Objective To study the incidence of malignant tumors in renal allografts and explore the mechanism of increased incidence.Method A retrospective study was performed on 1814 renal allografts under immunosuppression from 1998-2010.Result Twenty-nine cases of malignant tumors were found in 1814 cases undergoing renal transplantation with the incidence being 1.60％.Among these cases,the incidence of urinary system tumor was 72.4％,that of hepatoma carcinoma was 10.3％,that of lung cancer was 6.9％,and each of lymphoma,cutaneous cancer or nasppharyngeal carcinoma was 3.4％.Most patients accepted operations,additional therapies including chemical or radiological and immunological therapies.Conclusion The incidence of malignant tumors in renal allografts was higher than normal persons.Besides the outcome of immunosuppression,the effects of transplantation itself and primary disease before transplantation,for instance,the higher incidence of uroepithelium malignancy was frequently associated with history of long term medications.

Objective To study the incidence of malignant tumors in the patients undergone renal transplantation, and to explore the mechanism of higher incidence. Methods A retrospective study was performed on 829 patients undergone renal transplantation followed by immunosuppression therapy from 1998-2006. 15 cases developed malignant tumors among the 829 patients with incidence of 1.9%. The incidence of urinary system tumor was 66.7%, of hepatoma was 13.3%, and 6.7% for lymphoma, cutaneous cancer and pulmonary carcinoma respectively. Results 15 patients suffered from renal tumors 11-73 months after kidney transplantation, in whom renal function was normal in 14 patients, and in 1 patient the grafted kidney showed dysfunction. No tumor metastasis was found in those cases, except in 3 patients ureteral lumen infiltration was found. Most patients accepted operations, with the dose of the immuosurpression drugs adjusted or reduced, and supplemented with chemotherapy or rediotherapy and immunotherapy. Conclusions The pathogenesis might be related with immunosuppression drugs postoperatively, and also the effects of transplantation itself and the primary disease before transplantation, for instance, uroepithelium malignancy was prolonged medication was frequently the reason for renal transplantation.

Objective To compare the applied value of BK virus DNA load detection in urine and plasma for diagnosis BK virus nephropathy (BKVN) in renal transplantation recipients.Method In 88 renal transplantation recipients receiving renal allograft from February 2011 to January 2012 in our institute,BK virus DNA load in urine and plasma was detected by using real-time PCR,and renal biopsy was performed on the recipients with gradual deterioration of the graft function or the loads of BKV replication being very high.The diagnosis of BKVN was confirmed by using immunohistochemistry.Results Of 88 recipients,there were 35 cases (39.8％) of viruria,18 cases (20.5％) of viremia and 5 cases (5.7％) of BKVN.The median BKV DNA load in both urine and plasma in BKVN recipients was significantly higher than in non-BKVN recipients (P＜0.05).The viruria sensitivity and specificity for BKVN were 100％ and 57.3％ (P =0.03),and the viremia sensitivity and specificity for BKVN was 100％ and 82.9％ (P =0.0002),respectively.We regraded viral load ≧ 105 copies/mL in plasma or ≥107 copies/mL in urine as the best discriminant cut-off value to predict the disease and to identify patients at risk of developing BKVAN.The positive cut-off value of urine's positive predictive value (PPV+) was 26.3％ and negative predictive vaule (PPV-) was 95.7％,and the positive cut-off value of plasma's positive predictive value (PPV +) was 83.3％ and negative predictive vaule (PPV-) was 98.8％.Conclusion The viral load ≥105 copies/mL in plasma can be used as the best discriminant cut-off value to predict the disease and to identify patients at risk of developing BKVAN,but the cut-off value of urine should be only used for screening BKV infection.

Objective To investigate the influence of BK virus (BKV) activation in renal transplant recipients on the renal allograft function.Method Recipients receiving renal transplantation during 2010.3-2011.4 were sdected as objectives,the urine and peripheral blood samples of them were taken and real-time PCR assays were performed to detect BKV DNA at 0.5,1,3,6,9,and 12 months post-transplantation.Results Among 88 recipients,BKV viruria occurred in 27 (30.68％) patients,and sustained viruria occurred in 17 patients.37.0％ (10/27) of patients with BKV viruria developed inot BKV viremia,and sustained viremia occurred in 5 patients.The viral load in plasma was higher in patients with sustained viremia than in those with transient viremia (P＜0.05),and serum creatinine concentrations were higher when BK viremia occurred (P＜0.05).Conclusion Graft function was impaired among patients with BK viremia,and regularly monitoring BK virus in renal transplant recipients and clinical imervention based on plasma PCR results can prevent transplant kidney damage effectively.

Objective To evaluate the role of 5-hydroxy trptarine 2A receptor (5-HT2A) in the pathogenesis of biliary fibrosis after liver transplantation in rats.Method Rats were randomly divided into control group Ⅰ and control group Ⅱ[(supplied livers were preserved for 1 or 12 h),ketanserin group (recipients of control group Ⅱ were intraperitoneally injected with ketanserin 24 h postoperatively at the dosage of 5 mg · kg-1 · day-1),and sham group (rats were subjected to transverse laparotomy and closure without manipulation of the liver).During 4-week observation period,serum biliary enzymes,5-HT content in the liver,the expression of fibrosis-related genes,cholangiocytes proliferation and biliary fibrosis were evaluated.Result Compared with the sham group,the serum ALP,GGT,TBil and 5-HT contents in the liver homogenate were increased on the postoperative day 1 (POD1) and then restored to the normal level.There was slight proliferation of bile duct epithelial cells on POD3 in the control group Ⅰ,with fewer collagen fibers and α-sooth muscle actin (α-SMA)-positive myofibroblasts in the portal area.The expression of matrix metalloproteinase-2 (MMP-2) and procollagen α1-mRNA in graft livers was not significantly increased in the control group Ⅰ.To the contrast,the control group Ⅱ demonstrated high levels of serotonin in the liver homogenate and enhanced serum biliary enzymes.Active cholangiocytes proliferation was triggered on POD3 and remained higher than in the control group Ⅰ and the sham group.The control group Ⅱ showed a large number of α-SMA-positive myofibroblasts and collegan fibers at the postoperative week 4.In parallel,the major profibrogenic transcripts MMP2 and procollagen α1 were significantly increased at 2nd,and 4th week postoperation in the control group Ⅱ.Importantly,we also found that ketanserin relieved the signs of biliary fibrosis at 4th week postoperation in 5-HT2A group by the demonstration of reduced collagen fibers and a-SMA-positive myofibroblast in the portal area,as well as the decrease in the fibrosis-related gene expression.In addition to the lower cholangiocytes proliferation,serum levels of biliary enzymes including GGT,ALP and TBil in 5-HT2A group were significantly decreased at 4th week postoperation as compared with the control group Ⅱ.Conclusion Selective 5-HT2A receptor antagonist,Ketanserin retards biliary fibrosis progression posttransplantation,suggesting that 5-HT2A receptor is a potential therapeutic target for ischemia-related biliary fibrosis after DCD liver transplantation.

Objective To analyze and discuss the dynamics of cellular immune response to persistent infection with BK virus after renal transplantation.Methods The recipients of renal transplantation in our center were selected and BK virus load in urine and blood was regularly observed.The victims of persistent infection with BK virus (defined as two successive positive results of BK virus load in urine or blood) were followed up and peripheral blood mononuclear cells (PBMCs) were collected for mixed cultivation with overlapping peptide pool,which contained peptide fragments (VP1,VP2,VP3,LT-Ag and st-Ag) extracted from BK virus.Flow cytometry was used to examine the in vitro proliferation of IFN-γ/IL-2/TNF-ininduced T cells and analyze the dynamics of cellular immune response to BK virus.Results A total of 46 recipients of renal transplantation were enrolled and 6 victims of persistent viruria were identified.Of the 6 victims,3 were complicated with persistent viremia,and 2 were diagnosed as BK virus nephropathy by biopsy,presenting with persistent viruria and viremia.The victims of persistent BK viremia after renal transplantation showed a significantly decreasing trend in cellular immune response to 5 BKV-specific proteins,according to the proliferation of TNF-γ/IL-2/TNF-α-induced T cells.However,this trend was not observed in the victims of persistent BK viruria.Conclusion At the stage of viremia,the victims of BKV infection after renal transplantation have seriously inhibited specific immune response to BKV.Thus,if the antiviral mechanisms are not restored in time,these recipients suffering persistent viremia are prone to virus nephropathy (BKVN),delayed graft function,and even graft loss.

Objective: To observe the soluble and dispersive characteristics of Liuwei Dihuang Ultra micro power. Methods: The similarity and difference between the soluble and dispersive characteristics of two powders with HPLC atlas were observed. The contents and dissolving characteristic of target compositions Ursolic acid and Paeonol of Liuwei Dihuang powder and ultra micro powder were compared and studied. Results: At the same retaining time two powders had the same absorbent peak, but the peak values of two powders had apparent difference. the ursonic acid and paeonol in ultra micro powder were 44.55% and 7.6% higher than those of the normal powder respectively. Conclusion: After Liuwei Dihuang is broken into ultra micro power, the chemical compositions do not change but the dissolving speed and contents increase greatly.

Objective To investigate the role of r-aminobutyric acid B receptor in the development of liver fibrosis.Methods Thirty-two Sprague-Dawley (SD) rats were divided into four groups including a control group,a model group,a baclofen group,and a CGP35348 group.Liver fibrosis was then induced by carbon tetrachloride (CCl4).Baclofen and CGP35348 treatment were carried out after the formation of liver fibrosis,followed by complete extraction of the eyeball to obtain blood sample to test liver function.Liver tissue specimens were cut and stored for histological staining,histochemistry,real-time polymerase chain-reaction (RT-PCR),and western blot analysis.Results Histological staining indicated that the degree of liver fibrosis was more severe in the CGP35348 group than in the baclofen group (P＜0.001).The levels of alanine transaminase (ALT),aspartate aminotransferase (AST),gamma-glutamyl transferase (GGT),total bilirubin (TBil),and direct bilirubin (DBil) were significantly lower in the baclofen group than in the CGP35348 group (P＜0.01).The levels of ALT,AST,GGT,TBil,and DBil were significantly higher in the CGP35348 group than in the model group (P＜0.05).Immunofluorescence results show that the hepatic cell migration was inhibited in the baclofen group.Western blot results showed that the expression levels of α-SMA protein were significantly lowered in the baclofen group when compared to that of the CGP35348 group and model group (P＜0.01).Conclusion GABAB receptor might play a role in the liver protection by inhibition of migration of hepatic cells in liver fibrosis.Further studies into the mechanism behind this function are further needed and may be a potential source of future anti-fibrotic treatment.

BACKGROUND:Wide variation between individuals leads to instability of drug concentration that stil troubles transplant recipients. Therefore, individual therapy has always been a hot topic folowing transplantation. OBJECTIVE:To review the research progress in the genomics and gene polymorphism of the main categories of immunosuppressive drugs after kidney transplantation. METHODS:A computer-based search of Wanfang and PubMed databases was used to retrieve relevant articles published from January 2005 to August 2014. The keywords were “renal transplantation; immunosuppressant drugs; polymorphism; individual treatment” in Chinese and English, respectively. Finaly, 50 articles related to genomics and gene polymorphisms of immunosuppressive drugs after kidney transplantation were enroled in result analysis. RESULTS AND CONCLUSION: Immunosuppressant drugs have been widely used among renal transplant recipients to decrease post-renal transplantation rejection rate and greatly improve the survival rate of renal transplant recipients. Because of its certain side effects and wide variation between individuals, therapeutic drug monitoring should be employed routinely after transplantation to keep blood levels within the therapeutic range. This monitor system is effective to avoid post-renal transplantation rejections and drug side effects to a certain extent. Research on the relationship between pharmacokinetics and pharmacodynamics and genetic factors which combined with therapeutic drug monitoring provides possibility to give specific doses that wil improve efficacy while decrease side effects of immunosuppressive drugs, thereby further improving the long-term graft survival rate.