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Objective To synthesize four related substances:1b,1c,1d,and 1e according to the synthetic process of aprepi-tant and its quality standard of USP and EP. Methods The impurities 1b,1c,and 1d were synthesized from 3,5-bis(trifluoromethyl) acetophenone through asymmetrical catalytic reduction reaction,condensation reaction,Grignard reaction ,catalytic hydrogenation and substitution. The impurity 1e was synthesized from(R)-α-methylbenzylamine through 7 reaction steps including esterification,reduc-tion,condensation ect. Results All the four related substances were confirmed by LC-MS and NMR. The results indicated that purity of the product surpassed 95%through HPLC. Conclusion These related substances can be taken as the references for the quality con-trol of aprepitant.
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Background The mitochondrial Na+/Ca2+exchanger, NCLX, plays an important role in the balance between Ca2+influx and efflux across the mitochondrial inner membrane in endothelial cells. Mitochondrial metabolism is likely to be affected by the activity of NCLX because Ca2+activates several enzymes of the Krebs cycle. It is currently believed that mitochondria are not only centers of energy produc-tion but are also important sites of reactive oxygen species (ROS) generation and nucleotide-binding oligomerization domain receptor 3 (NLRP3) inflammasome activation. Methods&Results This study focused on NCLX function, in rat aortic endothelial cells (RAECs), induced by glucose. First, we detected an increase in NCLX expression in the endothelia of rats with diabetes mellitus, which was induced by an injection of streptozotocin. Next, colocalization of NCLX expression and mitochondria was detected using confocal analysis. Suppression of NCLX expression, using an siRNA construct (siNCLX), enhanced mitochondrial Ca2+influx and blocked efflux induced by glucose. Un-expectedly, silencing of NCLX expression induced increased ROS generation and NLRP3 inflammasome activation. Conclusions These findings suggest that NCLX affects glucose-dependent mitochondrial Ca2+signaling, thereby regulating ROS generation and NLRP3 in-flammasome activation in high glucose conditions. In the early stages of high glucose stimulation, NCLX expression increases to compensate in order to self-protect mitochondrial maintenance, stability, and function in endothelial cells.
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Recently,many researches showed that vitamin D was involved in the pathophysiological processes of cardiovascular diseases.The incidence of vitamin D deficiency was increased with aging,and might be associated with an increased prevalence of cardiovascular disease with aging.In this paper,the association of vitamin D with cardiovascular diseases and the possible mechanisms are reviewed.
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Objective To explore the clinic value and efficacy of color Doppler ultrasound guided percutaneous microwave/radiorequency thermoablation for secondary hyperparathyroidism. Methods Fifty-six cases of secondary hyperparathyroidism who came from nephrology department of Beijing Friendship Hospital in the period of September 2012 to September 2013 were treated by color Doppler ultrasound guided percutaneous microwave/radiorequency thermoablation. One hundred and thirty-eight glands underwent this treatment and were evaluated by contrast enhanced ultrasound before, during and after operation. The levels of serum parathyroid hormone (PTH) were measured before and at 1 week, 1 month, 6 months and 1 year after treatment. Results The whole 56 cases achieved 1 month follow-up and 34 cases and 12 cases achieved 6 months and 1 year follow-up, respectively. Two special cases had been excluded. The PTH levels of 54 cases were signiifcantly different between after and before treatment [(369.5±183.4) ng/L vs (1321.6±471.4) ng/L, t=10.727, P=0.000]. The PTH levels continued to fall at the ifrst week after treatment, but there was no statistical signiifcance between the ifrst week and the ifrst day after treatment [(324.6±172.8) ng/L vs (369.5±183.4) ng/L], while there was signiifcantly different between the ifrst week after treatment and before treatment [(324.6±172.8) ng/L vs (1321.6±471.4) ng/L, t=9.364, P=0.000]. The PTH levels increased from (324.6±172.8) ng/L to (332.5±164.9) ng/L at 1 week and 1 month after ablation, while there was no signiifcant difference.But there is signiifcantly different between 1 month after treatment and before treatment (t=11.348, P=0.000). The PTH level at 6 months after treatment [(205.2±136.3) ng/L] and 1 year after treatment [(177.1±171.5) ng/L] had signiifcant difference compared with the value before treatment (t=8.737, P=0.000; t=7.655, P=0.017). Conclusion Color Doppler ultrasound guided percutaneous microwave/radiorequency thermoablation can be considered as a feasible and effective nonsurgical alternative treatment for secondary hyperparathyroidism patients.