Objective:To conduct a retrospective analysis of efficacy and safety of different conversion schemes of tacrolimus to slow-release dosage forms for recipients in stable phase after renal transplantation to provide rationales for the conversion strategy of tacrolimus.Methods:From January 2020 to June 2020, clinical data were reviewed for 101 kidney transplant recipients converting from common tacrolimus dosage form to tacrolimus sustained-release dosage form during postoperative stable period.There were 62 males and 49 females with an age range of 19 to 69 years.They were divided into two groups according to iso-dose and incremental-dose switching schemes.The common dosage form of tacrolimus was converted into a sustained-release dosage form with different conversion doses, They were divided into two groups of 1∶1 conversion( n=55)and >1∶1 conversion( n=46). The clinical parameters of serum creatinine(Scr), blood urea nitrogen(BUN), alanine aminotransferase(ALT)and aspartate aminotransferase(AST), alkaline phosphatase(ALP), serum albumin(ALB), white blood cell count(WBC), urinary white blood cell(UWBC), hemoglobin(Hb)and fasting blood glucose(Glu)were compared between two groups after conversion. Results:Regarding numerical change trend after switching to tacrolimus sustained-release dosage form, drug dose/variation trend was smaller and blood drug concentration more stabilized.In two subgroups converted by 1∶1 and 1>1 initial dose, change trend of dose/blood concentration in 1∶1 conversion group appeared to be more stable.However, no inter-group difference existed in long-term parameters.Scr was lower at 1 week and 3 months after switching to extended-release dosage form( P<0.05)and BUN was lower at 2 weeks( P<0.05). In addition, at 5 months after conversion, ALT and AST significantly improved as compared with common dosage form( P<0.05). Significant differences existed in urinary WBC(UWBC)at 2/3 weeks( P<0.05). After switching for 2 weeks, hemoglobin significantly improved compared with common dosage form( P<0.05). No significant differences existed in ALP, ALB or Glu at other timepoints and pre-conversion( P>0.05). In 1∶1 switch group, renal function tended to improve.At 2 weeks, BUN was lower than pre-conversion; at 1/3 weeks, Scr was lower than pre-conversion( P<0.05). In addition, there was also a trend of improvement in liver function in 1∶1 conversion group.At 1 week and 5 months, ALT was lower than pre-conversion( P<0.05). However, no significant differences existed in AST, ALB, ALP, Glu, UWBC and serum WBC count at each timepoint between two different dose conversion groups( P>0.05). After conversion, intra-individual variability of tacrolimus trough concentration significantly improved( P<0.05). Conclusions:With the same safety and efficacy as common dosage form, sustained-release dosage form of tacrolimus may improve drug variability of individuals.When converting common dosage form into sustained-release dosage form, individual differences should be considered.While monitoring trough concentrations, proper doses should be adjusted on the basis of various clinical parameters.

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.

Objective:To explore the diagnosis and treatment of focal segmental glomerulosclerosis (FSGS) post-kidney transplantation in children.Methods:Clinical data were retrospectively analyzed for 6 FSGS children after transplantation from 2015 to 2019. Massive proteinuria (3.2-13 g/24 h) occurred at 4 days-49 days post-transplantation. For proteinuria, glucocorticoid plus therapeutic plasma exchange and/or rituximab were provided with supplemental ACEI/ARB drugs. Five cases received tacrolimus as maintenance therapy while another case had cyclosporin A as an initial intensive therapy and switched to tacrolimus.Results:Four cases achieved complete remission after therapy. One recipient showed partial remission. During a follow up period of 11 months to 4 years, serum creatinine remained normal and stable in five cases while one died from severe pulmonary infection.Conclusions:Once FSGS occurs post-transplantation, prompt treatment of pulse glucocorticoid plus therapeutic plasma exchange and/or rituximab with supplemental ACEI/ARB drugs may yield favorable outcomes.

Objective:To summarize the patient profiles and therapeutic efficacies of ABO-incompatible living-related kidney transplantations at 19 domestic transplant centers and provide rationales for clinical application of ABOi-KT.Methods:Clinical cases of ABO-incompatible/compatible kidney transplantation (ABOi-KT/ABOc-KT) from December 2006 to December 2009 were collected. Then, statistical analyses were conducted from the aspects of tissue matching, perioperative managements, complications and survival rates of renal allograft or recipients.Results:Clinical data of 342 ABOi-KT and 779 ABOc-KT indicated that (1) no inter-group differences existed in age, body mass index (BMI), donor-recipient relationship or waiting time of pre-operative dialysis; (2) ABO blood type: blood type O recipients had the longest waiting list and transplantations from blood type A to blood type O accounted for the largest proportion; (3) HLA matching: no statistical significance existed in mismatch rate or positive rate of PRA I/II between two types of surgery; (4) CD20 should be properly used on the basis of different phrases; (5) hemorrhage was a common complication during an early postoperative period and microthrombosis appeared later; (6) no difference existed in postoperative incidence of complications or survival rate of renal allograft and recipients at 1/3/5/10 years between ABOi-KT and ABOc-KT. The acute rejection rate and serum creatinine levels of ABOi-KT recipients were comparable to those of ABOc-KT recipients within 1 year.Conclusions:ABOi-KT is both safe and effective so that it may be applied at all transplant centers as needed.

Objective To assess the efficacy and safety of febuxostat in the treatment of hypemricemia in renal transplant recipients.Methods A total of 124 renal transplant patients with hyperuricemia receiving febuxostat between June 2016 and July 2018 were retrospectively analyzed.Uric acid (UA),liver function and renal function parameters before and 3 months after treatment were compared.Adverse events,recipient and renal allograft survival were recorded throughout the follow-up period.Results Serum level of uric acid significantly decreased after 3-month treatment (P＜0.001).And 66.1％ of them achieved target UA level at Month 3 after dosing.Estimated glomerular filtration rate (eGFR) was maintained.No severe adverse event was observed.All recipient and renal grafts survived during the follow-up period.Conclusions Febuxostat is both effective and safe in the treatment of hyperuricemia in renal transplant.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulators may attenuate PCSK9-induced low-density lipoprotein receptor (LDLR) degradation in lysosome and promote the clearance of circulating low-density lipoprotein cholesterol (LDL-C). A novel series of tetrahydroprotoberberine derivatives (THPBs) were designed, synthesized, and evaluated as PCSK9 modulators for the treatment of hyperlipidemia. Among them, eight compounds exhibited excellent activities in downregulating hepatic PCSK9 expression better than berberine in HepG2 cells. In addition, five compounds , , , ()-, and ()- showed better performance in the low-density lipoprotein, labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate (DiI-LDL) uptake assay, compared with berberine at the same concentration. Compound , selected for evaluation, demonstrated significant reductions of total cholesterol (TC) and LDL-C in hyperlipidemic hamsters with a good pharmacokinetic profile. Further exploring of the lipid-lowering mechanism showed that compound promoted hepatic LDLR expression in a dose-dependent manner in HepG2 cells. Additional results of human related gene (hERG) inhibition assay indicated the potential druggability for compound , which is a promising lead compound for the development of PCSK9 modulator for the treatment of hyperlipidemia.

Objective To explore the clinical outcome of renal transplantation and analyze the risk factors influencing the kidney allograft survival after transplantation.Methods The clinical data of 524 cases of renal transplantation between January 2007 and December 2015 were retrospectively analyzed.Serum creatinine was determined,and glomerular filtration rate(GFR) was estimated.The 1-,2-and 3-year patient and graft survival after transplantation was calculated.Adverse events were recorded.Results The median follow-up time was 17.2 months.The 1-,2-and 3-year graft survival rate after transplantation was 97％,95.8％ and 95.3％,respectively.The 1-,2-and 3-year patient survival rate after transplantation was 97.8％,97％ and 97％,respectively.The eGFR was (67.6 ± 24.1),(68.9±24.2) and (72.7 ± 26.2) ml·min-1 ·1.73 m-2 at 1st,2nd and 3rd year after transplantation.The incidence of delayed graft function(DGF) was 20.6％ (108/524).Multivariate analysis revealed donor type (P =0.005) and the terminal creatinine (P＜0.001) were the independent risk factors of DGF.Elder recipients (P =0.004),recipients with diabetes(P =0.031),preoperative positivity of panel reactive antibody(PRA) (P =0.023),and donor with hypertension (P =0.046) were risk factors influencing the kidney allograft survival.Conclusion Kidney transplantation showed good outcomes at 3rd year after transplantation.The recipient age,recipient's history of diabetes,preoperative PRA and donor's history of hypertension are independent risk factors for renal graft survival.

Objective Hepatocellular carcinoma with bile duct tumor thrombus (BDTT) is rare,and surgical treatment is currently considered as the most effective treatment.Whether resectional surgery should be carried out on these patients remains controversial.Therefore,this Meta-analysis aimed to find out the long-term survival after resectional surgical treatment.Methods We conducted a literature search on PubMed,Embase and Web of Science from inception to September 2016.11 studies were included which involved 5295 patients.Each study was evaluated using the Newcastle-Ottawa Scale.The pooled effect was calculated and the associations between BDTT and overall survival (OS) or disease-free survival (DFS)were reevaluated using Meta-analysis with hazard ratio (HR) and 95％ confidence interval (CI).Results The HR for OS and DFS was 2.34 and 1.81,the 95％ CI were 1.26 ～ 4.36 and 1.17 ～ 2.78,respectively.Conclusion HCC patients with BDTT had a bad prognosis after hepatic resection or liver transplantation.

Metabolism is the necessary process for cell growth and survival,and it is dramatically altered in cancer cells compared with that in normal cells,and these alterations are known as the Warburg effect.Glutamine plays a decisive role in the metabolic processes.And the glutaminase as a enzyme in the processes has also become a hot topic of research in recent years.This article could focus on the recent research progress on glutaminase.

Objective To investigate the effects of simulated microgravity by rotary cell culture system (RCCS) on expression profiles of miRNA in mouse fibroblasts L929 cell line.Methods L929 cells were cultured in vitro and divided into simulated microgravity (SMG) group and normal gravity (NG) group according to the simple random method.Samples of two groups were collected on 7th day of culture and the total RNAs were extracted,labeled,and hybridized in sequence.Feature Extraction Software was used to collect the array images and get raw data,which were analyzed by Genespring Software.Differentially expressed miRNAs were identified and then validated by qRT-PCR.Target genes of differentially expressed miRNAs were predicted by the databases of Targetscan and microRNAorg,and the intersections of databases were identified as potential regulatory target genes.Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analysis were applied to determine the roles of these target genes.Relevant biological functions and/or signaling pathways of the regulated genes especially related with wound healing process were categorized based on their enrichments.Then integration predictions of the miRNA and mRNA expression profiles had been proposed to refine the functional miRNA-mRNA relationships.The miRNA-mRNA functional network and miRNA-mRNA control network were constructed.Results Four miRNA genes were up-regulated significantly including mmumiR-669j,-122-5p,-30a-3p,-6516-3p,among which mmu-miR-669j was up-regulated at 52.84 folds with the greatest significance (P ＜ 0.05).Seventeen miRNA genes were down-regulated significantly including mmu-miR-21a-3p,-miR-28a-5p,-218-5p,-210-3p,-miR-19a-3p,-miR-31-3p,and-miR-19b-3p,among which mmu-miR-28a-5p was down-regulated at 15.47 folds with the greatest significance (P ＜ 0.05).The qRT-PCR showed a high concordance with the microarray results (P ＜ 0.05).Target gene prediction and functional enrichment analysis suggested that a variety of biological processes and signaling pathways involved in wound repair were significantly enriched (P ＜ 0.05).Function network and regulation network of miRNA-mRNA covered all the differentially expressed miRNAs,which suggested that miR-21 a-3p and predicted target gene Smad3 might play an important role in wound healing under microgravity.Conclusions Simulated microgravity by RCCS can significantly affect the expression of stress-related miRNAs in mouse fibroblasts L929.The miRNA target gene prediction and functional enrichment analysis based on gene chip technology may provide theoretical basis for illustrating the mechanism and management of weightlessness stress injury.