Background Nonpharmacologic interventions that modify lifestyle can lower blood pressure (BP) and have been assessed in numerous randomized controlled trials and pairwise meta‐analyses. It is still unclear which intervention would be most efficacious. Methods and Results Bayesian network meta‐analyses were performed to estimate the comparative effectiveness of different interventions for lowering BP. From 60 166 potentially relevant articles, 120 eligible articles (14 923 participants) with a median follow‐up of 12 weeks, assessing 22 nonpharmacologic interventions, were included. According to the surface under the cumulative ranking probabilities and Grading of Recommendations Assessment, Development and Evaluation (GRADE) quality of evidence, for adults with prehypertension to established hypertension, high‐quality evidence indicated that the Dietary Approach to Stop Hypertension (DASH) was superior to usual care and all other nonpharmacologic interventions in lowering systolic BP (weighted mean difference, 6.97 mm Hg; 95% credible interval, 4.50–9.47) and diastolic BP (weighted mean difference, 3.54 mm Hg; 95% credible interval, 1.80–5.28). Compared with usual care, moderate‐ to high‐quality evidence indicated that aerobic exercise, isometric training, low‐sodium and high‐potassium salt, comprehensive lifestyle modification, breathing‐control, and meditation could lower systolic BP and diastolic BP. For patients with hypertension, moderate‐ to high‐quality evidence suggested that the interventions listed (except comprehensive lifestyle modification) were associated with greater systolic BP and diastolic BP reduction than usual care; salt restriction was also effective in lowering both systolic BP and diastolic BP. Among overweight and obese participants, low‐calorie diet and low‐calorie diet plus exercise could lower more BP than exercise. Conclusions DASH might be the most effective intervention in lowering BP for adults with prehypertension to established hypertension. Aerobic exercise, isometric training, low‐sodium and high‐potassium salt, comprehensive lifestyle modification, salt restriction, breathing‐control, meditation and low‐calorie diet also have obvious effects on BP reduction.

Background: M-type phospholipase A₂ receptor (PLA₂R) has been identified as the major target antigen in idiopathic membranous nephropathy (IMN). However, the role of glomerular PLA₂R (gPLA₂R) and the associations of serum anti-PLA₂R antibody (sPLA₂R-Ab) titre with diagnosis, treatment and prognosis in IMN need to be further investigated. Methods: We screened 148 consecutive patients with biopsy-proven membranous nephropathy (MN; 113 with IMN and 35 with secondary MN (SMN)) who were followed up for ≤20 months. Serum and urine samples were simultaneously collected at different time points. The levels of sPLA₂R-Ab were detected using immunofluorescence and enzyme-linked immunosorbent assay. gPLA₂R was assessed by immunofluorescence. Results: Most patients with IMN displayed both gPLA₂R and sPLA₂R-Ab positive (85.8 and 82.3%, respectively). In contrast, very few patients with SMN showed either gPLA₂R or sPLA₂R-Ab positive. The sPLA₂R-Ab titre, not gPLA₂R, was significantly correlated with proteinuria. Surprisingly, changes in sPLA₂R-Ab titre occurred earlier and faster than proteinuria in patients who were followed up for ≤20 months during the whole period of observation. Survival analysis of IMN patients indicated a significant association between sPLA₂R-Ab titre and outcome, whereas, no significant difference was observed between the gPLA₂R intensity and outcome. Conclusions: These data indicate that sPLA₂R-Ab might be a better biomarker for IMN diagnosis and treatment outcome. In addition, monitoring sPLA₂R-Ab titre may assist in determining when to initiate the administration of immunosuppressive agents and in evaluating treatment efficacy.

Cyclooxygenase-2 (COX-2) plays an important role in lung cancer development and progression. Using streptavidin-agarose pulldown and proteomics assay, we identified and validated Ku80, a dimer of Ku participating in the repair of broken DNA double strands, as a new binding protein of the COX-2 gene promoter. Overexpression of Ku80 up-regulated COX-2 promoter activation and COX-2 expression in lung cancer cells. Silencing of Ku80 by siRNA down-regulated COX-2 expression and inhibited tumor cell growth in vitro and in a xenograft mouse model. Ku80 knockdown suppressed phosphorylation of ERK, resulting in an inactivation of the MAPK pathway. Moreover, CBP, a transcription co-activator, interacted with and acetylated Ku80 to co-regulate the activation of COX-2 promoter. Overexpression of CBP increased Ku80 acetylation, thereby promoting COX-2 expression and cell growth. Suppression of CBP by a CBP-specific inhibitor or siRNA inhibited COX-2 expression as well as tumor cell growth. Tissue microarray immunohistochemical analysis of lung adenocarcinomas revealed a strong positive correlation between levels of Ku80 and COX-2 and clinicopathologic variables. Overexpression of Ku80 was associated with poor prognosis in patients with lung cancers. We conclude that Ku80 promotes COX-2 expression and tumor growth and is a potential therapeutic target in lung cancer.

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Y-box binding protein 1 (YBX1) is involved in the multi-tumor occurrence and development. However, the regulation of YBX1 in lung tumorigenesis and the underlying mechanisms, especially its relationship with CDC25a, was remains unclear. In this study, we analyzed the expression and clinical significance of YBX1 and CDC25a in lung adenocarcinoma and identified their roles in the regulation of lung cancer growth. The retrospective analysis of 116 patients with lung adenocarcinoma indicated that YBX1 was positively correlated with CDC25a expression. The Cox-regression analysis showed only high-ranking TNM stage and low CDC25a expression were an independent risk factor of prognosis in enrolled patients. High expression of YBX1 or CDC25a protein was also observed in lung adenocarcinoma cells compared with HLF cells. ChIP assay demonstrated the binding of endogenous YBX1 to the CDC25a promoter region. Overexpression of exogenous YBX1 up-regulated the expression of the CDC25a promoter-driven luciferase. By contrast, inhibition of YBX1 by siRNA markedly decreased the capability of YBX1 binding to CDC25a promoter in A549 and H322 cells. Inhibition of YBX1 expression also blocked cell cycle progression, suppressed cell proliferation and induced apoptosis via the CDC25a pathway in vitro. Moreover, inhibition of YBX1 by siRNA suppressed tumorigenesis in a xenograft mouse model and down-regulated the expression of YBX1, CDC25a, Ki67 and cleaved caspase 3 in the tumor tissues of mice. Collectively, these results demonstrate inhibition of YBX1 suppressed lung cancer growth partly via the CDC25a pathway and high expression of YBX1/CDC25a predicts poor prognosis in human lung adenocarcinoma.