Icosapent ethyl therapy for very high triglyceride levels: a 12-week, multi-center, placebo-controlled, randomized, double-blinded, phase III clinical trial in China.

OBJECTIVES: Eicosapentaenoic acid in its ethyl ester form is the single active component of icosapent ethyl (IPE). This study was a phase III, multi-center trial assessing the safety and efficiency of IPE for treating very high triglyceride (TG) in a Chinese cohort. METHODS: Patients having TG levels (5.6-22.6 mmol/L) were enrolled and randomly assigned to receive a treatment of oral intake of 4 g or 2 g/day of IPE, or placebo. Before and after 12 weeks of treatment, TG levels were assessed and the median was calculated to determine the change between the baseline and week 12. In addition to examining TG levels, the impact of such treatments on other lipid changes was also investigated. The official Drug Clinical Trial Information Management Platform has registered this study (CTR20170362). RESULTS: Random assignments were performed on 373 patients (mean age 48.9 years; 75.1% male). IPE (4 g/day) lowered TG levels by an average of 28.4% from baseline and by an average of 19.9% after correction for placebo (95% CI: 29.8%-10.0%, P < 0.001). In addition, plasma concentration of non-high-density lipoprotein cholesterol (non-HDL-C), very low-density lipoprotein (VLDL) cholesterol, and VLDL-TG remarkedly reduced after IPE (4 g/day) treatment by a median of 14.6%, 27.9%, and 25.2%, respectively compared with participants in placebo group. Compared to the placebo, neither 4 nor 2 g of IPE daily elevated LDL-C levels with statistical significance. IPE was well tolerated by all the treatment groups. CONCLUSIONS: IPE at 4 g/day dramatically lowered other atherogenic lipids without a noticeable increase in LDL-C, thereby decreasing TG levels in an exceptionally high-TG Chinese population.

STAT3-induced long noncoding RNA LINC00668 promotes migration and invasion of non-small cell lung cancer via the miR-193a/KLF7 axis.

Long noncoding RNAs (lncRNAs) have been demonstrated to play significant roles in non-small cell lung cancer (NSCLC) progression. Recently, a newly identified lncRNA, LncRNA LINC00668 (LINC00668), was reported to be involved in the regulation of progression of several tumors. However, the expression pattern and biological function of LINC00668 in NSCLC remains largely unclear. In this study, we found that LINC00668 expression was significantly up-regulated in both NSCLC tissues and cell lines. we also showed that LINC00668 upregulation was induced by transcription factor STAT3. Clinical investigation demonstrated that high expression level of LINC00668 was associated with advanced TNM stage, histological grade and lymph node metastasis. Moreover, multivariate analysis confirmed LINC00668 expression level to be an independent prognostic indicator for overall survival of NSCLC patients. Functional assays indicated that knockdown of LINC00668 suppressed NSCLC cells proliferation, migration and invasion, and promoted apoptosis. Mechanistic studies indicated that LINC00668 is a direct target of miR-193a, leading to down-regulation in the expression of its target gene KLF7. Our findings suggested that STAT3-induced LINC00668 contributed to NSCLC progression through upregulating KLF7 expression by sponging miR-193a, and may serve as a prognostic biomarker and a potential target for NSCLC.