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Background Second-line anti-tuberculosis drugs are widely used in clinic for multi-drug resistant tuberculosis (MDR-TB) . At present, there are several reticulated meta-analyses investigating them, but the effect is not very satisfactory. Objective To systematically evaluate the efficacy and safety of five anti-tuberculosis chemotherapy regimens in the treatment of MDR-TB. Methods Randomized controlled trials (RCTs) on anti-tuberculosis drug for MDR-TB were retrieved from PubMed, Medline, Web of Science, VIP, and Wanfang data from January 2010 to March 2022. The experimental group was treated with individualized treatment combined with moxifloxacin (Mfx) , levofloxacin (Lfx) , linezolid (Lzd) , clofazimine (Cfz) and bedaquiline (Bdq) . The control group was treated with individualized treatment combined with placebo or Lfx. After literature screening and data extraction, quality assessment was performed using the risk of bias assessment tool provided by the Cochrane system evaluator handbook 5.1.0. Bayesian network Meta-analysis on the rate of sputum culture conversion, clinical efficacy rate and incidence of adverse reactions was conducted using GeMTC 0.14.3 software and Stata SE 15.0 software. Results A total of 39 RCTs and 3 860 patients were included. Results of Meta-analysis showed that the rate of sputum culture conversion of Bdq, Cfz, Lfx, Lzd, Mfx, were higher than those of placebo〔OR=3.49, 95%CI (2.11, 5.73) ; OR=2.85, 95%CI (1.93, 4.23) ; OR=2.93, 95%CI (1.45, 6.94) ; OR=6.37, 95%CI (3.67, 11.31) ; OR=8.15, 95%CI (3.97, 18.47) 〕 (PLzd (82.1%) >Bdq (50.2%) >Lfx (37.5%) >Cfz (35.9%) >placebo (0.1%) . The clinical response rates for Bdq, Cfz, Lfx, Lzd and Mfx were all higher than that of placebo〔OR=2.80, 95%CI (1.74, 4.46) ; OR=2.02, 95%CI (1.33, 3.08) ; OR=4. 93, 95%CI (2.13, 11.50) ; OR=5.72, 95%CI (3.44, 10.08) ; OR=3.20, 95%CI (1.16, 9.21) 〕 (PLzd (86.2%) >Lfx (54.6%) >Bdq (47.3%) >Cfz (24.3%) >placebo (0.1%) . There were no significant differences both in the incidence of adverse reactions among the 5 anti-tuberculosis drugs and placebo (P>0.05) and in the incidence of adverse reactions of each anti-tuberculosis drugs between groups (P>0.05) . Conclusion Current evidence suggests that Mfx and Lzd are more effective than other drugs in the treatment of MDR-TB. The results of the study need to be further verified due to the small number clinical studies and sample size.

Background: Although systemic corticosteroids (SCS) have long been used to treat patients with COPD exacerbation, the recommended dose remains controversial. We aimed to perform a meta-analysis and an indirect treatment comparison to investigate the efficacy and safety of different doses of SCS in subjects with COPD exacerbation., Methods: Studies were identified by searching different databases for randomized controlled trials that investigated the efficacy and safety of SCS with placebo in subjects with exacerbation of COPD. The different doses of SCS were assigned to low-dose (ie, initial dose ≤ 40 mg prednisone equivalent/d [PE/d]), medium-dose (initial dose = 40-100 mg PE/d, and high-dose (initial dose > 100 mg PE/d) groups. The indirect treatment comparison was performed between low-, medium-, and high-dose SCS groups., Results: Twelve trials with 1,375 participates were included. Compared to placebo, the risk of treatment failure was lower in the low-dose SCS groups (risk ratio 0.61 [95% CI 0.43-0.88], P = .007) and high-dose SCS groups (risk ratio 0.64 [95% CI 0.48-0.85], P = .002); the FEV 1 was significantly improved in low-dose (mean difference 0.09 [95% CI 0.06-0.12], P < .001), medium-dose (mean difference 0.23 [95% CI 0.02-0.44], P = .036), and high-dose SCS groups (mean difference 0.09, [95% CI 0.03-0.15], P < .001, respectively). Regarding safety, the incidence of hyperglycemia was higher in high-dose SCS groups versus placebo (risk ratio 2.52 [95% CI 1.13-5.62], P = .02). The indirect comparison between low-, medium-, and high-dose SCS found that the risk of treatment failure and changes in FEV 1 were similar between these doses of SCS., Conclusions: This meta-analysis indicates that low-dose SCS (initial dose ≤ 40 mg PE/d) was sufficient and safer for treating subjects with COPD exacerbation, and it was noninferior to higher doses of SCS (initial dose > 40 mg PE/d) in improving FEV 1 and reducing the risk of treatment failure. However, our findings need to be verified in head-to-head randomized controlled trials., Competing Interests: The authors have disclosed no conflicts of interest., (Copyright © 2021 by Daedalus Enterprises.)

Drug addiction is a chronic relapsing brain disease. Alterations of glucose uptake and metabolism are found in the brain of drug addicts. Insulin mediates brain glucose metabolism and its abnormality could induce brain injury and cognitive impairment. Here, we established a rat model of phenobarbital addiction by 90 days of dose escalation and evaluated addiction-related symptoms. We also performed 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) to detect glucose uptake in the brain and proteomic analysis of the function of the differentially expressed (DE) proteins via bioinformatics in brain tissues by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) on days 60 and 90 of phenobarbital or 0.5% carboxymethyl cellulose sodium (CMC-Na) (vehicle) administration. The results showed that phenobarbital-addictive rats developed severe withdrawal symptoms after abstinence and glucose uptake was significantly increased in the brain. Proteomics analysis showed that numerous DE proteins were enriched after phenobarbital administration, among which CALM1, ARAF, and Cbl proteins (related to the insulin signaling pathway) were significantly downregulated on day 60 but not day 90. However, SLC27A3 and NF-κB1 proteins (related to insulin resistance) were significantly upregulated on day 90 (data are available via ProteomeXchange with identifier PXD021101). Our data indicate that the insulin signaling pathway and insulin resistance may play a role in the development of phenobarbital addiction and brain injury, so the findings may have important clinical implications.