The current data demonstrate that GABAergic mechanisms in the RVLM are responsible for the hypotension and sympathoinhibition of moxonidine.

Pancreatic neuroendocrine neoplasms (pNENs) are endocrine tumors arising in pancreas and is the most common neuroendocrine tumors. Mounting evidence indicates lncRNA H19 could be a determinant of tumor progression. However, the expression and mechanism of H19 and the relevant genes mediated by H19 in pNENs remain undefined. Microarray analysis was conducted to identify the differentially expressed lncRNAs in pNENs. H19 expression was analyzed in 39 paired pNEN tissues by qPCR. The biological role of H19 was determined by functional experiments. RNA pulldown, mass spectroscopy and RNA immunoprecipitation were performed to confirm the interaction between H19 and VGF. RNA-seq assays were performed after knockdown H19 or VGF. H19 was significantly upregulated in pNEN tissues with malignant behaviors, and the upregulation predicted poor prognosis in pNENs. In vitro and in vivo data showed that H19 overexpression promoted tumor growth and metastasis, whereas H19 knockdown led to the opposite phenotypes. H19 interacted with VGF, which was significantly upregulated in pNENs, and higher VGF expression was markedly related to poor differentiation and advanced stage. Furthermore, VGF was downregulated when H19 was knocked down, and VGF promoted cell proliferation, migration and invasion. Mechanistic investigations revealed that H19 activated PI3K/AKT/CREB signaling and promoted pNEN progression by interacting with VGF. These findings indicate that H19 is a promising prognostic factor in pNENs with malignant behaviors and functions as an oncogene via the VGF-mediated PI3K/AKT/CREB pathway. In addition, our study implies that VGF may also serve as a candidate prognostic biomarker and therapeutic target in pNENs.

Background. Pancreatic cancer is a highly malignant solid tumor with a high lethality rate, but there is a lack of clinical biomarkers that can assess patient prognosis to optimize treatment. Methods. Gene-expression datasets of pancreatic cancer tissues and normal pancreatic tissues were obtained from the GEO database, and differentially expressed genes analysis and WGCNA analysis were performed after merging and normalizing the datasets. Univariate Cox regression analysis and Lasso Cox regression analysis were used to screen the prognosis-related genes in the modules with the strongest association with pancreatic cancer and construct risk signatures. The performance of the risk signature was subsequently validated by Kaplan–Meier curves, receiver operating characteristic (ROC), and univariate and multivariate Cox analyses. Result. A three-gene risk signature containing CDKN2A, BRCA1, and UBL3 was established. Based on KM curves, ROC curves, and univariate and multivariate Cox regression analyses in the TRAIN cohort and TEST cohort, it was suggested that the three-gene risk signature had better performance in predicting overall survival. Conclusion. This study identifies a three-gene risk signature, constructs a nomogram that can be used to predict pancreatic cancer prognosis, and identifies pathways that may be associated with pancreatic cancer prognosis.

Background: Pancreatic fistula is a life-threatening complication of pancreaticoduodenectomy.Omega-like duct-to-mucosa pancreatojejunostomy is a novel technique which helps reduce the risk of fistulation. This study aimed to compare early postoperative outcomes of omega-like and conventional pancreatojejunostomy.Methods: A retrospective single-centre cohort study comparing outcomes of adult patients who underwent open pancreatoduodenectomy with conventional (CDMP) or omega-like duct-to-mucosa pancreatojejunostomy (ODMP) between 1 January 2015 and 31 December 2019. The primary outcome measure was the pancreatic fistula rate.Results: 440 patients were included in this study of whom 233 underwent CDMP and 207 ODMP. The rate of clinically relevant pancreatic fistula (grade B/C) was significantly higher after CDMP than ODMP (18.5% vs. 10.6%, P = 0.021). 153 patients in CDMP group and 99 patients in ODMP group developed one or more complications (65.7% vs. 47.8%, P = 0.004). The average hospitalization expenses were numerically decreased in ODMP group, although this was not statistically significant (120,000 ± 42,000 [Chinese Yuan] vs. 100,000 ± 40,000 [Chinese Yuan] or 18,581 ± 6503 [United States Dollar] vs. 15,484 ± 6194 [United States Dollar], P = 0.402). Conclusion: ODMP may reduce the incidence of pancreatic fistula and other early postoperative complications after pancreatoduodenectomy.