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For rs4961280, none of the meta-analyses yielded statistically significant results. We conclude that genetic variants rs636832 and rs595961 located within AGO1 may represent susceptibility variants for specific types of cancer, while the association with malignant diseases was not determined for AGO2 variant rs4961280. To date, most studies investigating the immune tumor microenvironment of non-small cell lung cancers (NSCLC) only consider a small number of immune cell subsets or do not reflect the distribution of these cells between different tumor compartments as they were performed on tissue microarrays (TMA). To address this, we analyzed the immune infiltrate in surgically resected NSCLCs, focusing on potential spatial heterogeneity. We evaluated 45 NSCLCs based on whole-slide sections using immunohistochemistry with eleven different antibodies (CD3, CD4, CD8, CD20, CD68, Gata3, FOXP3, T-bet, kappa, lambda, PD-L1). While most markers were relatively evenly distributed among different tumor compartments as well as within the same tumor compartment, some immune cell subsets showed a considerable variance. Notably, the immune infiltrate at the tumor invasion front was dominated by B cells. Concerning markers for T cell differentiation, FoxP3 (Th2) was predominantly expressed in stromal lymphocytes, while T-bet (Th1) was most commonly expressed in intraepithelial immune cells. Although most immune cell subtypes showed a heterogenous distribution within in the intraepithelial compartment, the results from a simulated TMA and core biopsy were mostly in line with the results from whole slide evaluation. Regarding disease specific survival, there were no clear correlations. Sodiumorthovanadate Interestingly, patients with intraepithelial T-bet positive lymphocytes had a significantly better outcome (p = 0.039), however, this difference was not preserved in multivariate analysis. In conclusion, our study shows that the immune tumor microenvironment of NSCLCs is complex and partially heterogenous, especially concerning markers for T cell differentiation. AIMS To investigate the role of IL-28B and CK-18 M30 in the diagnosis of non-alcoholic steatohepatitis (NASH) in rats. METHODS The rat NASH model was constructed by high-fat diet feeding and confirmed by liver tissue pathology analysis. The CK-18 M30, IL-28B, liver function and blood lipid were detected. The pathology of liver tissues was observed by H&E staining. The ROC curves of liver pathological scores, IL-28B, and CK-18 M30 were plotted and the sensitivity/specificity of each index was calculated. RESULTS The liver tissue pathology at the end of the 12th week met NASH diagnostic criteria. The liver pathological scores of NASH model were higher than those of the control group (P less then 0.05). Compared with the control group, the body weight of rats in the NASH group was lower (P less then 0.05) and the liver index was higher (P less then 0.05). Moreover, the serum levels of alanine aminotransferase, triglyceride, low-density lipoprotein, total cholesterol and CK-18 M30 in the NASH group were higher (P less then 0.05) and positively correlated with liver pathological scores (P less then 0.05), but IL-28B in serum and liver tissue was lower (P less then 0.05) and negatively correlated with liver pathological scores (P less then 0.05). According to the ROC curves, the sensitivity/specificity of each index was shown as following liver pathological scores (1.000/1.000), IL-28B of liver tissue (1.000/0.857), serum CK-18 M30 plus IL-28B (0.857/1.000), serum IL-28B (0.857/0.857) and serum CK-18 M30 (1.000/0.857). CONCLUSIONS IL-28B level is related to the pathological changes of livers in SD rats during the development of NASH. The combination of serum CK-18 M30 level and serum IL-28B level may be a promising non-invasive detection method for the diagnosis of NASH. AIM To describe the burden of esophageal dilatations in patients following esophageal atresia (EA) repair. METHOD A retrospective review was performed at The Royal Children's Hospital, Melbourne, of all neonates undergoing operative repair for EA over a 17-year period (1999-2015). Stricture was defined by radiological and/or intra-operative findings of narrowing at the esophageal anastomosis. Data recorded included EA type, perinatal details, operative approach, esophageal anastomosis outcome, dilatation requirement, and survival. Key endpoints were anastomotic leakage and tension, esophageal dilatation technique, dilatation frequency, fundoplication, and complications. RESULTS During the study period, 287 newborn EA patients were admitted, of which 258 underwent operative repair and survived to primary discharge. Excluding 11 patients with isolated tracheoesophageal fistula, 247 patients were included in the final analysis. Intra-operative anastomotic tension was documented in 41/247 (16.6%), anastomotic leative review. LEVEL OF EVIDENCE II. Crown All rights reserved.The pectus bar removal procedure is often considered a simple, straightforward surgery with a low incidence of complications. However, life-threatening bleeding complications have been reported requiring major measures for hemostatic control. Our objective is to share a simple maneuver that our group has systematically included in the bar removal procedure to facilitate bleeding control in case hemorrhage occurs. AIMS Randomised controlled trials have shown comparable early oncological outcomes after hypofractionated and conventionally fractionated radiotherapy in the radical treatment of prostate cancer (PCa). The effect of hypofractionation on treatment-related gastrointestinal and genitourinary toxicity remains uncertain, especially in older men and those with locally advanced PCa. MATERIALS AND METHODS A population-based study of all patients treated with radical conventionally fractionated radiotherapy (n = 9106) and hypofractionated radiotherapy (n = 3027) in all radiotherapy centres in the English National Health Service between 2014 and 2016 was carried out. We identified severe gastrointestinal and genitourinary toxicity using a validated coding framework and compared conventionally fractionated and hypofractionated radiotherapy using a competing-risks proportional hazards regression analysis. RESULTS The median age in our cohort was 72 years old and most patients had locally advanced disease (65%). There was no difference in gastrointestinal toxicity (conventionally fractionated radiotherapy 5.
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