Citrus alkaline extracts improve LPS-induced pulmonary fibrosis via epithelial mesenchymal transition signals.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a serious life threatening clinical critical illness. ARDS-related pulmonary fibrosis is a common complication of ARDS. The occurrence of early pulmonary fibrosis indicates a higher incidence and mortality of multiple organ failure. LPS-induced ARDS-related pulmonary fibrosis model in mice was established in this study. And we have explored the anti-pulmonary fibrosis effects and molecular mechanisms of the Citrus Alkaline Extracts (CAE) in vivo and in vitro. METHODS: Pulmonary fibrosis mouse model and lung epithelial cell injury model were established in this study. H&E, Masson and Sirius Red staining were used to estimate lung tissue damage. Immunohistochemistry and western blotting were used to analyze proteins expression. Protein-protein interaction was observed by Co-Immunoprecipitation. Systemic impact of CAE on signaling pathway was examined by RNA-seq. RESULTS: Through H&E, Masson and Sirius Red staining, it was convincingly indicated that therapeutic administration of CAE alleviated lung injury and fibrosis, while pretreated administration of CAE showed weak improvement. In vitro experiments showed that CAE had dual regulation to E-cadherin and N-cadherin, the important indicators of epithelial-mesenchymal transition (EMT). And it was further demonstrated that CAE reversed TGF-ß1-induced EMT mainly through Wnt/ß-catenin, Stat3/6 and COX2/PGE2 signals. Through RNA-Seq, we discovered important mechanisms by which CAE exerts its therapeutic effect. And network pharmacology analysis demonstrated core potential targets of CAE in EMT. CONCLUSION: Thus, this study provides new therapeutic effects of CAE in anti-fibrosis, and offers potential mechanisms for CAE in LPS-induced pulmonary fibrosis.

The effect of kanglaite injection in combination with gefitinib versus gefitinib alone in patients with nonsmall cell lung cancer: A meta-analysis.

OBJECTIVE: The objective of the study was to evaluate the clinical efficacy of kanglaite (KLT) injection combined with gefitinib versus gefitinib alone in the treatment of nonsmall cell lung cancer (NSCLC). METHODS: The randomized controlled trials involving NSCLC treatment with KLT injection combined with gefitinib versus gefitinib alone were searched on seven medical databases up to October 2016. Two reviewers independently assessed the methodological quality of the included studies. The RevMan 5.3 software was employed for data analysis. RESULTS: Seven randomized trials involving 554 patients met our criteria. Compared with gefitinib alone, KLT injection combined with gefitinib showed significant effects in increasing objective response rate (relative risk [RR] =1.38; 95% confidence interval [CI], 1.09-1.75), improving the performance status (RR = 1.80; 95% CI: 1.34-2.42), raising the percentages of CD4+ cells (weighted mean difference [WMD] = 4.45; 95% CI: 2.61-6.28), natural killer cells (WMD = 4.43; 95% CI: 3.85-5.01), and ratio of CD4+/CD8+ (WMD = 0.08; 95% CI: 0.02-0.14), whereas the difference was not significant in gefitinib toxicity including rash (RR 0.90; 95% CI: 0.58-1.40, P = 0.65), diarrhea (RR 1.04; 95% CI: 0.66-1.64, P = 0.88), and liver injury (RR 1.00; 95% CI: 0.58-1.73, P = 1.00), CD3+ cells (WMD = 1.16; 95% CI: -2.64-4.97) and CD8+ cells (WMD = 6.78; 95% CI: -1.68-15.23). CONCLUSION: Co-use of KLT injection and gefitinib may benefit the patients with NSCLC through enhancing the therapeutic effectiveness compared with gefitinib alone. To confirm these results, further rigorously designed trials are warranted.

Effect of sequential treatment with TCM syndrome differentiation on acute exacerbation of chronic obstructive pulmonary disease and AECOPD risk window.

OBJECTIVE: To evaluate the efficacy and safety of the comprehensive interventions based on three Traditional Chinese medicine (TCM) patterns therapy in acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and AECOPD risk window. METHODS: A prospective, multi-center, single-blinded, double-dummy and randomized controlled clinical trial is being conducted to test the therapeutic effects of a sequential two stage treatment. A total of 364 patients were enrolled into this study with 182 in each treatment group (TCM and conventional). Patients received medication (or control) according to their assigned group. TCM treatment according to syndrome differentiation for AECOPD were administered twice daily to patients with AECOPD over 7-21days, followed by TCM for AECOPD risk window (RW) over 28days. All patients were followed up for 6 months. Exacerbations were used as the primary outcome measures. Forced expiratory volume in the first second (FEV1) and the modified medical research council dyspnea (MMRC) scale, quality of life and mortality rate were used as secondary outcome measures. RESULTS: Of 364 randomized patients, 353 were included in the intention-to-treat analysis and 290 in the per-protocol analysis. In the TCM group, 16 patients (10.4%) reached the primary end point; 24 (17.7%) in the conventional group (RR 0.59, 95% CI 0.33-1.06; p=0.074). Among patients with a re-exacerbation, the median time to event was 107.5days (interquartile range [IQR], 39.5-129.0) in the TCM and 50days (IQR, 31-130.5) in the conventional group (P=0.011). After exacerbation therapy and a further 180-days follow-up, patients in the TCM group had significant improvements in dyspnea, as measured by MMRC (P=0.003), Patients in the TCM group also had improvements in health-related quality of life (P=0.002), as measured COPD Assessment Test (CAT). There was no difference between groups in death, and recovery of lung function. There were no differences between the TCM and conventional treatment group in adverse events. CONCLUSIONS: In patients presenting to the respiratory department with acute exacerbations of COPD, TCM treatments with syndrome differentiation will have beneficial effects with regard to re-exacerbation, relieving symptoms, improving quality of life for COPD patients.