Organ transplantation is the most effective treatment for endu2010stage organ disease. One of the major challenges in organ transplantation is organ shortage. For this reason, more and more extended criteria donor organs, including those from donation after circulatory determination of death (DCDD), are used in clinical practice. However, DCDD organs suffer from additional warm ischemic damage, which seriously affects transplant outcomes and organ utilization. Recent studies at home and abroad have shown that the application of normothermic regional perfusion (NRP) is able to improve the quality of organs and transplantation outcomes. At present, an expert consensus on the clinical application of NRP in DCDD is lacking in China, which limits the standardization and highu2010quality development of DCDD in our country. We summarized the results of clinical studies and conducted inu2010depth discussions based on the principles of evidenceu2010based medicine to form this consensus on the application of NRP in DCDD. This consensus focuses on the executive specification and corresponding research evidence of applying NRP technology in DCDD, aiming to provide reference opinions and guidance for the standardization of NRP in organ transplantation and to promote the rapid development of NRP technology and DCDD organ transplantation in China.

The occurrence of fungal infection seriously affects the survival and life quality of transplanted patients. The accurate diagnosis is of particular importance in the early stage of infection. To develop a novel diagnostic method for this kind of patient, we established a post-transplant immunosuppressed mice model with fungus inoculation and collected their peripheral blood at specific time points after infection. After screening by microarray, differentially expressed miRNAs and lncRNAs were selected and homologously analyzed with those of human beings from the gene database. These miRNAs and lncRNAs candidates were validated by qRT-PCR in peripheral blood samples from transplanted patients. We found that, compared with normal transplanted patients, the levels of miR-215 and miR-let-7 c were up-regulated in the plasma of patients with fungal infection (P < 0.01), while levels of miR-154, miR-193a, NR_027669.1, and NR_036506.1 were down-regulated in their peripheral blood mononuclear cells (P < 0.01). Principal component analysis shows that the expression pattern of the above RNAs was different between the two groups. A 6-noncoding-RNA detection panel was established by the support vector machine analysis, whose area under the ROC curve was 0.927. The accuracy, precision, sensitivity, and specificity of this model were 0.928, 0.919, 0.944, and 0.910, respectively. Though our detection panel has excellent diagnostic efficacy, its clinical application value still needs to be further confirmed by multi-center prospective clinical trials.

Viral infection seriously affects the survival and life quality of transplanted patients without an accurate diagnosis during the early stage. Herein, we aimed to develop a novel diagnostic method based on non-coding RNAs expression in peripheral blood. An immunosuppressive mouse model of viral infection after transplantation was established. Differentially expressed non-coding RNAs were distinguished by microarray analyses in the virus-infected group. After homology analysis, 46 miRNAs and 24 lncRNAs were further verified by qRT-PCR in the peripheral blood samples of transplanted patients. Compared with normal transplanted patients, miR-29b, miR-185, and NR_073415.2 were significantly downregulated in the PBMC of post-transplant patients with viral infection. Based on the expression of the above three RNAs, principal component analysis (PCA) identified a slight overlap between the two groups. A 3-non-coding-RNA detection panel was constructed by the support vector machine analysis (SVM), whose loss rate was 14.71%. The area under the curve of it was 0.909. With the optimal cut-off value (Y = 0.328), the sensitivity was 0.929 and the specificity was 0.781. Therefore, based on non-coding RNAs expressions, a detection panel for viral infection after organ transplantation was formed with high diagnostic specificity and sensitivity.

Vascular invasion, rather than tumor size, was applied into the 7th edition of the AJCC TNM staging system to predict survival of solitary hepatocellular carcinoma (HCC) patients. However, does this mean tumor size is of little value in prognostic prediction? The current study was designed to explore the prognostic ability of tumor sizes in solitary HCC.

Exportin‐T (XPOT) belongs to the RAN‐GTPase exportin family that mediates export of tRNA from the nucleus to the cytoplasm. Up‐regulation of XPOT indicates poor prognosis in breast cancer patients. However, the correlation between XPOT and hepatocellular carcinoma (HCC) remains unclear. Here, we found that high expression of XPOT in HCC indicated worse prognosis via bioinformatics analysis. Consistently, immunohistochemical staining of 95 pairs of tumors and adjacent normal liver tissues (ANLT) also showed up‐regulation of XPOT. Small interfering (si) RNA transfection was used to down‐regulate XPOT in HepG2 and 7721 cell lines. Cell Counting Kit‐8 (CCK8) assays were performed to analyze cell proliferation. Cell migration and invasion were measured by scratch wound healing assays and migration assays. Subcutaneous xenograft models were using to explore the role of XPOT in tumor formation in vivo. Down‐regulation of XPOT significantly inhibited tumor proliferation and invasion in vitro and vivo. Gene set enrichment analysis (GSEA) results indicated that XPOT may affect tumor progression through cell cycle and ubiquitin‐mediated proteolysis. Furthermore, knockdown of XPOT caused a block in G0/G1 phase as evidenced by down‐regulation of cyclin‐dependent kinase 1 (CDK1), cyclin‐dependent kinase 2 (CDK2), cyclin‐dependent kinase 4 (CDK4), CyclinA1 (CCNA1), CyclinB1 (CCNB1), CyclinB2 (CCNB2), and CyclinE2 (CCNE2) in HCC cells. In conclusion, our findings indicate that XPOT could serve as a novel biomarker for prognoses and a potential therapeutic target for patients with HCC.

目的 评估熊去氧胆酸(UDCA)降低肝移植受者术后胆道并发症(BC)的临床疗效.方法 选取2011年7月至2013年12月于中山大学附属第一医院行肝移植术的215例受者作为本次研究的评估对象.采用随机对照研究方法.入组病例按2:1随机分为用药组和空白组,用药组受者于肝移植术后第1天起每天服用UDCA 250 mg,2次/d;空白组不服用UDCA或其他安慰剂,治疗时间为6个月,停药后继续随访6个月.研究观察终点为复合观察终点,包括非外科因素引起的缺血性胆道病变(ITBL)、术后1个月后由非外科及排斥反应引起的总胆红素(TBIL)>51.3μmol/L、移植物失功、受者死亡.比较两组受者术前一般情况、手术相关情况、术后各项生化指标、术后转归情况、复合观察终点累积发生率、受者生存比例及移植物累积存活率.采用两独立样本t检验或基于秩次的两独立样本Wilcoxon检验比较年龄、Child-Pugh评分和冷缺血时间等定量资料.用卡方检验或Fisher确切概率法比较开腹手术史、激素诱导等定性资料.采用Kaplan-Meier法绘制生存曲线,利用log-rank检验比较两组复合观察终点累计发生率.P<0.05为差异有统计学意义.结果 60例受者纳入研究:空白组20例,用药组40例.两组受者术前基线情况可比.手术相关情况(冷缺血时间、手术时间、无肝期、热缺血时间、术中出血量、红细胞输注量、ICU住院时间及激素诱导情况)差异均无统计学意义(t=1.12,U=298,U=331,U=359,U=344,U=398,U=329,χ2=0.01,P均>0.05).空白组受者肝移植术后第1、2、3周血清γ-谷氨酰转肽酶,第2、3、4周血清碱性磷酸酶及第2、3、6个月血清总胆汁酸水平均高于用药组,差异均有统计学意义(U=206、160、148、222、211、219、144、140和94,P均<0.05).空白组受者术后第1、6、12个月复合观察终点累计发生率分别为15%、15%、28%,用药组分别为3%、18%、18%,两组差异均无统计学意义(χ2=0.66,P>0.05).空白组受者术后第1、6、12个月生存比例分别为90%、90%、84%,用药组均为97.5%.两组差异均无统计学意义(χ2=3.28,P>0.05).空白组受者术后第1、6、12个月移植物累积存活率分别为90.0%、84.4%、77.9%,用药组均为97.5%,两组差异均有统计学意义(χ2=5.13,P<0.05).结论 UDCA对移植肝具有保护作用,可有效减轻由缺血再灌注及疏水性胆汁酸造成的移植肝损伤,促进移植肝酶学指标恢复正常. 用药组移植物存活率优于空白组,但在复合观察终点比较中未能显示出降低胆道并发症的临床效果.

Objective To observe the diagnosis and treatment of acute pancreatitis (AP) induced by the brain trauma and cerebral stroke in donors from donation after citizen death (DCD),and maintenance of organ functions.Method The clinical data of 32 patients with different degrees of AP after brain trauma and cerebral stroke admitted by organ donation program between July 2011 and June 2015 were retrospectively analyzed.The donors with abdominal trauma and trauma after drinking were recruited.The serum amylase and lipase levels were increased in the first time,will be diagnosed as acute pancreatitis;Based on the original treatment,immediately given Ulinastatin,somatostatin and strengthen anti infection treatment;monitoring of serum amylase and lipase levels;color Doppler ultrasound examination of the pancreas;Identification of pancreatitis grading by careful investigation of the pancreatic appearances in organ procurement operation.Result 24 males and 8 females,aged from 16 to 57 years,Median-age 36 years.Cerebral stroke 13 cases,brain trauma 19 cases;Initial examination of serum amylase 440.06 ± 144.93 U/L (normal reference value ranges from 30 to 110 U/L),serum lipase 1045.22 ± 103.20 U/L (normal reference value 20-300 U/L);Treatment after 72h,serum amylase 120.78 ± 40.34 U/L,serum lipase 279.63 ± 103.20 U/L;Diagnostic accuracy of color Doppler ultrasound in acute pancreatitis was about 56％.Results from organ procurement operation:31 cases of acute pancreatitis,1 cases of normal appearance.Conclusion After potential donor into the donation program,routinely monitoring of pancreatitis related blood index including serum amylase and serum lipase,early diagnosis and early treatment,continuous monitoring of Results of the index to observe the effect of treatment,The condition of acute pancreatitis-induced by the brain trauma and cerebral stroke donors is not serious,they will be reversible after treatment and reduce the damage for other organs to be donated.

Objective To investigate the surgical techniques of simplified abdominal multiple organs transplantation in patients with end stage liver disease and diabetes.Method The clinical data of 22 cases of simplified abdominal multiple organs transplantation were retrospectively analyzed.The primary diseases included liver cirrhosis after hepatitis B (9 cases), hepatocellular carcinoma (11 cases), cholangiocellular carcinoma (1 case) and primary biliary cirrhosis (1 case).All patients were rendered dependent from insulin therapy before transplantation.Duration of diabetes was (4.8 ± 3.8) years.Mean level of glycosylated hemoglobin and C-peptide in all recipients was (7.5 ± 1.5)％ and 0.66 ± 0.35 nmol/L respectively before transplantation.The pancreas and the whole digestive tract of the recipients were reserved.The liver and pancreas duodenal organ cluster grafts were implanted after the resection of the diseased liver.The liver and kidney function, blood glucose, C-peptide, infection, rejection, vascular complications, biliary complications and other indicators were monitored postoperatively.Result Median posttransplant follow-up was 15.0 months (1.0 to 78.0 months).From two weeks after operations, no insulin was used in 21 patients, and the blood glucose levels were returned to almost normal.Mean glycosylated hemoglobin values decreased from pretransplant (7.5 ± 1.5)％ to (4.9 ± 0.3)％ 3 months posttransplantation (P＜0.05).Mean C-peptide values increased from pretransplant 0.66 ± 0.35 nmol/L to 1.13 ± 0.69 nmol/L 3 months posttransplantation (P＜ 0.05).There was only one recipient who remained exogenous insulin (24 U/day) dependence 10 months after transplantation.Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin became normal after 1 week.So far of the followed up, there was no bilary complication.Among the 22 patients, calculated 1 , 2-and 5-year survival rate was currently 95.5％, 88.1 ％ and 88.1 ％, respectively.Conclusion Our results indicate that simplified abdominal multiple organs transplantation is technically feasible and leads to less operation time than traditional multiple organs transplantation, with excellent control of glucose metabolism in patients with end-stage liver disease and diabetes.

尽管我国已有多个中心开展腹部多器官移植手术,但形成规模并取得良好疗效和社会效益的中心有限,这与移植器官来源短缺,移植医师对此类手术认识不足,缺乏相关手术技术及围手术期管理经验等因素有关.为推动我国腹部多器官移植的临床应用,提高移植疗效,作者结合中山大学附属第一医院器官移植中心的临床实践,着重从腹部多器官移植适应证、手术方式选择、围手术期处理、长期疗效几个方面展开介绍.

Objective To analyze the experience of donation after citizens death,and investigate the questions in our country.Method The organs were obtained from 130 cases of organ donation in a single center,and the clinical data were analyzed retrospectively.Result From July 2011 to June 2014,there were 105 males and 25 females in the enrolled 130 donors,and the oldest age was 62 years and youngest one was only 10 months.130 donations included 15 cases of donation after brain death (DBD),73 cases of donation after cardiac death(DCD),and 42 cases of donation after brain death awaiting cardiac death(DBCD).In 73 cases of DCD,there were 66 cases of Maastricht category Ⅲ and 7 cases of Maastricht category Ⅴ.With these donated organs,122 cases of liver transplantations,228 cases of renal transplantations,12 cases of heart transplantation,2 cases of lung transplantations,6 cases of multivisceral transplantation and 4 cases of in vivo splitting liver transplantation were carried out successfully.Conclusion By strict screening and evaluation,the organs of donation after death can be utilized in clinical organ transplantation safely and effectively.

BACKGROUND AND OBJECTIVES:Chronic kidney disease (CKD) has become a critical problem due to immunosuppressant related nephrotoxicity in liver transplant (LTx) recipients, especially in patients with pre-transplant risk factors. LTx recipients with uraemia and diabetes have poor prognosis even when treated with dialysis and insulin. Simultaneous pancreas and kidney transplantation (SPK) has been proven to be an effective treatment for patients with diabetic uraemia, but rarely performed in patients after LTx. Two cases of SPK after LTx were performed in our centre and we present our experience here. PATIENTS AND METHODS:Two patients received LTx because of HBV related liver cirrhosis; both of them had pre-transplant diabetes mellitus (DM), which worsened after the administration of immunosuppressive drugs. These two patients suffered from CKD and developed uraemia due to diabetic nephropathy and immunosuppressive drugs induced renal toxicity years after LTx. They relied on dialysis and insulin injection. SPK were performed years after LTx and the clinical data was retrospectively analyzed. RESULTS:SPK was successfully performed in these two patients. Pancreatic fluid drainage was achieved via a side-to-side duodenojejunostomy into the proximal jejunum. No serious surgical complications, including pancreatitis or pancreatic fistula were observed postoperatively. In both cases, kidney and pancreatic grafts were functioning well as evidenced by euglycemia without the need for insulin injections and normal serum-creatinine level 7days after the operation. One of the patients presented with renal graft impairment 1week after the operation. FK506 was tapered and rapamycin was used when the renal graft biopsy indicated drug toxicity. The patient's kidney graft function recovered gradually after the adjustment. Both patients have good function of liver, kidney and pancreas grafts during a 60-month and 30-month period of follow up. CONCLUSIONS:SPK could serve as an effective option for patients with diabetes and uremia after LTx. Perioperative management, especially the immunosuppressive strategy is crucial to improve the outcome of this procedure.

Objective To investigate the clinical efficacy of combined en-bloc liver-pancreas transplantation in patients with end-stage liver disease and diabetes mellitus.Method The clinical data of 19 cases of combined en-bloc liver-pancreas transplantation were retrospectively analyzed.The primary diseases of 19 cases included 9 cases of liver cirrhosis after hepatitis B,7 cases of hepatocellular carcinoma,and cholangiocellular carcinoma,and alcoholic cirrhosis of the liver and biliary complications after liver transplantation in 1 case each.All patients were rendered dependent from insulin therapy (62.3 ± 26.8 U/day) before transplantation,and duration of diabetes mellitus was (4.0 ± 3.6) years.Mean levels of glycosylated hemoglobin and C-peptide in all recipients were (7.9 ± 1.7)％ and (0.68 ± 0.40) nmol/L before transplantation.The pancreas and the whole digestive tract of the recipients were reserved.The liver and pancreas duodenal organ cluster grafts were implanted after the resection of the diseased liver.The liver and kidney function,blood glucose,C-peptide,infection,rejection,vascular complications,biliary complications and other indicators were monitored postoperatively.Result Median posttransplant follow-up was currently 25.8 ± 25.4 months (1 to 96 months).From two weeks after operations,no insulin was used in 18 patients,and the blood glucose levels returned to almost normal.Mean glycosylated hemoglobin values decreased from pretransplant (7.9 ± 1.7)％ to (5.0 ± 0.3)％ 3 months posttransplantation (P＜0.05).Mean C-peptide values increased from pretransplant 0.68 ± 0.40 nmol/L to 1.20 ± 0.78 nmol/L 3 months posttransplantation (P ＜ 0.05).There was only one recipient (5.3 ％) who remained exogenous insulin (24 U/day) dependence 45 days posttransplantation.Alanine aminotransferase (ALT),aspartate aminotransferase (AST) and total bilirubin became normal after one week.So far of the followed up,there was no bilary complication.Among the 19 patients,only three recipients died.One died of graft-versus-host disease at first month after operation,one died of acute monocytic leukemia at 12.5 months after operation,and one died of digestive tract perforation and peritonitis at 26 months after operation.Conclusion Our results indicate that combined en-bloc liver-pancreas transplantation is technically feasible and leads to excellent long-term control of glucose metabolism in patients with end-stage liver disease and diabetes mellitus.