin vitroagainstMycobacterium abscessus(M. abscessus) and was suggested as one of the antibiotic regimens for adults withM. abscessusdisease. However, some other studies showed that MFX showed less or none activity againstM. abscessus. In our study we aim to evaluate MFX activity againstM. abscessususing zebrafish (ZF) modelin vivo. MIC of each drugs were determined by broth microdilution method.M. abscessuslabeled by CM-DiI, were micro-injected into ZF. Survival curves were determined by recording dead ZF every day. After 4 days of incubation ZF were lysed. Colony-forming unit (CFU) were enumerated and results are expressed as mean log10 CFU per ZF. Bacteria dissemination and fluorescence intensity in ZF were observed and analyzed. Inhibition rate was also calculated. In our study MFX showed good activityin vitro. Butin vivoMFX showed limited restriction toM. abscessus. The association between increased survival and high dose of MFX is not significant. Same results were observed in bacterial fluorescence intensity and inhibition rates, with no significant difference when compared with no drug group (P > 0.05). However, significant difference was observed in azithromycin (AZM) group. MFX showed limited efficacy onMycobacterium abscessus in vivousing ZF model. MFX’s activityin vivoneed to be confirmed.

Moxifloxacin (MFX) showed good activity against () and was suggested as one of the antibiotic regimens for adults with disease. However, some other studies showed that MFX showed less or none activity against . In our study we aim to evaluate MFX activity against using zebrafish (ZF) model . MIC of each drugs were determined by broth microdilution method. labeled by CM-DiI, were micro-injected into ZF. Survival curves were determined by recording dead ZF every day. After 4 days of incubation ZF were lysed. Colony-forming unit (CFU) were enumerated and results are expressed as mean log10 CFU per ZF. Bacteria dissemination and fluorescence intensity in ZF were observed and analyzed. Inhibition rate was also calculated. In our study MFX showed good activity . But MFX showed limited restriction to . The association between increased survival and high dose of MFX is not significant. Same results were observed in bacterial fluorescence intensity and inhibition rates, with no significant difference when compared with no drug group (P > 0.05). However, significant difference was observed in azithromycin (AZM) group. MFX showed limited efficacy on using ZF model. MFX’s activity need to be confirmed.

WHO在2006年将结核病药物分为5组.为适应分子生物学的发展,2016年又将药物分为4组,将氯法齐明和利胺唑胺作为核心药物.目前有8个药物在开展临床试验,其中2个为新的化合物.治疗敏感结核的有利福喷丁和莫西沙星,治疗耐药结核病的有上市药品,如利奈唑胺、氯法齐明、环丝氨酸等.已上市的新型化合物有贝达喹啉和利奈唑胺,还有未上市的如PA-824、TBA-354、sutezolid、AZD5847、SQ-109等,这些药物的逐渐上市为耐药结核病治疗提供了强大的武器.

目的 分析含环丝氨酸(Cs)化疗方案治疗耐多药肺结核患者发生药物不良反应的情况.方法 选取2013年1月至2016年6月全国11家单位纳入全球基金第五轮耐多药结核病防治项目、符合选例标准的耐多药肺结核患者作为研究对象,共计623例.所有患者均采用标准化治疗方案,即:6PZA-Am(Cm)-Lfx(Mfx)-Pto-Cs/18PZA-Lfx(Mfx)-Pto-Cs;替代方案:PAS替代Pto,Cm替代Am,Mfx替代Lfx(PZA:吡嗪酰胺;Am:阿米卡星;Cm:卷曲霉素;Lfx:左氧氟沙星;Mfx:莫西沙星;Pto:丙硫异烟胺;Cs:环丝氨酸;PAS:对氨基水杨酸钠).收集患者在治疗过程中的药物不良反应发生情况,分析药物不良反应的临床特征、严重程度、发生时间、持续时间、处理方法及预后,并判定其与药物之间的相关性.结果 623例研究对象中有316例(50.7％)发生至少一种药物不良反应,36例(5.8％)患者由于药物不良反应停服药物或者更改治疗方案.最常见的药物不良反应为高尿酸血症(22.8％,142/623)和肝功能异常(18.8％,117/623);出现与Cs很可能相关的中枢神经系统或精神症状者有27例(4.3％),发生时间的中位数(四分位数)[M(Q1,Q3)]为3(2,6)个月,对患者进行停用Cs或心理辅导等处理后,症状消失.结论 应用含Cs的标准化疗方案进行治疗的耐多药肺结核患者中,发生中枢神经系统或精神症状与Cs有关,在对患者使用含Cs方案治疗期间需密切监测其中枢神经系统或精神系统症状.

Mild cognitive impairment (MCI), which generally represents the transition state between normal aging and the early changes related to Alzheimer’s disease (AD), has drawn increasing attention from neuroscientists due that efficient AD treatments need early initiation ahead of irreversible brain tissue damage. Thus effective MCI identification methods are desperately needed, which may be of great importance for the clinical intervention of AD. In this article, the range scaled analysis, which could effectively detect the temporal complexity of a time series, was utilized to calculate the Hurst exponent (HE) of functional magnetic resonance imaging (fMRI) data at a voxel level from 64 MCI patients and 60 healthy controls (HCs). Then the average HE values of each region of interest (ROI) in brainnetome atlas were extracted and compared between MCI and HC. At last, the abnormal average HE values were adopted as the classification features for a proposed support vector machine (SVM) based identification algorithm, and the classification performance was estimated with leave-one-out cross-validation (LOOCV). Our results indicated 83.1% accuracy, 82.8% sensitivity and 83.3% specificity, and an area under curve of 0.88, suggesting that the HE index could serve as an effective feature for the MCI identification. Furthermore, the abnormal HE brain regions in MCI were predominately involved in left middle frontal gyrus, right hippocampus, bilateral parahippocampal gyrus, bilateral amygdala, left cingulate gyrus, left insular gyrus, left fusiform gyrus, left superior parietal gyrus, left orbital gyrus and left basal ganglia.

ABSTRACT We performed a multicenter, prospective, randomized study to investigate the efficacy and safety of clofazimine (CLO) for treatment of extensively drug-resistant tuberculosis (XDR-TB) in China. Forty-nine patients infected with XDR-TB were randomly assigned to either the control group or the CLO group, both of which received 36 months of individually customized treatment. The primary endpoint was the time to sputum culture conversion on solid medium. Clinical outcomes of patients were evaluated at the time of treatment completion. Of the 22 patients in the experimental group, 7 (31.8%) met the treatment criterion of “cure” and 1 (4.5%) “complete treatment,” for a total of 8 (36.4%) exhibiting successful treatment outcomes without relapse. In the control group, 6 patients (22.2%) were cured and 6 (22.2%) completed treatment by the end of the study. Statistical analysis revealed no significant difference in successful outcome rates between the CLO group and the control group. The average sputum culture conversion time for the experimental group was 19.7 months, which was not statistically different from that for the control group (20.3 months; P = 0.57). Of the 22 patients in the CLO group, 12 (54.5%) experienced adverse events after starting CLO treatment. The most frequently observed adverse event was liver damage, with 31.8% of patients (7/22 patients) in the CLO group versus 11.1% (3/27 patients) in the control group exhibiting this adverse event. Our study demonstrates that inclusion of CLO in background treatment regimens for XDR-TB is of limited benefit, especially since hepatic disorders arise as major adverse events with CLO treatment. (This study is registered with the Chinese Clinical Trial Registry [ChiCTR, www.chictr.org.cn ] under identifier ChiCTR1800014800.)

We assessed the incidence of adverse drug reactions (ADRs) with anti-TB medications and evaluated the risk factors for developing ADRs in previously treated tuberculosis patients in China. All patients received the first-line anti-TB regimen (2HREZS/6HRE) as recommended by the national guidelines. Clinical and laboratory evaluations were performed once a month. Out of the 354 participants, 262 (74.0%) experienced ADRs such as hyperuricemia (65.0%, 230/354), hepatotoxicity (6.2%, 22/354) and hearing disturbances (4.8%, 17/354). ADRs were significantly associated with diabetes mellitus [OR (95% CI): 15.5 (2.07-115.87)]; however, weight more than 50 kg [OR (95% CI): 0.41 (0.22-0.85)] was a protective factor for occurrence of ADRs. Hyperuricemia is the most common adverse event but, most patients with hyperuricemia showed increased tolerance for high uric acid levels. Low body weight and diabetes mellitus increased the risk of the occurrence of ADRs during anti-TB treatment.

目的 评价芪甲利肺胶囊治疗复治肺结核的临床疗效.方法 将2012年1月至2014年10月在首都医科大学附属北京胸科医院住院的复治肺结核患者109例,随机分为研究组(化疗加芪甲利肺胶囊组,53例)和对照组(单纯化疗组,56例).观察治疗前及治疗后2个月、5个月和8个月的临床疗效、症状改善及免疫功能变化.结果 研究组治疗2个月和5个月后痰涂片的转阴率分别为50.0％(28/56),53.6％(30/56),明显高于对照组的30.2％(16/53),34.0％(18/53),差异有统计学意义(x2=4.40,P=0.036;x2=4.21,P=0.040);治疗8个月后痰涂片的转阴率研究组为76.8％(43/56),与对照组的71.7％(38/53)比较,差异无统计学意义(x2=0.37,P=0.545);治疗3个月和8个月后研究组病灶显著吸收率分别为44.6％(25/56)、62.5％(35/56),明显高于对照组的26.4％(14/53)、43.4％(23、53),差异均有统计学意义(x2=3.94,P=0.047;x2 =3.99,P=0.046);治疗8个月后研究组空洞闭合率58.5％(24/41),与对照组的34.2％(13/38)比较,差异有统计学意义(x2=4.69,P=0.031);研究组CD4+T淋巴细胞、CD4+/CD8+比值治疗后分别达(820.9±255.2)个/mm3、2.02±0.1,与对照组[分别为(707.8±254.6)个/mm3、1.69±0.4]比较,差异有统计学意义(x2=0.72,P=0.036;x2=2.76,P=0.041).结论 芪甲利肺胶囊具有加速痰菌转阴及促进病灶吸收的作用,芪甲利肺胶囊可能有调节免疫功能,从而起到辅助抗结核作用.