Predictive performance and analysis of a vancomycin population pharmacokinetic model in Chinese pediatric patients / 药学学报

This study aimed to evaluate the predictive performance of a vancomycin population pharmacokinetic model in 0-10 year Chinese pediatric patients. This study was approved by the Ethics Research Committee of the First Affiliated Hospital of Guangxi Medical University, data from hospitalized children ≤ 10 years of age who receiving vancomycin were collected retrospectively. Individual predictive values (IPRED) were estimated by Bayesian Analysis based on a previous published population pharmacokinetic model, and compared with the observed steady state trough concentration. As results, a total of 371 vancomycin serum concentrations from 191 patients were taken for the external validation. The mean error (ME), the mean relative prediction error (ME%), the mean absolute error (MAE) and the root mean square error (RMSE) in individual prediction method for the total patients were -0.50 mg·L-1, 6.03%, 1.84 mg·L-1, 2.86 mg·L-1 respectively. The correlation coefficient between individual predictions and detection values was 0.95. The stability and the predictive performance of model were accepted by goodness-of-fit, visual predictive check (VPC) and Bland-Altman. The percentage of individual prediction error within ± 30% was 82.75%. The above results suggest that, this Chinese pediatric population pharmacokinetic model in 0-10 years old has a good prediction performance. It can be applied to the design of initial treatment plan and predicting the extent of drug exposure.

Serum miRNA-767-3p level in patients with colorectal cancer and its diagnostic value / 复旦学报（医学版）

Objective To assess potential diagnostic value of miRNA-767-3p in colorectal cancer (CRC).Methods The serum miRNA-767-3p levels in CRC patients,colorectal adenoma patients and healthy people were determined using real time quantitative PCR (qRT-PCR).The concentration of carcino embryonic antigen (CEA) was detected via chemiluminescent immunoassay (CLIA) in above three groups.Receiver operating curves (ROC) were established to evaluate the diagnostic efficiencies of miRNA-767-3p and combination with CEA in CRC patients.Results The levels of miRNA-767-3p were declined in CRC patients,colorectal adenoma patients and healthy people,respectively.ROC curves illustrated that the area under ROC curve (AUC) of miRNA-767-3p was up to 0.770 (95％CI:0.698-0.842),with sensitivity of 80％ and the specificity of 68％ in CRC diagnosis.Moreover,a higher AUC up to 0.862 (95％CI:0.806-0.918) with the sensitivity of 73％ and the specificity of 84％ was achieved when miRNA-767-3p and CEA were combined.Conclusions Serum miRNA-767-3p could be considered as an independent diagnostic marker of CRC,and miRNA-767-3p combined with CEA would increase the detective quantum efficiency of CRC.

Melanocortin-4 receptor expression in the cuneiform nucleus is involved in modulation of opioidergic signaling / 华中科技大学学报（医学）（英德文版）

Substantial evidence has suggested that deep brain stimulation of the cuneiform nucleus has become a remarkable treatment option for intractable pain, but the possible mechanism is poorly understood. Using a melanocortin-4 receptor (MC4R)-green fluorescent protein (GFP) reporter knockin mouse, we showed that a large number of MC4R-GFP-positive neurons were expressed in the cuneiform nucleus. Immunofluorescence revealed that approximately 40%-50% of MC4R-GFP-positive neurons expressed mu opioid receptors, indicating that they were opioidergic signaling. Our findings support the hypothesis that MC4R expression in the cuneiform nucleus is involved in the modulation of opioidergic signaling.

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.

Platelet phospholipase A2 mRNA content changes and cDNA cloning in rat blood with bacteria infection / 药学学报

<p><b>AIM</b>To explore the changes of rat platelet phospholipase A2 (PLA2) mRNA content in bacteria infected rat and study the cDNA and amino acid sequences of the PLA2 structure to lay a good foundation for the development of new antibiotics.</p><p><b>METHODS</b>The PLA2 mRNA level in blood was determined by RT-PCR. The DNA sequence was cloned and analyzed.</p><p><b>RESULTS</b>After injection of bacteria in rats, the mRNA level of PLA2 in blood increased markedly. The cDNA and amino acid sequence were highly homologous to other PLA2 cDNA from different tissues of the rat.</p><p><b>CONCLUSION</b>Platelet PLA2 in blood responded quickly to bacteria infection in gene level. Therefore, the PLA2 protein was produced increasingly which was shown to control the infection with bacteria. Although there are little difference between PLA2 cDNA cloned from blood and other sources in DNA and amino acid sequences, the catalytic site for enzymatic activity and basic structure are identical.</p>