Generation of a human induced pluripotent stem cell line overexpressing CCL22 with islet cells differentiation potential.

CCL22 is a macrophage-derived immunosuppressive chemokine that recruits regulatory T cells through the CCL22:CCR4 axis, playing an important role in homeostatic and inflammatory responses. A CCL22-overexpressing human induced pluripotent stem cell line (CNNDi001-A-2) was generated by lentiviral transduction to further study the function of CCL22. The cell line was confirmed to have normal proliferation and pluripotency and could be further differentiated into islet cells for cell replacement therapy in diabetes.

Whole-process ultrasound-guided percutaneous portal vein puncture islet transplantation for diabetes: a report of 16 cases / 中华器官移植杂志

Objective:To explore the application value of whole-process ultrasound-guided percutaneous portal vein puncture islet transplantation.Methods:From October 2018 to May 2021, 16 diabetics underwent whole-process ultrasound-guided percutaneous portal vein puncture islet transplantation at First Affiliated Hospital of Sun Yat-sen University.The whole process was guided by ultrasound for completing percutaneous portal vein puncture catheterization, islet infusion monitoring, bleeding prevention and ablation hemostasis after bleeding.Results:Ten patients [8 males and 2 females with a mean age of(45.9±21.1)years]underwent 16 islet transplants, including one islet(5 cases), two islets(4 cases)and three islets(1 case). A single puncture was successfully performed without damage to other extrahepatic organs, persistent portal hypertension, portal vein embolism or infection.Bleeding at liver puncture site occurred in 3 cases and ultrasound radiofrequency ablation was performed for immediate hemostasis.Among them, postoperative blood glucose stabilized at 4~12 mmol/l post-operation.And 5 cases(31.3%)achieved insulin independence for>2 months and 10 cases(62.5%)lowered insulin dosage by>50% as compared with preoperative level.The level of fasting C-peptide recovered or was higher than normal in 10 cases(62.5%)and became obviously elevated in the remainders.In 11 cases(68.8%)of them, liver transaminase was briefly and mildly elevated post-operation, and no other complications were observed.Conclusions:The whole-process ultrasound-guided percutaneous portal vein islet transplantation is both safe and feseasible.It avoids the injury of transplanted kidney caused by contrast agent and radiological radiation to operator and patient.It is a method of islet transplantation worth a wider popularization.

The comparison of fully-covered self-expandable metal stent and plastic stent on the treatment of post liver transplantation anastomotic biliary stricture / 中华肝胆外科杂志

Objective:To investigate the effectiveness and safety of fully-covered self-expandable metal stent (FCSEMS) with plastic stent over the treatment of post liver transplantation anastomotic biliary stricture (AS).Methods:The clinical data of AS patients after liver transplantation admitted to the First Affiliated Hospital of Sun Yat-sen University from January 2014 to April 2018 was collected for the retrospective study. According to different implanted stents, patients were divided into FCSEMS group and plastic stent group. The general information of the two groups of patients, surgical success rate, postoperative complications, the number of endoscopic retrograde cholangiopancreatography (ERCP), the number of indwelling stents and other indicators were compared and analyzed.Results:A total of 54 patients were enrolled, including 41 males and 13 females, with a median age of 48 (34-65) years. A total of 23 cases were included in the FCSEMS group and 31 cases were included in the plastic stent group. The overall technical success rate of the operation was 98.3% (176/179). In the FCSEMS group, there were 21 patients recovered and 2 patients were relieved; in the plastic stent group, 29 patients were recovered, 1 case was relieved, and 1 case failed. There were no statistically significant differences in the efficacy and complication rate between the two groups (all P>0.05). The median stent indwelling time, ERCP times, and the number of indwelling stents in the FCSEMS group were 5.9 months, 2 times, and 1, respectively, and in the plastic stent group were 9.5 months, 4 times, and 8 respectively. There were statistical differences between the two groups (all P<0.05). Conclusions:FCSEMS for treatment of AS showed less duration of stenting, numbers of stents and endoscopic treatment sessions with the similar efficacy as plastic stents. It’s indicated that it’s necessary to pay attention to the probability of stent migration and pancreatitis.

The ileal FGF15/19 to hepatic FGFR4 axis regulates liver regeneration after partial hepatectomy in mice

Fibroblast growth factor (FGF) has been considered to modulate liver regeneration (LR) after partial hepatectomy (PH) at the tissue level. Previous studies have demonstrated that FGF15 and FGF19 induce the activation of its receptor, FGF receptor 4 (FGFR4), which can promote hepatocellular carcinoma progression and regulate liver lipid metabolism. In this study, we aimed to explore the role of the ileal FGF15/19- hepatic FGFR4 axis in the LR after PH. Male C57BL/6 mice aged 8-12 weeks were partially hepatectomized and assessed for expression of ileal FGF15/19 to hepatic FGFR4 signaling. We used recombinant human FGF19 protein and a small interfering RNA (siRNA) of FGFR4 to regulate expression of the FGF15/19-FGFR4 axis in vitro and in vivo. The proliferation and cell cycle of hepatocytes, the expression levels of FGF15/19-FGFR4 downstream molecules, liver recovery, and lipid metabolism were assessed. We found that both ileal and serum FGF15 expression were upregulated and hepatic FGFR4 was activated after PH in mice. FGF15/19 promoted cell cycle progression, enhanced proliferation, and reduced hepatic lipid accumulation of hepatocytes both in vitro and in vivo. Furthermore, the proliferative effect and lipid regulatory properties of FGF15/19 were dependent on FGFR4 in hepatocytes. In addition, ileal FGF15/19-hepatic FGFR4 transduction during hepatocyte proliferation was regulated by extracellular regulated protein kinase (ERK) 1/2. In conclusion, the ileal FGF15/19 to hepatic FGFR4 axis is activated and promotes LR after PH in mice, supporting the potential of ileal FGF15/19 to hepatic FGFR4 axis-targeted therapy to enhance LR after PH

Application of Shear Wave Elastography in assessing liver allograft function in patients using organs from deceased citizens / 中华器官移植杂志

Objective To investigate the correlation between the elastographic characteristics of liver and postoperative function of liver allografts.Methods Forty-eight cases of liver transplantation from The First Affiliated Hospital of Sun Yat-sen University were analyzed,Shear wave elastography (SWE) was performed before operation or at one week or one month post-operation.Liver function was evaluated by measuring alanine aminotransferase (ALT),aspartate transaminase (AST),total bilirubin (TBIL),γ-glutamine transferase (GGT),albumin (ALB),alkaline phosphatase (ALP),prothrombin time (PT),activated partial thromboplastin time (APTT),and international normalized ratio (INR).Early allograft dysfunction (EAD) was also analyzed with reference to SWE among liver transplant recipients.Results SWE at one week after transplantation was significantly correlated with TBIL (r=0.525 6,P<0.01),APTT (r=0.668 3,P<0.000 1),PT (r=0.593 7,P=0.000 1),INR (r=0.609 6,P<0.000 1) and prealbumin (r=-0.464 1,P<0.01).However,no significant correlation was observed between pre-operative SWE and parameters of post-operative liver function.SWE in EAD patients was higher than that of patients without EAD (17.60±1.09 kPa vs.13.38±0.99 kPa,P<0.01).The optimal cut-off value of SWE at one week post-operation was 14.85 kPa.Conclusion Postoperative SWE is significantly correlated with postoperative liver function tests and EAD,suggesting SWE is a potential test for evaluating the quality of liver allografts.

Early clinical observation of 8 cases of organ donation after death pancreas-kidney transplantation / 中华器官移植杂志

Objective To observe the early effect of organ donation after pancreas-kidney transplantation.Methods Eight cases of diabetic nephropathy received combined pancreas kidney transplantation.There were 8 donors,including 6 males and 2 females,with an average age of (26 10) years old (range from 15 to 42 years).There were 4 cases of donors with China during the transition period of brain heart double death organ donation (C-Ⅲ) standard,3 cases of donors in line with the international standard of brain death organ donation (C-Ⅰ) standard,1 case of international standard of heart death organ donation (C-lⅡ M-Ⅲ) citizen donors.There were 6 men and 2 women for recipients of the same blood type.Results Eight cases were awake 4-6 h postoperation and the ventilator was removed 8-14 h after operation.The rehabilitation therapy began 2 days postoperation from surgery intensive care unit (SICU) to the common wards.Serum C-peptide and insulin levels achieved normal range in 1-2 weeks after transplant.Blood glucose returned to the normal level in 2-3 weeks,and the creatinine level decreased to the normal level in 2 weeks postoperation.Duodenal intramural hematoma occurred in one patient intraoperatively,and the pancreatic graft was removed for safe consideration.Other patients had no serious surgical complications within 2 weeks after transplantation.Conclusion For organ donation after death of pancreas kidney transplantation,early organ function recovered well.Under the strict preoperative evaluation,the young donors can be safely used in combined pancreas and kidney transplantation.

Simultaneous pancreas and kidney transplantation for liver transplant recipients with diabetes and uremia / 中华器官移植杂志

ObjectiveTo summarize the clinical experience of simultaneous pancreas and kidney transplantation (SPK) after liver transplantation for patients with diabetes and uremia.MethodsThe clinical data of two patients who received SPK after liver transplantation were retrospectively analyzed.The two male patients had type 2 diabetes mellitus before liver transplantation,and suffered from endstage uremia due to diabetic nephropathy and immunosuppressant-induced toxicity.Rapid technique for combined abdominal multiple viscera procurement was performed.Kidneys,pancreas,duodenum segment and spleen were procured.Renal allograft was placed in the left iliac fossa,whereas pancreas allograft in the right iliac fossa. The pancreatic allograft exocrine secretion was drained into the proximal jejunum via a side-to-side duodenojujunostomy. Quadruple immunosuppressive regime including IL2 receptor monoclonal antibody induction,tacrolimus (Tac),mycophenolate mofetil (MMF) and steroid were used in case 1,and ATG and methylprednisolone were used in case 2.ResultsSPK was successfully applied to these two patients without serious surgical complications such as pancreatitis,graft and pancreatic fistula. The immunosuppressive regimen was based on tacrolimus with ATG induction,MMF and steroids.In the second case,serum creatinine level was decreased to the normal range within 1 week after the operation and then elevated continuously even he received empirical anti rejection treatment,Tac was tampered and rapamycin was used when the renal graft biopsy indicated drug toxicity,and creatinine level was decreased 3 weeks after the operation and recovered to the normal range at 5th week post-transplant. Both of the two patients achieved euglycemia with insulin independence about 10 days after the operation.And now these two patients have been followed up for 36 and 9 months,and the grafts function of the liver,kidney and pancreas was normal. Conclusion Immunologic reaction in patients undergoing simultaneous pancreas and kidneytransplantationafterlivertransplantationseemsmorecomplex, andareasonable immunosuppressive regimen is important to improVe the outcome.

Donation after cardiac death used in abdominal multiple visceral organ transplantation / 中华器官移植杂志

Objective To evaluate the therapeutic effect of abdominal multiple visceral organ transplantation for hepatic cirrhosis combined with diabetes by using donation after cardiac death (DCD).Methods Two patients suffering from hepatitis B-related liver cirrhosis,hepatocellular carcinoma combined with insulin dependent type 2 diabetes mellitus were given multiple visceral organ transplantation from May to June 2012.The transplanted organs including the liver,pancreas and duodenum were obtained from two donors after cardiac death which accorded with C-Ⅲ criteria.The donor internal and external iliac arteries were anastomosed to celiac axis and superior mesenteric artery and then the donor arteria iliaca communis was anastomosed to recipient abdominal aorta.The portal vein reconstruction was performed by end-to-side anastomosis between the donor and recipient portal vein.The pancreatic juice drainage was achieved by side to side anastomosis between donor duodenum and recipient jejunum.The pancreases of recipients were retained.Results The alanine aminotransferase,aspartate aminotransferase and total bilirubin of two patients were recovered to normal level at 2nd week after operation.The blood glucose and serum amylase returned to normal levels at 7th d and 4th d respectively.The fasting serum C-peptide and insulin were also at normal level at 2nd week.One patient with local intestinal anastomotic fistula was given percutaneous puncture drainage for four weeks and recovered.One patient recovered smoothly one month after transplantation without surgical complications.Conclusion Abdominal multiple visceral organ transplantation is an effective treatment for hepatic cirrhosis combined with diabetes by using DCD donor.

Etiology and management of intra-abdominal hemorrhage after orthotopic liver transplantation / 中华普通外科杂志

Objective To explore the causes and management of intra-abdominal hemorrhage after orthotopic liver transplantation (OLT). Methods Clinical data of 638 OLT patients were analyzed retrospectively from January 2004 to December 2008 in the First Affiliated Hospital of Sun Yat-Sen University. The diagnosis and treatment of postoperative intra-abdominal hemorrhage after OLT were reviewed. Results Among the 638 patients, 53 suffered from posttransplant intra-abdominal hemorrhage,the morbidity was 8. 3% (53/638). Thirty-one cases suffering from bleeding on raw surfaces or around the liver due to impairment of coagulation function were treated by non-surgery methods, 22 cases who suffered from active postoperative intra-abdominal hemorrhage due to surgical factors underwent laparotomy and bleeding control operation after failure of anti-shock treatments such as hemostatic drugs, blood reperfusion.Among the 53 patients who suffered from intra-abdominal hemorrhage, 12 patients died, and the main causes were serious infections and multiple organ dysfunction syndrome. The mortality associated with intraabdominal hemorrhage was 22. 6%. Conclusions Intra-abdominal hemorrhage at different locations were found after OLT, and the fatal rate is quite high. Timely and appropriate treatments especially laparotomy may improve the prosnosis of these patients.

Immunosuppression regimen with Basiliximab induction in liver transplantation: efficacy and safety / 中华器官移植杂志

ObjectiveTo investigate the effectiveness and tolerability of immunosuppressive regimen with daclizumab induction therapy. MethodsIn study group, 139 patients received immunosuppressive regimen with daclizumab induction therapy. In historical control group, 106 recipients received immunosuppressive regimen without daclizumab induction therapy. All patients were followed up at least for 1year. The acute rejection episodes, infectious and metabolic complications at one month and one year post-transplantation were compared between two groups.ResultsThe one-month incidence of acute rejection, new-onset diabetes mellitus, hypertension and infection was 7. 9 ％, 33. 8 ％, 21.6 ％ and 22. 3 ％, respectively in study group, as compared with 15. 1 ％, 72. 6 0％, 40. 6 ％ and 43. 4 ％, respectively in control group ( P ＜ 0. 05 ). The one-year incidence of acute rejection, new-onset diabetes mellitus, hypertension and hyperlipidemia was 10. 8 ％,5. 0 ％ ,4. 3 ％ and 7. 9 ％, respectively in study group, as compared with 19. 8 ％, 9. 4 ％, 8. 5 ％ and 14. 2 ％, respectively in control group (P＜0. 05). The one-year survival rate was comparable between two groups (P＞0. 05). ConclusionThe immunosuppressive regimen with daclizumab can enable early steroid withdrawal, significantly reduce acute rejection rate and various side effects mediated by longterm steroids use.

Resistance rate and epidemiology of gram-negative bacilli in bloodstream infection after liver transplantation / 中华器官移植杂志

ObjectiveTo define the resistance rate and epidemiology of Gram-negative bacilli (GNB) of bloodstream infections (BSI) after liver transplantation. MethodsFrom Jan. 1998 to Dec.2009,a retrospective analysis of GNB in liver transplants was conducted. Bacterial, CMV and fungal infections were prevented by piperacillin/tazobactam, ganciclovir, fluconazole postoperatively. Bacterial inoculation,isolation and culture were mandated by national test standard. Vitek 2 Compact was used to evaluate identification and antimicrobial susceptibility testing. ResultsEighty-eight BSI occurred in 83 patients of the 768 patients,in which a total of 88 GNB were isolated. The incidence was 10. 8 ％(83/768) ,and the most frequent pathogens were Escherichia coli (37 strains) and Klebsiella spp (18strains). The rate of infection (23. 9 ％) was high in the interval of 1998-2000, and then decreased to 12. 4 ％ or below. Carbapenems and Piperacillin/tazobactam were the most consistently active against the Escherichia coli and Klebsiella spp, while resistance rate of Escherichia coli to Ciprofloxacin,Gentamycin, Ampicillin-clavulanic acid or Klebsiella spp after 2005 to Ciprofloxacin, Ticarcillinclavulanic acid was over 60 ％. ConclusionGNB after liver transplantation were resistant to agents but active to Carbapenems and Piperacillin/tazobactam commonly, in which Escherichia coli and Klebsiella spp are common.

Salvage liver transplantation for patients with recurrent hepatocellular carcinoma after curative resection / 中华器官移植杂志

Objective To summarize the experience with salvage liver transplantation for patients with recurrent hetaptocellular carcinoma(HCC)after primary liver resection.Methods From 2004 to 2008,376 patients with HCC received liver transplantation in our single center.Among these patients,36 (9.6 %)underwent salvage liver transplantation after primary liver curative resection due to intrahepatic recurrence.There were 29 males and 7 females with the mean age of 46 years old.Sixteen received right lobectomy,10 received left lobectomy and the others received sectionectomy or segmentectomy.As a control group for comparison,we used clinical data of the 147 patients who underwent primary OLT for HCC within Milan Criteria.Results The mean interval between initial liver resection and salvage transplantation was 34.9±16.2 months(1-63 months).Intraoperative bleeding volume,transfusion volume and operative time in the salvage group were significantly different from those in control group (P0.05).Conclusion In comparison with primary OLT,although salvage liver transplantation would increase the operation difficulties,it still remains a good option for patients with HCC recurrence after curative resection.

A comparative study of pancreatic endocrine function and related metabolism after long-term survival between the patients with combined kidney-pancreas transplantation vs those with combined en bloc' liver-pancreas transplantation / 中华器官移植杂志

Objective To compare the effects of combined ‘en bloc' liver-pancreas transplantation (LPT) with portal vein drainage and simultaneous combined kidney-pancreas transplantation (KPT) with systemic venous drainage on the pancreatic endocrine function and related metabolism.Methods Four LPT patients and 6 KPT ones with normal hepato-renal function, good quality of life and periodic follow-up received measurement of serum insulin, insulin provocation test, fasting glucose, oral glucose tolerance test, C-peptide, glycated hemoglobin, triglyceride and total cholesterol; and their laboratory test parameters were compared and analyzed.Results In KPT group, 2-h insulin level, C-peptide level and total cholesterol level were significantly higher at 6th month, 3rd and 6th month postoperation (all P<0.05). But there was no significant difference in other parameters between the two groups at 6th month after operation.Conclusion Either KPT or LPT can achieve excellent endocrine function, carbohydrate and lipid metabolism; and the results show that portal venous drainage does not offer major metabolic advantages within 6 months after operation.

Modified upper abdominal cluster transplantation in patients with end-stage liver diseases associated with insulin dependent type 2 diabetes mellitus / 中华器官移植杂志

Objective Modified upper abdominal cluster transplantation (MCT), which was inspired by the classical cluster transplant technique, has been proven more effective and feasible in the treatment of patients with end stage liver diseases associated with insulin-dependent diabetes mellitus (DM) than orthotopic liver transplantation (OLT) alone. In this study, we summarized our experience with MCT in 5 consecutive patients suffering from end stage liver diseases associated with insulin-dependent type 2 DM in our single center.Methods Five patients with hepatitis B-related chronic liver cirrhosis and insulin dependent type 2 DM received MCT in our single center. The biliary and exocrine pancreatic drainage reconstructions were achieved by a Roux-en-Y duodenojejunostomy or a side-to-side duodenojejunostomy. A quadruple immunosuppressive regimen based on tacrolimus including Basiliximab induction, mycophenolate mofetil (MMF) and steroids was used in the early stage post-transplant, and then converted to tacrolimus monotherapy.Results All of the patients experienced an uneventful post-operative recovery. They were rendered independent from insulin therapy shortly after transplantation. The fasting glucose and glycosylated hemoglobin levels were within normal range. In addition, the fasting C-peptide value was increased from much lower than the normal range pre-transplant to within normal range post-transplant and maintained stable since then. However, the third patient suffered from graft verse host disease (GVHD) 20 days post-operatively and died from severe infection on the post-operative 47 days. The other 4 patients had returned to work and a normal lifestyle over 22, 15, 5 and 4 months of follow-up.Conclusion MCT is an effective method in treating patients suffering from end stage liver diseases combined with insulin-dependent type 2 DM. Whether a cluster graft would increase the risk of GVHD needs further investigation.

Immunosuppressive regimen after simultaneous pancreas and kidney transplantation / 中国组织工程研究

BACKGROUND: Simultaneous pancreas and kidney transplantation (SPK) has been considered an effective therapeutic means of diabetes mellitus (including type 1 and type 2) combined with end stage uremia. Because the pancreas possesses high immunogenicity, so a feasible immunosuppressive regimen is a key to successful pancreas transplantation. OBJECTIVE: To investigate the feasible immunosuppressive regimen after simultaneous pancreas and kidney transplantation (SPK). METHODS: From January 2005 to June 2009, 9 patients with diabetic nephropathy and end stage uremia, consisting of 5 males and 4 females, received SPK. The pancreatic allograft exocrine secretion was drained into the proximal jejunum via a side-to-side duodenojujunostomy. Quadruple immunosuppressive regimen including induction of interleukin-2 receptor monoclonal antibody, tacrolimus, mycophenolate mofetil and steroid, and gradual tacrolimus monotherapy. The clinical data of the 9 patients were analyzed retrospectively. RESULTS AND CONCLUSION: SPK was successfully applied to all patients without serious surgical complications such as pancreatitis, graft dysfunction and pancreatic fistula. One patient died of cardiovascular accident in the early stage after SPK. The other 8 patients were followed up for 4-50 months. Serum creatinine decreased to normal range within 1 week after surgery. The 8 patients achieved euglycemia during early postoperative stage with insulin independence time (11.5±3.5) days and with fasting blood glucose recovery time (15.4±6.3) days. Acute rejection of the renal graft occurred in 4 patients, 1 patient died of cardiovascular accident and the other 3 recovered after antihuman thymocyte globulin or steroids bolus treatment. No rejection was noted in pancreatic grafts. These findings indicate that SPK is an effective treatment for patients with diabetes mellitus-related middle- and end-stage uremia．Quadruple immunosuppressive regime including interleukin-2 receptor monoclonal antibody induction is feasible after SPK, and such a regimen can be safely converted to tacrolimus monotherapy.

The diagnosis and treatment of biliary complications in liver transplant patients / 中华普通外科杂志

Objective To investigate the treatment of biliary complications in perioperative stage of live transplantation. Methods From January 2007 to December 2009, 23 patients suffered from surgical biliary complications after liver transplantation. The clinical data including the types of biliary leakage,treatment, prognosis were analyzed retrospectively. Results Of 12 biliary leakage patients, 7 were anastomotic leakage, 3 with leakage of bile duct on the cutting surface of the graft of living ralated liver transplation, 1 with cystic duct leakage and 1 with leakage of aberrant biliary duct. Of 11 biliary stricture patients, 4 patients were anastomotic stenosis and 7 patients were no-anastomotic stenosis. The anastomotic biliary leakage of 7 patients was cured with biliary tract reconstruction in 2 patients, with cholangioenterostomy in 2 patients, with biliary reparation in 1 patient and peritoneal drainage in 1 patient but the patient with dual graft received re-transplantation. Three patients with biliary leakage on liver cut surface respectively receiving reparation or drainage were cured, of which 1 patient suffered from bile duct stricture and was finally cured by ERCP. One patient with biliary leakage of aberrant bile duct and 1 with biliary leakage of cystic duct were cured by salvage surgery. For the 4 patients with anastomotic stenosis, 3 patients were cured by ERCP and 1 patient recovered by biliary reconstruction. Among the patients with nonanastomotic stenosis, 3 cases were alleviated by ERCP or PTCD, another 3 patients had to receive retransplantation, of which 2 patients recovered well without surgery-related complications, one died of severe infection. Conclusions Biliary complications are common among liver transplant patients often causing significant mortality and morbidity necessitating comprehensive salvage procedures, though most of them are preventable.

Sirolimus conversion in liver transplant recipients with calcineurin inhibitor-related renal insufficiency after liver transplantation / 中华肝胆外科杂志

Objective To investigate the efficacy and safety of sirolimus in treating calcineurin inhibitor-related renal insufficiency after liver transplantation. Methods Eleven patients with calci-neurin inhibitor-related renal insufficiency after liver transplantation received sirolimus conversion.Simultaneously, the dose of tacrolimus was decreased or tacrolimus was withdrawn. Blood creatinine,sirolimus level, tacrolimus level, liver function, rejection episodes and drug side-effect were moni-tored. Results All the 11 patients survived today with 6 to 20 months of follow-up. All patients showed improvement of renal function after conversion to sirolimus. Blood creatinine level was reduced from (163.8±47.9)μmol/L to(108.1±26.6)μmol/l. (P<0.05). One patient's liver function had an acute rejection episode that was successfully treated with increase of dose of tacrolimus. The side-effects of sirolimus included hyperlipidemia (4 patients), anaemia (1) and mouth ulcers (2).Conclusion Siolimus can be effectively and safely used in liver transplant recipients suffering from ta-crolimus-related renal insufficiency.

Surgical techniques used in simultaneous pancreas-kidney transplantation / 中华普通外科杂志

Objective To evaluate the surgical techniques and short-term clinical results of simultaneous pancreaticoduodenum-kidney transplantation(SPK)with the enteric drainage(ED)of exocrine secretions of the pancreas.Method From Jan 2005 to Jun 2009,ten diabetic patients with uremia diabetes underwent SPK.The pancreas graft was placed intraperitoneally with exocrine secretions drained into the proximal iejunum by side-to-side anastomosis.The multivisceral cluster grafts(liver,kidney,pancreas and duodenum)were procured after simultaneously rapid perfusion with cool UW solution through donor's abdominal aorta and superior mesenterie vein in 10 no heart beating cadeveric donors.Quadruple immunosuppressive therapy with anti-CD25 monoclonal antibody,tacrolimus,mycophenolate mofetil and steroids was adopted.Results SPK was successfully performed in all cases.The mean warm ischemia time of donor organ was(5.9 ±2.6)min,the mean cold ischemic time of the kidney was(5.2 ±2.2)hours and that of the pancreas was(9.3±3.6)hours.Patient and graft survival rates were 90.0% and 90% at 6 month after transplant,respectively.None of the grafts lost due to enteric or pancreatic leakage or intraabdominal infection.The most common surgical complications were wound infection(n=3),and enteric anastomostic hemorrage(n=2),which were all cured by nonoperative management.Three biopsy-proven acute renal rejection episodes occurred within 12 months postoperation,2 of them were reversed Successfully.and 1 died of cerebral complication during the recovery from continuous renal replacement therapy(CRRT)after the failure of aggressive antirejection treatment.Other patients(n=9)became insulin-free euglycemie at(9.3±3.8)day postoperatively,and are well and insulin-free at a follow-up of 6～12 months.Conclusions High quality procurement of donor grafts and suitable arterioplasty are prerequisites for a successful combination kidney and pancreas transplantation.Enteric exocrine drainage by direct side-to-side anastomosis seems to be a simple and reliable technique.

Dynamic expression of E-cadherin in embryonic stem cell differentiation in vitro and correlation with cell adhesion / 中国组织工程研究

BACKGROUND:E-cadhedn plays an important role in development of liver tissue in the embryonic stage.Therefore,it is importance for investigating the feasibility of dynamic expression of E-cadherin in embryonic stern cell differentiation to in vitro development of liver tissue.OBJECTIVE:To observe the dynamic expression of E-cadherin in embryonic stem cell differentiation and the effect on cell adhesion.DESIGN,TIME AND SETTING:An in vitro cytological observation was performed at Surgical Laboratory of the First Affiliated Hospital of Sun Yat-sen University from December 2007 to December 2008.MATERIALS:Embryonic stem cells of BALB/c mice were obtained from Professor Huang (Department of Ophthalmology,Sun Yat-sen University).Twenty 13-day-old pregnant BALB/c mice of clean grade were provided by the Experimental Animal Centar of Sun Yat-sen University.METHODS:Following trypsinization,embryonic stem cells were suspend-incubated in DMEM culture medium containing fetal bovine serum,2-mercaptoethanol,HEPES,penicillin,and streptomycin.Embryoid body was formed 5 days after normal development and incubated in the culture plate at day 6.Liver tissue which was obtained from 13-day-old pregnant BALB/c mice was prepared for fetal liver cells which were frozen-sectioned as the controls.MAIN OUTCOME MEASURES:E-cadherin expression was detected using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunocytochemistry st varying time points of 1,5,9,13,and 17 days in stages of initial differentiation of embryonic stem cells,formation of embryoid body,and formation of differentiated clusters.Additionally,the effect of E-cadherin expression on cell adhesion was also detected.RESULTS:RT-PCR showed that E-cadherin mRNA expression was not observed at day 1 but peaked at day 5;gradually,the expression was decreased until the expression was stopped at day 17.E-cadherin mRNA expression was strong in fetal liver cells in the control group.Immunocytochemistry showed a similar outcome.Morphologically,embryonic stem cells developed from unicells into compact three-embryonic layer embryoid body and into incompact cell population.CONCLUSION:E-cadherin expression correlates with differentiated cell adhesion;additionally,the lost expression in an in vitro environment may be an important cause for unable regularization of differentiated cells.

Stable transfection of E-cadherin gene into mouse embryonic stem cells and its effects on adhesive capacity of differentiated cells / 中国组织工程研究

BACKGROUND: During the embryonic stage, E-cadherin expression plays a critical role in the formation of hepatic tissue.OBJECTIVE: E-cadherin gene was transfected into mouse embryonic stem cells (ESCs) to observe its effects on adhesive capacity of differentiated cells.DESIGN, TIME AND SETTING: A cytological in vitro observation was performed at the Laboratory of Surgery, First Hospital Affiliated to Sun Yat-sen University between December 2007 and December 2008.MATERIALS: BALB/c mice at gestational 13 days, of clean grade, were provided by Laboratory Animal Center, Sun Yat-sen University. BALB/c mouse ESCs were preserved by professor Huang Bing from the Department of Ophthalmology, Sun Yat-sen University. CMV promoter-containing eukaryotic expression plasmid pEGFP-N1 was gifted by doctor Lu Zhi-yue from Medical College, Sun Yat-sen University.METHODS: Total RNA was extracted from BALB/c mouse fresh hepatic tissue and synthesized into cDNA by reverse transcription (RT). The synthesized cDNA was used as a template to perform a polymerase chain reaction (PCR) that amplifies a targeted fragment. Following double enzyme digestion, pEGFP-E-cadherin plasmids were reconstructed and transfected into mouse ESCs. In vitro differentiation of transfected mouse ESCs was performed.MAIN OUTCOME MEASURES: Detection of E-cadherin expression in the differentiation system using RT-PCR and immunocytochemistry and observation of adhesive capacity of differentiated cells.RESULTS: E-cadherin gene-transfected ESCs could stably express E-cadherin during differentiational 1-17 days, while non-transfected ESCs expressed a decreasing amount of E-cadherin. The adhesive capacity of differentiated cells that stably expressed E-cadherin was markedly enhanced. Compact cell connection and multi-layer growth state remained at 19 days. While non-transfected ESCs gradually changed from embryoid bodies into noncohesive cell populations.CONCLUSION: Differentiating E-cadherin ESCs exhibit markedly enhanced adhesive capacity and maintain multi-layer growth state.