Background and objectives: Chinese type 2 diabetes mellitus (T2DM) patients are characterized by a low body mass index (BMI), and significant insulin resistance (IR). The triglyceride glucose (TyG) index has not been studied as a means of assessing IR in Chinese T2DM patients with a BMI < 35 kg/m². Materials and Methods: An open-label cross-sectional study recruited 102 Chinese T2DM patients with a BMI < 35 kg/m². The hyper-insulinemic euglycemic clamp, homeostatic model assessment of IR (HOMA-IR), and TyG index were used to determine the level of IR. Based on Pearson’s correlations, glucose disposal rate (GDR), TyG index, and HOMA-IR were analyzed. HOMA-IR and TyG index for IR were evaluated using multiple linear regression and multivariate logistic regression analyses. On the basis of the receiver operating characteristic (ROC) curve, the sensitivity, specificity, and optimal cut-off value of HOMA-IR and the TyG index were determined. Results: The mean values of GDR, HOMA-IR, and TyG index were 4.25 ± 1.81, 8.05 ± 7.98, and 8.12 ± 0.86 mg/kg/min, respectively. Pearson’s correlation coefficient was −0.418 between GDR and TyG index and −0.324 between GDR and HOMA-IR. ROC curve analysis showed that, among both sexes, the TyG index was a better discriminator of IR than HOMA-IR. The area under the ROC curve (AUC) of the TyG index (0.785, 0.691–0.879) was higher than that of HOMA-IR (0.73, 0.588–0.873) in all genders. The optimal cut-off values of the TyG index and HOMA-IR were 7.99 and 3.39, respectively. Conclusions: The TyG index showed more effectiveness in identifying IR in Chinese T2DM patients with a BMI < 35 kg/m² compared to HOMA-IR.

The inhibitor of apoptosis protein survivin has a critical regulatory role in carcinogenesis and treatment tolerance in colorectal cancer (CRC). However, the targeted drugs for survivin protein are extremely limited. In the present research, we discovered that Tanshinone IIA (Tan IIA) played a dual regulatory role in inhibiting tumorigenesis and reversing 5-Fu tolerance via modulating the expression and phosphorylation of survivin in CRC cells. Mechanistically, Tan IIA suppressed the Akt/WEE1/CDK1 signaling pathway, which led to the downregulation of survivin Thr34 phosphorylation and destruction of the interaction between USP1 and survivin to promote survivin ubiquitination and degradation. Furthermore, Tan IIA significantly facilitated chemoresistant CRC cells to 5-Fu sensitivity. These results revealed that Tan IIA possessed a strong antitumor activity against CRC cells and could act as an up-and-coming agent for treating CRC and overcoming chemotherapy resistance.

Background: Obesity is associated with a significant predisposition towards cardiovascular events and acts as an important risk factor for mortality. Herein, we conducted a comprehensive meta-analysis to estimate the protective effect of bariatric surgery on disease-specific mortality and major adverse cardiovascular events (MACEs) in patients with severe obesity. Methods: PubMed and Embase were searched from inception to 4 June 2022. Eligible studies were age, sex, and BMI-matched cohort studies. The protocol for this meta-analysis was registered on PROSPERO (ID: CRD42022337319). Results: Forty matched cohort studies were identified. Bariatric surgery was associated with a lower risk of disease-specific mortality including cancer mortality [hazard ratio with 95% confidence interval: 0.46 (0.37–0.58)], cardiovascular mortality [0.38 (0.29–0.50)], and diabetes mortality [0.25 (0.11–0.57)]. Bariatric surgery was associated with a lower incidence of MACEs [0.58 (0.51–0.66)] and its components including all-cause mortality [0.52 (0.47–0.58)], atrial fibrillation [0.79 (0.68–0.92)], heart failure [0.52 (0.42–0.65)], myocardial infarction [0.55 (0.41–0.74)], and stroke [0.75 (0.63–0.89)]. According to subgroup analysis on all-cause mortality, patients with severe obesity and type 2 diabetes benefited more from bariatric surgery than those with severe obesity only (heterogeneity between groups: P=0.001), while different surgical approaches brought similar benefits (heterogeneity between groups: P=0.87). Conclusions: This meta-analysis of 40 matched cohort studies supports that bariatric surgery reduces disease-specific mortality and incidence of both MACEs and its components in patients with severe obesity compared with nonsurgical subjects. Bariatric surgery deserves a more aggressive consideration in the management of severe obesity.

The increased secretion of glucagon-like peptide-1 (GLP-1) after Roux-en-Y gastric bypass (RYGB) is regarded as the main reason for the improvement of blood glucose. However, the single-nucleotide polymorphisms (SNPs) of GLP-1 Receptor (GLP1R) impair receptor function, subsequently affecting β cell insulin secretion function, ultimately affecting the efficacy of RYGB. In this study, we revealed that two SNPs in GLP1R gene, rs3765467 and rs10305492, could significantly reduce the insulin secreted by β cells and the cyclic AMP concentration, whereas promote β cell apoptosis. Under high glucose exposure, rs3765467 and rs10305492 impaired β cell secretion of insulin and β cell viability in the same way; in other words, GLP1R rs3765467 and rs10305492 exert an effect on pancreatic β cell glucose-stimulated insulin secretion. Moreover, GLP-1 antagonist Exendin (9-39) further enhanced, whereas GLP-1 agonist Exendin-4 partially attenuated the effects of SNPs on the functions and apoptosis of β cells. In conclusion, the rs3765467 and rs10305492 SNPs in GLP1R show to exert a critical effect on regulating insulin secretory capacity of β cells and β cell mass. Through leading to the dysfunction and apoptosis of β cells, GLP1R rs3765467 and rs10305492 might also impair GLP-1 interaction with GLP1R, therefore attenuating the therapeutic effect of RYGB.