LINC02086 inhibits ferroptosis and promotes malignant phenotypes of pancreatic cancer via miR-342-3p/CA9 axis.

Long noncoding RNAs (lncRNAs) play important roles in modulating the tumorigenesis and progression of malignant tumors. LINC02086 is a newly identified oncogene associated with tumorigenesis, but its role in pancreatic cancer (PC) has not been fully elucidated. In this study we examined the expression levels of LINC02086, miR-342-3p, and CA9 in PC. The relationship of ferroptosis with these factors was analyzed by detecting the expression levels of Fe2+, reactive oxygen species (ROS), and ferroptosis marker proteins. The expression of these genes was altered to observe their effects on cell proliferation, migration, and invasion ability. Bioinformatics was used to predict target genes, and the binding relationship was verified luciferase reporter assay. Finally, the function of LINC02086 was evaluated in vivo. The findings suggest that LINC02086 is highly expressed in PC tissues and cell lines and is correlated with a poor prognosis. In vitro experiments demonstrated that LINC02086 knockdown promoted ferroptosis in PC cells to suppress their malignant phenotype. LINC02086 acts as a competitive endogenous RNA that adsorbed miR-342-3p. miR-342-3p hinders the malignant progression of PC by promoting ferroptosis. In addition, miR-342-3p targets CA9 and affects its function. Further mechanistic studies revealed that LINC02086 inhibits ferroptosis and promotes PC progression by acting as a sponge for miR-342-3p to upregulate CA9 expression. In vivo experiments further confirmed this mechanism. Taken together, LINC02086 upregulates CA9 expression by competitively binding with miR-342-3p, thereby inhibiting ferroptosis in PC cells and promoting their malignant phenotype. The results of our study provide new insights into how LINC02086 contributes to the progression of PC.

Clinical significance of tumor suppressor genes methylation in circulating tumor DNA of patients with pancreatic cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has emerged as a potential diagnostic and prognostic biomarker in various tumors. However, the role of tumor suppressor genes (TSGs) methylation in ctDNA of patients with pancreatic cancer (PC) remains largely unclear. METHODS: Patients with PC (n = 43), pancreatic benign diseases (n = 39), and healthy controls (n = 20) were enrolled in the study. Quantitative analysis of methylation pattern of five candidate TSGs including NPTX2, RASSF1A, EYA2, p16, and ppENK in ctDNA was performed by next generation sequencing (NGS). The diagnostic performances of these 5-TSGs methylation were assessed by the operating characteristic (ROC) curve and clinicopathological features correlation analysis. Meanwhile, the changes in methylation levels of these 5-TSGs on the 7th postoperative day were evaluated in 23 PC patients who underwent radical resection. RESULTS: The methylation levels of RASSF1A, EYA2, ppENK and p16 genes in patients with PC were significantly higher than those in healthy controls. EYA2, p16 and ppENK genes showed significantly hypermethylation in PC than those in pancreatic benign diseases. NPTX2, RASSF1A, EYA2, p16 and ppENK genes showed significantly hypermethylation in pancreatic benign diseases than those in healthy controls (P < 0.05). The methylation levels of these 5 candidate TSGs were not correlated with the tumor size, nerve invasion, lymph node metastasis and TNM stage of PC. The AUC of these biomarkers for diagnosis of PC ranged from 0.65 to 0.96. The AUC values of these methylated genes and CpG sites for differentiating malignant and benign pancreatic diseases were ranging from 0.68 to 0.92. Combined the hypermethylated genes improved the detective ability of PC than single gene. The methylation levels of NPTX2, EYA2 and ppENK genes were significantly decreased after radical resection of PC. CONCLUSION: Quantitative analysis of methylation pattern of NPTX2, RASSF1A, EYA2, p16 and ppENK in ctDNA by NGS could be a valuable non-invasive tool for detection and monitoring of PC.

Biliary Tract Exploration After Laparoscopic Left-sided Hepatectomy: A Comparative Study of Left Hepatic Duct Orifice Versus Common Bile Duct Approach.

BACKGROUND: Laparoscopic left-sided hepatectomy (LLH) and additional biliary tract exploration are effective methods to treat left-sided hepatolithiasis (LSH) combined with extrahepatic bile duct stones. Although biliary tract exploration through common bile duct (CBD) incision has been widely accepted, the safety and effectiveness of the left hepatic duct (LHD) orifice approach after LLH is still in debate. METHODS: One hundred and forty-four patients with LSH who underwent LLH and biliary tract exploration in our institution from April 2014 to September 2021 were enrolled in the retrospectively study. They were divided into 3 groups: LHD group (n=67), CBD/T-tube group (n=58), and CBD/PC group (n=19). Patients' demographic characteristics, intraoperative, and postoperative outcomes were retrospectively analyzed. RESULTS: LHD group exhibited a shorter operative time (202.8±42.2 vs. 232.7±47.5 min, P =0.000), time to first bowel movement (2.3±0.5 vs. 2.9±0.7 d, P =0.000) and postoperative hospital stay (7.5±2.1 vs. 9.8±5.2 d, P =0.001) compared with the CBD/T-tube group. The lithotomy time in the LHD group was significantly longer than that in the CBD/T-tube group (33.6±7.3 vs. 29.0±6.3 min, P =0.000) and CBD/PC group (33.6±7.3 vs. 28.7±3.7, P =0.006). Intraoperative blood loss, blood transfusion rate, initial stone clearance rate, and stone recurrence rate all had no significant differences between the 3 groups (all P >0.05). LHD group showed less rate of electrolyte imbalance than that of the CBD/T-tube group (3.0% vs. 19.0%, P =0.004) but it was equivalent to the CBD/PC group ( P >0.05). The type of biliary tract exploration (odds ratio: 5.43, 95% confidence interval: 0.04-0.95, P =0.032) as independent predictors of electrolyte imbalance. No reoperation and mortality occurred in the 3 groups. The conversion rate was comparable among 3 groups (1.5% vs. 1.7% vs. 0, all P >0.05). No significant difference in stone recurrence rate was seen (1.5% vs. 3.4% vs. 0, all P >0.05). CONCLUSION: Biliary tract exploration through LHD orifice after LLH is a safe and effective treatment for selected patients with LSH, with an advantage over the T-tube drainage in the field of operative time, the incidence of electrolyte imbalance, recovery of gastrointestinal function, and postoperative hospital stay.

Prediction of Prognosis and Molecular Mechanism of Ferroptosis in Hepatocellular Carcinoma Based on Bioinformatics Methods.

Background: As an iron-dependent type of programmed cell death, ferroptosis plays an important role in the pathogenesis and progression of hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) have been linked to the prognosis of patients with HCC in a number of studies. Nevertheless, the predictive value of lncRNAs (FRLs) associated with ferroptosis in HCC has not been fully elucidated. Methods: Download RNA sequencing data and clinical profiles of HCC patients from The Cancer Genome Atlas (TCGA) database. The FRLs associated with prognosis were determined by Pearson's correlation analysis. After that, prognostic signature for FRLs was established using Cox and LASSO regression analyses. Meanwhile, survival analysis, correlation analysis of clinicopathological features, Cox regression, receiver operating characteristic (ROC) curve, and nomogram were used to analyze the FRL signature's predictive capacity. The relationship between signature risk score, immune cell infiltration, and chemotherapy drug sensitivity is further studied. Results: In total, 93 FRLs were found to be of prognostic value in patients with HCC. A five-FRL signature comprising AC015908.3, LINC01138, AC009283.1, Z83851.1, and LUCAT1 was created in order to enhance the prognosis prediction with HCC patients. The signature demonstrated a good predictive potency, according to the Kaplan-Meier and ROC curves. The five-FRL signature was found to be a risk factor independent of various clinical factors using Cox regression and stratified survival analysis. The high-risk group was shown to be enriched in tumorigenesis and immune-related pathways according to GSEA analysis. Additionally, immune cell infiltration, immune checkpoint molecules, and half-inhibitory concentrations differed considerably between risk groups, implying that this signature could be used to evaluate the clinical efficacy of chemotherapy and immunotherapy. Conclusion: The five-FRL risk signature is helpful for assessing the prognosis of HCC patients and improving therapy options, so it can be further applied clinically.

Electric Field Improvement for High-Voltage Bushings.

Resin-impregnated paper (RIP) bushing has gained significant interest due to its extended application in Extra High Voltage (EHV) and Ultra High Voltage (UHV) electricity transmission systems. However, the design criterion of its overall structure, the geometry parameters of the condenser layers, and stress release devices, etc., are still not fully understood. This article proposes a unique electric field optimization technique to integrate both the analytical and the numerical methods. The charge simulation method (CSM) is employed to create the overall equipotential surface, within which the finite element analysis (FEA) is adapted to study the localized field enhancement effects, taking into consideration the multi-physics coupled fields. A case study is performed on an actual UHV bushing. The results are compared to the traditional methods, to demonstrate the benefit of the hybrid method.

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.