Wei F, et al. J Gastric Cancer. 2019 Dec;19(4):393-407. https://doi.org/10.5230/jgc.2019.19.e36

Beta-adrenergic blockade has been hypothesized to have a protective effect on intestinal dysfunction and increased intestinal permeability associated with the epinephrine surge after traumatic brain injury (TBI). Wister rats were subjected to either a weight drop TBI, and intraperitoneally injected or not with labetalol, or a sham procedure (18 rats per group). After 3, 6, or 12h (6 rats per subgroup), intestinal permeability to 4.4 kDa FITC-Dextran and plasma epinephrine levels were measured as was intestinal tight junction protein ZO-1 expression at 12h. Terminal ileum was harvested to measure levels of intestinal tumor necrosis factor (TNF)-α and to evaluate histopathology. In TBI group vs. sham group, intestinal permeability (P<0.01) was significantly higher at all time-points, and intestinal ZO-1 expression was lower at 12h. In TBI with vs. without labetalol group, 1) intestinal permeability was significantly lower at 6 and 12h (94.31±7.64 vs. 102.16±6.40 μg/mL; 110.21±7.52 vs. 118.95±7.11 μg/mL, respectively); 2) levels of plasma epinephrine and intestinal TNF-α were significantly lower at 3, 6 and 12h; and 3) intestinal ZO-1 expression was higher at 3, 6 and 12h (p=0.018). Histopathological evaluation showed that labetalol use preserved intestinal architecture throughout. In a rat model of TBI, labetalol reduced TBI-induced sympathetic hyperactivity, and prevented histopathological intestinal injury accompanied by changes in gut permeability and gut TNF-α expression.

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.

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, P0.8 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.