With the increasing incidence of pancreatic ductal adenocarcinoma (PDAC) in patients, it is estimated to be the second leading cause of cancer-related mortality in China. Despite the survival rate of PDAC patients is still poor. PDAC is characterized by the high complexity of stomal tissue, which includes immune cells, various growth factors, extracellular matrix and fibroblasts. TME accounts for about 15%-85% of the whole tumor component in PDAC. Emerging evidences have suggested that TME might play important roles in the tumor progress and drug-resistance of chemotherapy and a plenty of promising TME-related target molecules have been under early clinical trials. Nevertheless, there still lacks effective therapeutic treatments for improving the overall survival of PDAC patients. At present, progress has been made in the research of targeted therapies combined with matrix depletion, drug delivery and immunoregulation in PDACs. Thus, this review will focus on the latest progress in the fields of TME components including immune cells, growth factors, extracellular matrix and fibroblasts, as well as the therapeutic targets produced by these TME components.

Objective To detect miR-34a expression in pancreatic cancer tissue and BxPC3 cells,determine the target genes and analyze the correlation of the expression of miR-34a and its target genes with clinicopathological parameters in pancreatic cancer as well as the influence on the proliferation and migration abilities of BxPC3 cells.Methods c-MET 3'UTR dual-luciferase reporter vectors cloned wild-type and mutant c-MET 3'UTR to validate that c-MET was the target gene of miR-34a,respectively.Liposome was used to establish miR-34a overexpressing BxPC3 cells (miR-34a group) and c-MET downregulating BxPC3 cells (c-METsi group).qPCR,Western blot and IHC was used to measure the mRNA and protein expression of miR-34a and c-MET.The cell viability and migration ability of miR-34a overexpressing BxPC3 cells was assessed by CCK-8 and transwell assay.Results In miR-34a group,the 3'UTR of wild-type c-MET was obviously downregulated compared with that of control group [(65.00 ± 4.04) ％ vs 100％,P =0.00131)],but no statistical difference was found between two mutant groups,which proved that c MET was the target gene of miR-34a.The expression level of miR-34a was significantly down-regulated in cancer tissues compared to adjacent normal tissues by an average fold change of 1.92,and the difference was statistically significant (P =0.003).Compared with control group,c-MET mRNA and protein expression was obviously decreased in miR-34a group (0.045 ±0.003 vs 0.085 ±0.001,0.400±0.058 vs 1.133 ±0.120).After 4-day culture,the cell viability of miR-34a group and c-METsi group was obviously decreased (P =0.0012;P =0.0001),the transmembrane cells was also obviously decreased(231 ± 12 vs 351 ± 16,P =0.0039;259 ±7 vs 351 ± 16,P=0.0066),and the differences were statistically significant.miR-34a overexpression and c-MET positively expression in pancreatic cancer were significantly associated with TNM stage and tumor differentiation (P ＜0.001),and the expression of c-MET negatively correlated with miR-34a (P ＜0.001).Conclusions miR-34a was lowly expressed in pancreatic cancer,and its tumor suppressive activity may be partly through inhibiting c-MET.Overexpressing miR-34a or inhibiting c-MET may be new targets for the diagnosis and treatment of pancreatic cancer.

Objective:To investigate the expression of tripartite motif 14 (TRIM14) in human pancreatic cancer and analyze its relationship with clinicopathological features and prognosis, and further explore its functional mechanism in the development and progression of pancreatic cancer.Methods:176 pairs of pancreatic cancer tissues and corresponding adjacent tissues resected by surgery in Changhai Hospital affiliated with Navy Medical University from January 2016 to December 2018 were collected. The protein expression of TRIM14 in pancreatic cancer and adjacent normal tissue was detected by immunohistochemical staining. TRIM14 and phosphorylated p65 expression in pancreatic cancer was measured by western blotting. NF-κB targeting gene Bcl-xl, CCND1, VEGF-C mRNA was tested by real time quantitative PCR. The correlation between TRIM14 expression and clinicopathological characteristics was analyzed. The relationship between TRIM14 expression and tumor-free survival and overall survival of pancreatic cancer patients was evaluated by univariate and multivariate Cox regression model. The internal relationship between TRIM14 expression and the activation of NF-κB signaling pathway was analyzed.Results:The positive TRIM14 expression rate in pancreatic cancer was obviously higher than that in adjacent normal tissue [86.93%(153/176) vs 27.27%(48/176)], and the difference was statistically significant ( P<0.05). The expression level of TRIM14 was correlated with the clinical stage, lymph node metastasis and invasion depth of pancreatic cancer ( P=0.000, 0.000, 0.021), but not obviously with gender, age, differentiation degree and distant metastasis. Cox regression analysis showed that the expression level of TRIM14 was the independent risk factor for tumor-free survival ( RR=1.706, 95% CI 1.237-2.429, P=0.029) and overall survival ( RR=1.806, 95% CI 1.984-2.831, P=0.029). The expression level of TRIM14 was tightly associated with the phosphorylation level of p65 ( R=0.86, P<0.01), and the mRNA expression of Bcl-xl, CCND1 and VEGF-C was highly correlated with TRIM14 expression ( R=0.85-0.92, P<0.01). Conclusions:TRIM14 was highly expressed in pancreatic cancer tissues and was an independent risk factor for prognosis of pancreatic cancer patients. TRIM14 participates in the development and malignant progression of pancreatic cancer potentially via activating NF-κB pathway.

Objective To investigate the clinical efficacy of pancreaticoduodenectomy using artery first approach and prior portal vein (PV)-superior mesenteric vein (SMV) shunting for complicated pancreatic head tumors.Methods The retrospective cohort study was conducted.The clinicopathological data of 91 patients with pancreatic head cancer who were admitted to the Changhai Hospital of Navy Medical University from February 2011 to December 2016 were collected.Among 91 patients undergoing pancreaticoduodenectomy combined with vascular resection and reconstruction,27 using artery first approach and PV-SMV shunting and reconstruction were allocated into the PD-PVR group,23 using conventional approach were allocated into the PD-CVR group,and 41 receiving pancreaticoduodenectomy with vascular resection were allocated into the PD-SVR group.Observation indicators:(1) comparison of intra-and post-operative situations among groups;(2) comparison of postoperative pathological results among groups;(3) comparison of postoperative survival among groups.Follow-up using outpatient examination and telephone interview was performed to detect postoperative survival up to December 2017.Comparisons among groups of count data were done by the chi-square test or Fisher exact probability.Measurement data with normal distribution were represented as x±s,comparisons among groups were analyzed using the ANOVA,and pairwise comparison was done using the LSD method.Measurement data with skewed distribution were described as M(Q),comparison among groups was analyzed using the Kurskal-Wallis rank sum test,and pairwise comparison was done using the paired comparison with adjusted P value.Ordinal data were compared using the nonparametric test.The survival rate and curve were respectively calculated and drawn by the Kaplan-Meier method,and Log-rank test was used for survival analysis.Results (1) Comparison of intra-and post-operative situations among groups:operation time,time of hepatic inflow occlusion,volume of intraoperative blood loss,cases with intraoperative blood transfusion,length of PV or SMV removal,cases with vascular grafts,grading 1,2,3,4 and 5 of Clavien-Dindo classification of postoperative complications and duration of hospital stay were respectively (274±36)minutes,(22±7)minutes,1 661 mL (110 mL,3 800 mL),20,(5.6±1.4)cm,6,11,1,1,1,1,(20±7)days in the PD-PVR group and (281±41)minutes,(27±5)minutes,1 888 mL (176 mL,4 162 mL),18,(5.4±1.5) cm,3,1,8,2,0,0,(21±7)days in the PD-CVR group and (201± 36)minutes,(16±6)minutes,1052 mL (74 mL,3 926 mL),17,(3.2±2.0) cm,5,15,2,3,1,1,(13± 6)days in the PD-SVR group,with statistically significant differences among groups (F=37.060,34.530,x2=13.771,14.015,F=32.260,x2 =39.309,F =19.880,P＜0.05).Patients with postoperative complications were improved by symptomatic and supporting treatment.(2) Comparison of postoperative pathological results among groups:mnaximum tumour dimension was respectively (3.6± 1.3) cm,(4.0± 1.3) cm and (2.6± 1.3) cm in the PD-PVR,PD-CVR and PD-SVR groups,with a statistically significant difference among groups (F =7.845,P＜0.05).Cases with high-differentiated,moderate-differentiated and low-differentiated tumors of tumor differentiation,staging Ⅱ A and Ⅱ B of tumor staging,nerve invasion,positive lymph node,positive resection margins in neck of pancreas,bile duct and SMV were respectively 0,13,14,17,10,17,21,0,0,0 in the PD-PVR group and 1,12,10,10,13,15,19,1,0,0 in the PD-CVR group and 1,29,11,17,24,30,29,2,1,1 in the PD-SVR group,with no statistically significant difference among groups (x2 =4.122,3.306,0.902,1.214,P＞0.05).(3) Comparisons of postoperative survival among groups:of 91 patients,52 were followed up for 3.0-69.3 months,with a median time of 18.0 months and follow-up rate of 57.1％ (52/91),including 16 in the PD-PVR group and 14 in the PD-CVR group and 22 in the PD-SVR group.The median survival time,1-,2-and 3-year overall survival rates in 52 patients were respectively 16.6 months,63.5％,35.7％ and 26.8％.The survival time in the PD-PVR,PD-CVR and PD-SVR groups were respectively 12.3 months (3.9-69.3 months),15.0 months (3.0-63.3 months) and 20.0 months (6.0-65.2 months),with a statistically significant difference in survival among groups (x2=6.201,P＜0.05),and between PD-PVR and PD-SVR groups (x2 =4.412,P＜0.05).There was no statistically significant difference in survival between PD-PVR and PD-CVR groups (x2 =0.001,P＞0.05).Conclusion Pancreaticoduodenectomy using artery first approach and PV-SMV shunting and reconstruction for complicated pancreatic head tumors can reduce the time of hepatic inflow occlusion,it also contributes to the risk control of surgery for complicated pancreatic tumors,increases surgical safety and improves patients' prognosis.

Objective:To analyze the risk factors of clinically significant bleeding in patients with severe acute pancreatitis (SAP).Methods:The clinical data of SAP patients who were managed at Changhai Hospital affiliated to Naval Medical University from January 1, 2014 to October 31, 2022 were retrospectively analyzed. Twenty-nine SAP patients with clinically significant bleeding were classified to form the bleeding group. There were 23 males and 6 females, aged (56.25±14.01) years old. Another 116 SAP patients with similar general data but with no clinically significant bleeding during the same hospitalization period were included to form the non-bleeding group based on a ratio of 1∶4. There were 94 males and 22 females, aged (56.14±13.96) years old in this non-bleeding group. The general data, modified CT severity index (MCTSI), bedside index for severity of acute pancreatitis (BISAP) and other clinical data of the two groups were collected to determine the risk factors of bleeding in SAP patients.Results:Of the 29 patients with bleeding, 6 had gastrointestinal bleeding, 14 had intra-abdominal bleeding, and 9 had mixed bleeding sites, 15 were cured and discharged, and 14 died. All the 29 SAP patients with bleeding received treatment using drugs. In addition, 8 patients underwent successful hemostasis using digital subtraction angiography, 3 underwent successful endoscopic hemostasis, 2 underwent successful surgical hemostasis, and 2 underwent successful conservative drug hemostasis. Multivariate logistic regression analysis showed that SAP patients with higher MCTSI ( OR=1.824, 95% CI: 1.187-2.802), longer prothrombin time (PT) ( OR=3.431, 95% CI: 1.470-8.007) and higher BISAP ( OR=2.286, 95% CI: 1.054-4.957) had an increased risk of bleeding (all P<0.05). Conclusion:The prognosis of SAP patients was compromised with bleeding. High MCTSI, prolonged PT, and high BISAP were independent risk factors for bleeding in SAP patients.