Expression of m6A RNA Methylation Regulators and Their Clinical Predictive Value in Intrahepatic Cholangiocarcinoma.

BACKGROUND: N6-methyladenosine (m6A) RNA methylation regulators have been implicated in the carcinogenesis and progress of a variety of cancers. Until now, the effects of them on intrahepatic cholangiocarcinoma (ICC) have been poorly understood. METHODS: We used the GEO databases to systematically evaluate the expression profiles of 36 m6A RNA methylation regulators in ICC patients and produced a signature to assess its prognostic values. In vitro experiments were implemented to confirm the expression level. RESULTS: Compared to normal intrahepatic bile duct tissues, more than half of these 36 genes showed different levels of expression in ICC tissues. Two groups emerged from the consensus cluster analysis of these 36 genes. The two cluster of patients had significantly different clinical outcomes. In addition, we created a m6A-related prognostic signature that performed exceptionally well in the prognostic categorization of ICC patients, based on the ROC curves, Kaplan-Meier curves, and univariate and multivariate Cox regression analyses. Further research showed that there was a significant association between the m6A-related signature and the manifestations of tumor immune microenvironment in ICC. The expression level and biological effect of METTL16, one of the two m6A RNA methylation regulators incorporated in the signature, were confirmed and explored by using in vitro experiments. CONCLUSIONS: This analysis revealed the predictive roles of m6A RNA methylation regulators in ICC.

Effects of dietary inulin during late gestation on sow physiology, farrowing duration and piglet performance.

In this study there was evaluation of effects of dietary inulin during late gestation on sow physiology, farrowing duration and piglet performance. At day 80 of gestation sows were randomly assigned to four groups：basal diet (CON); or basal diet with 0.8 %; 1.6 %; or 2.4 % inulin. The feeding of the diet with 1.6 % inulin resulted in larger weights of the litter at birth a shorter duration of the farrowing period, lesser average birth interval between piglets, lesser number of piglets dead at birth, and fewer piglets/sow dead at birth (P < 0.05). When sows were fed 0.8 % and 1.6 % IN, there was a larger litter weight at weaning, sow average daily feed intake and piglet average daily gain during lactation compared with values for these variables in the CON group (P <  0.05). Additionally, there was an increase in serum concentration of free fatty acid, total cholesterol, and high-density lipoprotein cholesterol with increasing amounts of inulin in the diet (linear, P <  0.05). Sows fed 1.6 % IN had greater serum concentrations of glucose than those in the CON group (P <  0.05). Furthermore, there was a linear increase in serum activity of total antioxidant capacity, total superoxide dismutase and glutathione peroxidase with increasing amounts of inulin in the diet (P <  0.05). In conclusion, results of the present study indicated feeding inulin during late gestation improved reproductive performance of sows, thus, may be a novel additive for the pig industry in improving efficiency of pork production.

Osteopontin-loaded PLGA nanoparticles enhance the intestinal mucosal barrier and alleviate inflammation via the NF-κB signaling pathway.

Osteopontin is a multifunctional glycoprotein that is secreted by a variety of tissues or cells, but the role of osteopontin in the epithelial mucosal barrier has not been clearly established. We loaded osteopontin into hyaluronic acid-functionalized polymeric nanoparticles, which were administered by gavage to a colitis mouse model. The disease activity index, weight gain and colon length were calculated to assess the degree of symptoms. Epithelial permeability was measured using fluorescein isothiocyanate-conjugated dextran. The enzymatic activity of myeloperoxidase in the colon and inflammatory cytokines were assayed to assess the levels of inflammation. The histological appearance of the colon was observed by H&E staining. Tight junction proteins and signaling pathway proteins (NF-κB and phospho-NF-κB) were determined by western blotting. The resultant spherical osteopontin-loaded nanoparticles were characterized by the expected particle size (approximately 272.3 nm) and a slightly negative zeta potential (approximately -5.3 mV). Interestingly, we found that the osteopontin-loaded nanoparticles exerted remedial effects on colitis by both enhancing the intestinal barrier and alleviating inflammation in vivo according to the tested parameters. These results suggest that OPN plays a positive role in protecting the epithelial mucosal barrier and may be a therapeutic drug in gut homeostasis.

Positive lymph node ratio as a novel indicator of prognosis in gastric signet ring cell carcinoma: a population-based retrospective study.

BACKGROUND: Lymph node status has a strong predictive effect on the prognosis of all patients with gastric cancer. It is unclear whether the positive lymph node ratio (PLNR) is a reliable prognostic factor for gastric signet ring cell carcinoma (SRCC). METHODS: Patients with SRCC were obtained from the Surveillance, Epidemiology and End Results (SEER) database for the years 1998-2013. Cutoff values of positive lymph node ratio (PLNR) were decided using X-tile program. Survival was determined using the Kaplan-Meier method. Univariate and multivariate analyses were used to identify prognosticator of gastric signet ring cell carcinoma. RESULTS: A total of 1,884 cases were identified. 0.8 as the optimal cutoff value to separate the patients into high and low risk subsets in accordance of cancer-caused survival in SRCC patients (the number as 0.8, P<0.0001). Patients with PLNR >0.8 remained to have a poorer prognosis compared with those with PLNR <0.8 as shown by both OS (HR =2.083, 95% CI: 1.862-2.33, P<0.001) and CSS (HR =2.052, 95% CI: 1.802-2.336, P=0.014) in the multivariate cox regression model. CONCLUSIONS: PLNR is of great significance in the evaluation of prognosis for patients with SRCC.

Postoperative Radiotherapy Improves Survival in Gastric Signet-Ring Cell Carcinoma: a SEER Database Analysis.

PURPOSE: To identify the potential therapeutic role of postoperative radiotherapy (RT) in patients with locally advanced (stage II and stage III) gastric signet ring cell carcinoma (SRC). MATERIALS AND METHODS: Patients with locally advanced gastric SRC from the Surveillance, Epidemiology, and End Results program database between 2004 and 2012 were included in our study. Univariate and multivariate Cox proportional models were performed, and survival curves were generated to evaluate the prognostic effect of postoperative RT and surgery alone on SRC patients. Propensity score matching (PSM) was used to avoid selection bias among the study cohorts. RESULTS: We found that patients with postoperative RT had better probability of survival compared with those who did not receive RT (overall survival [OS], P<0.001; cancer-specific survival [CSS], P<0.001). After PSM, analysis of both overall and CSS showed that patients who underwent postoperative RT had better prognosis than those receiving surgery alone in the matched cohort (OS, P=0.00079; CSS, P=0.0036). Multivariate Cox proportional model indicated that postoperative RT had better effect on prognosis compared with surgery alone with respect to both overall (hazard ratio [HR], 0.716; 95% confidence interval [95% CI], 0.590-0.87; P=0.001) and CSS (HR, 0.713; 95% CI, 0.570-0.890; P=0.003). CONCLUSIONS: Postoperative RT had better prognosis compared with surgery alone for both overall and CSS for patients with locally advanced gastric SRC.