Objective:To study the characteristics of the adverse reactions caused by tacrolimus and analyze the risk factors. Methods:Totally 280 cases of renal transplant recipients received standard treatment options were selected from 1997 to 2013 in Wuhan general hospital of Guangzhou military command. The tacrolimus-related adverse reactions and their risk factors were analyzed statistically. Results:Totally 39. 65% of the patients had the tacrolimus-related adverse reactions. The main adverse reactions were hematotoxicity,diabetes mellitus and hyperlipidemia. The univariate analysis showed that age,weight,BMI and treatment course were the suspected risk factors. The multivariate analysis results showed that age,BMI and treatment course were the risk factors of tacrolimus-related adverse reactions. Conclusion:The incidence of tacrolimus-related adverse reactions is relatively high,and if the patient is in advanced age,with poor nutritional status or long-term medication,the probability of adverse reactions will be increased.

Objective To offer a theory that supports the individualized tacrolimus dosage regimen by retrospectively investigating the influences of gene polymorphism and other clinical factors on tacrolimus concentration in renal transplant recipients. Methods A total of 280 renal transplant recipients were genotyped for CYP3A4?5, CYP3A4?6, CYP3A4?18B, CYP3A5?3, MDR1 1236C>T, MDR1 2677G>T/A, MDR1 3435C>T polymorphisms by PCR followed by restriction fragment length polymorphism (RFLP) analysis.PXR 6bp deletions (rs3842689) genotypes were determined by Allelic Special-Touch down PCR.Correlation between gene polymorphisms and tacrolimus concentrations was analyzed. Results The mutation frequency of CYP3A4?18B, CYP3A5?3, MDR1 1236C>T, 2677G>T/A, 3435C>T and PXR rs3842689 in the renal transplant recipients was 29.11%, 69.29%, 43.57%, 49.64%, 36.43% and 26.07%, respectively.Multiple regression analysis showed that, CYP3A5?3 and red blood cell count were associated with the value of C0/D of FK506, the best regression model was:D=C0/(-60.445 +95.777×CYP3A5 +34.938×RBC), and the equation could explain 38.8% of tacrolimus individual differences. Conclusion Gene polymorphism of CYP3A5?3 and red blood cell count may be responsible, in part, for the large interindividual variability of FK506 dose and concentration.

Objective To investigate the value of DWI before treatment on predicting sensitivity of concurrent chemoradiation in nasopharyngeal carcinoma.Methods Seventy patients with nasopharyngeal carcinoma proved by nasopharyngoscope and biopsy pathology conducted DWI before concurrent chemoradiation and reexamined on receiving dose of 50 Gy.The mean, maximum and minimum ADC value of tumor were measured on DWI and maximum area of tumor before and during treatment ( on dose of 50 Gy) was delineated to calculate the tumor regression rate ( RS0-50 ).The patients were classified into three groups according to the RS0-50 as sensitive, moderate, and resistant therapeutic effect.Patients were classified into different groups according to the pathologic type and clinical stage respectively .Spearman correlation analysis was used between RS 0-50 and ADC values of all tumors , different pathologic types and clinical stages , respectively.ROC was used to evaluate the cutoff and value of ADC which had highest correlation to RS0-50 on predicting therapeutic effect.Results DWI of 3 patients were excluded due to obvious swallow artifact which influenced the measurement , and finally 67 patients were included in this study, with pathological type of nonkeratinized differentiated undifferentiated carcinoma in 49 cases, nonkeratinized undifferentiated carcinoma in 18 cases, clinical T1 stage in 7 cases, T2 in 14 cases, T3 in 17 cases and T4 in 29 cases.During treatment , there were 13 cases with sensitive therapeutic effect , 42 cases with moderate therapeutic effect and 12 cases with resistant therapeutic effect.RS0-50 [ ( 65.6 ± 3.1) %] showed mildly and moderately negative correlation to mean ADC [(1.06 ±0.19) ×10 -3 mm2/s] and maximum ADC [(1.29 ±0.33) ×10 -3 mm2/s] respectively ( r =-0.276, P =0.024 and r =-0.434, P=0.001, respectively).ROC showed when setting threshold at maximum ADC value of lower than 1.06 ×10 -3 mm2/s for predicting sensitive therapeutic effect , the specificity , sensitivity , and accuracy was 69.2%(9/13), 88.9%(48/54) and 85.1% (57/67), respectively, and when setting threshold at maximum ADC value of higher than and equal to 1.30 ×10 -3 mm2/s for predicting resistant therapeutic effect, the specificity, sensitivity, and accuracy was 75.0% (9/12), 65.5% (36/55) and 67.2%(45/67), respectively.Conclusion Pretreatment maximum ADC value were able to predict the tumor regression rate and sensitivity of concurrent chemoradiation in nasopharyngeal carcinoma .

Objective To evaluate 3.0T MR diffusion weighted imaging (DWI) and ADC value in diagnosis, histological grade, tumor staging and short-time therapeutic outcome of clear cell renal cell carcinomas (CCRCC). Methods DWI of 51 patients of CCRCC confirmed with surgery and pathology were retrospectively reviewed. ADC values of tumors and the corresponding areas of lateral normal renal parenchyma were measured. Taking ADC value at 1.8×10~(-3) mm~2/s as a cut-off value, the patients were divided into two groups. The tumors' histological grade, T-staging, clinical staging, tumor short-term control rate within 1 year follow-up were compared between the two groups with statistical test. Results Statistical difference of ADC value was observed between CCRCC ([1.778±0.582]×10~(-3) mm~2/s) and those of normal renal parenchyma ([2.314±0.223]×10~(-3) mm~2/s) (P<0.01). ADC values of 24 patients were less than 1.8×10~(-3) mm~2/s and those of 27 patients were more than or equal to 1.8×10~(-3) mm~2/s. There were statistical differences in histological grade, T-staging, clinical staging, tumor short-term control rate within 1 year follow-up between the two groups (P＜0.01). Conclusion 3.0T MR DWI can accurately differentiate CCRCC from normal renal parenchyma. Quantitative analysis of ADC value is helpful to evaluate the histological grade, tumor staging and short-term therapeutic outcome of CCRCC.

Objective To evaluate 3.0T MR diffusion weighted imaging (DWI) and ADC value in diagnosis of different pathological types and grades of malignant renal tumors. Methods DWI images of 66 patients of malignant renal tumors proved pathologically were retrospectively reviewed. ADC values of tumors and the corresponding areas of lateral normal renal parenchyma were measured and analyzed statistically. Results There was significant difference between the mean ADC value of malignant renal carcinomas ([1.653±0.598]×10~(-3) mm~2/s) and that of normal renal parenchyma ([2.305±0.218]×10~(-3) mm~2/s, P<0.001). ROC curve showed that taking ADC value of lower than 2.0×10~(-3) mm~2/s as a threshold for diagnosing renal malignant tumor, the specificity, sensitivity and accuracy was 93.94%, 71.21% and 82.58%, respectively. Statistical differences were found between clear cell carcinoma and non-clear cell carcinoma (P=0.001), as well as clear cell carcinoma grade Ⅰ and Ⅲ (P=0.002), grade Ⅱ and Ⅲ (P=0.004) respectively. However, no statistical difference was observed between grade Ⅰ and Ⅱ (P=1.000). Conclusion 3.0T MR DWI can be used in diagnosis of malignant renal tumors, and ADC value may help to differentiate the pathological type and grade.

Objective To examine the effect of berberine hydrochloride ( BER ) on the pharmacokinetic profiles of midazolam,a substrate of CYP3A,in rats. Methods The rats were intragastrically given different doses of BER (50,100, 200 mg?kg-1) or ketoconazole (75 mg?kg-1) for 10 days.Single-pass duodenum perfusion of 20 mg?kg-1 MDZ was performed and the inguinal artery was cannulated for blood sampling.Plasma concentrations of MDZ and 1'-OH-MDZ were analyzed by high performance liquid chromatography ( HPLC) with the CYP3A inhibitor ketoconazole serving as positive control. Results BER (50,100,200 mg?kg-1) and ketoconazole (75 mg?kg-1) could significantly increase the AUC(0-t),AUMC(0-t)and Cmax of MDZ in a dose-dependent manner ( P<0.05) ,and reduce the clearance rate ( CLz ) of MDA and its apparent volume of distribution in the body ( Vz ) ( P<0. 05). But they failed to dramatically affect the half-life ( t1/2z ) and the peak time ( tmax ) of MDZ. Additionally,BER ( 100,200 mg?kg-1 ) and ketoconazole ( 75 mg?kg-1 ) could significantly dose-dependently decrease the AUC(0-t),AUMC(0-t)and Cmaxof 1'-OH-MDZ,and profoundly increase the CLz,tmax and Vz of 1'-OH-MDZ (P<0.05),but they had no remarkable influences on the t1/2z.The ratio of AUC(1'-OH-MDZ)/AUC(MDZ) was decreased with the increase of BER concentration. Conclusion BER can inhibit the in vivo metabolism of MDZ in a dose-dependant manner, which is associated with the suppression of the activity of CYP3A.

Objective To investigate the diagnositic value of uhrasonography in fetuses with persistent right umbilical vein.Methods Three cases of persistent right umbilical vein diagnosed in our hospital were analyzed,including the sonographic findings and clinical outcome.Results In all cases the fetal gallbladder was located between the intraabdominal umbilical vein and the stomach,the umbilical vein was connected to the right portal vein,and the portal vein curved toward the stomach.Other intracranial malformations were detected in one case,and the baby died after birth.No addional malformations were found in the other two babies,and both of them were healthy at the age of 6 months.Conclusions Persistent right umbilical vein has typical prenatal sonographic appearances.The neonatal prognosis is favorable when other anomalies are ruled out.It's clinically important for early diagnosis and genetics consultation.

Objective To evaluate the value of MR and CT examinations in the diagnosis of nasopharyngeal carcinoma (NPC) and compare 2008 staging system with 1992 staging system and 2002 UICC staging system for NPC. Methods MR and CT images of seventy-six cases with NPC were studied. According to 2008 staging system and taking MR as a standard, differences between these two examinations were evaluated under the new NPC staging system, and three staging system were compared by MR findings. Results MR was inconsistent with CT in eveluating invasion of medial pterygoid muscle(22,24 cases), lateral pterygoid muscle( 15, 11 cases), skull base(35, 32 cases) and intracranial fossa( 11,6 cases), but no statistical diffence existed ( P ＞ 0. 05 ). There were statistical difference ( P ＜ 0. 05 )between MR and CT in determining invasion of parapharyngeal space( 50, 61 cases), retropharyngeal lymph node metastasis(48, 23 cases), stage T1 (18, 11 cases), T2 (15, 22 cases), N0 (18, 24 cases) and N1(33, 27 cases) with differences of 11 cases, 25 cases, 7 cases, 7 cases, 6 cases and 6cases respectively.For invasion of parapharyngeal space, CT showed 11 cases more than MR while 5 cases were comfirmed as compression by local tumor and 6 cases were proved as retropharyngeal lymph node metastasis according to MR. For retropharyngeal lymph node metastasis, MR presented 25 cases more than CT. These two reasons above mainly caused the differences of T-staging and N-staging. For 2008 staging system, when compared with 1992 staging system, there were 9 cases upstaging and 1 case downstaging in T classification, 16 cases upstaging in N classification, and 15 cases upstaging and 1 case downstaging in clinical classification; and when compared with 2002 UICC staging system, there were 7 cases, 10 cases and 12 cases upstaging in T,N, and clinical staging respectively. Conclusions Compared with MR examination which was regarded as standard by 2008 staging system of NPC, there were some differences in demonstrating invasion of parapharyngeal space and retropharyngeal lymph node metastasis by CT. Compared to 1992 staging system and 2002 UICC staging system, 2008 staging system mainly made T and N classification of tumor upstage,resulting in upstaging in clinical classification.

Objective To establish a sensitive method for the determination of rhodamine 123 (Rh123) in rat plasma by high performance liquid chromatography (HPLC).Methods The plasma samples were extracted by acetonitrile,and then separated on a Hypersil BDS C18 colunm (4.6 mm×100 mm,5 μm) equipped with a guard column kept at 25 ℃.The mobile phase consisted of acetonitrile and phosphate buffer (0.02 mol·L-1,pH4.0) (60:40) and was pumped at a constant rate of 1.0 mL·min-1.The peak was detected using a fluorescence detector set at FLD1A:Ex=485 nm,Em=546 nm.Results In this study,the method was validated for the Rh123 range of 0.1 to 32.0 μg·L-1,and the lower limit of quantitation (LLO Q) was 0.1 μg·L-1.The intra-and inter-day precisions for Rh123 were less than 7%,and the mean recoveries of Rh123 were 87.93%,89.03%,86.11% at low,mid,and high concentrations,respectively.Conclusion A simple,rapid and reproducible HPLC method was developed for the determination of Rh123 in rat plasma,which was an applicable method in modeling and description of the possible pharmacological interactions between the medicines and P-glycolprotein transporter.

Objective To detect the plasma amino-terminal pro-B-type natriuretic peptide (NT-ProBNP) of children with congenital heart disease(CHD) prior to heart surgery,to analysize its sensitivity,specificity and Youden index by receiver operating characteristic(ROC) curve,to explore the cut-off values of plasma NTProBNP for the diagnosis of congestive heart failure(CHF) in children under 5 years old before and after age stratification.Method The plasma NT-proBNP was detected for 100 children with CHD prior to heart surgery (experimental group) and 100 normal children(control group) between January 2011 to January 2013.Age stratification(0 ～ 1 year group,～3 years group and ～ 5 year group) was conducted in children with CHF younger than 5 years old to explore the cut-off values of plasma NT-ProBNP for the diagnosis of CHF.Results The NT-proBNP of 34 patients with CHF(n =100) was in accordance to Ross criteria The cut-off values were 502 ng/ L before age stratification,and they were 552 ng/L,449 ng/L,349 ng/L after age stratification for 0 ～ 1 year group,～ 3 years group and ～ 5 group.Conclusion The cut-off values of plasma NT-ProBNP for CHF were 552 ng/L、449 ng/L、349 ng/L for 0 ～ 1 year group,～ 3 years group and ～ 5 year group.