Cholangiocarcinoma (CCA) invasion and metastasis are the primary causes of poor survival rates in patients. The epithelial-mesenchymal transition (EMT) is a crucial step in cancer invasion and metastasis. However, it is still unclear of the molecular mechanism. In this study, the expression of 14-3-3ζ and atypical protein kinase C-ι (aPKC-ι) was further detected in CCA tissues and cell lines. Meanwhile, we established the EMT model of CCA cells and investigated 14-3-3ζ and aPKC-ι co-regulatory effect on the EMT in vitro and in vivo. Further, we identified the downstream molecular glycogen synthase kinase 3 beta (GSK-3β)/Snail signalling pathway that contribute to regulating the EMT. Our data showed that the expression of 14-3-3ζ and aPKC-ι was synergistically increased in CCA tissues compared with adjacent noncancerous tissues and was intimately associated with differentiation and the tumour-node-metastasis (TNM) stage. Multivariate Cox regression analysis indicated that high 14-3-3ζ and aPKC-ι expression separately predicted a poor prognosis and were independent prognostic indicators in patients with CCA. The CO-IP experiment confirmed that the mutual binding relationship between 14-3-3ζ and aPKC-ι. Small interfering RNAs and siRNA rescue experiment demonstrated that 14-3-3ζ and aPKC-ι regulated each other. In addition, 14-3-3ζ and aPKC-ι pretreatment by si-RNA inhibit the phosphorylated GSK-3β and Snail expression during EMT. Meanwhile, silence of 14-3-3ζ or aPKC-ι suppressed CCA cells migration, metastasis and proliferation in vitro and in vivo. Our study demonstrates that 14-3-3ζ and aPKC-ι synergistically facilitate EMT of CCA via GSK-3β/Snail signalling pathway, and may be potential therapeutic target for CCA.
Objective Discussion of the Joint choledochoscope in laparoscopic common bile duct exploration surgery value.MethodsA retrospective analysis from 2004 to 2008,98 cases of laparoscopic United choledochoscope common bile duct exploration surgery in patients with clinical data.ResultsⅠperiod of the common bile duct suture,46 cases of laparoscopic placed T-tube drainage of 52 cases.91 cases of minimally invasive surgery successful,4 cases of conversion,T tube 14 to 19 days after extubation,the average length of stay is 10 days,1 case of residual stones,complicated by bile leakage in 2 cases.ConclusionCholedochoscope in the united laparoscopic common bile duct exploration surgery is safe and reliable,and less trauma and faster to restore.
Objective: To investigate the dynamic changes in serum β2-microglobulin, retinol-binding protein, and cystatin C in chronic hepatitis B(CHB)patients treated with tenofovir or entecavir alone as the anti-HBV therapy, as well as their value in identifying early renal dysfunction. Methods: A total of 61 previously untreated CHB patients who were diagnosed and treated in the Department of Infectious Diseases in Henan Provincial People's Hospital from June 2013 to August 2015 were enrolled and divided into tenofovir group and entecavir group. The serum levels of β2-microglobulin, retinol-binding protein, cystatin C, and creatinine and estimated glomerular filtration rate(eGFR)were compared between the two groups at baseline and 4, 8, 39, 52, 78, and 104 weeks after antiviral therapy. The independent samples t-test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data. P < 0.05 was considered statistically significant. Results: A total of 61 CHB patients were enrolled, with 31 in the tenofovir group and 30 in the entecavir group. The two groups had comparable serum levels of β2-microglobulin, retinol-binding protein, and cystatin C at baseline, but there were significant differences in β2-microglobulin and retinol-binding protein over time(both P < 0.05). There was a significant difference in cystatin C at 78 weeks(t = -2.062, P = 0.044), but there was no significant difference at 104 weeks(t = -1.544, P = 0.128). There were no significant differences in serum creatinine or eGFR at any time point between the two groups(P > 0.05). At 104 weeks, there were no significant differences in HBV-DNA clearance rate or the level of virologic breakthrough between the two groups(P > 0.05). Conclusion: Serum β2-microglobulin, retinol binding protein, and cystatin C are more sensitive than eGFR in the monitoring of early renal dysfunction during the anti-HBV therapy with tenofovir or entecavir alone.
Objective To investigate the management of traumatic bile duct injury.Methods The clinical data of 26 patients with traumatic bile duct injury were retrospectively analyzed.All the patients were admitted to the Tongji Hospital of the Huazhong University of Science and Technology from July 2009 to May 2014.All the 26 patients had the history of trauma.The trauma of the patients were typed according to the Mattox injury typing system.Besides anti-shock treatment,cholecystectomy,bile duct repair,end-to-end anastomosis of bile duct,choledochojejunostomy and quadrate lobectomy + hilar bile duct reshaping + hepaticojejunostomy were selected according to the site and degree of the injury.Symptomatic treatment was applied to patients who were combined with other organs injury.Patients were followed up via out-patient examination and telephone interview till October 2014.Results Twenty-six patients received exploratory laparotomy,and gallbladder injury was detected in 15 patients,common bile duct injury in 5 patients,common hepatic duct injury in 3 patients,left hepatic duct injury in 2 patients,right hepatic duct in 1 patient.Eleven patients were combined with hepatic rupture,1 with splenic rupture,5 with renal rupture,4 with small intestinal rupture.Eleven patients were with type Ⅰ bile duct injury,4 with type Ⅱ bile duct injury,8 with type Ⅳ bile duct injury and 3 with type Ⅴ bile duct injury.Of the 15patients with gallbladder injury,5 patients with slight bruise of the gallbladder did not receive cholecystectomy.Six patients and 4 patients with type Ⅰ and Ⅱ bruise of the gallbladder received cholecystectomy.Of the 11 patients with hepatic and bile duct injury,5 patients with type Ⅳ received bile duct repair + T tube drainage,1 patient with type Ⅳ received end-to-end bile duct anastomosis + T tube drainage,1 patient with type Ⅳ received biliojejunostomy and 1 patient with type Ⅳ received quadrate lobectomy + hilar bile duct reshaping + hepatojejunostomy; 3 patients with type Ⅴ received biliojejunostomy.Eleven patients additionally received repair of the liver or hepatectomy,1 received splenectomy,5 received nephrectomy,4 received partial small bowel resection + endto-end anastomosis.One patient died of hemorrhagic shock perioperatively; 3 patients were complicated with bile leakage,1 with incisional infection,and they were cured by symptomatic treatment.Twenty-five patients were followed up at postoperative month 1,3,6,12,and no patient was complicated with delayed bile leakage and biliary stricture recurrence.Conclusions Traumatic bile duct injury is often diagnosed during the operation.Patients with traumatic bile duct are often combined with shock and other organs injury.As for the treatment,laparotomy should be applied as soon as possible on the base of anti-shock treatment,and the appropriate method for biliary reconstruction should be selected according to the site and degree of injury.
Key words:
Bile duct injury; Trauma; Management
Objective
To illuminate the mechanism of 14-3-3ζ/atypical protein kinase C-iota (aPKC-ι) to promote the invasion and metastasis of cholangiocarcinoma (CCA).
Methods
The expression of 14-3-3ζ and aPKC-ιwereexamined in the samples of 64 CCA, peritumoural and normal tissues respectively by immunohistochemistry, Western blotting and quantitative real-time polymerase chain reaction. And the independent prognostic factors were analyzed by Kaplan-Meier survival analysis and Multivariate Cox regression analysis. Furthermore, theepithelial-mesenchymaltransition (EMT) model of CCA mediated by Transforming Growth Factor-β1 (TGF-β1) was established to analyze the regulation mechanism of 14-3-3ζand aPKC-ι. Finally, the capacity of invasion, migration, proliferation and metastasis of CCA cells with14-3-3ζdepleted were assessed by transwell cell invasion, wound healing, colony formation assays in vitro.
Results
Overexpression of 14-3-3ζ and aPKC-ιwas detected in CCA tissue (56.25%, 36/64, and 51.56%, 33/64), there was a significant positive correlation between 14-3-3ζ and aPKC-ι(r=0.406, P=0.001). Low expression of14-3-3ζ or aPKC-ιhad a better overall survival compared with those of overexpression (14-3-3ζ: χ2=10.140, P=0.001; aPKC-ι: χ2=12.575, P=0.000). Moreover, both 14-3-3ζ and aPKC-ιwere the independent prognostic factors of CCA. Interfering with 14-3-3ζ or aPKC-ιsignificantly suppressed the changes in EMT-related markers in CCA cells. In vitro, the inhibition of 14-3-3ζ impaired CCA cell invasion, metastasis and proliferation.
Conclusion
Our study demonstrated that 14-3-3ζ may combine with aPKC-ιandsynergistically facilitate EMT of CCA to promote CCA invasion and metastasis.
Key words:
14-3-3ζ; Atypical protein kinase C-iota; Cholangiocarcinoma; Epithelial-mesenchymal transition; Invasion and metastasis
The prevention and treatment of liver transplant rejection remain challenging. We investigated the pathophysiological mechanisms of liver transplant rejection in rats and screened candidate genes to determine their degree of rejection response for possible development of potential therapeutic targets.
Pancreatic duct decompression relieves pancreatic duct stone (PDS)-associated abdominal pain, though a consensus indication for the drainage procedure of the main pancreatic duct (MPD) is lacking. Moreover, major prognostic factors for postsurgical long-term pain relief and recurrence are largely unknown.The clinical outcomes of 65 consecutive PDS patients undergoing surgery from 2008-2012 with 3+ years of follow-up were assessed.At postsurgical follow-up (median, 4.5 years; range, 3-7 years; procedure: Partington, n = 32; Frey, n = 27; pancreatoduodenectomy, n = 3; distal pancreatectomy, n = 3), the early complication and complete stone clearance rates were 29.2% and 97%, respectively. Long-term, complete and partial pain relief were 93.9%, 83.1%, and 10.8%, respectively. The risk of pancreatic fistula was higher in the <8 mm group than in the >8 mm group (P < 0.05), and 80% of the pancreatic fistula cases occurred in the <8 mm group. A shorter pain duration (P = 0.007), smaller MPD diameter (P = 0.04), and lower Izbicki pain score (P < 0.001) predicted long-term pain relief. Pain recurrence after initial remission occurred in 5 patients and was only related to pain duration (P = 0.02). Stone recurrence and pancreatic exocrine functional and endocrine functional deterioration occurred in 2, 5, and 11 patients, respectively.Surgery provides excellent stone clearance, long-term pain relief, and acceptable postoperative morbidity. Using 8 mm as the criterion for drainage surgery can minimize the postoperative pancreatic fistula risk. Individualized and timely surgical treatment may improve the effect of surgery.
The tumor-promoting roles of ST8SIA6-AS1 and miR-145-5p have been found in several cancers, but their function in cholangiocarcinoma (CHOL) remains speculative. The purpose of this study was to examine the regulatory functions of the ST8SIA6-AS1/MAL2/miR-145-5p pathway in CHOL progression.RT-qPCR assay was used to detect ST8SIA6-AS1 expression in CHOL tissues and cell lines. Cell migration, apoptosis, invasion, and proliferation abilities were assessed by RIP, RNA pull-down, and luciferase assays. CCK-8, BrdU, transwell, and FITC assays to investigate the regulatory functions of ST8SIA6-AS1, miR-145-5p, and MAL2 function in CHOL cells.Findings revealed the enrichment of ST8SIA6-AS1 in CHOL tissues and cell lines. It was also found that ST8SIA6-AS1 facilitated cell growth and migration, but it reduced the apoptosis level of the CHOL cells. The results of experiments showed that ST8SIA6-AS1 sponged miR-145-5p, thereby allowing MAL2 to exert its biological function on CHOL cells.This research suggested that the ST8SIA6-AS1/miR-145-5p/MAL2 axis could enhance CHOL progression, which might be useful to improve the clinical outcomes of CHOL patients.
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