Background Recent evidence from cohort studies and meta‐analyses suggests that the obesity paradox phenomenon may exist in patients with diabetes mellitus. The goal of this study was to assess the association between adverse events and obesity by using 2 different measures of obesity, body mass index (BMI; kg/m 2 ) and waist circumference, in patients with a mean 10‐year history of type 2 diabetes mellitus. Methods and Results We used data from the ACCORD (the Action to Control Cardiovascular Risk in Diabetes) study to evaluate the relationship between obesity and adverse events in patients with a mean 10‐year history of type 2 diabetes mellitus. The primary outcome of this study was all‐cause mortality. Secondary outcomes were cardiac death, nonfatal myocardial infarction, and stroke. Patients who were class III obese with BMI ≥40 had the highest risk of all‐cause mortality, followed by patients with class II obesity, whereas overweight patients had the lowest risk. We found significant correlations between BMI and waist circumference ( r =0.802). We observed that the relationships between waist circumference and primary and second end points were much like the relationships between BMI and primary and second end points (J‐shaped relationship for all‐cause mortality, V‐shaped relationship for cardiac death, U‐shaped relationship for nonfatal myocardial infarction, and reverse linear relationship for noncardiac death). Conclusions No evidence of the obesity paradox was observed in patients with a 10‐year history of diabetes mellitus. Class III obese patients showed the highest risk of adverse events (all‐cause mortality, cardiac death, nonfatal myocardial infarction, and noncardiac death). BMI and waist circumference showed similar relationships with adverse events. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 00000620.

* ese authors contributed equally to this work PEG10 promotes the migration of human Burkitt's lymphoma cells by up-regulating the expression of matrix metalloproteinase-2 and -9 Abstract Purpose: Paternally expressed gene 10 (PEG10) is important for apoptosis resistance in cancer cells; however, the e ect of PEG10 on tumor cell migration remains poorly understood. In this study, we investigated the e ects of PEG10 on proliferation, apoptosis, adhesion and migration in the Burkitt's lymphoma cell line, Raji.Methods: Apoptosis was induced by 5-uorouracil (5-FU) in pcDNA3.0/PEG10 transiently transfected HEK293T cells and PEG10-suppressed Raji cells. siRNAPEG10 was used to inhibit PEG10 expression. Fluorescence-activated cell sorting (FACS) were performed to analyze the e ect of PEG10 on apoptosis. CCK-8 were performed to detect cell proliferation and adhesion. Matrigel invasion were performed using PEG10-suppressed Raji cells to investigate cell migration. e expression levels of matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9) were analyzed in PEG10-suppressed Raji cells using both real-time RT-PCR and Western blot analysis.Results: HEK293T cells that overexpressed PEG10 exhibited greater viability 48 h following treatment with 5-FU, relative to control cells. Speci c inhibition of PEG10 expression by siRNA resulted in inhibition of growth and apoptosis in Raji cells. Adherence and invasion capabilities were downregulated and expression levels of MMP-2 and MMP-9 were reduced in PEG10-suppressed Raji cells.Conclusions: Our ndings demonstrated that PEG10 enhances the apoptotic resistance and viability of Raji cells. e migration and adherence invasion capacity of Raji cells could potentially be a ected by regulation of the expression of MMP-2 and MMP-9. Our research provides a promising strategy for cancer immunotherapy of lymphoma.

Endothelium‐dependent relaxation (EDR) is an initial key step leading to various vascular complications in patients with diabetes. However, the underlying mechanism of EDR impairment in diabetes is not fully understood. Present study defined the role of high‐mobility group protein (HMGB1) in EDR related to diabetes. Serum level of HMGB1 was increased in diabetic patients and in db/db mice. Serum HMGB1 level was also positively correlated with HbA1c and negatively correlated with nitric oxide (NO) in diabetic patients. Results from wire myograph showed that recombinant HMGB1 (rHMGB1) was capable of impairing EDR of aortas from wild‐type (WT) mice by an eNOS‐dependent mechanism. Consistently, HMGB1 inhibitor glycyrrhizin acid (GA) decreased the serum level of HMGB1 and rescued EDR impairment partly in db/db mice. Furthermore, rHMGB1 mediated EDR impairment was abolished in aortas of TLR4−/− mice. In addition, high‐glucose‐induced HMGB1 upregulation and secretion in endothelial cells. In conclusion, HMGB1 contributes to the EDR impairment through TLR4/eNOS pathway in the setting of diabetes. GA as the HMGB1 inhibitor could attenuate EDR impairment in an animal model of diabetes.

BackgroundThe association between metabolic syndrome (MS) and bladder cancer (BC) was not fully investigated, and most primary studies and pooled analyses were only focused on certain specific components.ObjectiveTo further investigate this issue and obtain more precise findings, we conducted this updated evidence synthesis of published studies, which involved not only MS components but also the MS in its entirety.Materials and methodsWe searched the PubMed, EMBASE, and Web of Science databases for observational studies on the association between BC susceptibility and/or mortality, and MS and its components. We extracted data from included studies, evaluated heterogeneity, and performed meta-analytic quantitative syntheses.ResultsA total of 95 studies with 97,795,299 subjects were included in the present study. According to the results, MS significantly increased the risk of BC (risk ratio [RR]=1.11, 95% CI=1.00–1.23); diabetes significantly increased the risk of BC (RR=1.29, 95% CI=1.19–1.39) and associated with poor survival (RR=1.24, 95% CI=1.08–1.43). Excessive body weight was associated with increased susceptibility (RR=1.07, 95% CI=1.02–1.12), recurrence (RR=1.46, 95% CI=1.18–1.81), and mortality (RR=1.17, 95% CI=1.00–1.37). As indicated by cumulative meta-analysis, sample size was inadequate for the association between BC susceptibility and MS, the association between BC recurrence and excessive body weight, and the association between BC survival and diabetes. The sample size of the meta-analysis was enough to reach a stable pooled effect for other associations.ConclusionDiabetes and excessive body weight as components of MS are associated with increased susceptibility and poor prognosis of BC. Uncertainty remains concerning the impact of overall MS, hypertension, and dyslipidemia on BC susceptibility and prognosis, for which further investigations are needed.