The aim of study was to discuss the correlation and regulatory mechanism of HIF-1 and miR-191 expression in pancreatic tumor. The association between the miR-191 and the clinicopathologic characteristics and the prognosis of pancreatic cancer was further explored. After hypoxic cultured for 6 and 12 h, qRT-PCR and Western blot were practiced to analyze the miR-191 and HIF-1 expression of MIA PaCa-2 and Aspac1 cells. We regulated the HIF-1 expression via plasmid and siRNA transfection to observe the alteration of HIF-1 and miR-191 expression. ChIP sequencing identified the binding sites of HIF-1 and miR-191. Dual luciferase assays were practiced to verify the binding sites. Immunohistochemical staining was practiced to analyze the expression of HIF-1, while qRT-PCR were done for investigating miR-191 in tumor tissues. Then, the association between the expression of them and the clinicopathologic characteristics and prognosis of pancreatic cancer were analyzed. After hypoxic cultured 12 h, the expression of HIF-1 protein, HIF-1mRNA and miR-191 of MIA PaCa-2 and AsPC-1 cells increased significantly (P < 0.05). After HIF-1 overexpressing plasmid transfected to the MIA PaCa-2 and AsPC-1 cells for 48 h, the expression of HIF-1 protein, HIF-1mRNA, and miR-191 upregulated significantly (P < 0.05). While after transfected the MIA PaCa-2 cells by HIF-1 siRNA, the significant decreasing of HIF-1 protein, HIF-1mRNA, and miR-191 expression were observed (P < 0.05). ChIP sequencing showed the protein synthesis of HIF-1 increased in hypoxia situation. Only the HRE5 (-1,169 bp, ChIP4) were significantly brighter in hypoxia in comparing with normoxic cells. In dual luciferase assays, after pGL3-miR-191 and HIF-1 overexpressing plasmid co-transfect the MIAPaCa-2 cells for 48 h, its relative expression of bioluminescence was higher than those co-transfected by mutant miR-191 vectors and HIF-1 overexpressing plasmid or by pGL3-miR-191 and HIF-1 empty plasmid. The expression of miR-191 closely associated with the tumor size, pTNM stage, lymph node metastasis, and perineural invasion (P < 0.05). Patients with higher expression of miR-191 were a risk factor for prognosis of pancreatic cancers. Expression of HIF-1 in pancreatic cancer cells increased under the condition of chronic hypoxia, which may bind to HRE2 in 5'flanking region of miR-191 and initiate transcription of miR-191. Expression of miR-191 was significantly higher in pancreatic tumor tissues. The expression of miR-191 closely associated with the tumor size, pTNM stage, lymph node metastasis and perineural invasion and poor prognosis of pancreatic cancer.

MicroRNA-212 (miR-212) is dysregulated in numerous tissues and cancer types and serves a role in the progression of human cancer. However, the function and mechanism of miR-212 in the development of pancreatic ductal adenocarcinoma (PDAC) remain unknown, particularly in a hypoxic microenvironment. In the present study, miR-212 expression was observed to be significantly upregulated in PDAC tissues compared with normal tissues. Clinical data analysis indicated that miR-212 was positively associated with a large tumor size, Tumor-Node-Metastasis stage, lymph node metastasis and vessel invasion, and influenced the overall survival time. Notably, there was a positive association between the expression of hypoxia-inducible factor-1α (HIF-1α) and miR-212 in vivo and in vitro in hypoxic conditions. Mechanistically, HIF-1α bound directly to a hypoxia response element in the miR-212 promoter region and activated miR-212 expression in PDAC cells. Collectively, these results demonstrated that HIF-1α positively regulated miR-212 expression and resulted in PDAC progression.

This review compares the effects of peripheral dexamethasone and dexmedetomidine on postoperative analgesia. We included six randomized controlled trials (354 patients) through a systematic literature search. We found that analgesia duration was comparable between dexamethasone and dexmedetomidine (58.59 min, 95% CI (confidence interval), −  66.13, 183.31 min) with extreme heterogeneity. Secondary outcome was also compared and no significant difference was observed in sensory block onset and duration and motor block duration and also for postoperative nausea and vomiting. It is noteworthy that dexamethasone reduced analgesic consumption (fentanyl) by 29.12 mcg compared with dexmedetomidine. We performed subgroup analyses and found no significant difference between the following: (1) lidocaine vs ropivacaine (P = 0.28), (2) nerve block vs nerve block + general anesthesia (P = 0.47), and (3) upper limb surgery vs thoracoscopic pneumonectomy (P = 0.27). We applied trial sequential analysis to assess the risks of type I and II errors and concluded that the meta-analysis was insufficiently powered to answer the clinical question, and further analysis is needed to establish which adjuvant is better. In conclusion, we believe that existing research indicates that dexamethasone and dexmedetomidine have equivalent analgesic effects in peripheral nerve blocks.

The aims of the present study were to clarify the prognostic value of peripheral blood variables in patients with pancreatic ductal adenocarcinoma (PDAC), including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR), and to determine the association between these variables and S100 calcium-binding protein A4 (S100A4) expression in tumor tissue, which is another prognostic factor for PDAC. Patients with PDAC were recruited at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China) between December 2008 and December 2014. A retrospective analysis was performed based on the recorded pre-treatment hematological parameters and clinical data. The prognostic value of NLR, PLR and LMR was examined. The association between these variables and S100A4 tissue expression was analyzed. Descriptive statistics and χ2 analyses were used in the present study. The median overall survival (OS) time of patients with PDAC was 9 months (range, 1–32 months). Univariate analysis revealed that NLR, LMR, carbohydrate antigen 19-9, surgery, chemotherapy, stage at diagnosis, tumor grade and age significantly affected OS. Although PLR exhibited no significant effects on OS, NLR and LMR were independent prognostic factors according to the multivariate analysis. Unpaired Student's t-test revealed differences between S100A4 expression and NLR, PLR and LMR. The results of the present study indicated that low NLR and high LMR were associated with a favorable prognosis in patients with PDAC. As a simply obtained and widely available index at diagnosis, NLR and LMR may become a novel predictive and classifying marker for PDAC in the clinical setting.

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