Objective To detect Nogo-A proteolytic fragment in CNS injury models and investigate its proteolytic mechanism as well as potential functions. Methods Western blot was performed to detect Nogo-A proteolytic fragment after spinal cord transection,brain ischemia and KA-induced cerebral cortex injury in rats. Results We detected Nogo-A proteolytic fragment in spinal cord transection and brain ischemia models,whereas no Nogo-A proteolytic fragment was found in KA-induced cerebral cortex injury model.Conclusion\ CNS mechanical and ischemic injury may induce the degradation of Nogo-A by certain mechanisms.

Objective To evaluate the complications and long-term efficacy of inside-out transobturator transvaginal tape ( TVT-O) for the treatment of stress urinary incontinence ( SUI) .Methods From January 2008 to December 2013,236 consecutive female patients (mean age 56 ±9 years,range 44-88 years)with the symptom of incontinence when abdominal pressure increasing (such as walking), underwent TVT-O operation.All these patients needed pads and were diagnosed with SUI by cough test and Marshall -bonny test before surgery , with the mean international consultation committee on incontinence questionnaire short form ( ICI-Q-SF) score of 15.6 ±3.9.Two grouping methods were used:the mid-term group including patients whose follow-up time was between 6 months and 3 years, the long-term group including patients whose follow-up time >3 years,the group of patients who underwent TVT-O only and the group of patients who underwent TVT-O plus pelvic floor repair at the same time . Their clinical and follow-up data , intraoperative and postoperative complications , subjective and objective effects were recorded and analyzed.Results Of these 236 patients,there were 1 case of bladder perforation (0.4%) and 1 case of intraoperative sling exposure to vagina ( 0.4%) .Postoperative complications included 36 ( 19.1%) groin/puncture point pain ,18 (9.5%) de novo frequency of micturition ,8 (4.2%) urinary retention /difficulty of urination.All the complications were relieved after symptomatic treatment or surgery except 2 cases of urinary retention/difficulty of urination.Their symptom kept existing after urethral dilatation and sling dissection and long-term intermittent self-catheterization was needed .One hundred and eighty-nine patients completed more than six months of follow-up, with mean follow-up time of ( 35.0 ±12.5 ) months.One hundred and sixteen (61.4%) cases was arranged to mid-term group and 73(38.6%) was arranged to long-term group.88.9%patients ( 168/189 ) were cured objectively and 9.5% patients ( 18/189 ) improved. There was also a significant subjective improvement ( ICI-Q-SF scores:15.6 ±3.9 preoperative versus 6.7 ± 2.3 postoperative,P<0.01).There was no significant difference of both objective and subjective efficacy between mid-term group and long-term group ( cured +improved rate 97.4% versus 95.9%;ICI-Q-SF scores 14.3 ±2.8 versus 16.7 ±3.4 preoperative ,5.8 ±1.2 versus 7.9 ±2.0 postoperative , P>0.05 ) . Patients who underwent TVT-O and those who underwent TVT-O +pelvic floor repair had no significant difference in efficacy (cured +improved rate 97.8%versus 100.0%,P>0.05).Conclusion TVT-O is a safe,effective and durable treatment for SUI , whether or not with concomitant procedure of pelvic floor repairment.

Objective To investigate the expression pattern and possible function of Nogo-A during neuronal growth. Methods E18 rat hippocampal neurons were primarily cultured both in high-density and low-density conditions. Immunohistochemistry and Western blot were performed to detect Nogo-A expression and distributional changes. Results Nogo-A was found in hippocampal neurons, mainly located in the cytoplasm, plasma membrane and neurites. It was detected at the proximal part of all neurites before axon formation. In axons, Nogo-A was enriched in the distal segment and axonal growth cone. In mature neurons, the fiber net work displayed a large number of Nogo-A immunoreactive varicosities. Conclusion The present results indicate that the neuronal Nogo-A may be involved in the process of neurite outgrowth and axonal projection.

Objecfive To study the effect of fibronectin(FN)and arginine-glycine-aspartateserine tetrapeptide (RGDS)on chemotherapy sensitivity of hepatocellular carcinoma(HCC)cell lines.Methods A HCC cell lines 7721 was divided into BSA group(BO),FN group(FO),RGDS group(RO)and FN+RGDS group(FR).Mitomycin-C(MMC)was added into each group with different concentrations for 2 h,12 h and 24 h.MTT assay was used to detect the survival rate of the tumor cell at different time,and fluorescent staining method and flow cytometry was used to detect the tumor cell's apoptosis.Results The survival rate and apoptosis rate was significantly different between each group with the treatment of MMC for 12 h or 24 h,and no statistical difference was found after incubation for 2 h.Conclusions With time FN down-regulates MMC induced apoptosis of the HCC cells.making HCC cells 1ess sensitive to chemotherapy,while RGDS enhances the sensitivity of HCC cells to chemotherapy.

Objective To investigate the occurrence and influencing factors of early allograft dysfunction (EAD) in patients receiving donation after cardiac death (DCD) liver Transplantation.Methods Forty-five patients received orthotopic liver transplantation in our center during January 2016 and May 2016 were included in this study.Based on the occurrence of EAD,patients were divided into EAD group and non-EAD group.Perioperative data of donors and recipients were collected to analyze the risk factors of EAD and the effect of EAD on the short-term prognosis of patients.Results In 45 patients,the incidence of EAD was 57.8％ (26 cases).During the follow-up period,the mortality of recipients in EAD group and non-EAD group was 15.4％ and 15.8％ respectively,which showed no significant difference.Donor age,preoperative ALT and AST levels,cold ischemia time (CIT) were significantly increased in EAD group than in non-EAD group (43.7 ±2.5 and36.2±2.5,P=0.0409;64.2 ±13.2 and 31.0 ± 5.9,P=0.0407;87.3±16.2 and48.2±6.2,P=0.047 3;629.5 ± 35.2 and 484.6 ± 30.5,P =0.004 0,respectively).Perioperative CRP level in EAD group was significantly higher than in non-EAD group (22.6 ± 5.9 and 4.7 ± 1.1,P =0.012 1).What's more,postoperative platelet level was significantly lower in EAD group than in nonEAD group (73.7 ± 8.0 and 111.7 ±16.0,P =0.0439).However,pre-and post-operative neutrophil-lymphocyte ratio (NLR) in recipients showed no significant difference between EAD group and non-EAD groups.Conclusion Older donor age,high levels of preoperative ALT and AST,prolonged cold ischemic time,as well as high level of preoperative CRP and decrease of postoperative platelet level in recipients are risk factors for the occurrence of EAD after liver transplantation.

Objective To investigate the clinical features and prognosis of patients with de novo digestive system malignancy after liver transplantation.Methods The clinical data of 10 patients with de novo digestive system malignancy out of 1 517 patients undergoing liver transplantation from January 2004 to December 2015 in the First Affiliated Hospital of Zhejiang University were collected.Immunosuppressive agents,type of de novo malignancy,process of treatment and prognosis were analyzed retrospectively.Results The incidence of de novo digestive system malignancy after liver transplantation was 0.7％ (10/1 517),including 3 cases of gastric cancer,3 cases of colon cancer,2 cases of liver cancer,2 cases of pancreatic cancer.All of the 10 patients received the corresponding treatment,and the dosage of immunosuppressive agents was reduced at the same time.The median time from liver transplantation to the diagnosis of de novo malignancy was 40.5 months (23 to 156 months).The median follow-up time was 10.5 months (3 to 61 months) after they had been diagnosed as malignancies,and 6 patients died of tumor progression.Conclusions The prognosis of patients with de novo digestive system malignancy after liver transplantation is poor,and early diagnosis and treatment is an important way to improve prognosis.Liver transplant recipients need to be closely followed up,especially in patients with high risk factors of digestive system malignancy.The modification of immunosuppressive drugs may be an effective way to prevent and improve prognosis.

Objective To investigate the role of B7/CD28 costimulation pathway blockade with adenovirus-mediated CTLA4-Ig gene in macrophage and CD8~+T cell infiltration and cell apoptosis in murine liver transplantation. Methods Rat pairs were divided into three groups: SD-to-Wistar transplantation control group, CsA-treated group and CTLA4-Ig-treated group. IHC and TUNEL were used to analyze the expression of CTLA4-Ig gene in liver and immune cells infiltrate and cell apoptosis in liver grafts. Pathology was done on all harvested grafts. ResultsCTLA4-Ig gene expression was positive in the donor liver on day 7 after administering adenovirus-mediated CTLA4-Ig gene via vein, and remained positive until day 60 after liver transplantation. Infiltration of immune cells in CTLA4-Ig-treated group was less than that in rejection control group. the apoptotic index of rejection group on day 3,5,7 was significantly higher than those of CTLA4-Ig-treated. Conclusions CTLA4-Ig gene was constantly expressed in the donor liver after single intravenousely injection into rats using adenovirus as vector. Adenovirus-mediated CTLA4-Ig gene therapy can inhibit infiltration of immune cells and apoptosis in grafts, thus prolonging the survival of recipients.

Objective To evaluate the management of biliary complications (BC) following orthotopic liver transplantation (OLT). Methods From Feb 1999 to Feb 2004, 236 cases underwent OLT with end-to-end choledocho-choledochostomy. Biliary anastomosis was performed by intermittent suture with T tube placement in 96 cases, without T tube in 39 cases, by continuous suture in posterior wall and intermittent suture in anterior wall and without T tube in 101 cases. Results Thirty-two (13.3%) patients developed BC, with incidences in group 1, 2 and 3 of 17.7%, 15.4% and 7.9%, respectively. The incidence of hepatic hilar and/or intrahepatic bile duct strictures was 8.3%, 2.6% and 1.0%, respectively. BC incidence in group 3 significantly decreased. Twenty patients with biliary stricture underwent endoscopic and/or radiological interventions, and stricture resolution was achieved in 90% of patients with anastomotic strictures and 60% of patients with hepatic hilar and/or intrahepatic strictures. Conclusions Modified biliary tract reconstruction technique contributes to the decrease of BC. Endoscopic and/or radiological interventions should be used for non-ischemic anastomotic biliary strictures or simple hepatic hilar strictures.

Objective This study is to summarize the experience of microsurgical reconstruction for donor liver anatomical variations of hepatic arteries in orthotopic liver transplantation. Methods During the bench surgery, the anatomy of donors′ hepatic arteries was carefully examined and microsurgical techniques were used for the anomalous arteries. The graft arterial flow was checked by Doppler ultrasound daily in the first week in postoperative period and periodically thereafter. Results The arterial anatomy was anomalousin 20 out of 141 (14%) donor livers. Nine cases (6.3%) needed arterial reconstruction. In these cases, 7(4.9%) aberrant right hepatic arteries originating from superior mesenteric artery were anastomosed to gastro-duodenal arteries and another two aberrant hepatic left or right arteries were anastomosed to the stump of the donor splenic arteries. Conclusions The variations of hepatic arteries in donors are common. To obtain the ideal arterial supply of liver graft, both careful checking on the origin of donor's artery and appropriate plastic performance with refined microsurgical techniques are necessary.

Objective To evaluate the efficacy and safety of daclizumab(zenapax) in liver transplantation patients with renal insufficiency. Methods We reviewed the use of daclizumab in 50 patients with renal insufficiency or at high risk of renal insufficiency during the period of liver transplantation between March 2001 to February 2003. The control group included 62 cases with no renal insufficiency at the same period. Results Renal function was recovered in 36 of 37 patients. The administration of daclizumab caused no vital organ dysfunction. Acute rejection was 6% (3/50) vs. 29 % (18/62) (P=0.826), infection was 56% (28/50) vs. 58% (36/62)(P=0.826). Conclusion Immunoprophylaxis with daclizumab regimen is safe, effective and well tolerated, and does not lead to increased opportunistic infections, and helps in improving renal function, by reducing the dosage and postponing the application of calcineurin inhibitor.