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Objective:To explore the clinical characteristics, diagnosis and treatment of secondary adrenocortical insufficiency(SACI)after kidney transplantation.Methods:Retrospective analysis was conducted for clinical data of 12 recipients with SACI after transplantation from March 2018 to November 2019(observation group). Meanwhile, 10 healthy subjects(control group)were randomly selected for in-hospital physical reexaminations during the same period. General data and morning cortisol levels of adrenocorticotropic hormone(ACTH)and aldosterone were compared between two groups.Results:In observation group, there were 8 male and 4 female with an average age of (43.67±8.81) years. Six cases(50.0%)of SACI occurred during recovery period within 30 days and 3 cases(25.0%)within 30 to 90 days post-transplantation. Deceased citizen donation(DCD)was performed in 9 cases(75.0%)and re-transplanted in 3 cases(25.0%). Oral immunosuppressive regiments were administered in a low-dose prednisone-based triple/quadruple regimen. The mean eGFR of observation group was(54.08±20.03)ml/min. The first patient had adrenal crisis, the fourth had sole symptom of fatigue and the remainder stayed asymptomatic. All of them had persistent hyperkalemia and hyponatremia. The average level of plasma cortisol was(62.24±24.16)mmol/L and it was much lower than normal in all patients at 8 am. The determination of plasma ACTH at 8 am showed that 7 patients(58.33%)were lower than normal and the remaining 5 slightly surpassed the low limit of normal. The average level of plasma cortisol at 8 am was significantly lower in observation group than that in control group(141.34±26.28)nmol/L( t=-7.349, P<0.001). The average ACTH level of observation group at 8 am was(1.08±0.515)pmol/l and it was significantly lower than that of control group(2.53±1.06)pmol/L( t=-4.178, P<0.001). The level of aldosterone was normal in both groups and showed no significant difference. All patients in observation group received an intravenous injection of hydrocortisone with satisfactory outcomes. Conclusions:Transplant surgeons should be on a high alert for an occurrence of SACI in renal transplant recipients. Serum potassium and sodium levels may be the predictors of SACI.
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Objective To explore whether therapeutic dosing timing of proteasome inhibitor bortezomib(BZ) would impact its clinical efficacy .Methods From 2012 to 2018 ,35 biopsy-confirmed cases of acute antibody-mediated kidney transplant rejection (AMR) were collected .They received intravenous immunoglobulin (IVIG) plus sirolimus (Sir) plus bortezomib (BZ) .Three groups were assigned according to dosing timing of BZ .After a diagnosis of AMR ,ET (early treatment ) group began BZ dosing within 7 days (n=16) while DT (delayed treatment) group within 8-14 days (n=11) and LT (late treatment) group > 14 days (n= 8).Their clinical parameters and incidence of complications were analyzed .Results DSA reversal rate of ET ,DT and LT groups was 87 .5％ , 45 .5％ and 25 .0％ (P=0 .006) while DSA declining rate 93 .8％ ,90 .9％ and 50％ respectively (P=0 .019);recurrent rate of AMR was lower in ET/DT group than LT group (6 .6％ vs 10％ vs 75％ , P=0 .042) .No significant differences existed in blood perfusion score of allograft at 1 month post-dosing among three groups .In three groups ,creatinine (Cr) of ET group was lower than DT group at month 1/3/12 while DT group was lower than LT group .No significant difference existed in the incidence of adverse reactions among 3 groups .Conclusions More likely to enter the window period , early dosing of BZ is more effective for treating acute AMR .An earlier intervention yields a better efficacy .
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Objective After the islet transplantation,observed blood glucose and survival time in the islet transplantation mice model to explore the effect of intestinal epithelial γδT cell in islet transplantation rejection.Methods Established the mice model of islet transplantation,divided into wild type mice group,γδ gene knockout mice group and γδ gene knockout γδT cell reinfusion mice group,observed blood glucose in 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29 days after surgery and pathological conditions aft er two weeks of transplantation.Results After transplantation,the rising blood glucose of wild type mice group and γδ gene knockout γδT cell reinfusion mice group were significantly slower than that of γδ gene knockout mice group (P＜0.05),but there was no significant difference in between two groups (P＞0.05).The survival time of wild-type mice group was (27±2) days,and γδ gene knockout γδT cell reinfusion mice group was (24±1) days,they were significantly longer than (17±3) days of γδ gene knockout mice group (P＜ 0.05).Conclusion As a special kind of T cells,γδT intestinal epithelial cell plays an important role in the islet transplantation rejection.
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Objective To investigate the etiology, clinical characteristics, diagnosis and treatment of intestinal complications after renal transplantation. Methods Clinical data of 47 patients presenting with intestinal complications following renal transplantation were retrospectively analyzed. The etiology, clinical characteristics and treatment experience of intestinal complications were summarized. Results Forty-seven patients with intestinal complications after renal transplantation were followed up for 3-36 months with the median time of 18 months. Intestinal complications included the upper gastrointestinal bleeding in 4 cases, the lower gastrointestinal bleeding in 1 case, acute enteritis in 25 cases, chronic enteritis in 12 cases, intestinal tuberculosis in 1 case, colon cancer in 1 case, and intestinal obstruction in 3 cases, respectively. Among patients with gastrointestinal bleeding, the symptoms occurred after the use of high-dose adrenal cortex hormone in 4 cases and 2 patients developed hemorrhagic shock. In patients with acute enteritis, 7 cases received immunosuppressants for the first time during the perioperative period of renal transplantation, the remaining18 patients had dirty diet or catched cold and 4 were positive for pathogens. Among patients with chronic enteritis,plasma concentrations of mycophenolic acid or tacrolimus were elevated in 12 patients, water, electrolyte, and acidbase imbalance was detected, 2 were positive for pathogens, and 8 were accompanied with severe anemia. One case of intestinal obstruction occurred during the perioperative period of renal transplantation, and 2 cases experienced toxic shock. According to the type and severity of disease, symptomatic and etiological treatments were actively implemented.In the 47 patients, 45 were cured and 2 died from the lower gastrointestinal bleeding and respiratory failure caused by lung metastasis of colon cancer. Three patients suffered from transplanted renal insufficiency. Conclusions The intestinal complications after renal transplantation are diverse, which are correlated with the imbalance of intestinal homeostasis.Both the acute and chronic diseases can cause various degrees of damage to the function of transplanted kidneys. Clinical prognosis is poor at the presence of severe complications. Active prevention and management should be implemented to reduce the risk of postoperative complications and enhance the cure rate.
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Objective To investigate the effect of mycophenolate mofetil (MMF) on the changes of intestinal gamma delta (γδ) T cells and the secretion of plasma IL-6 and TNF-α.Methods Adult male C57BL/6 (C57) mice were randomly divided into two groups by SAS 9.1.3 software:normal saline (NS) group and MMF group.The changes of γδ T cells in each intestinal segment of mice were detected by flow cytometry.ELISA was used to determine the levels of serum IL-6 and TNF-α.Results As compared with the NS group,the ratio of γδ T cells in the epithelial cell to lymphocyte (IEL) of the intestinal tract decreased,and the concentrations of plasma IL-6 and TNF-α increased in MFF group (P＜0.05 for all).Conclusion In mycophenolic acid-related enteritis,the proportion of γδ T cells in intestinal IEL decreased,and the secretion of IL-6 and TNF-α increased.
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Objective To investigate the effect of preoperative hyperbaric oxygen therapy upon the incidence of hypoxemia in patients after renal transplantation. Methods In the experimental group, 55 patients received hyperbaric oxygen therapy prior to renal transplantation, and 66 counterparts in the control group underwent conventional renal transplantation. Postoperatively, the incidence of hypoxemia, pulmonary infection, time of in-bed oxygen inhalation and length of hospital stay were statistically compared between two groups. Results In the experimental group, 12 among 55 patients (22%) presented with hypoxemia after renal transplantation, and 20 of 66 (30%) in the control group. In the experimental group, 4 cases suffered from pulmonary infection with an incidence of b7%, and 14 (21%) in the control group. In the experimental group, the incidences of hypoxemia and pulmonary infection were lower than those in the control group (both P<0.05). Inthe experimental group, the time of in-bed oxygen inhalation and length of hospital stay were (5.9±2.0) d and (17.7±3.7) d, significantly shorter compared with (6.8±2.6) d and (20.5±4.2) d in the control group (both P<0.05). Conclusions Prior to renal transplantation, hyperbaric oxygen therapy can significantly reduce the risk of hypoxemia and pulmonary infection after renal transplantation, which can be served as a conventional preventive measure against the incidence of hypoxemia following renal transplantation.
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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.
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Objective To explore the feasibility of making cystoscope training model with rapid prototyping technology and its training method in cystoscope operation. Methods Constructed a cystoscope training model, and designed a set of corresponding training methods ac-cording to the process and behavioral essentials of cystoscope operation. Selected 20 students who have never learned cystoscope operation and trained them with the new designed cystoscope training mode and training methods, and the training results were verified. Results Compared before and after the training, the operation time of all the trainees were significantly shortened, and their operation steps and skills were more proficient. Conclusion Cystoscope training model can help beginners to grasp the theoretical basis of cystoscopy, operation steps, and behavioral essentials, so as to shorten the learning curve of the cystoscope operation.
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Objective To investigate the hemostatic function of biological glue in renal trauma.Methods Establishment of rab-bit kidney scratch,partial nephrectomy and renal injury penetrating wound models were available with a biological glue and hemo-static powder processing,observed and recorded the amount of bleeding and bleeding time.Tissue sample were transected from the wound of kidneys in each group after a month,and the renal wound healing condition was observed by pathological examination.Re-sults The hemostatic function of biological glue was better than styptic powder,the amount of bleeding in biological glue group and hemostatic powder group of kidney scratched model were(1.39±0.09)mL,(1.77±0.44)mL,the difference was not statistically significant(P =0.115);the bleeding time were(5.02 ±0.23)s,(66.40± 7.35)s,the difference was statistically significant(P <0.01);the amount of bleeding in two models of partial nephrectomy and renal penetrating wound were(2.07±0.25)mL,(11.42± 1.33)mL;(2.01 ± 0.36)mL,(3.95 ± 0.39)mL and bleeding time were(6.16 ± 0.69)s,(139.38 ± 8.97)s;(7.68 ± 0.80)s, (144.26±9.27)s,the differences were statistically significant(P <0.01).Pathology results showed that the wounds healed well. Conclusion The hemostatic function of biological glue in renal trauma were remarkable and stable,and was worth to be further promoted.
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This article describes a novel Multifunctional and Transparent Urinary System Model (MTUSM), which can be applied to anatomy teaching, operational training of clinical skills as well as simulated experiments in vitro. This model covers kidneys, ureters, bladder, prostate, male and female urethra, bracket and pedestal, etc. Based on human anatomy structure and parameters, MTUSM consists of two transparent layers i. e. transparent organic glass external layer, which constraints the internal layer and maintains shape of the model, and transparent silica gel internal layer, which possesses perfect elasticity and deformability. It is obvious that this model is preferable in simulating the structure of human urinary system by applying hierarchical fabrication. Meanwhile, the transparent design, which makes the inner structure, internal operations and experiments visual, facilitates teaching instruction and understanding. With the advantages of simple making, high-findelity, unique structure and multiple functions, this model will have a broad application prospect and great practical value.
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Female , Humans , Male , Kidney , Models, Anatomic , Models, Biological , Prostate , Ureter , Urethra , Urinary Bladder , Urogenital SystemABSTRACT
Objective To evaluate the efficacy and safety of retroperitoneal laparoscopic pyelolithotomy ( RLP) combined with holmium laser lithotripsy under flexible cystoscopy in the treatment of complicated nephrolithiasis. Methods The retrospective analysis was made on the clinical data of 37 patients who underwent RLP and holmium laser lithotripsy under flexible cystoscopy for complicated nephrolithiasis from January 2013 to January 2014. The clinic parameters involved basic data of patients,operational time,blood loss,post-operative hospital stay,the status of stone-free,perioperative complications,and the follow-up data of patients were observed. Results No patient was converted to open surgery. The mean stone size was (2. 8 ± 0. 9) cm in diameter,operational time was (89 ± 24) min,blood loss was (21. 3 ± 7. 7) mL,post-operative hospital stay was (6. 8 ± 1. 7) d,the stone removal rate in one session was 94. 6%. One case occurred urinary leakage,1 case occurred fever after operation,who were all recovered through conservative treatment. All cases were followed up at the sixth months after operation. Conclusion RLP combined with holmium laser lithotripsy under flexible cystoscopy is effective and safe for the treatment of com-plicated nephrolithiasis.
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s:Objective Discuss the application of CTA for renal vascular control in laparoscopic renal transplantation of relative renal donors. Methods 83 cases of relative renal transplantation donors which are completed in our department during March 2007 to Junuary 2012 were divided into 3 Groups. There were 35 cases in group A ( laparoscopic nephrectomy with preoperative CTA examination) , 15 cases in group B ( laparoscopic nephrectomy without preoperative CTA examination) , and 33 cases group C ( conventional nephrectomy) . In group A, the location and quantity of renal arteries and veins were observed with preoperative CTA to make plan for vascular control. And the oper-ation time, amount of bleeding, vascular injury cases, the renal warm ischemia time in the graft, mean time of postoperative hospitalization were compared with those of group B and group C. Results 5 cases of renal vascular anomalies were observed in Group A, including 2 cases of single accessory renal artery, 2 cases of early branch of renal artery and 1 case of double renal veins. And all of them were intraoperatively comfirmed. 3 cases of renal vascular anomalies were observed in group B, including 1 case of renal arteriovenous ectopic, 1 case of injury in the accessory renal artery with diameter of 0. 6 cm, and it were given artery elongation with inferior epigastric artery postoperatively, and 1 case of renal vein injure during blocking lumbar vein with Hemolock which were repaired postoperatively. 5 cases of renal vascular anomalies were observed in group C, including 1 case of single accessory renal artery, 3 cases of early branch of renal artery, and 1 case of accessory renal artery with the diameter of 0. 1cm in the right renal was injured during surgery. The operation time, amount of bleeding, cases with vascular injury , renal warm ischemia time of donor , and the mean time of postoperative hospitalization in group A were superior to those in group B and group C. Conclusion CTA is a simple noninvasive imaging method, which can provide the details of the renal vascular preop-eratively to ensure the safety of patients during surgery and improve survival quality of donor renal, and it is of great advance in laparoscopic renal transplantation of living-related renal donors.
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Objective The purification methods of the exosomes derived form T cells were established in order to get high quan-tity exosomes .Methods Exosomes from T cells culture supernatants were purified by ExoQuick Precipitation ,ultrafiltration and sucrose gradient centrifugation ,differential ultracentrifugation ,and confirmed via using transmission electron microscopy .The pro-tein expression of the exosomes were analyzed by SDS-PAGE electrophoresis .Western blotting was used to test the expression of IL-2 .Results The protein concentration of the exosomes purified through ExoQuick Precipitation ,ultrafiltration and sucrose gradi-ent centrifugation were higher than through differential ultracentrifugation (P<0 .05) .SDS-PAGE displayed the difference among the exosome purified by three methods .Three kinds of exosomes all expressed IL-2 .Conclusion ExoQuick Precipitation ,ultrafiltra-tion and sucrose gradient centrifugation technique can obtain high purity and complete exosome sample .
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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.
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Objective To demonstrate the efficacy and safety of Hangzhou tacrolimus capsule(Saishi Tac capsule, Hangzhou Zhongmei Huadong Pharmaceutical Co. Ltd, China) in Chinese kidney transplant recipients. Methods Multicenter, randomized open-labeled, prospective controlled clinical trial was performed in de novo Chinese kidney transplant recipients. According to including and excluding criterions, 65 kidney recipients from 9 transplant centers were enrolled. The mean age of recipients was (36.53 ± 5.71 ) years, and 8 received living donor transplantion. The time of cold ischemia and warm ischemia was (4.08 ± 5.43) h and (3.90 ± 2.15) min respectively. The number of mismatched HLA was (2.1 ± 0.8). The recipients accepted Saishi Tac capsule + mycophenolate steroid 60 days, followed by 5-10 μg/L until the terminal observation time point (12 weeks after transplantation). The efficacy and safety were estimated during the period. The primary efficacy endpoint of the study was the incidence of biopsy-confirmed acute rejection. Graft survival and renal function (evaluated by serum creatinine) were the secondary endpoints. Safety was assessed by monitoring laboratory parameters and adverse events reported over the course of the study, such as infection, hepatic damage, hypertension, hyperlipema, diabetes mellitus and other adverse affairs.Results The dose of Tac at 1 st, 2nd, 4th and 8th week postoperation was (6.54 ± 1.69), (6.39 ±1.45),(6.73± 1.25), (6.25 ± 1.02) and (6.03 ± 1.16) mg, corresponding values to the C0 were (8.24±2.09),(9.39± 1.35),(9.93± 1.87),(7.23± 1.16) and (6.43± 1.26) μg/L. During 12weeks of follow-up, the incidence of biopsy-confirmed acute rejection was 12.3% (8/65), among which 6 cases were reversed by implosive therapy. The survival rate of graft kidney was 96.9% (63/65). The incidence of hypertension and hepatic damage was both 7.7% and morbidity of lung infection was 7.6%. There were 3 patients (4.6%) complicated with hyperlipema and diabetes mellitus respectively. Conclusion During the first 3 months of treatment Saishi Tac capsule was safe and effective to Chinese kidney transplant recipients.
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Objective To explore the feasibility of mediating recipient lymphocyte reaction with donor dendritic cells (DCs) in renal allograft recipients. Methods Donor bone marrow monocytes (BMMCs) were isolated and cryopreserved in liquid nitrogen before kidney transplantation. At 0 day, 1month,3 month, 6 month and 9 month post-operation, CD34+ cells which were isolated from frozen BMMCs and cultured into DCs as well as the peripheral blood lymphocytes (PBLs) of donors were used as the stimulating cells to the PBLs of recipients and healthy volunteers. The number of viable DCs from frozen- and room temperature-preserved BMMCs was counted and the reactions of recipients'and healthy volunteers' lymphocytes to DCs and donor PBLs were measured. Results 6. 8 × 107BMMCs were isolated from each 10 ml of donor bone marrow on average while (4. 10 ± 0. 58) × 105CD34+ cells were isolated by magnetic active cell sorting (MACS). There was no significant difference in the isolating rate of recovered CD34+ cells at each observation point postoperatively. The percentage of viable BMMCs and CD34+ was decreased significantly at 1 month after surgery, then, decreased slowly and progressively. The decreasing rate of BMMCs was higher than CD34+. The rate of viable DCs was maintained stable (93. 2%-94. 8% ) in each group. The reactions of recipients' and healthy volunteers' lymphocytes to DCs were stronger than those to donor PBLs (P＜0. 05). The reactions of healthy volunteers' lymphocytes to DCs were maintained stable while those of recipients' were fluctuating. Conclusion Bone marrow-derived DCs are superior to PBLs in mediating long-term lymphocyte reaction after kidney transplantation due to their stable viability and stimulating ability to lymphocytes. Only once collection of a small quality of bone marrow of donors is needed to meet the demand of immune monitoring at any time after transplantation.
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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.
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BACKGROUND: the development of magnetic separation technique,it is feasibility to in vitro sort and amplify CD4+CD25+Treg cells for transplantation; however,the application dosage and immune tolerance have been less reported yet.OBJECTIVE: To investigate dose-effect relationship of CD4+CD25+Treg cells during allograft transplantation.METHODS: SD rats which were considered as the donors and Wistar rats as receptors were used to establish allograff kidney transplantation models.CD4+CD25+Treg cells were separated from splenic cells of Wistar rats and induced phenotype of donor antigenic specificity in vitro.According to the quantities of CD4+CD25+Treg cells injecting through tail vein during the operation of allograft kidney transplantation,models were rolled into four experiment groups: group 1(2×105),group 2(5×105),group 3(1×106),and group 4(2×106).The models out injection were considered as controls.Survival status of kidney was detected at day 15 postoperatively; creatinine level and pathological changes were detected at days 4,9 and 15 according to Banff Schema diagnostic standard; semi-quantitative scores were measured Watanabe technique.RESULTS AND CONCLUSION: The death rate was the highest in control group(83.3%),and then group 1(66.7%),group 4(58.3%),and group 2(33.3%); but rats in the group 3 were all survival.Creatinine level in experimental groups was significantly less than control group at days 4,9,and 15 postoperatively(P<0.05,P<0.01); the creatinine levels in the group1 and group 2 were significantly greater than in the group 3 and group 4 at days 9 and 15 postoperatively(P<0.05),Semi-quantitative scores demonstrated that there was no significant difference between group 2 and group 1; but the scores in the group 3 and group 4 were significantly greater than control group(P < 0.05).The results indicated that CD4+CD25+Treg cells could improve kidney function following transplantation,and prolong survival time of transplanted kidney.The 1×106 was the best dosaae for application.
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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.
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0.05) and the histopathological results of the test group did not show any inflammatory reaction in incisions of liver and kidney tissues.Muscular tissues allowed a little inflammatory cells infiltrate at two days,after four days,there was not inflammation or fibrous tissue envelope.CONCLUSION:The prepared PHS granules have good biocompatibility without any acute or chronic toxicity,reject reaction,immunological reaction and anaphylactic response in animals.