1.Molecular changes of PI_3K-AKT signal pathway in K562 cells treated with simvastatin in vitro and in vivo
Dingan ZHOU ; Wenfang HUANG ; Mingchuan ZHANG ; Shen ZHAO ; Yi XU
Journal of Third Military Medical University 2003;0(21):-
Objective To analyze the apoptosis mechanisms of K562 cells in a PI3K-AKT-dependent manner.Methods K562 cells were cultured in vitro for experiments below:the proliferation assay of K562 cells detected by MTT,the analysis of apoptosis rate and cell cycle of K562 cells measured by flow cytometry(FCM),the construction of chronic myeloid leukemia(CML) animal model through the subcutaneous inoculation of K562 cells to 12 BALB/c-nu/nu nude mice,the early apoptosis changes of K562 cells detected by TdT-mediated dUTP nick end labeling(TUNEL) and the in vitro and in vivo changes of N-ras,PI3K,AKT1,IKK-?,NF-?B1 at transcription level detected by RT-PCR.Results Simvastatin inhibited the proliferation of K562 cells and induced their G0/G1 arrest and significant apoptosis.N-ras and most genes of PI3K-AKT signal pathway were expressed differentially in vitro.K562 cells on nude mice could be induced to apoptosis by simvastatin and the apoptotic index increased with the dose accumulation of simvastatin(P=0.000).The differential mRNA expression changes of N-Ras and most genes of PI3K-AKT signal pathway in K562 cells were observed after treatment of simvastatin at different doses(P=0.000 or P=0.003).However,mRNA expres-sion of the genes in PI3K-AKT pathway in vitro differed to that in vivo.Conclusion The differential expression at transcription levels of N-ras and the most genes in PI3K-AKT pathway that are involved in anti-apoptosis in K562 cells,to some degree,indicates that simvastatin can induce the apoptosis of K562 cells in a PI3K-AKT pathway-dependent fashion in vitro.The animal experiments confirm that there are different mechanisms of simvastatin in inducing the apoptosis of K562 cells in vitro and in vivo.
2.Clinical efficacy of dual-kidney transplantation from infant donors to adult recipients
Mingchuan HUANG ; Chenglin WU ; Jun LI ; Xiaopeng YUAN ; Ronghai DENG ; Yitao ZHENG ; Longshan LIU ; Shenghui WU ; Xixi GAN ; Changxi WANG
Chinese Journal of Organ Transplantation 2021;42(1):8-13
Objective:To explore the clinical efficacy of dual-kidney transplantation from infant donors to adult recipients.Methods:From December 2012 to November 2020 in Organ Transplant Center First Affiliated Hospital Sun Yat-sen University, rertrospective reviews were conducted for clinical data of 25 pairs of infant donors and adult recipients. The survival rates were calculated for both recipients and transplanted kidneys at Year 1/3/5 post-transplantation. And the postoperative recovery status and the postoperative incidence of adverse events of recipients were observed.Results:The survival rates of recipients were all 95.8% at Year 1/3/5 and those of transplanted kidney and dealth-cancelling transplanted kidney all 87.2%. One case died due to acute inferior-wall cardiac infarction while three others lost renal functions for vascular thrombosis, ureteral stenosis and urinary fistula. Except for loss of renal function and death, the postoperative estimated golmerular fitration rate was (99.35±21.78), (103.11±29.20) and (114.99±28.55) ml/(min·1.73 m 2) at Year 1/2/3 respectively. Conclusions:Selecting proper recipients, standardizing donor acquisition and surgical procedures and strengthening perioperative managements may expand the donor pool. The overall outcomes are excellent for adult recipients with dual-kidney transplantation from donations after infants' death.
3.Retrospective analysis of pediatric kidney transplantation: a report of 244 cases
Huanxi ZHANG ; Jun LI ; Mingchuan HUANG ; Shenghui WU ; Qian FU ; Longshan LIU ; Ronghai DENG ; Chenglin WU ; Bowen XU ; Lizhong CHEN ; Jiang QIU ; Guodong CHEN ; Gang HUANG ; Jiguang FEI ; Suxiong DENG ; Changxi WANG
Chinese Journal of Organ Transplantation 2020;41(1):9-14
Objective:To explore the clinical characteristics and outcomes of pediatric kidney transplantations at a single center and discuss the related clinical issues.Methods:From January 1990 to October 2019, clinical data were analyzed retrospectively for 244 pediatric renal transplants. The youngest recipient was aged 1.8 years and the median age of pediatric recipients was 12.2 years. The major disease was primary or hereditary glomerulonephritis ( n=160, 69.0%), congenital anomalies of kidney and urinary tract (CAKUT), cystic renopathy and other hereditary nephropathies ( n=55, 23.7%). The donor sources included traditional deceased donor ( n=42, 17.2%), living-related donor ( n=19, 7.8%) and organ donation ( n=183, 75.0%). The median age of donors was 2 years (0-51) and the median weight 12.0(2.7-72.0) kg. From January 2013 to October 2019, 170 cases), the major induction immunosuppression regimen was anti-thymocyte globulin (ATG) ( n=110, 64.7%) or basiliximab ( n=58, 34.1%). The maintenance regimen was tacrolimus + mycophenolic acid (MPA) + glucocorticosteroids. Finally the outcomes and the complications were analyzed. Results:The survival rates of 244 kidney allograft recipients were 98.1%, 94.5% and 93.4% and the graft survival rates 92.6%, 84.2% and 82.0% at 1/3/5 years respectively. Ten recipients died of accident ( n=2, 20.0%), pneumonia after transplantation ( n=2, 20.0%) and intracranial hemorrhage ( n=2, 20.0%). Thirty-three recipients lost their allografts mainly due to intravascular thrombosis in graft ( n=5, 14.3%), acute rejection ( n=5, 14.3%) and death ( n=9, 25.7%). Besides, among 109 deceased donor allograft recipients, the postoperative outcomes were delayed graft function recovery (DGF) ( n=27, 24.8%), arterial thrombosis ( n=6, 5.5%), venous thrombosis ( n=1, 0.9%), graft perirenal hematoma ( n=6, 5.5%), raft artery stenosis ( n=10, 9.2%) and graft ureteral fistula ( n=1, 0.9%). The incidence of acute rejection was 17.5% and 23.2% at 1/3 year respectively. The recurrent rate of primary disease was 6.9%, including primary FSGS ( n=3, 42.9%) and IgA nephropathy ( n=2, 28.6%). At 1/3 year post-operation, the incidence of pulmonary infection was 16.9% and 22.4% and the incidence of urinary tract infection 26.9% and 31.7%. Excluding recipients with graft failure, the estimated glomerular filtration rate (eGFR) at 1/2/3 year postoperatively was (80.3±25.2), (81.4±27.8) and (71.8±27.6) ml/(min·1.73 m 2)respectively. Conclusions:The outcomes of pediatric renal transplantations are excellent at our center. Future efforts shall be devoted to optimizing the strategies of donor kidney selection and strengthening preoperative evaluations, perioperative and postoperative managements for improving the long-term outcomes of pediatric renal transplantations.