[ ABSTRACT] AIM:To explore the effects of romidepsin ( FK228) , a novel histone deacetylase inhibitor, on the effector and regulatory T cells in vitro.METHODS:As the reactive cells, lymphocytes, CD4 +T cells and CD8 +T cells were labelled with CFSE, and stimulated with anti-CD3 and anti-CD28 mAbs in the presence and absence of different levels of romidepsin (experimental group and positive control group), or PBS (placebo group).After 72 h, the proliferation of the cells was detected in different groups.The lymphocytes were stimulated with anti-CD3 and anti-CD28 mAbs in the pres-ence and absence of different levels of romidepsin ( experimental group and positive control group ) , or PBS ( placebo group) .After 72 h, the percentage of CD4+Foxp3 +T cells and the levels of related cytokines were detected in different groups.RESULTS:The proliferation of CFSE-labelled lymphocytes, CD4 +T cells and CD8+T cells triggered by anti-CD3 and anti-CD28 mAbs all were inhibited when cultured with romidepsin at concentrations of 1 μmol/L, 3 μmol/L and 5 μmol/L in a dose-dependent manner (P<0.05).Compared with placebo group, in the presence of anti-CD3 and anti-CD28 mAbs, 1 μmol/L romidepsin did not increase the percentage of CD4 +Foxp3 +T cells ( P>0.05 ) .When cultured with romidepsin at concentrations of 3 μmol/L and 5 μmol/L, the percentage of CD4 + Foxp3 +T cells was enhanced markedly ( P<0.05) .The levels of IL-10 and TNF-αin the supernatant were markedly increased in positive control group
and 3 experimental groups ( P<0.05 ) , and the levels of cytokines in different experimental groups were gradually de-creased with the elevation of FK228 concentration (P<0.05).The level of TGF-βwas slightly increased in positive con-trol group with no significant difference compared with placebo group (P>0.05).With the increase in the concentration of FK228 in different experimental groups, the TGF-βlevel was increased in a dose-dependent manner and there were signifi-cant differences in the 3 experimental groups.Meanwhile, significant differences existed between experimental groups and placebo group and between experimental groups and positive control group (P<0.05).CONCLUSION:Romidepsin in-hibits the proliferation of CD4 +and CD8 +effector T cells and increases the percentage of CD4 +Foxp3 +regulatory T cells. It may be related to the increased level of TGF-β, but independent of IL-10.

Objective To analyze the outcomes of renal transplantation from donation after citizen death (DCD) in our single center.Method We retrospectively investigated the recipient outcomes of renal allografts from DCD.Between November 2010 and 31st December 2014,our institution performed 242 renal transplants from DCD.Outcome variables (survival of recipients/allografts and adverse events) and characteristics of marginal donor transplants were analyzed.Result There were 139 males and 44 females in the enrolled 183 donors,and the range of age was from 2 days to 68 years.183 donors included 102 cases of donation after brain death (category Ⅰ),22 cases of donation after circulatory death (category Ⅱ) and 59 cases of donation after brain death followed by circulatory death (category Ⅲ).Utilizing these renal allografts,we performed 242 kidney transplantations including 237 single kidney transplants and 5 pediatric en bloc kidney transplants.The age of recipients ranged from 12 to 64 years.The data indicated that the 1-year recipient/allograft survival rate was 93.8％ and 90.5％,respectively.The rate of delayed graft function (DGF) was 33.1 ％,higher than that from executed prisoners allografts (23.6％,P＜0.05).However,the rate of 1-year acute rejection,interstitial pneumonia and the other adverse events (urinary fistula,ureteral obstruction and cardiac and cerebral vascular accident,etc.) was similar to that from executed prisoners allografts.In addition,good results from pediatric and elder donor renal transplantation were shown in our data,even though the discard rate of elder donor kidney was high.Conclusion By comprehensive evaluation,strictly screening donors and enhancing the rnanagenent of donors,the long-term survival of recipients may be prolonged and the incidence of DGF and primary graft non-function (PNF) may be decreased.The marginal donors from pediatric and elder DCD donors could be utilized in clinical transplantation safely and effectively as long as reasonable evaluation was carried out.

Objective To evaluate the role of native ureter for the management of renal transplantation urological complications retrospectively.Method Twenty-six renal transplant recipients (18 males and 8 females) experienced the following urological complications:upper ureter injury,urinary leaks and moderate or severe ureteric obstructions secondary to ureterovesical anastomotic stricture.These complications have been managed with minimally invasive endourologic techniques or percutaneous nephrostomy as the first-line intervention.While endourologic treatment did not succeed,and the recipients have been treated with intraperitoneal open surgical correction.Urinary continuity was established by pyeloureterostomy or ureteroureterostomy using recipient native ureter.A pigtail ureteral stent was placed with the tip positioned in the pelvis of the graft and native bladder and removed after 4 to 6 weeks.Result The recipients were managed successfully during a follow-up period of 6 months to 6 years without occurrence of urological complications.One case underwent graft loss due to chronic rejection 5 years later postoperation,and the rest developed stable renal function with baseline serum creatinine.Conclusion Excellent outcomes have been achieved by the use of recipient native ureter for the management of urological transplant complications.This simple and efficient procedure should be considered as the superior choice for the recipients who experienced urological complications while less invasive endourologic techniques failed.

Objective To investigate the effects of treatment on end-stage liver disease and diabetes mellitus by simultaneous liver-pancreas-duodenum transplantation with the pancreas of the recipients reserved.Method Simultaneous liver-pancreas-duodenum transplantations were carried out in three patients with the pancreas of the recipients reserved.The diseases of the recipient 1,2,and 3 were alcoholic liver cirrhosis and diabetes mellitus,chronic hepatitis B liver cirrhosis and diabetes mellitus,and chronic hepatitis B liver cirrhosis and diabetes mellitus complicated with renal function failure.The recipient 3 received simultaneous renal transplantation.Result The recipient 1 suffered from pancreatitis after the operation and discharged with normal liver function and blood glucose levels,and he was treated with insulin at 4th year after the operation.Intestinal fistula occurred in the recipient 2 and drainage was done without acute peritonitis,the liver allograft was experienced an acute rejection episode treated by intravenous bolus methylpredisolone at 19th month after operation,but gastrointestinal perforation happened and the patient died of acute peritonitis.In the recipient 3,peripancreatic effusion and pancreatitis happened and were treated by drainage,and the recipient survived to now with normal liver and kidney functions,but given insulin at first year after operation.Conclusion It is effective to implement simultaneous liver-pancreas-duodenum transplantation with the pancreas of the recipients reserved on the patients with end-stage liver disease and diabetes mellitus.However,how to maintain the pancreatic endocrine function after the transplantation for a long period awaits further investigation.

Objective To analysis and summarize the diagnosis and treatment of acute humoral rejection after liver transplantation.Method The clinical data of 2 patients with humoral rejection after liver transplantation were analyzed.One patient with severe hepatitis B underwent ABO-incompatible liver transplantation and the donor blood type was AB and recipient blood type was A.Another patient with autoimmune liver disease was subjected to liver transplantation with the same blood type.Result Two patients were given tacrolimus,mycophenolate mofetil and prednisone immune suppression scheme.Anti-human lymphocyte immune globulin was used in case 1 for induction therapy.Both cases recovered well after liver transplantation in one week evaluated by the transplanted liver function,but liver function deteriorated from 7 days after transplantation.Titer of anti blood type B antibody was increased in case 1,and biopsy of transplantation liver confirmed acute humoral rejection.Plasma exchange,bortezomib plus intravenous immunoglobulin (IVIG) were used for therapy for acute humoral rejection,and acute humoral rejection in case 1 was reversed after treatment and graft function recovered gradually.However,the graft function was not improved after treatment in case 2,and liver graft biopsy showed no acute cellular rejection signs.Only few liver cells necrosis and cholangiole cholestasis were seen.The levels of HLA Ⅰ and Ⅱ class antibody were 3.4％ and 95.9％ respectively.We suspected acute humoral rejection in case 2.Plasma exchange,bortezomib plus IVIG were given,but liver graft function was not improved after treatment,and liver re-transplantation was done 2 months after first liver transplantation.Acute humoral rejection diagnosed pathologically.Conclusion We should alert the occurrence of acute humoral rejection in ABO-incompatible liver transplantation,and the patients with autoimmune liver disease due to the disorder of immune function after liver transplantation.Liver graft biopsy,and detection of the levels of panel reactive antibodies will help to diagnose the acute humoral rejection.The treatment should seize the opportunity and combine a variety of approaches.Liver re-transplantation is performed once the rejection can not be reversed

We report a case of reversible hepatofugal portal flow after auxiliary partial orthotopic liver transplantation (APOLT) from a living donor in this study. On postoperative day 6, continuous hepatofugal portal flow was observed in the grafted liver without portal thrombosis and obstruction of the hepatic vein. Based on histological findings, acute rejection was the suspected cause. The normal portal venous flow was restored after steroid pulse and antithymocyte globulin (ATG) therapies. The patient was discharged on the 30th postoperative day. It was concluded that hepatofugal flow after liver transplantation is a sign of serious acute rejection, and can be successfully treated by anti-rejection therapy.

Objective To analyze the curative effect of simultaneous liver and kidney transplantation (SLKT) for patients with end-stage liver and kidney diseases and liver cirrhosis patients with hepatorenal syndrome.Methods All SLKTs (n=21) performed at our center from January 1999 to December 2010 were reviewed and SLKT outcomes were compared with those of kidney transplantation (KT) (n=609) and liver transplantation (LT) (n=133) performed during the same period.Results There were 3 deaths due to infection 2 weeks, 6 months and 5 years respectively after operation. One patient died due to multiple organ dysfunction syndrome 2 weeks after operation. One patient was dead 5 years after operation because of rejection. MELD level between SLKT and LT had no significant difference, but serum creatinine in SLKT group was significantly higher than in LT group (516.0±329.9 vs 111.4±138.1 mmol/L, P<0.01). The 1-year acute kidney rejection rate and rate of delayed graft function (DGF) of the kidney had no significant difference between SLKT group (0 vs 9.5 %) and KT group (6 % vs 17.3 %). There was no significant difference in one-, 3- and 5-year patient survival rate between SLKT group (87.7 %, 67.8 % and 67.8 %) and LT group (84.2 %, 73.5 % and 69.4 %).Conclusion SLKT is a safe and effective treatment for end-stage liver and kidney diseases.

Objective To explore the factors associated with the quality of life (QOL) in patients after liver and kidney transplantation.Methods A multicenter cross-sectional survey was carried out in 5 Level Ⅲ Class A hospitals.153 liver transplant recipients and 301 kidney transplant recipients of outpatient clinic follow-up from March to December in 2015 were selected and investigated with a self-designed general state questionnaire,and Quality of Life Scale for Liver and Kidney Transplant Recipients which developed by our research group.Results There were significant differences in QOL total score in liver and kidney transplant recipients among groups of marital status and occupation.Divorced,unemployed and low-educated patients showed lower QOL total score than married,employed and high-educated ones (P ＜ 0.05).As compared with non-living-related transplantation group,patients undergoing living-related transplantation presented a better status in QOL total scores (P＜0.05).The QOL total score was obviously lower in patients suffering from complications and rejection than in those without occurrence of complications and rejection (P＜ 0.01).Postoperative time was correlated positively and significantly with QOL scores,and variances existed among different stages postoperation (P ＜ 0.01).Multivariable regression analysis demonstrated that education,marital status,postoperative time,type of donor and chemotherapy were the factors influencing liver transplant recipients' QOL,while marital status,postoperative time,type of donor,medical care assurance,complications and rejection after operation had effect on kidney transplant recipients.Conclusion Attaching importance to QOF among liver and kidney transplant recipients,and implementing scientific and effective nursing intervention based on the characteristics of them are necessary.

Objective To analyze the clinical effects of the diverse prevention strategies on donation after citizen's death (DCD) donor fungal infection.Methods A retrospective study was performed on the clinical data of the antifungal preventive scheme to 261 DCD donors from January 2015 to August 2015 (the first period) and September 2015 to December 2016 (the second period) in Tongji Hospital.During the first period,the donors were administrated by ICU doctors and the antifungal agents were not applied as routine.The processes of organ procurement and trim were in accordance with the past experience.During the second period,the donor maintenance was reinforced,including antifungal preventive scheme,aseptic manipulation of organ procurement and rinsing and immersing allografts with broad-spectrum antibiotics or diluting povidone-iodine solutions during organ trim.Microbial culture specimens were performed in 1 574 samples including blood samples,perfusion fluids and arterial tissues and the pathogen distribution at the different periods was identified.Result In the microbial culture specimens of 1 574 samples,907 strains of pathogens were detected,including 799 strains of bacteria and 108 strains of fungi.The positive rate of fungi was 12.0％ (108/907) of all pathogens,and 17.3％ (108/626) of fungal cultures specimens.The fungi positive rate in the second period (13.6％,59/433) was significantly lower than that in the first period (25.4％,49/193,P＜ 0.05).Conclusion It is essential to reduce the incidence of donor fungal infection by increasing the microbial cultures and antifungal preventive scheme.And it is necessary that the organ procurement organization team enhances the risk awareness of donor-derived fungal infection and improves the aseptic manipulation of organ procurement.Additionally,rinsing and immersing allografts with broad-spectrum antibiotics or diluting povidone-iodine solutions may be a better option for preventing the donor-derived fungal infection during the allograft trim.

Objective To report the modified technique and the short-term results of simultaneous pancreaticoduodenum-kidney transplantation (SPK) with the enteric drainage (ED) of exocrine secretions. Method Between June 2000 and Jan 2006, thirty-five patients with diabetes and uremia underwent SPK. The pancreas graft is placed intraperitoneally with its exocrine secretions drained into the proximal jejunum without Roux-en-Y procedure. The mean cold ischemic times of kidney was 6. 92?2. 17 hours and that of pancreas, 9. 65?2. 02 hours. Quadruple immunosuppressive therapy with antilymphocyte globulin or antiCD25 monoclonal antibody ( Zenapax ) , tacrolimus, mycophenolate mofetil and steroids was adopted. Results Postoperative patient and graft survival rates were 97. 3%. All patients achieved insulin-free euglycemia at 8.3?4.5 days postoperatively. Preoperative patient's mean fasting insulin and C-peptide values were 7.45?7. 35 mU/L and 5. 68?4. 66 mU/L. After operation, patients had fasting insulin and C-peptide values of 11. 9?5.70 mU/L and 5. 57?4. 90 mU/L, respectively, which peaked to an insulin level of 57. 9?46.6 mU/L and a C-peptide level of 11.75?6.99 mU/L with stimulation. The pancreas grafts also functioned well as evidenced also by normal serum amylase values of 92. 10?12. 24 U/L on 10th postoperative day. There were five cases of delayed renal graft function. All other patients achieved immediate renal graft function. No graft losses occurred due to leakage or intra-abdominal infection. The most commn surgical complications were wound infection (n - 11) , enteric anastomostic hemorrage ( n = 5) , and peri-renal hemorrage (n =2). Conclusions SPK is a effective treatment option for patients with diabetes mellitus and uremia. Enteric exocrine drainage by direct side-to-side anastomosis (without Roux-en-Y loop) seems to be a simple and reliable technique.