Predictive Effect of Triglyceride-Glucose Index on Adverse Prognostic Events in Patients with Type 2 Diabetes Mellitus and Ischemic Cardiomyopathy.

Background: The triglyceride-glucose (TyG) index is regarded as an independent predictor of cardiovascular (CV) consequences and a reliable surrogate measure of insulin resistance (IR). However, the predictive significance of the TyG index in patients with type 2 diabetes mellitus (T2DM) and ischemic cardiomyopathy (ICM) remains unknown. Methods: This study included 1514 consecutive subjects with ICM and T2DM. The tertile of the TyG index values was used to categorize these patients into three groups. Major adverse cardiac and cerebral events (MACCEs) were also noted. The TyG index was calculated using the [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2] equation. Results: After adjusting for age, BMI, and other potential confounders, the scores of multivariate Cox proportional hazards regression models for chest pain [9.056 (4.370 to 18.767), p<0.001], acute myocardial infarction [4.437 (1.420 to 13.869), p=0.010], heart failure [7.334 (3.424 to 15.708), p<0.001], cardiogenic shock [3.707 (1.207 to 11.384), p=0.022], malignant arrhythmia [5.309 (2.367 to 11.908), p<0.001], cerebral infarction [3.127 (1.596 to 6.128), p<0.001], gastrointestinal bleeding [4.326 (1.612 to 11.613), p=0.004], all-cause death [4.502 (3.478 to 5.827), p<0.001] and cumulative incidence of MACCEs [4.856 (3.842 to 6.136), p<0.001] increased significantly with an increase in TyG index levels (all p<0.05). Time-dependent ROC analysis revealed that the area under the TyG index curve (AUC) reached 0.653 in the 3rd year, 0.688 in the 5th year, and 0.764 in the 10th year. The predictive efficiency of this model on MACCEs improved [net reclassification improvement (NRI): 0.361 (0.253 to 0.454); C-index: 0.678 (0.658 to 0.698); integrated discrimination improvement (IDI): 0.138 (0.098 to 0.175), all p<0.05] following the incorporation of the TyG index into the base risk model. Conclusion: TyG index could be useful in predicting MACCEs and initiating preventive measures in subjects with ICM and T2DM.

SLC27A5 promotes sorafenib-induced ferroptosis in hepatocellular carcinoma by downregulating glutathione reductase.

Sorafenib, a first-line drug for advanced hepatocellular carcinoma (HCC), shows a favorable anti-tumor effect while resistance is a barrier impeding patients from benefiting from it. Thus, more efforts are needed to lift this restriction. Herein, we first find that solute carrier family 27 member 5 (SLC27A5/FATP5), an enzyme involved in the metabolism of fatty acid and bile acid, is downregulated in sorafenib-resistant HCC. SLC27A5 deficiency facilitates the resistance towards sorafenib in HCC cells, which is mediated by suppressing ferroptosis. Further mechanism studies reveal that the loss of SLC27A5 enhances the glutathione reductase (GSR) expression in a nuclear factor erythroid 2-related factor 2 (NRF2)-dependent manner, which maintains glutathione (GSH) homeostasis and renders insensitive to sorafenib-induced ferroptosis. Notably, SLC27A5 negatively correlates with GSR, and genetic or pharmacological inhibition of GSR strengthens the efficacy of sorafenib through GSH depletion and the accumulation of lipid peroxide products in SLC27A5-knockout and sorafenib-resistant HCC cells. Based on our results, the combination of sorafenib and carmustine (BCNU), a selective inhibitor of GSR, remarkably hamper tumor growth by enhancing ferroptotic cell death in vivo. In conclusion, we describe that SLC27A5 serves as a suppressor in sorafenib resistance and promotes sorafenib-triggered ferroptosis via restraining the NRF2/GSR pathway in HCC, providing a potential therapeutic strategy for overcoming sorafenib resistance.

Allele-specific polymerase chain reaction for detection of a mutation in the relax circular DNA and the covalently closed circular DNA of hepatitis B virus.

The relax circle DNA (rcDNA) sequence and the covalently closed circle DNA (cccDNA) sequence in hepatitis B virus (HBV) are crucial regions for HBV infections. To analyze mutations in rcDNA and cccDNA, DNA sequencing is often used, although it is time-consuming and expensive. Herein, we report a simple, economic, albeit accurate allele-specific polymerase chain reaction (AS-PCR) to detect mutations in these regions of HBV. This method can be extensively used to screen for mutations at specific positions of HBV genome.