Hong-Bin Xu

Pulmonary resection for patients with multidrug-resistant tuberculosis: systematic review and meta-analysis

OBJECTIVES Multidrug-resistant tuberculosis (MDR-TB) has become an emerging global public health crisis. Several studies have suggested that pulmonary resection has efficacy in the treatment of MDR-TB. A systematic review of the available therapeutic studies was conducted to determine the treatment outcome among patients with MDR-TB who underwent pulmonary resection. METHODS To evaluate pulmonary resection for MDR-TB, a random-effect meta-analysis of the available studies was used to assess the overall treatment outcome. Subgroup analyses were also conducted by separating studies based on each characteristic independently. RESULTS After screening 4996 articles, 15 clinical reports with a mean of 63 patients per report met the inclusion criteria. Analysis of the studies showed that the estimated pooled treatment success rate of pulmonary resection for patients with MDR-TB was 84% [95% confidence interval (CI) 78%-89%]. The rates of failure, relapse, death and default were 6% (95% CI 4%-8%), 3% (95% CI 1%-4%), 5% (95% CI 2%-8%) and 3% (95% CI 1%-5%), respectively. The proportion of patients treated successfully did not differ significantly on the basis of any of the individual study characteristics. CONCLUSIONS Substantial heterogeneity in the study characteristics prevented a more conclusive determination of what factors had the greatest effect on the proportion of patients that achieve treatment success and limited the validity of this analysis. Some important variables, including patient HIV status, were inconsistently reported between studies. These results underscore the importance of strong patient support and treatment follow-up systems to develop successful MDR-TB treatment programmes.

Chinese herbal medicine in treatment of diabetic peripheral neuropathy: A systematic review and meta-analysis

AIM OF STUDY There are multimodal and multidisciplinary approaches to treat diabetic peripheral neuropathy (DPN). However, the intractable adverse effects limited their widespread use. Chinese herbal medicine (CHM) is increasingly used for the treatment of DPN. The aim of this study was to review existing evidence on the effectiveness of CHM for the treatment of DPN. MATERIALS AND METHODS Searches were performed with Medline, Embase, Cochrane Central Register of Controlled Trials, CNKI, CBM and Wangfan databases. Controlled trials comparing CHM with other medicine for the treatment of DPN were analyzed. RESULTS Eighteen trials met the inclusion criteria. All trials used vitamin B12 and/or B1 as control. Clinical therapeutic effect, divided by three grades including marked effective, effective and ineffective according to the improved degree of subjective symptom, tendon reflex, and nerve conduction velocity, was the only end point reported in all trials, and thus evaluated. The results showed CHM treatment was associated with a superiority in marked effective (odds ratio [OR], 2.40; 95% confidence interval [CI]: 0.94 to 2.97; p<0.001), and effective (OR, 1.39; 95% CI: 1.16 to 1.67; p<0.001). Patients who received CHM treatment was associated with a less likely to report ineffective (OR, 0.26; 95% CI: 0.21 to 0.33, p<0.001). No adverse events were reported in any of the included trials. CONCLUSIONS According to the pooled results of our study and the poor quality of the included trials, it might be uncertainty that there was a superiority of CHM for treating DPN. More rigorous controlled trials are required to substantiate or refute these early findings.

Comparative roles of moxifloxacin and levofloxacin in the treatment of pulmonary multidrug-resistant tuberculosis: a retrospective study

This study compared the efficacy of moxifloxacin and levofloxacin in the treatment of multidrug-resistant tuberculosis (MDR-TB) in Shanghai, China. A retrospective analysis of 158 patients with MDR-TB receiving either moxifloxacin- or levofloxacin-containing regimens was performed. Clinical data from patients were subjected to univariate analysis, stratification and multiple logistic regression to compare the roles of moxifloxacin and levofloxacin in multidrug regimens. In total, 72 patients received 400mg of moxifloxacin once daily and 86 patients received 509.9 ± 79.4 mg (mean ± standard deviation) of levofloxacin once daily together with similar active agents for similar durations. The times to sputum culture conversion were similar. Adverse reactions occurred at comparable rates. The combined treatment success rate was 60.1%, being higher among ofloxacin-susceptible than ofloxacin-resistant cases (67.5% vs. 52.0%; P < 0.05). The success rates for the moxifloxacin group were 65.3% (overall), 77.1% (ofloxacin-susceptible cases) and 54.1% (ofloxacin-resistant cases) in comparison with 55.8%, 60.4% and 50.0%, respectively, for the levofloxacin group. No demographic, clinical, bacteriological or treatment characteristics were independent predictors of favourable outcome. Fourteen patients from the moxifloxacin group and twelve patients from the levofloxacin group had bacteriological relapse after treatment cessation. In conclusion, compared with levofloxacin, moxifloxacin did not show superior efficacy when incorporated into multidrug regimens used for the treatment of MDR-TB.

PCR-Single-Strand Conformational Polymorphism Method for Rapid Detection of Rifampin-Resistant Mycobacterium tuberculosis: Systematic Review and Meta-Analysis

ABSTRACT The reference standard methods for drug susceptibility testing of Mycobacterium tuberculosis, such as culture on Lowenstein-Jensen or Middlebrook 7H10/11 medium, are very slow to give results; and due to the emergence of multidrug-resistant M. tuberculosis and extensively drug-resistant M. tuberculosis, there is an urgent demand for new, rapid, and accurate drug susceptibility testing methods. PCR-single-strand conformational polymorphism (PCR-SSCP) analysis has been proposed as a rapid method for the detection of resistance to rifampin, but its accuracy has not been systematically evaluated. We performed a systematic review and meta-analysis to evaluate the accuracy of PCR-SSCP analysis for the detection of rifampin-resistant tuberculosis. We searched the Medline, Embase, Web of Science, BIOSIS, and LILACS databases and contacted authors if additional information was required. Ten studies met our inclusion criteria for rifampin resistance detection. We applied the summary receiver operating characteristic (SROC) curve to perform the meta-analysis and to summarize diagnostic accuracy. The sensitivity of PCR-SSCP analysis for the rapid detection of rifampin-resistant tuberculosis was 0.79 (95% confidence interval [CI], 0.75 to 0.82), the specificity was 0.96 (95% CI, 0.94 to 0.98), the positive likelihood ratio was 16.10 (95% CI, 5.87 to 44.13), the negative likelihood ratio was 0.20 (95% CI, 0.10 to 0.40), and the diagnostic odds ratio was 100.93 (95% CI, 31.95 to 318.83). PCR-SSCP analysis is a sensitive and specific test for the rapid detection of rifampin-resistant M. tuberculosis. Additional studies in countries with a high prevalence of multidrug-resistant M. tuberculosis and also cost-effectiveness analysis are required in order to obtain a complete picture on the utility of this method for rapid drug resistance detection in M. tuberculosis.

Guggulsterone of Commiphora mukul resin reverses drug resistance in imatinib-resistant leukemic cells by inhibiting cyclooxygenase-2 and P-glycoprotein.

The purpose of this study was to investigate the effects of guggulsterone on cyclooxygenase-2 and P-glycoprotein mediated drug resistance in imatinib-resistant K562 cells (K562/IMA). MTT cytotoxicity assay, flow cytometry, western blot analysis, and ELISA were performed to investigate the anti-proliferative effect, the reversal action of drug resistance, and the inhibitory effect on cyclooxygenase-2, P-glycoprotein, BCR/ABL kinase, and PGE2 release in K562/IMA cells by guggulsterone. The results showed that co-administration of guggulsterone resulted in a significant increase in chemo-sensitivity of K562/IMA cells to imatinib, compared with imatinib treatment alone. Rhodamine123 accumulation in K562/IMA cells was significantly enhanced after incubation with guggulsterone (60, 120 μM), compared with untreated K562/IMA cells (p<0.05). When imatinib (1 μM) was combined with guggulsterone (60, 120 μM), the mean apoptotic population of K562/IMA cells was 15.47% and 24.91%. It was increased by 3.82 and 6.79 times, compared with imatinib (1 μM) treatment alone. Furthermore, guggulsterone had significantly inhibitory effects on the levels of cyclooxygenase-2, P-glycoprotein and prostaglandin E2. However, guggulsterone had little inhibitory effect on the activity of BCR/ABL kinase. The present study indicates guggulsterone induces apoptosis by inhibiting cyclooxygenase-2 and down-regulating P-glycoprotein expression in K562/IMA cells.

Role of clofazimine in the treatment of multidrug-resistant tuberculosis: a retrospective observational cohort assessment

Results: Out of 144 MDR/XDR-TB patients, 44 were treated with clofazimine. Of these, none experienced major side effects attributed to clofazimine requiring discontinuations. However, 20 patients had the clofazimine reduced to manage adverse events. Outcomes were similar in patients treated with and without clofazimine, although clofazimine-treated cases had a more frequent history of previous treatment with a fluoroquinolone and an injectable agent (43.2% versus 20%, P,0.05). Patients treated with clofazimine took a long time for sputum culture conversion and achieved a low percentage of conversion overall. Conclusions: Clofazimine did not improve the chance of bacterial conversion, providing a chance of treatment success in MDR-TB cases. However, 100 mg of clofazimine once daily added to an individualized multidrug regimen was well tolerated in our study. It might be used as an alternative drug for the treatment of complicated MDR/XDR-TB patients.

Guggulsterone sensitized drug-resistant human hepatocarcinoma cells to doxorubicin through a Cox-2/P-gp dependent pathway

Abstract Previous researches indicated that cyclooxygenase‐2 (Cox‐2) might be involved in P‐glycoprotein (P‐gp)‐mediated multidrug resistance in hepatocellular carcinoma cells. Doxorubicin‐resistant hepatocellular carcinoma PLC/PRF/5 cells (PLC/PRF/5R) and HepG2 (HepG2R) cells were developed in the present study. The modulatory effect of guggulsterone on Cox‐2 and P‐gp in PLC/PRF/5R and HepG2R cells was investigated. Cells proliferation, Cox‐2 and P‐gp expression, and prostaglandin E2 release were examined using MTT, flow cytometry, western blot and ELISA assays. Small interfering RNA (siRNA) targeted against Cox‐2 and multidrug resistance protein (Mdr‐1) was used to regulate the expression of Cox‐2 and P‐gp. The results showed that co‐administration of guggulsterone resulted in a significant increase in chemo‐sensitivity of PLC/PRF/5R cells to doxorubicin, as compared with doxorubicin treatment alone. When doxorubicin (10 &mgr;M) was combined with guggulsterone (50 &mgr;M), the mean apoptotic population of PLC/PRF/5R cells was 20.16%. It was increased by 1.5 times, as compared with doxorubicin (10 &mgr;M) treatment alone. Furthermore, guggulsterone had significantly inhibitory effect on the levels of Cox‐2, P‐gp and prostaglandin E2. However, guggulsterone did not show significantly inhibitory effect on the expression of prostaglandin E receptors. In addition, Cox‐2 siRNA simultaneously reduced the expression of Cox‐2 and P‐gp in PLC/PRF/5R cells. Mdr‐1 siRNA had no influence on Cox‐2, but inhibited P‐gp expression. The present study suggested that guggulsterone might enhance the cytotoxic effect of doxorubicin to PLC/PRF/5R cells through a Cox‐2/P‐gp dependent pathway.

Outcomes of Chinese herb medicine for the treatment of multidrug-resistant tuberculosis: a systematic review and meta-analysis

Several studies have suggested that Chinese herb medicine (CHM) in combination with chemotherapy has efficacy in the treatment of multidrug-resistant tuberculosis (MDR-TB). The purpose of this meta-analysis was to assess the efficacy of CHM as a concomitant therapy for MDR-TB. Six databases were searched up to October 2014. Controlled trials comparing CHM combined with chemotherapy (treatment group) with chemotherapy alone (control group) for the treatment of MDR-TB were analyzed. Twenty studies, comprising 1823 patients across China, were included in this review. The meta-analysis showed CHM combined with chemotherapy was associated with a superiority in treatment success (odds ratio [OR], 1.33; 95% confidence interval [CI]: 1.15-1.54; P<0.001), and radiological improvement (OR, 1.32; 95% CI: 1.14-1.52; P<0.001). Patients who received CHM combined with chemotherapy were associated with a similar likely to relapse (OR, 0.88; 95% CI: 0.62-1.25, P=0.478). CHM combination with chemotherapy appeared to be associated with a low incidence of adverse effects for MDT-TB treatment. According to the pooled results and the poor quality of the included trials, it might be uncertainty that there was a superiority of CHM combined with chemotherapy for treating MDR-TB. More rigorous controlled trials are required to substantiate or refute these early findings.

Guggulsterone regulates the function and expression of P-glycoprotein in rat brain microvessel endothelial cells

Our previous studies found that guggulsterone could inhibit P-glycoprotein-mediated multidrug resistance in P-glycoprotein over-expressed human cancer cell lines. However, the effects of guggulsterone on the ;P-glycoprotein function and expression in rat brain microvessel endothelial cells (rBMECs) are poorly understood. In the present study, we investigated whether guggulsterone has a modulative effect on the function and expression of P-glycoprotein in rBMECs. rhodamine 123 acts as a good substrate for P-glycoprotein, and agents that block P-glycoprotein have been found to increase the retention of rhodamine in cells. The results showed that the accumulation of rhodamine 123 in rBMECs was potentiated in a time-dependent manner after incubation with 30, 100 μM guggulsterone (P<0.05). Efflux of intracellular rhodamine 123 was decreased in a time-dependent manner from after 30, 100 μM guggulsterone treatment. The inhibitory effect of guggulsterone on P-glycoprotein function was reversible and remained at 120 min after removal of 30, 100 μM guggulsterone from the medium. Further results showed that guggulsterone (30, 100 μM) down-regulated the expression of P-glycoprotein, and had no influence on the expression of breast cancer resistance protein in rBMECs. In addition, the present study revealed that guggulsterone promoted the activity of P-glycoprotein ATPase in a dose-dependent manner. These results indicated that guggulsterone suppressed the function and expression of P-glycoprotein in rBMECs primary cultures.

Meta-analysis of the effects of Bifidobacterium preparations for the prevention and treatment of pediatric antibiotic-associated diarrhea in China

Bifidobacterium preparations are increasingly used for pediatric antibiotic-associated diarrhea (AAD) in China. The aim of this study was to review existing evidence on the efficacy of Bifidobacterium preparations for the prevention and treatment of pediatric AAD in China. Searches were performed with Medline, Embase, Cochrane Central Register of Controlled Trials, CNKI, and CBM databases. Thirty trials met the inclusion criteria. Of the 30 trials, five Bifidobacterium preparations were included. The preparations were all Bifidobacterium based, in combined with Lactobacillus, Enterococcus, Bacillus, Streptococcus or Clostridium strains. The pooled results of the 30 trials, which included 7225 participants, indicated a statistically significant association of Bifidobacterium preparations administration with reduction in pediatric AAD (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.29-0.39; P<0.01). When the meta-analysis was re-performed according to the trials explicitly aiming to prevent or treat pediatric AAD, respectively, the pooled results were similar (Bifidobacterium preparations use for preventing pediatric AAD (n=21): pooled OR, 0.34, 95% CI, 0.28-0.41, P<0.01; Bifidobacterium preparations use for treating pediatric AAD (n=9): pooled OR, 0.32, 95% CI, 0.23-0.43, P<0.01). Subgroup analyses which based on Bifidobacterium preparations variety, clinical condition, or participants age also showed statistically significant benefit of adjunct Bifidobacterium preparations for the prevention and treatment of pediatric AAD in China. The pooled evidence suggested that Bifidobacterium preparations might be efficacious for the prevention and treatment of pediatric AAD in China.