BACKGROUND: The incidence of atrial fibrillation (AF) is increasing, conferring a major health-care issue in Asia. No risk score for predicting incident AF has been specifically developed in Asian subjects. Our aim was to investigate risk factors for incident AF in Asian subjects and to combine them into a simple clinical risk score. METHODS: Risk factors for incident AF were analyzed in 471,446 subjects from the Chinese Yunnan Insurance Database (internal derivation cohort) and then combined into a simple clinical risk score. External application of the new score was performed in 451,199 subjects from the Korean National Health Insurance Service (external cohort). RESULTS: In the internal cohort, structural heart disease (SHD), heart failure (HF), age $ 75 years, coronary artery disease (CAD), hyperthyroidism, COPD, and hypertension were associated with incident AF. Given the low prevalence and the strong association of SHD with incident AF (hazard ratio, 26.07; 95% CI, 18.22-37.30; P < .001), these patients should be independently considered as high risk for AF and were excluded from the analysis. The remaining predictors were combined into the new simple C 2 HEST score: C 2 : CAD/COPD (1 point each); H: hypertension (1 point); E: elderly (age $ 75 years, 2 points); S: systolic HF (2 points); and T: thyroid disease (hyperthyroidism, 1 point). The C 2 HEST score showed good discrimination with the area under the curve (AUC) of 0.75 (95% CI, 0.73-0.77) and had good calibration (P ¼ .774). The score was internally validated by bootstrap sampling procedure, giving an AUC of 0.75 (95% CI, 0.73-0.77). External application gave an AUC of 0.65 (95% CI, 0.65-0.66). The C 2 HEST score was superior to CHADS 2 and CHA 2 DS 2-VASc scores in both cohorts in predicting incident AF. CONCLUSIONS: We have developed and validated the C 2 HEST score as a simple clinical tool to assess the individual risk of developing AF in the Asian population without SHD.

To describe the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on serum uric acid (SUA) in patients with type 2 diabetes mellitus (T2DM). PubMed, EMBASE, and CENTRAL were searched for randomized controlled trials of SGLT2 inhibitors in patients with T2DM up to Aug 10, 2017, without language or date restrictions. Thirty-one studies totaling 13,650 patients were included. SGLT2 inhibitors significantly decreased SUA levels compared with placebo, canagliflozin WMD –37.02 μmol/L, 95% CI [–38.41, –35.63], dapagliflozin WMD –38.05 μmol/L, 95% CI [–44.47, –31.62], empagliflozin WMD –42.07 μmol/L, 95% CI [–46.27, –37.86]. The drug class effect of SUA reduction suggesting SGLT2 inhibitors might be beneficial for diabetic patients with hyperuricemia.

This study is designed to investigate the effect of artemether on type 2 diabetic db/db mice. The experiments consisted of three groups: normal control (NC, db/+, 1% methylcellulose, intragastric administration), diabetic control (DM, db/db, 1% methylcellulose, intragastric administration), and artemether treated (artemether, db/db, 200 mg/kg of artemether, intragastric administration). The treatment lasted for two weeks. The food intake, body weight, and fasting blood glucose of mice were measured every three days. At the start and end of the experiment, the intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (IPITT) were performed. We determined the serum insulin and glucagon levels by ELISA kits and calculated insulin resistance index (HOME-IR). HE staining was used to observe the morphologies of pancreas and liver in mice. The damage of pancreatic beta cells was evaluated by TUNEL staining and immunofluorescence. We found the following: (1) compared with the DM group, the food intake and weight increase rate of artemether group significantly reduced (P < 0.05); (2) compared with pretreatment, artemether significantly reduced the fasting blood glucose levels, and the areas under the curves (AUCs) of IPGTT were decreased significantly, increasing the tolerance to glucose of db/db mice. (P < 0.05); (3) artemether improved hyperinsulinemia and decreased the AUCs of IPITT and HOME-IR, increasing the insulin sensitivity of db/db mice. (4) Artemether significantly ameliorated islet vacuolar degeneration and hepatic steatosis in db/db mice. (5) Artemether reduced the apoptosis of pancreatic beta cells and increased insulin secretion in db/db mice compared with DM group (P < 0.05). Our results indicated that artemether significantly improved glucose homeostasis and insulin resistance and had the potential activity to prevent obesity, reduced the severity of fatty liver, and protected pancreatic beta cells, promising to treat type 2 diabetes.

The prevalence of clinically significant CAS varies significantly by race. Native American and Caucasian individuals have the highest prevalence of CAS, whereas African American males and Asian females appear to have the lowest prevalence. This information adds evidence to the hypothesis that the increased stroke rate in African American subjects is likely not related to extracranial cerebrovascular disease. Furthermore, this is a novel report of an extremely high prevalence of CAS in the Native American population.

The risks of major bleeding and intracranial hemorrhage (ICH) are higher in Asian patients with atrial fibrillation (AF) compared to non-Asians. We aimed to investigate risk factors for bleeding, and validate the predictive value of available bleeding risk scores (mOBRI, HEMORR2HAGES, Shireman, HAS-BLED, ATRIA and ORBIT) in a large cohort of Chinese inpatients with AF. Using hospital electronic medical databases, we identified 4824 AF patients (mean age 67 years; 34.9% female) from January 1, 1995 to May 30, 2015, with median (interquartile) in-hospital days of 10 (7–16) days. On multivariate analysis, prior bleeds, vascular disease, anemia, prior stroke, and liver dysfunction were independent risk factors of major bleeding (all p < 0.05). C-statistics (95%CI) of the HAS-BLED score were 0.72 (0.65–0.79) for major bleeding events and 0.83 (0.75–0.91) for ICH (all p < 0.001). Compared to other risk scores, the HAS-BLED score was significantly better in predicting major bleeding events (Delong test, all P < 0.05, apart from mOBRI, HEMORR2HAGES) and ICH (all p < 0.05), and additionally, resulted in a net reclassification improvement (NRI) of 17.1–65.5% in predicting major bleeding events and 29.5–67.3% in predicting ICH (all p < 0.05). We conclude that the HAS-BLED score had the best predictive and discriminatory ability for major bleeding and ICH in an Asian/Chinese AF population.

Micropeptides (microproteins) encoded by transcripts previously annotated as long noncoding RNAs (lncRNAs) are emerging as important mediators of fundamental biological processes in health and disease. Here, we applied two computational tools to identify putative micropeptides encoded by lncRNAs that are expressed in the human pancreas. We experimentally verified one such micropeptide encoded by a b cell-and neural cell-enriched lncRNA TCL1 Upstream Neural Differentiation-Associated RNA (TUNAR, also known as TUNA, HI-LNC78, or LINC00617). We named this highly conserved 48-amino-acid micropeptide beta cell-and neural cell-regulin (BNLN). BNLN contains a single-pass transmembrane domain and localizes at the endoplasmic reticulum (ER) in pancreatic b cells. Overexpression of BNLN lowered ER calcium levels, maintained ER homeostasis, and elevated glucosestimulated insulin secretion in pancreatic b cells. We further assessed the BNLN expression in islets from mice fed a highfat diet and a regular diet and found that BNLN is suppressed by diet-induced obesity (DIO). Conversely, overexpression of BNLN enhanced insulin secretion in islets from lean and obese mice as well as from humans. Taken together, our study provides the first evidence that lncRNA-encoded micropeptides play a critical role in pancreatic b cell functions and provides a foundation for future comprehensive analyses of micropeptide function and pathophysiological impact on diabetes.

Online controlled experiments, also called A/B testing, have been established as the mantra for data-driven decision making in many web-facing companies. A/B Testing support decision making by directly comparing two variants at a time. It can be used for comparison between (1) two candidate treatments and (2) a candidate treatment and an established control. In practice, one typically runs an experiment with multiple treatments together with a control to make decision for both purposes simultaneously. This is known to have two issues. First, having multiple treatments increases false positives due to multiple comparison. Second, the selection process causes an upward bias in estimated effect size of the best observed treatment. To overcome these two issues, a two stage process is recommended, in which we select the best treatment from the first screening stage and then run the same experiment with only the selected best treatment and the control in the validation stage. Traditional application of this two-stage design often focus only on results from the second stage. In this paper, we propose a general methodology for combining the first screening stage data together with validation stage data for more sensitive hypothesis testing and more accurate point estimation of the treatment effect. Our method is widely applicable to existing online controlled experimentation systems.

Background: Artemether, a commonly used artemisinin derivative, has been shown to possess potential antidiabetic activities. However, only limited information is available on the mechanisms of artemether in type 2 diabetes. Therefore, in this study, we examined some of the possible mechanisms of artemether (ATM) upon glycolipid metabolism in the db/db mouse model of diabetes. Materials and Methods: Male C57BL/KsJ-db/db and C57BL/KsJ-db/+ mice at 4 weeks of age were divided into four groups (N=6/group): ( 1) NC (normal controldb/+ mice, 1% methylcellulose, intragastric administration), ( 2) DM (diabetic modeldb/db mice, 1% methylcellulose, intragastric administration), (3) ATM 100 (DM + 100 mg/kg of artemether) and ( 4) ATM 200 (DM + 200 mg/kg of artemether). A number of assays related to diabetes were then performed following a 4-week period of these treatments.Results: Artemether at both doses significantly reduced rates of weight gain and fasting blood glucose levels, improved islet function and insulin resistance and reduced serum lipid levels to varying degrees in db/db mice. Artemether exerted a positive effect on islet vacuolar degeneration and hepatic steatosis, and increased expressions of AMP-activated protein kinase, glucose transporter 4 and Insulin receptor β protein in the liver of these db/db mice. With the use of liver protein chip detection, we found that artemether significantly improved the immune microenvironment, downregulated the expression of inflammatory factors and activated the cytokine-mediated signaling pathway through cytokine-cytokine receptor interactions. Conclusion:Artemether may regulate glycolipid metabolism in db/db mice by improving the immune microenvironment. The results of this study provide important new information that can serve as the foundation for future research into the use of artemether as a means to improve glycolipid metabolism.