Proinflammatory Th17 cells and CD4(+)CD25(+) regulatory T (Treg) cells are two newly identified T lymphocyte subsets, which have opposite effects on autoimmunity and inflammation. To assess the Th17/Treg pattern and cytokine microenvironment in peripheral blood of patients with RA, we included 66 RA patients and 20 healthy volunteers. Of all these subjects, peripheral Th17 and Treg frequencies were analyzed by flow cytometry (FCM) and the plasma levels of interleukin (IL)-17, 23, 6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β1 were detected by ELISA. The results demonstrated that RA patients revealed an obvious increase in peripheral Th17 frequencies and levels of Th17-related cytokines (IL-17, IL-23, IL-6, TNF-α) while a significant decrease in Treg frequencies and Treg-related cytokine (TGF-β1) levels when compared with healthy people. Our study indicated that development of RA is associated with peripheral Th17/Treg imbalance and characterized by a proinflammatory cytokine microenvironment, which supports continuing generation of Th17 cells.

BackgroundThe WHO recommends moderate physical activity to combat the increasing risk of death from chronic diseases. We conducted a meta-analysis to assess the association between physical activity and cancer mortality and the WHO recommendations to reduce the latter.MethodsMEDLINE and EMBASE were searched up until May 2014 for cohort studies examining physical activity and cancer mortality in the general population and cancer survivors. Combined HRs were estimated using fixed-effect or random-effect meta-analysis of binary analysis. Associated HRs with defined increments and recommended levels of recreational physical activity were estimated by two-stage random-effects dose–response meta-analysis.ResultsA total of 71 cohort studies met the inclusion criteria and were analysed. Binary analyses determined that individuals who participated in the most physical activity had an HR of 0.83 (95% CI 0.79 to 0.87) and 0.78 (95% CI 0.74 to 0.84) for cancer mortality in the general population and among cancer survivors, respectively. There was an inverse non-linear dose–response between the effects of physical activity and cancer mortality. In the general population, a minimum of 2.5 h/week of moderate-intensity activity led to a significant 13% reduction in cancer mortality. Cancer survivors who completed 15 metabolic equivalents of task (MET)-h/week of physical activity had a 27% lower risk of cancer mortality. A greater protective effect occurred in cancer survivors undertaking physical activity postdiagnosis versus prediagnosis, where 15 MET-h/week decreased the risk by 35% and 21%, respectively.ConclusionsOur meta-analysis supports that current physical activity recommendations from WHO reduce cancer mortality in both the general population and cancer survivors. We infer that physical activity after a cancer diagnosis may result in significant protection among cancer survivors.

PDNV affects a substantial number of patients after ambulatory surgery. We developed and validated a simplified risk score to identify patients who would benefit from long-acting prophylactic antiemetics at discharge from the ambulatory care center.

Introduction: Tacrolimus (Tac) is effective in preventing acute rejection but has considerable toxicity and inter-individual variability in pharmacokinetics and pharmacodynamics. Part of this is explained by polymorphisms in genes encoding Tac-metabolizing enzymes and transporters. A better understanding of Tac pharmacokinetics and pharmacodynamics may help to minimize different outcomes amongst transplant recipients by personalizing immunosuppression. Areas covered: The pharmacogenetic contribution of Tac metabolism will be examined, with a focus on recent discoveries, new developments and ethnic considerations. Expert opinion: The strongest and most consistent association in pharmacogenetics is between the CYP3A5 genotype and Tac dose requirement, with CYP3A5 expressers having a~40-50% higher dose requirement compared to non-expressers. Two recent randomized-controlled clinical trials using CYP3A5 genotype, however, did not show a decrease in acute rejections nor reduced toxicity. CYP3A4*22, CYP3A4*26, and POR*28 are also associated with Tac dose requirements and may be included to provide the expected improvement of Tac therapy. Studies focusing on the intracellular drug concentrations and on calcineurin inhibitor-induced nephrotoxicity also seem promising. For all studies, however, the ethnic prevalence of genotypes should be taken into account, as this may significantly impact the effect of pre-emptive genotyping.ARTICLE HISTORY

Our meta-analysis indicates that the current WHO recommendation of physical activity can result in a 7% reduction in cancer risk, which is mainly attributed to its protective role against breast cancer and colorectal cancer. Furthermore, two-fold of current recommendation level is considered to give its saturated protection against cancer.