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Objective:To investigate the effects and molecular mechanism of neuropilin and tolloid-like 2 (NETO2) on proliferation, migration, cell cycle, and apoptosis in gallbladder cancer (GBC).Methods:The NETO2 mRNA and protein expression in GBC-SD, ZJU-0430, NOZ GBC cells were detected by quantitative real-time polymerase chain reaction and Western blot. NETO2 overexpression and knockdown stable cell lines were constructed by plasmid transfection. Cell counting kit-8 assay, colony formation assay, transwell assay, flow cytometry and WB assay were performed to evaluate proliferation, migration, cell cycle, apoptosis, epithelial-mesenchymal transition (EMT) and changes of phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway.Results:GBC-SD and ZJU-0430 cells with NETO2 gene overexpression and NOZ cells with NETO2 gene knockdown were effectively constructed. NETO2 overexpression in gallbladder cancer cell lines significantly improved cell proliferation and migration, advanced cell cycle progression from G0/G1 to S phase, and inhibited cell apoptosis. In the ZJU-0430 and GBC-SD cells, the clone number increased from (78.5±9.2), (217.0±6.4) to (213.5±10.3), (296.3±9.3)( t=10.98, 6.51; P=0.008, 0.023); The number of migrating cells increased from (198.6±8.4), (233.3±11.0) to (382.7±12.4), (379.0±7.3) ( t=16.98, 16.85, both P<0.001); The total apoptosis rate reduced from (29.7±0.9)%, (35.6±1.1)% to (19.2±0.5)%, (29.1±0.4)% ( t=9.74, 9.05; both P<0.001); The expression of EMT related proteins such as N-cadherin, Vimentin, Snail, and Slug were upregulated, while E-cadherin expression was downregulated. Phosphorylated PI3K (p-PI3K) and Akt (p-Akt) protein expression were significantly increased (all P<0.05). In contrast, NETO2 knockdown had the opposite effect on all these parameters. Conclusion:NETO2 influences the EMT process by regulating the PI3K/Akt signaling pathway, thus promotes GBC cell proliferation, migration and cell cycle progression, and inhibits cancer cell apoptosis.
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Objective:The safety and effectiveness of the enhanced recovery after surgery (ERAS) in the treatment of distal pancreatectomy (DP) were evaluated by meta-analysis.Methods:Pancreatic body and tail resection, distal pancreatic resection, ERAS, rapid recovery after surgery, pancreatectomy, DP and ERAS were used as key words, and the network database such as Chinese journal full-text database, Wanfang data knowledge service platform, Weipu database, Chinese biomedical literature database, Pubmed, Embase, Cochrane library, Web of science, Sciencedirect and so on were searched. The retrospective literatures published from the database establishment to May 2022 were retrieved from the network database, and the papers were screened and the quality was evaluated according to the pre-set inclusion and exclusion criteria; and important data were extracted. The software Review Manager 5.4 was used for meta-analysis.Results:9 papers were finally included, and a total of 650 patients with DP were enrolled (311 in the ERAS group and 339 in the NO-ERAS group). Meta-anaysis showed that compared with NO-ERAS group, ERAS group could reduce intraoperative bleeding ( MD=-73.88, 95% CI -121.21--26.55, P=0.002), decrease the incidence of postoperative complications ( OR=0.48, 95% CI 0.32-0.72, P<0.001) and pulmonary complications ( OR=0.47, 95% CI 0.24-0.93, P=0.030), shorten the postoperative exhaust time (MD=-8.76, 95% CI -11.23--6.29, P<0.001), postoperative length of hospital stay ( MD=-2.65, 95% CI -3.06--2.07, P<0.001) and abdominal drainage tube removal time ( MD=-1.45, 95% CI -1.81--1.09, P<0.001). However, ERAS could not shorten the operative time ( MD=6.25, 95% CI -4.56-17.07, P=0.260), reduce the incidence of postoperative pancreatic fistula ( OR=0.92, 95% CI 0.53--1.60, P=0.780) and the re-admission rate within 30 days after surgery ( OR=1.00, 95% CI 0.47-2.11, P=0.990). Conclusions:ERAS is safe and effective for patients undergoing DP, because it can reduce intraoperative bleeding and postoperative complications, shorten postoperative hospital stay and postoperative abdominal drainage tube removal time.
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Gallbladder carcinoma （GBC） is a type of malignant tumor with an extremely poor prognosis， and at present， surgical operation is the most effective treatment method for this disease. Unfortunately， due to a lack of typical symptoms in the early stage， most patients have progressed to the advanced stage at the time of confirmed diagnosis and lost the opportunity for radical surgery. Among the currently available adjuvant treatments， targeted therapy has higher specificity and fewer side effects and has improved the prognosis of a variety of malignancies. With reference to the latest research advances in targeted therapy for GBC， this article reviews the current research status， potential targets， and targeted medications of targeted therapy for GBC， in order to provide a reference for the clinical treatment of GBC patients.