OBJECTIVE To investigate the effect of vitamin D receptor(VDR) genetic polymorphism on the concentration of tacrolimus in renal transplant recipients at early stage after transplantation.METHODS The 360 cases of renal transplant recipients who received tacrolimus, mycophenolic acid, and glucocorticoid were recruited. CYP3A5(rs776746) and VDR(VDR ApaI rs7975232, VDR BsmI rs1544410, VDR FokI rs2228570 and VDR TaqI rs731236) genotypes were determined. The differences of concentration(C), dose(D) and the ratio of concentration to dose(C/D) of tacrolimus were compared among all of the genotype groups at the seventh day after renal transplantation. RESULTS The C and C/D of tacrolimus in CYP3A5 non-expresser(GG genotype) were all significantly higher than CYP3A5 expresser(AA and AG genotype)(P<0.05). When taking the different CYP3A5 genotypes in consideration, it was found that the C/D in patients with VDR ApaI rs7975232 AA genotype was significantly lower than those with AC and CC genotypes for CYP3A5 non-expresser(P<0.05). However, VDR ApaI rs7975232 gene polymorphism had no influence on C and C/D of tacrolimus in CYP3A5 expresser. Besides, no matter in CYP3A5 expresser or in non-expresser, VDR BsmI rs1544410, VDR TaqI rs731236 and VDR FokI rs2228570 had no effect on C, D and C/D of tacrolimus. CONCLUSION During the early stage of renal transplantation, the polymorphism of VDR ApaI rs7975232 show significant relevance with tacrolimus concentration in CYP3A5 non-expresser. The detection of the genotype might be helpful to guide individual therapy.

OBJECTIVE:To establish population pharmacokinetics(PPK)model of vancomycin so as to evaluate the effects of cystatin C(Cys C)on the pharmacokinetics parameters of vancomycin. METHODS:Totally 333 times therapeutic drug monitoring (TDM)were retrospectively collected from 225 patients who received vancomycin. Using sex,age,body weight(mT),Scr and Cys C as covariates,PPK model was established by using nonlinear mixed effect model method. Bootstrap method and normal prediction distribution error(NPDE)method were adopted for internal validation of model. Forty times of TDM data were collected from other 27 patients for external validation. Predicted accuracy and precision of model were investigated with mean prediction error (MPE) and root mean square error (RMSE). The effects of Cys C change on pharmacokinetic parameters of vancomycin were evaluated with steady state trough concentration and apparent clearance rate (CL/F) of vancomycin in typical patient (65 year-old,64 kg,Scr 66 μmol/L,1 000 mg,q12 h)forecasted with the final model at different levels of Cys C. RESULTS:CL/F of vancomycin was significantly influenced by age,body weight,the levels of Scr and Cys C. The final model was CL/F(L/h)＝3.68×(Scr/66)－0.431×(mT/64)1.1×(Age/65)－0.368×(Cys C/1.04)－0.693,V/F was equal to 82.5 L. The robust rate verified by Bootstrap method was 100%. Except for the interindividual variation of V/F,the relative bias of other pharmacokinetic parameters was less than 5%,and the estimated parameters of the final model were in the 95% confidence intervals of estimated values of Bootstrap. NPDE results showed that the homogeneity of variance was consistent with normal distribution (P＞0.05). In external validation,MPE and RMSE of the simplest model were －1.52 μg/mL and 6.87 μg/mL. MPE and RMSE of the final model were －0.32 μg/mL and 4.27 μg/mL,the accuracy and precision were improved significantly in the final model. When Cys C levle of typical patient was 0.3-4.0 mg/L,the steady state trough concentration predicted by final model were 5.25-29.97 μ g/mL and CL/F were 1.45-8.71 L/h. CONCLUSIONS:Age,body weight,the levels of Scr and Cys C significantly influence the pharmacokinetic parameters of vancomycin;moreover,the level of Cys C can change blood concentration of vancomycin. Established PPK model is of great predictive performance,which can be used to estimate the individual pharmacokinetics parameters of vancomycin.

Aim To investigate the mechanism of dia-betes changing the hepatic CYP1 A2 through in vitro cell culture study.Methods The function of CYP1 A2 in HepG2 and Fa2N-4 cells were evaluated by determi-ning the level of phenacetin metabolism,and the mR-NA expression of CYP1 A2 in cells was detected by real time PCR.HepG2 cells were co-cultured with serum of diabetic rats(type 1 and type 2)and normal rats,then the CYP1 A2 function in cells were evaluated.Then, the HepG2 and Fa2N-4 cells were co-cultured with a series of concentrations of saturated (including palmitic acid and stearic acid)and unsaturated fatty acids(in-cluding oleic acid and linoleic acid)for 48 h,and the function and expression of CYP1 A2 in the cells were compared.Results It was found that the activities of CYP1 A2 were higher in cells incubated with diabetic serum of both type.All high concentration of fatty acids could increase the function and expression of CYP1 A2 in both HepG2 and Fa2N-4 cells.Conclusion It is speculated that the abnormal level of fatty acids under diabetic state might be part of the reasons why diabetes change the hepatic CYP1 A2,which provides the basis for future study.

Objective:To investigate the correlation of the blood concentration of tacrolimus ( Tac) and serum cystatin C ( SCysC) and serum creatinine (Scr) in the patients with renal transplantation. Methods:Totally 84 cases of renal transplantation patients (67 male/17 female) treated with Tac were involved. The blood concentration of Tac, SCysC and Scr were monitored after the operation. Data results were categorized according to the postoperative time and the blood concentration. The correlations of Tac blood concentra-tion,SCysC and Scr were analyzed and compared by using Pearson correlation analysis. Results: The blood concentration of Tac was not significantly associated with SCysC and Scr in different postoperative time groups and different drug concentration groups ( P >0. 05). As the extension of time,the blood concentration of Tac showed a gradual declining trend, while SCysC and Scr levels de-creased first, and then increased gradually after two years of the operation. Conclusion:The blood concentration of Tac has no effect on the function evaluation of transplanted kidney by the biochemical indicators such as SCysC and Scr.

Objective To evaluate prognostic value of N-terminal B-type brain natriuretic peptide (NT-proBNP) combined with galectin 3 of prognostic value in patients with chronic heart failure (CHF).Methods Determination of 92 cases of CHF patients on admission and at discharge plasma NT-proBNP and galectin-3 levels,then after the patients discharge we follow up 16 months and observe the internal recurrent heart failure hospitalization rate and mortality.Results In patients the heart function of New York Heart Association (NYHA) Ⅰ,Ⅱ,Ⅲ,Ⅳ level,NT-proBNP were (351.6 ± 467.5) pg/ml,(493.2 ± 411.7) pg/ml,(1 289.6 ± 737.8) pg/ml,(2 719.2 ± 1 044.1) pg/ml,galectin-3 (12.23 ± 6.12) ng/ml,(13.59± 5.46) ng/ml,(19.18 ± 7.44) ng/ml,(26.61 ± 8.82) ng/ml as well.NT-proBNP and galectin-3 levels were increased with the depression of cardiac function.The patients who had higher NT-proBNP or galectin3 levels discharged and occurred the more probability of re-hospitalization on account of heart failure or death.Compared to those patients with one of them increased,the patients whose discharge NT-proBNP and galectin-3 value were both increased with significantly poor outcome.Conclusions Both NT-proBNP and galectin-3 were independent predictors of poor prognosis in patients with heart failure.Galectin-3 combined with NT-proBNP can assess the prognosis of patients with CHF more effectively.

Objective To establish reference interval of hemoglobin A1c(HbA1c) determined in healthy adults in northeast Si-chuan .Methods Venous blood was pumped from 494 individuals without previously diagnosed diabetes and other critical illness . The HbA1c level ,blood routine examination ,blood lipids ,fasting plasma glucose ,liver and kidney function were measured . Reference value of HbA1c was determined by 95% confidence interval through the mean of HbA1c .Results The HbA1c level took on normal distribution in 494 healthy individuals ,and the reference interval was 4 .482% -6 .012% .There was no statistical signifi-cance of HbA1c level between different genders(t= -0 .905 ,P= 0 .366) .The levels of HbA1c in 20 - < 35 years old people , 35- <65 years old people and ≥65 years old people were(5 .109 ± 0 .150)% ,(5 .224 ± 0 .122)% ,(5 .444 ± 0 .125)% ,and the differences were statistically significant among different age group(P<0 .05) .The HbA1c level and age were positively correlated (r=0 .338 ,P<0 .01) .Conclusion It is necessary to establish appropriate reference intervals of HbA1c for different laboratories or areas .

OBJECTIVEWe ascertained the effect of bone morphogenetic protein-2 (BMP-2) and basic fibroblast growth factor (bFGF) by a series of experiments: Proliferation and differentiation of bone marrow stromal cells (BMSCs) in vitro, ectopic and in situ bone formation and loaded porous calcium phosphate cement (CPC) on the repair of bone defects around dental implants.

METHODSBMSCs from Beagle dogs were cultured in vitro with basic culture medium containing BMP-2, bFGF, and BMP-2+bFGF. Proliferation and differentiation of BMSCs were quantified using methyl thiazolyl tetrazolium (MTT) and alkaline phosphatase (ALP) test. The CPC seeded with BMSCs and BMP-2, bFGF, combined BMP-2 with bFGF were implanted subcutaneously into nude rats in ectopic bone formation, and were implanted into critical-sized bone defects of Beagle dogs in the in situ bone formation. The bone formation was detected by histology examination and quantified using an image analysis system. Polychrome sequential fluorescent labels and fluorescence histological examinations of undecalcified sections were performed post-operatively.

RESULTSIt was determined that BMP-2+bFGF promoted BMSCs statistically significant proliferation and differentiation compared to either BMP-2 or bFGF in vitro. The CPC with BMP-2+bFGF group yielded more bone than those with either BMP-2 or bFGF in ectopic bone formation test. The percentages of newly ectopic formed bone were higher in the BMP-2+bFGF group (48.79% +/- 11.31%) than those in other groups (BMP-2 group, 30.71% +/- 10.85%; bFGF group, 27.33% +/- 9.67%; and the control group, 10.65% +/- 6.05%). Undecalcified showed that new bone was actively formed in the BMP-2+bFGF group after 12 weeks in the in situ bone formation test. The bone mineralization apposition rate (MAR) was better in the BMP-2+bFGF group than in other groups (P<0.01).

CONCLUSIONBMP-2 combined with bFGF are more effective than one alone in promoting the formation of new bone.

Animals ; Bone Marrow Cells ; Bone Morphogenetic Protein 2 ; Bone and Bones ; Calcium Phosphates ; Cell Differentiation ; Cells, Cultured ; Dogs ; Fibroblast Growth Factor 2 ; Mesenchymal Stromal Cells ; Rats

Experimental report is an important segment of the experimental teaching pro-cess.This article analyzes the current status and factors that influence the quality of experimental report,puts foreword some countermeasures on how to enhance the experimental teaching by im-proving the writing of experimental reports,in order to achieve the purpose of improving the quality of clinical experimental teaching of clinical biochemistry and laboratory.

0.05), but significant difference when compared the older-age group with the young & middle-age group(P

OBJECTIVE: To analyze the therapeutic drug monitoring results of valproic acid( anti- epileptic drug) . METH-ODS: The concentrations of valproic acid in 226 cases in our hospital were determined by fluorescence polarization immunoassay. RESULTS: The results showed that 47. 79% were within the normal referenced concentration range, with average concentration at( 66. 19? 12. 13) ? g? mL- 1, 46. 90% were below the lower limit and 5. 31% were above the upper limit. CONCLUS-ION: The monitoring results are far from satisfactory. It is advisable to adopt individualized administration so as to achieve the goal of treatment.