The association between high glycemic variability and all-cause mortality has been widely investigated in epidemiological studies but rarely validated in glucoselowering clinical trials. We aimed to identify the prognostic significance of visit-tovisit HbA 1c variability in treated patients in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial population. RESEARCH DESIGN AND METHODSWe studied the risk of all-cause mortality in relation to long-term visit-to-visit HbA 1c variability, expressed as coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV), from the 8th month to the transition from intensive to standard glycemic therapy. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (HR) and 95% CI. RESULTSCompared with the standard therapy group (n 5 4,728), the intensive therapy group (n 5 4,755) had significantly lower mean HbA 1c (6.6% [49 mmol/mol] vs. 7.7% [61 mmol/mol], P < 0.0001) and lower CV, VIM, and ARV (P < 0.0001). In multivariate adjusted analysis, all three HbA 1c variability indices were significantly associated with total mortality in all patients as well as in the standard-and intensive-therapy groups analyzed separately. The hazard ratios for a 1-SD increase in HbA 1c variability indices for all-cause mortality were 1.19 and 1.23 in intensive and standard therapy, respectively. Cross-tabulation analysis showed the third tertile of HbA 1c mean and VIM had significantly higher all-cause mortality (HR 2.05; 95% CI 1.17-3.61; P < 0.01) only in the intensive-therapy group. CONCLUSIONSLong-term visit-to-visit HbA 1c variability was a strong predictor of all-cause mortality. HbA 1c VIM combined with HbA 1c mean conferred an increased risk for all-cause mortality in the intensive-therapy group.Type 2 diabetes is a common and potent risk factor for cardiovascular disease (CVD) events, and observational studies have consistently shown an association between the degree of hyperglycemia and the risk of these outcomes (1-4). However, several randomized clinical trials of intensive glycemic control in patients with type 2 diabetes did not demonstrate beneficial effects on these vascular outcomes (5-7). Moreover, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial

Keloid is one of the most frustrating problems related to wounding healing and presents a great challenge in clinic. MicroRNAs (miRs) have shown their potential as a novel therapy for the prevention and treatment of keloid. Vascular endothelial growth factor (VEGF) plays a critical role in the regulation of scar development. In the current study, it was hypothesized that miR-205-5p was capable of suppressing keloid formation by inhibiting the VEGF-mediated wound healing cascade. The expression statuses of miR-205-5p and VEGF in clinical keloid tissues and keloid cell line human keloid fibroblasts (HKF) were detected. Then the direct action of miR-205-5p on VEGF gene was assessed using dual-luciferase assay. Thereafter, orchestrated administrations on HKF with miR-205-5p mimic, specific VEGF siRNA, PI3K agonist (740 Y-P), and PI3K inhibitor (LY294002) were performed to reveal the roles of miR-205-5p and VEGF in keloid formation and further explain the mechanism through which miR-205-5p affected the VEGF-mediated signaling transductions. Our results showed that there was significant low expression of miR-205-5p in keloid tissue specimens and the cell line while the expression of VEGF in keloid tissues was augmented. Moreover, miR-205-5p overexpression dramatically impaired the cell viability, induced the cell apoptosis, and inhibited the cell invasion and migration ability in HKF. Based on the detection of dual luciferase assay and detection at protein level, miR-205-5p antagonized the keloids by directly targeting VEGF expression and subsequently inhibiting PI3K/Akt pathway. The current study is the first one demonstrating that miR-205-5p inhibits the pathogenesis of keloids, indicating the potential of miR-205-5p in the development of therapies for prevention and treatment of keloids.

ObjectiveThe aim of this study was to evaluate clinicopathologic factors that could possibly affect the outcome of patients with triple negative breast cancer and subsequently build a prognostic model to predict patients’ outcome.MethodsWe retrospectively analyzed clinicopathologic characteristics and outcome of 504 patients diagnosed with triple-negative invasive ductal breast cancer. 185 patients enrolled between 2000 and 2002 were designated to the training set. The variables that had statistically significant correlation with prognosis were combined to build a model. The prognostic value of the model was further validated in the separate validation set containing 319 patients enrolled between 2003 and 2006. ResultsThe median follow-up duration was 66 months. 174 patients experienced recurrence, and 111 patients died. Positivity for ≥4 lymph nodes, Cathepsin-D positivity, and Ki-67 index ≥20% were independent factors for DFS, while the lymph nodes status and Ki-67 index were the prognostic factors for OS. The prognostic model was established based on the sum of all three factors, where positivity for ≥4 lymph nodes, Cathepsin-D and Ki-67 index ≥20% would individually contribute 1 point to the risk score. The patients in the validation set were assigned to a low-risk group (0 and 1 point) and a high-risk group (2 and 3 points). The external validation analysis also demonstrated that our prognostic model provided the independent high predictive accuracy of recurrence.ConclusionThis model has a considerable clinical value in predicting recurrence, and will help clinicians to design an appropriate level of adjuvant treatment and schedule adequate appointments of surveillance visits.