Objective:To study the influence of donor dendritic cells (DCs) modified with ICOS extracellular region on the survival of renal allografts in rats. Methods:Bone marrow derived DCs of Brown Norway(BN) rats were modified with ICOS extracellular region gene recombined adenovirus and injected into Lewis rats 24 h before BN→Lewis kidney transplantation. Survival time of renal allografts was observed and one-way mixed splenic cell reaction (MSR) of the recipients to donors and the third party rats were performed by means of MTT on the 20th postoperative day. Results:Survival time of renal allografts was prolonged significantly [comparedwith control, (23.2?3.08) d vs(8.5?1.4) d,P

Objective To study the effect of synthetic HLA-derived peptide (P), HLA-B*2702.75-84, on the mean survival time (MST) of cardiac allografts in mice.Methods NIH mice cardiac allografts were heterotopically transplanted into the posterior of Balb/c ears. The HLA-derived peptide in combination with a subtherapeutic dose of CsA were perioperatively administrated. The pulsation of the cardiac allograft observed under the operating microscope was considered as the indication of the cardiac allograft surviving time or rejection. Results MST was ( 7.5? 0.5) days in untreated control group, ( 8.5? 1.5) days in CsA group and ( 7.0? 1.5) days in control peptide or P groups respectively, whereas MST was ( 26.5? 3.5) days in experimental group.Conclusion The synthetic HLA-derived peptide combined with subtherapeutic CsA can significantly prolong cardiac allograft survival in mice as compared with control groups.

Objective To discuss the efficiency and safety of conversion from tacrolimus(Tac)to cyclosporine A(CsA) in patients with new onset diabetes after transplantation (NODAT).Methods The glucose metabolism parameters and related clinical indicators in 45 Tac treated renal transplantation recipients who developed NODAT were retrospectively analyzed.The oral immunosuppressive strategy was Tac + mycophenolate mofetil (MMF) + prednisone(Pred).Results 32 cases were converted to CsA whereas 13 patients stuck to Tac.After conversion,fasting plasma glucose (FPG)decreased from(8.2 ± 2.7)mmol/L to(5.9 ± 1.2)mmol/L(P ＜ 0.01)and HbA1c level decreased from (7.0 ± 0.9) ％ to (6.1 ± 0.7) ％ (P ＜ 0.05).The level of FPG and HbA1c was lower in the conversion group than in the control group(P ＜ 0.05).During the 1-year follow-up,the curative rate of NODAT was 53.1％ (17/32) in the conversion group while it was 0％ in the control group.No acute rejection happened after the conversion.There was no obvious change in renal function.The 1-year survival rate of patient and the transplanted kidney was 100％.Blood pressure and lipid levels were stable after the conversion.Conclusion Conversion from Tac to CsA is a simple and effective strategy to improve glucose metabolism in renal transplantation recipients with NODAT.

Objective To describe the experiences when different methods were used to treat early-onset antibody-mediated rejection (AMR) after kidney transplantation.Methods The clinical data of 42 recipients who experienced early-onset acute AMR after kidney transplantation in our department from Jan.2010 to Apr.2016 were retrospectively analyzed.The recipients were divided into 3 groups based on different strategies against AMR:group A (plasma exchange with intravenous immunoglobin);group B (bortezomib solo),and group C (combination of bortezomib and sirolimus).Results All the AMR episodes were diagnosed by kidney biopsy 9-27 days after transplantation.The AMR reversal rate in groups B and C was significantly higher than that in group A (100％ versus 60.00％,P=0.034;100％ versus 60.00％,P=0.007).The AMR recurrence rate in groups B and C was significantly lower than that in group A (0 versus 41.67％,P =0.035;0 versus 41.67％,P =0.007).The recipient survival rate was 100％ in all the three groups.There were 11 graft losses in group A,and none in group B or C.The graft survival rate in group B at 6 months,1 year and 3 years was significantly higher than in group A (100％ versus 60.00％,P =0.034;100％ versus 55.00％,P =0.021;100％ versus 50.00％,P =0.013).The graft survival rate in group C at 6 months and 1 year was significantly higher than in group A (100％ versus 60.00％,P =0.007;100％ versus 55.00％,P =0.003).There was no significant difference in AMR reversal rate,AMR recurrence rate and graft survival rate between groups B and C.There was no significant difference in incidences of infection,hyperlipidemia and bone marrow suppression among the three groups.The incidence of diarrhea in groups B and C was significantly higher than in group A (50.00％ versus 0,P =0.001;42.86％ versus 0,P =0.001).The incidence of peripheral neuritis in group B was significantly higher than in group A (25.00％ versus 0,P =0.02),but similar to group C.There was no significant difference in average serum creatinine level among three groups within 1 year after treatment (P＞ 0.05).Antibodies against human leukocyte antigen (HLA) and donor specific antibodies were detected in all the 42 recipients before treatment.The negative conversion ratio of panel reactive antibody (PRA) in group A was significantly lower than in groups B and C (10.00％ versus 87.50％,P＜ 0.001;10.00％ versus 92.86％,P ＜ 0.001).The PRA recurrence rate in group A was significantly higher than in groups B and C (85.00％ versus 37.50％,P＜0.001;85.00％ versus 0,P＜0.001),while that in group B was significantly higher than in group C (37.50％ versus 0,P =0.014).The ratio of Treg in peripheral blood at 3-12 month after treatment in group C was significantly higher than in groups A and B (P＜0.05).Conclusion Treatment for early-onset AMR after kidney transplantation based on bortezomib might be an effective and safe strategy.Graft longterm survival might benefit from the combination of bortezomib and sirolimus.

Objective To observe the protective role of enalapril as a specific angiotensin converting enzyme inhibitor on allograft in renal transplant recipients.Methods From Jan 2000 to Jun 2001,22 cases of renal transplant recipients with normal renal function and urine TGF-?_1 concentration being higher than 250.0 pg/mg Cr(group A) underwent therapy with angiotensin converting enzyme inhibitor(enalapril) one year after surgery.Enalapril was administered at a dose of 50 mg/d for the patients in group A for at least one year.Twenty-three recipients who never received angiotensin converting enzyme inhibitor in the same condition were studied as Group B.The adverse reactions of enalapril were investigated in group A and the expression of TGF-?_1mRNA in renal grafts were compared between before and 1 year after enalapril therapy.At the end of 3-year study period,the renal function,the decrement of creatinine clearance rate(Ccr) and the concentration of TGF-?_1 in blood and urine were compared between the two groups respectively.Results The Ccr decreased faster in group B than in group A.During three years study period,the decrements of Ccr were(5.1?4.6) and(13.7?9.5)(ml/min) in group A and group B respectively,and there were 2 cases and 9 cases with chronic allograft nephropathy(CAN) respectively.The decrement of Ccr and the number of CAN cases were significant difference between group A and group B(all P

BACKGROUND: Previous studies showed that donor systemic injection of B7/CD28 costimulatory blocker cytotoxic T lymphocyte associated antigen 4 immunoglobulin (CTLA-4Ig) needed in T cell activation can markedly prolong the survival time of rat renal allografts, which, however, has limitations, such as high dose, extensive influence, poor specificity, systemic adverse reactions.OBJECTIVE: In order to improve the targeting of CTLA-4Ig, we modified the dendritic cells of donors and recipients in vitro with CTLA- 4Ig and observed the influence of two kinds of dendritic cells applied alone or together on the survival of renal allografis in rats.DESIGN, TIME AND SETTING: The randomized controlled animal experiment was performed between April 2003 and July 2004 at Laboratory of Department of Urinary Surgery, Xinqiao Hospital, the Third Military Medical University, Chongqing, China.MATERIALS: Kidney donor: inbred Brown-Norway rats, kidney recipient: inbred Lewis rats, unrelated lymphocyte donor: Wistar rats.METHODS: Bone marrow derived dendritic cells of Lewis and Brown Norway rats were modified with CTLA- 4Ig gene recombinant adenovirus in vitro. Animal models of kidney transplantation were built with Brown Norway rats as donors while Lewis rats as recipients. The modified dendritic cells were injected into Lewis rats through femoral vein 24 hours before kidney transplantation alone (group 1 (n=8), donor dendritic cells; group 2 (n=8), recipient dendritic cells) and in combination (group 3 (n=8), donor and recipient dendritic cells). While the recipients without injection were used as control (group 4 (n=6)).MAIN OUTCOME MEASURES: Survival time of renal allografts; the reaction degrees of splenocytes to donor and unrelated antigen determined by MTT method on day 20 postoperation.RESULTS: Survival time of renal allografts in group 2 was not prolonged compared with group 4 while the survival time was markedly prolonged in group 3 (P < 0.01). The response of rat splenocytes to donor antigen in group 1 and group 3 was obviously lower than that in group 4 (P < 0.01), while the response to unrelated antigen was similar to group 4.CONCLUSION: Donor dendritic cells modified with CTLA- 4Ig can significantly prolonged survival time of rat renal allografts and the administration of both donor and recipient dendritic cells modified with CTLA- 4Ig can induce a longer survival time of renal allografts. Recipient dendritic cells cannot prolong the survival time of renal allografts.

Objective To investigate whether reduced or discontinued calcineurin inhibitor (CNI) can improve the renal functions of renal transplant recipients with chronic allograft nephropathy (CAN). Methods A total of 46 renal transplant recipients with declining graft function and biopsy proven CAN were studied. Within 1～2 weeks, CNI (Cyclosporine A or Tacrolimus ) in 27 recipients (group A) was discontinued or reduced to one third of their original doses, but Azathioprine (Aza) or mycophenolate mofetil (MMF) was increased properly. The doses of CNI in the 19 recipients (group B) were not changed obviously, but Aza or MMF was increased properly. At least 1-year follow-up was performed in all patients. Renal functions were compared between the two groups. The incidence of acute renal graft rejection was calculated in both groups. Results One year later, there were 17 patients (63.0%) with stabilized or improved graft function in group A, and 2 (10.5%) in group B. The difference was significant. The incidences of acute rejection in both groups were not significantly different. Conclusion For some renal transplant recipients with declining graft function and biopsy proven CAN, remarkably reduced or discontinued CNI can stabilize or improve their renal functions. Adjusting the doses of immunosuppressive agents does not increase the risk of acute rejection.

Objective To observe the efficacy of local gene transfection in CD154 extracellular domain on the survival of renal allografts. Methods The kidneys of Brown Norway (BN) rats were transfected with CD154 extracellular domain gene recombined adenovirus. The transfected kidneys were transplanted to Lewis rats (transfection group). BN→Lewis kidney transplantation with non transplanted kidneys served as the controls. The allograft survival time and the allograft function between the two groups were compared. Results The allograft survival time of the transfection group was longer than that of the controls significantly [(28?7.3)d vs (8.6?1.2) d, P

ObjectiveTo explore the feasibility of mediating recipient lymphocyte reaction with donor dendritic cells (DCs) in renal allograft recipients to guide individualized inmunosuppressive therapy. Methods From Jan. 2008 to Jan. 2010, 30 recipients received living related kidney transplantation were successively and divided into 2 groups according to the strategies of the correction of the dosage of immunosuppressant, 15 in each group. The strategy of immunosuppressive therapy in both groups was Tac + MMF + Pred. The correction of the dosage of immunosuppressant in experimental group was conducted by recipient lymphocyte reaction with donor DC (LR) combined with Tac and MPA blood concentration monitoring. Only blood concentration monitoring of drugs was applied in control group. Examinations of liver and renal function, blood and urine routine as well as blood sugar were done monthly for 1 year. ResultsDuring the follow-up period, the rate of acute rejection in experimental group and control group was 13. 3 ％ and 46. 7 ％ respectively (P＜0. 05) ;the rate of infection in experimental group and control group was 6. 7％ and 40. 0％ (P＜0. 05)respectively; the adverse reaction rate in experimental group and control group was 13. 3％ and 46. 7％(P＜0. 05). There was no significant difference in the serum creatinine level between the two groups at each observation point. ConclusionThe application of combined recipient LR with donor DC and blood concentration monitoring of drugs in individualized irnmunosuppressive therapy is more comprehensive and accurate.

AIM: To explore the protective effect of curcumin on high glucose-induced decrease in contraction of isolated rat aortic rings, and to elucidate its underlying mechanism. METHODS: The thoracic aortic rings with endothelium of male Sprague-Dawley rats were mounted on a bath system. Isometric contractions of aortic rings were measured. HO activity was also evaluated. RESULTS: (1)Four hours after incubated with 44 mmol/L of glucose (high glucose),the vascular contraction responses to phenylephrine (PE) decreased compared to control group (containing 11 mmol/L of glucose). (2)Coincubation with curcumin (3×10~(-11)-3×10~(-10) mol/L) and high glucose,the high glucose-induced decrease in contraction responses to PE of arteries was partly inhibited. (3)Four hours after incubation with curcumin,the HO activity in thoracic aorta increased. ZnPP,an inhibitor of HO-1,completely abrogated the protection effect of curcumin. (4)Methylene blue,an inhibitor of guanylate cyclase (GC),partly abolished the protective effect of curcumin. CONCLUSION: Curcumin prevents the high glucose-induced decrease in contraction responses to PE in intact aortic rings. The mechanism might be mainly involved in the activation of HO-1 and GC.