BACKGROUND: Liver cells are regulated by proliferation and apoptosis following ischemia/reperfusion injury, and the liver regeneration is obvious inhabited after ischemia/reperfusion injury, which can be relieved by ischemic preconditioning. However, the mechanism is still poorly understood.OBJECTIVE: To explore the effects of ischemic preconditioning on remained liver cell apoptosis and proliferation following autologous liver transplantation.DESIGN, TIME AND SETTING: The randomized controlled animal experiment was performed at the experimental animal center of Xiangya Medical College of Central South University from September 2006 to July 2007.MATERIALS: Totally 144 male Sprague Daweley rats were randomly divided into hepatic resection, auto-transplantation, ischemic preconditioning groups, with 48 animals in each group.METHODS: Rats in the hepatic resection group were underwent left hepatic lobe and median lobe resection without blocking blood current at the right hepatic lobe and caudal lobe. In the auto-transplantation group Venous traffic branches of rats were broke, with liberating caudate lobe, first porta hepatis, and inferior vena cava, followed by blocking and continuous hypothermical perfusion preservative fluid via porta hepatic, simultaneously, anemia hepatectomy was performed (left hepatic lobe and median lobe was resected). The liver was washed and preserved in cold preservation solution for 15 minutes. At the end, portal triad clamping was removed and underwent abdominal closure. The procedure of rats in the ischemic preconditioning group was identical to auto-transplantation group except 10 minutes blocking and 10 minutes recover the blood flow at right hepatic lobe and caudal lobe prior to portal vein perfusion. Liver tissues were harvested at hours 0, 1, 3, 6, 12, 24, 48 and 72 after hepatic resection in 3 groups. MAIN OUTCOME MEASURES: Contents of aspartate aminotransferase and alanine aminotransferase were calculated by biochemical analyzer. The index of cell apoptosis was detected by flow cytometry. In addition, proliferation of liver cells was measured by Ki-67 expression. RESULTS: Compared to the auto-transplantation group, the levels of alanine aminotransferase and aspartate aminotransferase were dramatically decreased in hepatic resection and ischemic preconditioning groups at each time point exception with 0 hour after operation (P < 0.05). Few apoptosis cells existed in each group at 0 hour after operation. The index of cell apoptosis increased slightly after resection in the hepatic resection group, which was sharp increased in the auto-transplantation group after reperfusion, reached a peak at 12 hour, and then gradually decreased. Compared auto-transplantation group, the index of cell apoptosis in ischemic preconditioning group was significantly decreased (P < 0.05). The expression of Ki-67 in 3 groups increased after hepatic resection, peaked at 24 hour after hepatic resection, then decreased lower and lower. Compared to the hepatic resection group, the expression of Ki-67 in auto-transplantation group was significantly lower after hepatic resection (P < 0.05). Compared to the auto-transplantation group, the expression of Ki-67 in ischemic preconditioning group was significantly increased after hepatic resection (P < 0.05).CONCLUSION: Ischemic preconditioning can decrease cell apoptosis and promote cell proliferation after rat's liver auto-transplantation, which may be one mechanisms of ischemic preconditioning in promoting liver regeneration.

Objective:To identify the polymorphisms of cytochrome P450 3A5 gene (CYP3A5) and multidrug resistance gene 1 (MDR-1) and their distributions in Hans renal transplant recipients in Hunan province, we analyzed the difference of the gene polymorphisms and distributions between Hunan province and 11 other provinces of China.
Methods:We collected 598 Hans renal transplant recipients who had operation or follow-up examination in 3rd Xiangya Hospital from Hunan province. We examined the gene polymorphisms of CYP3A5 and MDR-1 and compared their distributions with the data from 11 other provinces of China by chi-square test.
Results:hTere were CYP3A5*1/*1 genotype in 58 cases (9.7%), CYP3A5*1/*3 genotype in 251 cases (42.0%), CYP3A5*3/*3 genotype in 289 cases (48.3%);MDR-1 3435CC genotype in 238 cases (39.8%), MDR-1 3435CT genotype in 263 cases (44.0%), MDR-1 3435TT genotype in 97 cases (16.2%). Frequency of CYP3A5*1/*1 and*1/*3 genotypes of Hunan province was higher than the that from the 11 other provinces of China and the frequency of mutator*3 was lower. Frequency of MDR-1 3435CC and 3435CT genotypes of Hunan province was higher and the frequency of mutator T was lower than that from the 11 other provinces of China.
Conclusions:There were significant difference in gene polymorphisms and distributions of CYP3A5 and MDR-1 between Hunan province and the 11 other provinces of China. It may be a guideline for us to use calcineurin inhibitor drugs in the early stage atfer renal transplantation.

Objective To summarize the clinical experience of standard piggyback liver transplantation(SPBLT) and modified piggy-back liver transplantation(MPBLT) in the treatment of Wilson′s disease(WD).Methods The clinical records of 29 cases of WD who underwent piggyback liver transplantation over the recent 12 years were analyzed retrospestively.Among them,there were 22 male and 7 female patients,with 6cases aged 8-14y and 23 cases aged 24-37y,who underwent liver transplantation because of chronic advanced liver disease(18cases),fulminant hepatic failure(2 cases),or with normal liver function(9 case),and among them,24 cases showed neurological dysfunction.The modes of operation included SPBLT(13 cases) and MPBLT(16 cases).Results The patients were followed up for 1 month-12 years with the median follow-up time of 47 months.Four patients died in the perioperative period,of which 2 died of hepatic failure due to obstruction of hepatic venous return after SPBLT,and 2 died of hepatic artery thrombosis and bile leakage combined with severe infection.The recipient survival rate at 1 year and 3 years was 86% and 79% respectively.One patient has survived for 12 years.All the levels of serum copper and copper-protein recovered to normal in four weeks post-operatively.Neurological symptoms improved in varying degrees after operation.Conclusions WD patients who undergo PBLT can expect a satisfactory clinical outcome and a good quality of life,and MPBLT can effectively reduce the complications of operation and improve the operation survival rate.

OBJECTIVE: To evaluate the risk factors of delayed graft function (DGF) and its impact on renal transplantation from donation after cardiac death (DCD). METHODS: We conducted a retrospective study consisting of 48 subjects who underwent a DCD kidney transplantation from February 2010 to March 2012. We classified the recipients into two groups: an IGF (immediate graft function) group (n=30) and a DGF group (n=18), and analyzed the risk factors of DGF and its impact on transplantation. RESULTS: DGF occurred in 18 of the 48 (37.5%) kidneys from DCD donors, and the occurrence of DGF did not adversely influence the survival of patients (P=0.098) and graft (P=0.447). In the univariate analysis, the preoperative dialysis time of recipients (P<0.001), HLA mismatch site (P<0.001), the cause of brain death (P=0.011), BMI (P<0.001), preoperative serum creatinine of donors (P=0.0001), norepinephrine used in donors (P<0.001), warm ischema time (WIT) (P<0.001), cold ischema time (CIT) (P<0.001) showed significant differences. In the multivariate analysis, cerebral hemorrhage as the cause of brain death (P=0.022, OR=39.652), preoperative serum creatinine of donors≥177 μmol/L (P=0.008, OR=57.148) and the preoperative dialysis time of recipients≥12 months (P=0.060, OR=15.060) were independent risk factors for DGF development. CONCLUSION The independent risk factors for DGF are the cause of brain death, the terminal creatinine level, and the preoperative dialysis time.
Brain Death ; Creatinine ; blood ; Delayed Graft Function ; Graft Survival ; Humans ; Kidney ; physiopathology ; Kidney Transplantation ; Multivariate Analysis ; Renal Dialysis ; Retrospective Studies ; Risk Factors ; Time Factors ; Tissue Donors

Objective To investigate modified technique of renal transplantation model in rats.Methods Sprague-Dawley rats were selected as donors ( n=21 ) and Wistar rats as recipients ( n=42 ) .Renal allografts of both sides were harvested from the donors for renal transplantation.After resection of left kidney , end-to-end anastomosis of renal arteries between donor and recipient was performed by the assistance of home-made catheter.And end-to-end anastomosis between recipient's renal vein and donor's inferior vena cava was also performed.The donor's ureter with bladder patch was anastomosed to the recipient's bladder.Finally the right kidney was removed , cefminox (10 mg) was injected intraperitoneally , and then the abdominal cavity was closed.The operation data were recorded , including the operation time , artery and vein anastomosis time , cold and warm ischemia time and so on.Living for 3 days after operation was regarded as a success model.The success rate of modeling was calculated and the cause of death was analyzed.Results The operation time of donor was (32.7 ±5.6) min, and repair time for kidney was (4.2 ±1.1) min.The operation time of recipient was (42.3 ±42.3) min, including (10.1 ±3.2) min of the artery anastomosis time , (13.9 ±2.5) min of vein anastomosis time, (6.3 ±1.4) min of urinary tract reconstruction time.Warm ischemia time was (5.4 ± 1.8) s, and cold ischemia time was (56.2 ±7.3) min.In 42 recipient rats, 40 rats were successful modeling and the success rate was 95.2%.Two rats died.One died of artery anastomosis hemorrhage , and the other died of diffuse peritonitis caused by urine leakage.Conclusions Renal transplantation model in rats with modified vascular end-to-end anastomosis has the characters of simple handling , short operation time and high success rate.

Objective To observe the clinical efficacy and safety of direct-acting antiviral agents(DAAs)in the treatment of hepatitis C after renal transplantation. Methods Six patients were complicated with hepatitis C virus(HCV) at 8 to 43 months after renal transplantation with a median time of 19 months. Prior to treatment, the virus load was detected from 4.03×103 to 8.18×107 IU/mL. Four cases were administered with tacrolimus(FK506)+mycophenolate mofetil(MMF)+prednisone(Pred), and the remaining 2 received cyclosporin(CsA)+MMF+Pred. The serum creatinine level was lower than 200μmol/L. The amount of urine and body weight remained stable. No severe mental irritation or trauma history wasreportedwithin6monthsbeforeantiviraltherapy.SixpatientsdidnotreceivegenotypetestofHCVbeforeDAAstherapy. Fourpatientswereadministeredwithsofosbuvir,1withsofosbuvir+ledipavirand1withsofosbuvir+daclatasvirfor12weeks. The complete blood cel count, serum transaminase level, creatinine level and blood concentration of immunosuppressive agents were measured each week and serum HCV RNA level was quantitatively detected every 4 weeks. Results Among 6 patients, 5 were negative for HCV at 4 weeks after DAAs therapy and obtained sustained virological response(SVR)after DAAs treatment. One case administered with sofosbuvir alone was positive for HCV after DAAs therapy. The patient was infected with genotype 5 HCV. After 12-week administration of sofosbuvir+daclatasvir, the patient was negative for HCV and obtained SVR. No significant changes were observed in complete blood cel count, serum transaminase level, creatinine level and blood concentration of immunosuppressive agents. Adverse reactions included evanescent eruption in 1 case and mild dizziness in 1 case. Conclusions DAAs treatment is an effective and safe approach for patients with stable renal function after renal transplantation. Combined use of sofosbuvir+daclatasvir is recommended as the optimal therapy.

Objective To investigate the correlation between red cell volume distribution width (RDW) and the mortality rate of acute respiratory distress syndrome (ARDS) patients after renal transplantation. Methods Clinical data of 106 ARDS patients undergoing renal transplantation were retrospectively analyzed. According to RDW, all patients were assigned into the normal (≤15.0%, n=68) and increasing RDW groups (>15.0%, n=38). Baseline data and the incidence of adverse events were statistically compared between two groups. Kaplan-Meier survival curve was adopted to compare the 50 d-mortality rate between two groups. Cox's proportional hazards regression model was utilized to identify the risk factors of the mortality of ARDS patients. Results Among 106 patients, the 50 d-mortality rate was calculated as 43.4% (46/106). The sequential organ failure assessment (SOFA) score, serum creatinine, hemoglobin and platelet count significantly differed between two groups (all P<0.05). In the increasing RDW group, the 50 d-mortality rate and the incidence of infectious shock were significantly higher than those in the normal RDW group (both P<0.05). Kaplan-Meier survival curve demonstrated that the 50 d-mortality rate significantly differed between two groups (P<0.01). Cox's proportional hazards regression model univariate analysis revealed that hemoglobin level<100 g/L, serum creatinine>133 μmol/L, platelet count<100×109/L, severe ARDS and RDW>15.0% were the potential risk factors of the 50 d-mortality rate in ARDS patients (all P<0.05). Multivariate analysis demonstrated that severe ARDS [odd ratio (OR)=12.77, 95%confidence interval (CI) 11.63-15.39, P<0.001] and RDW>15.0% (OR=2.01, 95%CI 1.02-3.94, P<0.043) were the independent risk factors of the 50 d-mortality rate in ARDS patients. Conclusions RDW elevation is correlated with the severity of disease and 50 d-mortality rate in ARDS patients following renal transplantation. RDW can serve as a clinical parameter to predict the prognosis of ARDS patients after renal transplantation.

OBJECTIVE: To evaluate the recovery of patients with end-stage renal disease (ESRD) receiving kidney transplant from cardiac death donors, and to assess graft survival in China from this type of donor. METHODS: A total of 48 cases of patients with ESRD have received the kidneys from cardiac death donors in our hospital between February 2010 and March 2012. We retrospectively analyzed data on the preoperative and postoperative serum creatinine concentrations, on the survival of recipients and allografts with a view to investigating prognoses after this type of kidney transplant. RESULTS: Primary non-function (PNF) did not occur in any of the 48 recipients. Delayed graft function (DGF) occurred in 18 of 48 (37.5%) of kidneys from cardiac death donors, but the occurrence of DGF did not adversely influence patient's survival (P=0.098) or graft survival (P=0.447). Seven of 48 (14.6%) recipients lost their graft. Over a median follow-up period of 8 months (range 0.5-23 months), 39 of 41(95.1%) recipients' graft function had fully recovered. The actuarial graft and patient's survival rates at 1, 3, 6 and 12 months after transplantation were 95.7%, 93.0%, 90.0%, 87.5%, and 100%, 94.9%, 90%, 87.5%, respectively. CONCLUSION As the legislation of donation after brain death (DBD) has not been ratified in China, the use of kidneys from cardiac death donors might be an effective way to increase the number of kidneys available for transplantation here. Our experience indicates good short- and mid-term outcomes with transplants from cardiac death donors.
Adult ; Brain Death ; Cadaver ; Death, Sudden, Cardiac ; Delayed Graft Function ; epidemiology ; Female ; Graft Survival ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; Tissue Donors ; statistics & numerical data

BACKGROUNDOur goal was to evaluate the outcomes of kidney transplants from controlled cardiac death donors compared with brain death donors by conducting a meta-analysis of cohort studies.

METHODSThe PubMed database and EMBASE were searched from January 1980 to July 2013 to identify studies that met pre-stated inclusion criteria. Reference lists of retrieved articles were also reviewed. Two authors independently extracted information on the designs of the studies, the characteristics of the study participants, and outcome assessments.

RESULTSNine cohort studies involving 84 398 participants were included in this meta-analysis; 3 014 received kidneys from controlled cardiac death donors and 80 684 from brain death donors. Warm ischemia time was significantly longer for the controlled cardiac death donor group. The incidence of delayed graft function was 2.74 times (P < 0.001) greater in the controlled cardiac death donor group. The results are in favor of the brain death donor group on short-term patient and graft survival while this difference became nonsignificant at mid-term and long term. Sensitivity analysis yielded similar results. No evidence of publication bias was observed.

CONCLUSIONThis meta-analysis of retrospective cohort studies suggests that the outcome after controlled cardiac death donors is comparable with that obtained using kidneys from brain death donors.