Population pharmacokinetics of vancomycin and prediction of pharmacodynamics in the Chinese people / 药学学报

Population pharmacokinetics of vancomycin (VAN) in the Chinese patients was described by using nonlinear mixed-effects modeling (NONMEM). 619 VAN serum concentrations data from 260 patients including 177 males and 83 females were collected separately from two centers. A one-compartment model was used to describe this sparse data. No significant difference was observed between two center datasets by introducing SID covariate. The final model was as CL= (θ (base0+ θ(max) x(1 -e(-θ(Age)(Age/72) and V = θ x θ (Age)(Age/72). The creatinine clearance (CL(Cr)) and Age were identified as the most significant covariate in the final model. Typical values of clearance (CL) and volume of distribution (V) in the final model were 2.91 L x h(-1) and 54.76 L, respectively. Internal model validation by Bootstrap and NPDE were performed to evaluate the robustness and prediction of the final model. The median and 95% confidence intervals for the final model parameters were based on 1000 Bootstraps. External model evaluation was conducted using an independent dataset that consisted of 34 patients to predict model performance. Pharmacodynamic assessment for VAN by AUC (0-24 h) to MIC ratios of over 400 was considered to be the best to predict treatment outcomes for patients. AUC (0-24 h) was calculated by clearance based on the above population model. The results indicate that the conventional dosing regimen probably being suboptimal concentrations in aged patients. The approach via population pharmacokinetic of VAN combined with the relationship of MIC, Age, CL(Cr) and AUC(0-24 h)/MIC can predict the rational dose for attaining efficacy.

Influence of educational status, burn area and coping behaviors on the complication of psychological disorders in severely burned patients / 中华烧伤杂志

<p><b>OBJECTIVE</b>To discuss how the educational status, burn area and coping behaviors influence the psychological disorders in severely burned patients.</p><p><b>METHODS</b>Sixty-four severely burned patients hospitalized in Guangzhou Red Cross Hospital, Guangdong Provincial Work Injury Rehabilitation Center, and Guangdong General Hospital were enrolled with cluster random sampling method. Data of their demography and situation of burns were collected. Then their coping behavior, psychological disorders including anxiety, depression and post-traumatic stress disorder (PTSD) plus its core symptoms of flashback, avoidance, and hypervigilance were assessed by medical coping modes questionnaire, self-rating anxiety scale (SAS), self-rating depression scale (SDS), PTSD checklist-civilian version (PCL-C) respectively. Correlation was analyzed between demography, burn area, coping behavior and psychological disorders. The predictive powers of educational status, burn area and coping behaviors on the psychological disorders were analyzed. The qualitative variables were assigned values. Data were processed with t test, Spearman rank correlation analysis, and multiple linear regression analysis.</p><p><b>RESULTS</b>(1) The patients scored (19.0 ± 3.4) points in confrontation coping behavior, which showed no statistically significant difference from the domestic norm score (19.5 ± 3.8) points (t = -1.13, P > 0.05). The patients scored (16.6 ± 2.4) and (11.0 ± 2.2) points in avoidance and resignation coping behaviors, which were significantly higher than the domestic norm score (14.4 ± 3.0), (8.8 ± 3.2) points (with t values respectively 7.06 and 7.76, P values both below 0.01). The patients' standard score of SAS, SDS, PCL-C were (50 ± 11), (54 ± 11), and (38 ± 12) points. Respectively 89.1% (57/64), 60.9% (39/64), 46.9% (30/64) of the patients showed anxiety, depression, and PTSD symptoms. (2) Four independent variables: age, gender, marital status, and time after burns, were correlated with the psychological disorders, but the correlativity was not statistically significant (with rs values from -0.089 to 0.245, P values all above 0.05). Educational status was significantly negatively correlated with anxiety, depression, PTSD and its core symptoms of flashback, avoidance (with rs values from -0.361 to -0.253, P values all below 0.05). Educational status was negatively correlated with hypervigilance, but the correlativity was not statistically significant (rs = -0.187, P > 0.05). Burn area was significantly positively correlated with the psychological disorders (with rs values from 0.306 to 0.478, P values all below 0.05). Confrontation coping behavior was positively correlated with the psychological disorders, but the correlativity was not statistically significant (with rs values from 0.121 to 0.550, P values all above 0.05). Avoidance coping behavior was correlated with the psychological disorders, but the correlativity was not statistically significant (with rs values from -0.144 to 0.193, P values all above 0.05). Resignation coping behavior was significantly positively correlated with the psychological disorder (with rs values from 0.377 to 0.596, P values all below 0.01). (3) Educational status had predictive power on the anxiety, PTSD and flash back symptoms of patients (with t values from -2.19 to -2.02, P values all below 0.05), but not on depression, avoidance and hypervigilance (with t values from -1.95 to -0.99, P values all above 0.05). Burn area had no predictive power on the psychological disorders (with t values from 0.55 to 1.78, P values all above 0.05). Resignation coping behavior had predictive power on the psychological disorders (with t values from 3.10 to 6.46, P values below 0.01). Confrontation and avoidance coping behaviors had no predictive power on the psychological disorders (with t values from 0.46 to 2.32 and -0.89 and 1.75 respectively, P values all above 0.05).</p><p><b>CONCLUSIONS</b>The severely burned patients with lower educational status, larger burn area, and the more frequently adapted resignation coping behavior are more likely to suffer from anxiety, depression, and PTSD.</p>

Relationship between NRAGE and the radioresistance of esophageal carcinoma cell line TE13R120 / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>The mRNA levels of 59 genes, detected by cDNA microarray, were up-regulated in the radioresistant human esophageal cacinoma cell line TE13R120 as compared with its parental cell line TE13 before and after radiation, and the expression of NRAGE gene showed a gradually up-regulating tendency. This study aimed to further detect the differences of NRAGE gene and protein expression and apoptosis between TE13R120 and TE13 cells, and to investigate the relationship between the NRAGE and the radioresistance of TE13R120 cells and its mechanism.</p><p><b>METHODS</b>The two cell lines were irradiated by ⁶⁰Co γ-ray at different conditions. Reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and immunocytochemistry were used to detect the expression of NRAGE. Flow cytometry (FCM) was used to detect the cell apoptosis before and after irradiation.</p><p><b>RESULTS</b>The mRNA level of NRAGE was higher in TE13R120 cells than in TE13 cells before and after irradiation (before radiation: 0.25 ± 0.03 vs. 0.49 ± 0.03; 4 Gy 4 h: 0.31 ± 0.03 vs. 0.53 ± 0.02; 4 Gy 16 h: 0.32 ± 0.04 vs. 0.59 ± 0.04; 4 Gy 24 h: 0.36 ± 0.05 vs. 0.72 ± 0.04; 2 Gy 12 h: 0.32 ± 0.02 vs. 0.64 ± 0.04; 6 Gy 12 h: 0.36 ± 0.02 vs. 0.79 ± 0.05; 10 Gy 12 h: 0.46 ± 0.04 vs. 0.85 ± 0.01; P < 0.01), and the mRNA level of NRAGE was increased gradually with the increase of radiation dose and time in the two cell lines (P < 0.05 and P < 0.01). Western blot results showed no difference of NRAGE protein level in cytoplasm between TE13R120 cells and TE13 cells before and after irradiation, but its level in nuclei was higher in TE13R120 cells than in TE13 cells at different radiation time and dosages. Immunocytochemistry showed similar results as Western blot. FCM showed no significant difference in apoptosis rate between TE13R120 and TE13 cells before and after radiation.</p><p><b>CONCLUSION</b>NRAGE may play an important role in the radiation responses of the two cell lines, and may participate in the formation of radioresistance of TE13R120 cells by changing its subcellular localization, but its relationship with cell apoptosis has not been confirmed.</p>