Distribution characteristics and clinical significance of infiltrating T cells in the tumor microenvironment of pancreatic cancer.

Tumor-infiltrating lymphocytes (TILs) are important components of the tumor microenvironment (TME). However, the distribution characteristics of TILs and their significance in pancreatic cancer (PC) remain largely unexplored. The levels of TILs, including the total number of T cells, cluster of differentiation (CD)4+ T cells, CD8+ cytotoxic T lymphocytes (CTLs), regulatory T-cells (Tregs), programmed cell death protein 1+ T cells and programmed cell death ligand 1 (PD-L1)+ T cells, in the TME of patients with PC were detected using multiple fluorescence immunohistochemistry. The associations between the number of TILs and the clinicopathological characteristics were investigated using χ2 tests. In addition, Kaplan-Meier survival and Cox regression analyses were used to assess the prognostic value of these TIL types. Compared with paracancerous tissues, in PC tissues, the proportions of total T cells, CD4+ T cells and CD8+ CTLs were markedly decreased, while those of Tregs and PD-L1+ T cells were significantly increased. The levels of CD4+ T cell and CD8+ CTL infiltrates were inversely associated with tumor differentiation. Higher infiltrates of Tregs and PD-L1+ T cells were closely associated with advanced N and TNM stages. It is important to note that the infiltrates of total T cells, CD4+ T cells, Tregs and PD-L1+ T cells in the TME were independent risk factors for the prognosis of PC. PC was characterized by an immunosuppressive TME with a decrease in the number of CD4+ T cells and CD8+ CTLs, and an increase in the number of Tregs and PD-L1+ T cells. Overall, the number of total T cells, CD4+ T cells, Tregs and PD-L1+ T cells in the TME was a potential predictive marker for the prognosis of PC.

Micro-Shear Bands and Their Enhancement on High Temperature Strength of Mg-Gd-Y-Zr Alloy.

When Mg-Gd-Y-Zr alloy is cold forged, a large number of nano-micro shear bands are formed inside the grains. It is observed that micro-shear bands hinder the sliding of dislocations, resulting in an increase in tensile strength at elevated temperatures. The subsequent aging treatment further strengthens the alloy. Compared with unforged aged alloys, aged samples with pre-generated micro-shear bands exhibit higher strength at room temperature to 250 °C, but exhibit similar properties at higher temperatures. Microstructure characterization and fracture behavior analysis indicate that the transformation of deformation mode from dislocation sliding to grain boundary activity is mainly due to the change of mechanical properties with temperature. In addition, the alloy precipitates with the aid of dislocations during tension, and exhibits higher strength at 200 °C than that at room temperature.

Deformation Mechanism, Microstructure, and Mechanical Properties Evolution of Mg-Gd-Y-Zr Alloy during Cold Torsion.

Mg-Gd-Y-Zr alloy was subjected to torsion of various strain levels at room temperature. Obvious traces of basal slip were observed in the twisted alloy. Dislocations of were also observed, but there were no signs of significant sliding. Even in the sample whose equivalent strain became 0.294, 101¯0 twinning and 101¯2 twinning were rarely seen. The deformation mode with predominant basal dislocations and subordinate dislocations resulted in a modified Y fiber texture with a basal pole slightly dispersed at about 70° from the twist axis. Mechanical tests revealed that the tensile strength and compressive strengths increased simultaneously after twisting.

Short- and long-term outcomes of 486 consecutive laparoscopic splenectomy in a single institution.

ABSTRACT: Since its introduction in 1991, laparoscopic splenectomy (LS) has become the gold standard in elective spleen surgery in many centres. However, there still lack the report of long-term outcomes of LS with the large-scale cases. The aim of the present study was to analyze the short- and long-term outcomes of LS in a single institution over 16 years, and to compare the perioperative outcomes of totally laparoscopic splenectomy (TLS) and hand-assisted laparoscopic splenectomy (HALS) for splenomegaly.Between November 2002 and December 2018, 486 consecutive patients undergoing elective LS were enrolled in this study, including 222 TLS and 264 HALS. The intraoperative, postoperative, and follow-up data were retrospectively analyzed.The 5 most common indications were hypersplenism (71.0%), immune thrombocytopenia (14.8%), splenic benign tumor (4.5%), splenic cyst (2.9%), and splenic malignant tumor (2.9%). The mean operative time, intraoperative blood loss, and length of stay were 149.4 ±â€Š63.3 minutes, 230.1 ±â€Š225.1 mL, and 6.7 ±â€Š3.2 days, respectively. The morbidity, mortality, reoperation, and conversion rate were 23.0%, 0, 0.4%, and 1.9%, respectively. Portal vein system thrombosis (PVST) was the most frequent complication with an incidence of 19.8%. The incidence of PVST in HALS was higher than that in TLS (23.9% vs 14.9%, P = .013). Compared with TLS, HALS had a shorter operative time (P = .000), lower intraoperative blood loss (P = .000), comparable conversion rate (P = .271), and morbidity (P = .922) for splenomegaly > 17.0 cm. During the follow-up period, the overall respond rate for immune thrombocytopenia was 77.8%, and the esophagogastric variceal bleeding rate was 6.9% in 320 patients with hypersplenism secondary to hepatic cirrhosis.LS is a safe, feasible, and effective procedure with satisfactory short- and long-term outcomes. HALS is a reasonable technique in patients with massive spleens.

MicroRNA-148a-3p suppresses epithelial-to-mesenchymal transition and stemness properties via Wnt1-mediated Wnt/ß-catenin pathway in pancreatic cancer.

Although miR-148a-3p has been reported to function as a tumour suppressor in various cancers, the molecular mechanism of miR-148a-3p in regulating epithelial-to-mesenchymal transition (EMT) and stemness properties of pancreatic cancer (PC) cells remains to be elucidated. In the present study, we demonstrated that miR-148a-3p expression was remarkably down-regulated in PC tissues and cell lines. Moreover, low expression of miR-148a-3p was associated with poorer overall survival (OS) in patients with PC. In vitro, gain-of-function and loss-of-function experiments showed that miR-148a-3p suppressed EMT and stemness properties as well as the proliferation, migration and invasion of PC cells. A dual-luciferase reporter assay demonstrated that Wnt1 was a direct target of miR-148a-3p, and its expression was inversely associated with miR-148a-3p in PC tissues. Furthermore, miR-148a-3p suppressed the Wnt/ß-catenin pathway via down-regulation of Wnt1. The effects of ectopic miR-148a-3p were rescued by Wnt1 overexpression. These biological functions of miR-148a-3p in PC were also confirmed in a nude mouse xenograft model. Taken together, these findings suggest that miR-148a-3p suppresses PC cell proliferation, invasion, EMT and stemness properties via inhibiting Wnt1-mediated Wnt/ß-catenin pathway and could be a potential prognostic biomarker as well as a therapeutic target in PC.

Enhanced Mechanical and Corrosion Performance by Forming Micro Shear Bands in Cold Forged Mg-Gd-Y-Zr Alloy.

Forging at room temperature was applied on the per-extruded Mg-Gd-Y-Zr alloy to investigate the effect of cold forging on the microstructure, mechanical properties and corrosion resistance of the alloy. Abundant micro shear bands with misorientations of 2-15° were generated in the as forged alloys. Tremendous enhancement in tensile yield strength was achieved after forging. With a quantitative investigation, micro band boundaries were considered to provide a great contribution to the reinforcement. The ultrafine structure resulting from the formation of micro shear bands led to increased corrosion resistance of the alloy.

Laparoscopic common bile duct exploration for elderly patients with choledocholithiasis: a systematic review and meta-analysis.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) has been becoming more and more popular in patients with symptomatic choledocholithiasis. However, the safety and effectiveness of LCBDE in elderly patients with choledocholithiasis is still uncertain. This meta-analysis is aimed to appraise the safety and feasibility of LCBDE for elderly patients with choledocholithiasis. MATERIALS AND METHODS: Studies comparing elderly patients and younger patients who underwent LCBDE for common bile duct stone were reviewed and collected from the PubMed, Medline, EMBASE, and Cochrane Library. Primary outcomes were stone clearance rate, overall complication rate, and mortality rate. Secondary outcomes were operative time, conversion rate, pulmonary complication, bile leakage, reoperation, residual stone rate, and recurrent stone rate. RESULTS: Nine studies, including two prospective studies and seven retrospective studies, met the inclusion criteria. There were 2004 patients in this meta-analysis, including 693 elderly patients and 1311 younger patients. There was no statistically significant difference between elderly patients and younger patients regarding stone clearance rate (OR 0.73; 95% CI 0.42-1.26; p = 0.25), overall complication rate (OR 1.31; 95% CI 0.94-1.82; p = 0.12), and mortality rate (OR 2.80; 95% CI 0.82-9.53; p = 0.10). Similarly, the operative time, conversion rate, bile leakage, reoperation, residual stone rate, and recurrent stone rate showed no significant difference between two groups (p > 0.05). While elderly patients showed high risk for pulmonary complication (OR 4.41; 95% CI 1.78-10.93; p = 0.001) compared with younger patients. CONCLUSION: Although there is associated with higher pulmonary complication, LCBDE is still considered as a safe and effective treatment for elderly patients with choledocholithiasis.