CYP2D6 is an important member of the cytochrome P450 (CYP450) enzyme super family, with at least 100 CYP2D6 alleles being previously identified. Genetic polymorphisms of CYP2D6 significantly influence the efficacy and safety of some drugs, which might cause adverse effects and therapeutic failure. The aim of this study was to clarify the catalytic activities of 24 CYP2D6 alleles on the oxidative in vitro metabolism of methadone. Reactions were incubated with 50-2000  µM methadone for 30 min at 37 °C and terminated by cooling to -80 °C immediately. Methadone and the major metabolite EDDP were analyzed by an ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) system. Compared with wild-type CYP2D6*1, most variants showed significantly altered values in V and intrinsic clearance (V /K ). Only three variants (CYP2D6*88, *91 and E215K) exhibited markedly increased intrinsic clearance values, and one variant CYP2D6*94 showed no significant difference. On the other hand, the kinetic parameters of two CYP2D6 variants (CYP2D6*92 and *96) could not be determined because they had no detectable enzyme activity, whereas 18 variants exhibited significantly decreased values. To sum up, this study demonstrated that more attention should be paid in clinical administration of methadone to individuals carrying these CYP2D6 alleles. Copyright © 2016 John Wiley & Sons, Ltd.

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BACKGROUND Fractional flow reserve (FFR) is the invasive gold standard for evaluating coronary arterial stenosis. However, there have been a few non-invasive methods such as computational fluid dynamics FFR (CFD-FFR) with coronary CT angiography (CCTA) images that can perform FFR assessment. This study aims to develop a new method based on the principle of static first-pass of CT perfusion imaging technique (SF-FFR) and evaluate the efficacy in direct comparisons between CFD-FFR and the invasive FFR.METHODS A total of 91 patients (105 coronary artery vessels) who were admitted from January 2015 to March 2019 were enrolled in this study, retrospectively. All patients underwent CCTA and invasive FFR. 64 patients (75 coronary artery vessels) were successfully analyzed. The correlation and diagnostic performance of SF-FFR method on per-vessel basis were analyzed, using invasive FFR as the gold standard. As a comparison, we also evaluated the correlation and diagnostic performance of CFD-FFR. RESULTSThe SF-FFR showed a good Pearson correlation (r = 0.70, P < 0.001) and intra-class correlation (r = 0.67, P < 0.001) with the gold standard. The Bland-Altman analysis showed that the average difference between the SF-FFR and invasive FFR was 0.03 (0.11-0.16); between CFD-FFR and invasive FFR was 0.04 (-0.10-0.19). Diagnostic accuracy and area under the ROC curve on a per-vessel level were 0.89, 0.94 for SF-FFR, and 0.87, 0.89 for CFD-FFR, respectively. The SF-FFR calculation time was about 2.5 s per case while CFD calculation was about 2 min on an Nvidia Tesla V100 graphic card.CONCLUSIONS The SF-FFR method is feasible and shows high correlation compared to the gold standard. This method could simplify the calculation procedure and save time compared to the CFD method.

In the integrated energy service system, distribution network shall manage to settle its own power balance issue. The market competition that grid corporations open the sale services of electricity to the society and interruptible load is encouraged to participate in ancillary services becomes a development tendency. At this time, a corresponding control strategy was required to instruct interruptible loads scheduling. In this paper, a control strategy using discrete Fourier transform is proposed in combination with the requirements of the electricity market. Under the constraint of the new evaluation criteria, different types of resident interruptible loads were on-demand dispatched in different periods. The root mean square error (RMSE) of the feeder daily forecast could improves the power load control capability of distribution network as well as the quality of power supply.