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Objective To explore the influencing factors of blood concentration of tacrolimus in pediatric living donor liver transplant recipients and provide rationales for individualized administration of tacrolimus .Methods Trough concentrations (C0 ) , doses of tacrolimus , recipient age , gender , body weight ,donor and recipient CYP3A5 genotypes ,hematocrit (HCT ) and liver/kidney function related indicators at 3 ,5 ,7 ,14 days ,1 month , 2 months and 3 months post living donor liver transplantation were collected from a total of 100 pediatric recipients .Taking ratio of concentration to dose (C0 /D) as a dependent variable ,the influencing factors of blood concentration of tacrolimus were analyzed by multivariate stepwise regression .Results The influencing factors of blood tacrolimus concentration at 3d post-transplantation were recipient CYP3A5 genotyp , donor CYP3A5 genotype and weight of recipients . The major influencing factors at 5d post-transplantation were recipient & donor CYP3A5 genotypes , recipient weight and HCT . The major relevant factors at 7d posttransplantation were CYP3A5 of recipients ,age and HCT .The influencing factors at 14 days were the same as those at 2 months ,i .e .CYP3A5 genotype and weight of recipients .At 1 month the major influencing factors were weight of recipients ,CYP3A5 of recipients and alkaline phosphatase (ALP) ; CYP3A5 genotype and weight of recipients at 3 months . Further study on CYP3A5 genotype of donors and recipients , the C0 /D ratio of CYP3A5 genotype non-expression group was significantly higher than that of expression group in recipients and C0 /D ratio of donor CYP3A5 genotype nonexpression group was significantly higher than that of expression group .Conclusions The influencing factors of concentration of tacrolimusvary at different timepoints after liver transplantation . Paying close attention to the changes of CYP3A5 genotype , weight of recipients and related biochemical indexes and considering various influencing factors facilitate individualized dosing for improving the prognosis of pediatric recipients .
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OBJECTIVE： To provide reference for reasonable selection of tyrosine kinase inhibitors （TKI） in chronic myeloid leukemia （CML） patients with BCR-ABL35INS mutation. METHODS： Using “BCR-ABL insertional mutation” “ABL1 35ins mutation” “BCR-ABL c.1423_1424ins35” “ABL1 p.C475Tyrfs*11” as keywords， retrieved from CNKI， Wanfang database， Medline and COSMIC database， BCR-ABL35INS mutation CML patients were summarized and analyzed in respects of general information and treatment （treatment plan， patient compliance and drug withdrawal）， therapeutic effect （molecular biological mitigation and disease progress） and safety data （ADR） during 2007-2018. RESULTS： Totally 9 related literatures were included， involving 70 patients with BCR-ABL35INS mutation， all of them were foreign cases. Among them， 39 cases were male and 31 cases were female， with a median age of 49.2 years. The median time from the diagnosis of CML to the detection of BCR-ABL35INS mutation was 19 months. After detecting gene mutation， 39 cases were treated with imatinib （initial dose of 400 mg， po， once a day）， and molecular biological remission was achieved in 5 patients （12.9％）； 15 cases （38.5％） had molecular biological response but had disease progression； 8 patients （20.5％） had no response. Seventeen patients were treated with dasatinib （100 mg， po， once a day or 2 divided dose）， and 8 cases （47.1％） achieved molecular biological response. Twenty-one patients were treated with nilotinib （400 mg， po， 2 divided dose）， and 3 patients （14.3％） achieved molecular biological response； 2 patients achieved molecular biological response， but the disease progressed. Seven， three and seven of these patients stopped taking drugs due to adverse reactions， accounting for 17.9％， 17.6％ and 33.3％ respectively. All the ADRs were classified as grade 3-4 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events， and most of them were hematological toxicity. CONCLUSIONS： CML patients with BCR-ABL35INS mutation are less likely to achieve molecular response on imatinib therapy but are more sensitive to dashatinib. In the course of treatment， we should strengthen the monitoring of blood system and other related indicators to ensure the safety and effectiveness of drug use.
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Objective:To establish a method for the determination of 11 trace elements in white vaselin. Methods:The contents of Mg,Al,Fe,Co,Ni,Cu,Zn,As,Cd,Hg and Pb in white vaselin were determined by inductively coupled plasma mass spectrome-try (ICP-MS). The parameters of ICP-MS were as follows:the Argon gas pressure was 0.6 MPa,the helium pressure was 0.12 MPa, the scan times were 200,the flush time was 45 s,the sampling time was 45 s and the internal standard was added online. Results:The linear relationship between concentration and response value of each element standard solution was within the range of 0-100 ng· m L-1. Except the correlation coefficients of Mg and Fe were 0.998 and 0.997,that of the other elements was all above 0.999. The recoveries of Mg,Fe,Ni,Zn,As and Pb were 74.9%-83.0%,those of Cd and Hg were 87.5%-94.4%,and those of Al,Co and Cu were 107.6%-118.7%. The detection limit of Mg, Al, Fe, Co, Ni, Cu, Zn, As, Cd, Hg and Pb was 1.9,0.59,0.61,0.16, 0.33,1.5,1.7,0.09,0.12,0.70 and 1.6 ng·ml-1,respectively. Among the 67 samples,the contents of Mg,Al,Fe,Ni,Cu, Zn, As and Hg were all detected out,while those of Co,Cd and Pb were only detected out in some samples. Conclusion:The method has the advantages of simple operation and high sensitivity,which can satisfy the determination of trace elements. It is suggested to se-lect 4 elements (Mg,Al,Fe and Ni) as the evaluation indices for white vaselin.
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Objective To analyze and compare the dosage,blood concentration and metabolic characteristics of Tacrolimus (Tac) for pediatric patients who underwent living related liver transplantation (LRLT) or donation after cardiac death liver transplantation (DDLT).Methods The clinical data of 75 liver transplantation pediatric patients from October 2012 to August 2015 were retrospectively analyzed.According to the different source of donors,the recipients were divided into two groups:LRLT group (40 cases) and DDLT group (35 cases).Results (1) Under the condition of same initial Tac dosage,the Tac dosage in LRLT group was less than in DDLT group during the first 28 days post-transplantation (P＞ 0.05).However,the Tac dosage in DDLT group was significantly higher than in LRLT group on the second and third months after sugery (P =0.000).(2) Correlation analysis revealed that graft-recipient body weight ratio (GRWR) was correlated with Tac dosage (mg·kg-1 ·d-1) on the 14th day postoperative (LRLT group:r=0.579,P＜0.05;DDLT group:r =0.583,P＜0.05) and Tac concentration/dosage ratio (LRLT group:r =-0.607,P＜0.05;DDLT group:r=-0.680,P＜0.05).Conclusion Tac has a satisfactory anti-rejection effect on liver transplantation pediatric patients while the metabolism varied with each individual.There is a positive correlation between the early Tac dosage and the GRWR in both groups.It is necessary to set individualized Tac administration regimen according to the metabolic characteristics and GRWR.
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Objective To investigate the efficacy,safety,economy evaluation of CYP3A5 * 3 gene polymorphism in providing individualized administration for the use of tacrolimus (Tac) in renal transplantation recipients.Method Pyrophosphate sequencing method was used to determine the CYP3A5 * 3 genotype of renal transplant patients in the first day after surgery.Computer-generated random numbers were used to assign 60 patients into experiment group or control group.Both groups of patients were routinely given the initial dose of Tac (4.0 mg/day) in the first day after surgery.The patients in the experiment group were given different doses of Tac based on the different CYP3A5 * 3 genotypes at the third day after surgery [for AA,AG:0.12 mg/(kg day),and for GG:0.06 mg/(kg day)].The patients in the control group were given different dosages of Tac according to drug concentration.The patients were followed up for 12 months,and different parameters were compared between two groups.A decision tree model was populated with data from the study and used to economics evaluation.Result At day 5 after the transplantation,significantly more patients in the experiment group were within the Tac target C0 range [90％ (27/30)] as compared to the control group [46.67％ (14/30) (P＜0.05).At this time point,the median Tac C0was 5.08 [(2.5-8.7) μg/ L] in the experiment group vs.5.29 [(1.3-13.6) μg/L] in the control group (P＜0.05).When C0/ D was analyzed according to CYP3A5 * 3 genotype,we found the mean C0/D in the both groups with CY3A5 * 3/* 3 ＞CYP3A5 * 3/* 1 ＞ CYP3A5 * 1/* 1.It was noted that the time to achieve target Tas was (4.40 ± 0.97) in the experiment group,vs.(7.57 ± 3.42) in the control group.In total,the number of daily dose modifications was 11 in the experiment group and 49 in the control group in two weeks after transplantation (P＜0.05).Renal function at day 14 after transplantation and adverse events during 12 months of follow-up were similar in both groups.In total,10 adverse events were reported in the experiment group and 11 in the control group (P＞0.05).The results of costeffectiveness analysis showed that the cumulative costs and effects in the experiment group were ￥ 38 067 and 0.90 quality-adjusted life years gained,and those in the control group were ￥38 681 and 0.87 quality-adjusted life years gained,respectively.In the base case analyses,experiment group was more cost-effective.Conclusion Individualized adjustment of Tac doses for patients according to recipients different CYP3A5 * 3 genotypes is beneficial for reaching target concentration as soon as possible and more cost-effective.But the demonstration of the clinical relevance of this approach was not achieved.Higher methodological quality,and larger sample size study are still needed.
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Objective To evaluate the efficacy and safety of sirolimus and tacrolimus after renal transplantation.Method PubMed,Web of knowledge,Medline and the Cochrane controlled trials register,Chinese Biomedicaldatabase,and Vip database were searched with the terms and Boolean operators as (kidney transplantation OR renal transplantation) AND (sirolimus OR rapamycin OR rapamune) AND (tacrolimus OR FK506 OR prograf).Results retrieved were updated on November,2015.Data were extracted for patient and graft mortality,acute rejection (AR),wound complications,infection,GFR,withdrawl.Professional meta analysis software RevMan 5.3 was employed.Result Altogether,1810 patients from 10 randomized controlled trials (RCTs) were included.Patients in the sirolimus group showed a decreased rate of graft mortality and infection (RR =0.63,95％ CI,0.45-0.89,P=0.009;RR=4.42,95％ CI,1.73-11.31,P=0.002).Patients in the sirolimus group showed an increased rate of AR,wound complications,GFR,withdrawl (SMD=-0.52,95％ CI,-0.73-0.31,P＜0.000 01;RR=0.54,95％ CI,0.40-0.73,P＜0.000 1;RR=0.17,95％ CI,0.11-0.25,P＜0.000 01;RR =0.44,95％ CI,0.37-0.51,P＜0.000 01).The patient mortality was insignificantly different between two groups.Conclusion This meta-analysis concluded that sirolimus showed advantage over tacrolimus about safety when used early after renal transplantation.The options of immunosuppressive regimens after kidney transplantation should be based on the specific condition.To obtain more reliable and accurate clinical data,the RCTs with more rational design,higher methodological quality,larger sample size,including domestic patients,longer follow-up are still needed.