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Several population pharmacokinetics (popPK) models for polymyxin B have been constructed to optimize therapeutic regimens. However, their predictive performance remains unclear when extrapolated to different clinical centers. Therefore, this study aimed to evaluate the predictive ability of polymyxin B popPK models. A literature search was conducted, and the predictive performance was determined for each selected model using an independent dataset of 20 patients (92 concentrations) from the Third Xiangya Hospital. Prediction- and simulation-based diagnostics were used to evaluate model predictability. The influence of prior information was assessed using Bayesian forecasting. Eight published studies were evaluated. In prediction-based diagnostics, the prediction error within ± 30% was over 50% in two models. In simulation-based diagnostics, the prediction- and variability-corrected visual predictive check (pvcVPC) showed satisfactory predictivity in three models, while the normalized prediction distribution error (NPDE) tests indicated model misspecification in all models. Bayesian forecasting demonstrated a substantially improvement in the model predictability even with one prior observation. Not all published models were satisfactory in prediction- and simulation-based diagnostics; however, Bayesian forecasting improved the predictability considerably with priors, which can be applied to guide polymyxin B dosing recommendations and adjustments for clinicians.

Background and Aim. Aberrant activation of the TGF-β1/Smad pathway contributes to the activation of hepatic stellate cells (HSCs). MicroRNA-195 has been shown to regulate the activation of HSCs. The aim of this study was to investigate the role of miRNA-195 in HSCs activation. Methods. A liver fibrotic rat model induced by diethylnitrosamine was established. Dual luciferase reporter assays were performed to verify that Smad7 was the target of miRNA-195. The expression levels of miR-195, Smad7, and α-SMA in HSC-T6 transfected, respectively, with miR-195 mimic, inhibitor, or control were measured by qRT-PCR. The protein expression of Smad7 was detected by Western blot analysis. Results. Enhanced miR-195 and decreased Smad7 were observed in diethylnitrosamine-induced liver fibrotic rats (P<0.05). Dual luciferase reporter assays showed that the miR-195 mimic significantly suppressed the luciferase activity of a reporter plasmid carrying the binding site of miR-195 on the 3′UTR of Smad7 (P<0.05). The miR-195 mimics activated HSCs, further elevated miR-195 and α-SMA (P<0.01), and reduced the Smad7 level (P<0.05). The miR-195 inhibitors blocked the activation of HSCs, reduced the expression of miR-195 and α-SMA (P<0.01), and upregulated the expression of Smad7 (P<0.05). Conclusion. Collectively, we demonstrated that miRNA-195 activated HSCs by targeting Smad7.

To determine the reversal effect of aloe emodin liposomes (AE-L) on cisplatin resistance human lung adenocarcinoma cell line A549/DDP.The un-cytotoxic and cytotoxic concentration of AE-L, and un-cytotoxic concentration of E-L were determined by MTT. The sensitivity of cisplatin were determined by MTT assay in above 3 groups. The intracellular concentration of cisplatin was detected by inductively coupled plasma mass spectrometry (ICP-MS).The maximum non-toxic concentration group of AE-L (2.0 mg x L(-1)) increased the sensitivity of cisplatin in A549/DDP, decreased IC50 of cisplatin in A549/DDP from 16.81 mg x L(-1) to 5.86 mg x L(-1), and the hyp-cytotoxic concentration (7.0 mg x L(-1) ) group's IC50 decreased to 4.34 mg x L(-1); AE-L groups significantly increased intracellular concentration of cisplatin in A549/DDP cells.The results showed that aloe emodin can reverse multidrug resistance (MDR) of A549/DDP cells and the mechanism might be associated with the increase of intracellular concentration of cisplatin.

To establish a simple and rapid HPLC-MS method for determining the contents of olmesartan in human plasma.Plasma were precipitated with trifluoroacetic acid, then analyzed on an HyPurity C(18) column (150 mm 2.1 mm, 5 microm). Samples at 40 degrees celsius;. The mobile phase consisted of water-methanol- acetonitrile(14:60:26) with a flow rate of 0.22 ml/min.The lower limit of qualification was 25 microg/L. The calibration curve was linear over the range of 25-3200 microg/L (r=0.9998), with the intra-day and inter-day RSD less than 15%.The method is sensitive, rapid and suitable for the study of pharmacokinetics and bioavailability of olmesartan.