放射治疗记录与验证系统质量控制指南

放疗记录与验证系统(RVS)是一套用于防止医用电子加速器等放疗设备治疗参数设置错误,并且记录所有放疗阶段执行参数的医用计算机软件控制系统。为确保患者的治疗安全,必须对记录与验证系统采取必要的质量控制措施。本指南内容涉及:RVS安装和参数设定过程中的质量控制;RVS的验收测试;RVS在临床使用过程中的持续质量控制;使用RVS过程中的典型错误类型;执行RVS验收测试的具体测试例。     

Recent advances in preclinical in vitro approaches towards quantitative prediction of hepatic clearance and drug-drug interactions involving organic anion transporting polypeptide (OATP) 1B transporters

Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CL_h) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CL_h involving OATP1B-mediated hepatic uptake. CL_h can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CL_h and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction.     

In Vivo Kinematics of Functional Ankle Instability Patients and Lateral Ankle Sprain Copers During Stair Descent

Patients with mechanic ankle instability experience increased tibiotalar and subtalar joint laxity. However, in vivo joint kinematics in functional ankle instability (FAI) patients and lateral ankle sprain (LAS) copers, especially during dynamic activities, are poorly understood. Ten FAI patients, 10 LAS copers, and 10 healthy controls were included in this study. A dual fluoroscopic imaging system was used to analyze the tibiotalar and subtalar joint kinematics during stair descent. Five key poses of stair descent were analyzed. Kinematic data from six degrees of freedom were calculated utilizing a solid modeling software. The range of motion and joint positions in each degree of freedom were compared among the three groups. The tibiotalar joints of FAI patients and LAS copers were significantly more inverted than those of healthy controls during the foot strike (p = 0.016, = 0.264). The subtalar joints of FAI patients were significantly more anteriorly translated (pose 2, p = 0.003, = 0.352; pose 3, p < 0.001, = 0.454; pose 4, p = 0.004, = 0.334), inverted (pose 4, p = 0.027, = 0.234; pose 5,p = 0.034, = 0.221), and externally rotated (pose 4, p = 0.037, = 0.217; pose 5; p = 0.004, = 0.331) than those of healthy controls during the mid‐stance and the heel off. The FAI patients showed excessive tibiotalar inversion and subtalar joint hypermobility during stair descent. Meanwhile, the LAS copers maintained subtalar joint stability, and only showed excessive tibiotalar inversion in foot strike. These data provide insight into the mechanisms behind the development of FAI after initial LAS. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1860–1867, 2019     

中低度近视SMILE术后超早期视觉质量变化的研究

目的观察飞秒激光小切口角膜基质透镜取出术(SMILE)术后超早期患者视觉质量变化,探讨其变化发生的可能原因。方法选取中低度近视患者23例46眼行SMILE术,术前及术后24 h超早期行主观视觉质量问卷,测量最佳矫正视力的全程视力(远视力5 m,中视力60 cm,近视力33 cm)、对比敏感度(CS)、眩光敏感度(GS)及集合近点(NPC)和调节幅度(AA)。结果视觉质量主观问卷显示术后超早期主观视觉质量较术前下降(P=0.001)。术后裸眼视力(UCVA)明显提高(P=0.0001)。术前与术后最佳矫正视力(BCVA)中远视力没有变化(P=0.096),而中视力和近视力均较术前下降(P=0.039,0.003)。术后CS、GS降低(PCS=0.0001,PGS=0.04),NPC、AA较术前无明显变化(P=0.68,0.13)。结论SMILE术后超早期患者可获得预期理想远视力,但中、近视力尚未恢复。超早期中出现的异常视觉质量改变可能与对比敏感度和眩光敏感度的改变有关。     

Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.     

Evolution of neuropsychological profile in motor subtypes of multiple system atrophy

IntroductionCognitive deficits and neuropsychiatric symptoms occur in parkinsonian and cerebellar subtypes of Multiple System Atrophy (MSA-P and MSA-C). These symptoms have been investigated mainly in cross-sectional studies. The present 1-year follow-up study aimed at evaluating the evolution of cognitive and neuropsychiatric profile in patients with MSA-C and MSA-P.MethodsTwenty-nine patients with MSA-P, 21 with MSA-C and 30 healthy subjects (HCs) underwent a neuropsychological battery and questionnaires assessing depression and apathy (T0). After 1 year (T1), patients with MSA-C and MSA-P underwent the same neuropsychological and neuropsychiatric tools employed at T0.ResultsAt T0, MSA-P and MSA-C groups were more depressed and apathetic and performed worse on tests assessing repetition abilities, executive and attentive functions than HCs. MSA-P and MSA-C groups did not differ on cognitive variables and neuropsychiatric scales. At T1, a significant worsening in spatial planning and psychomotor speed in MSA-C group and a significant worsening in memory, spatial planning, repetition abilities and functional autonomy in MSA-P group were found. The prevalence of apathy increased in both subtypes, whereas the prevalence of depression was reduced in MSA-C and relatively consistent in MSA-P.ConclusionsThe finding revealed a wide-ranging worsening of cognitive functions in MSA-P and a significant decline in processing speed in MSA-C. These results underline the relevance of evaluating cognitive and psychiatric features of MSA over the course of the disease in the daily clinical practice.     

桃红四物汤化学成分、药理作用、临床应用的研究进展及质量标志物的预测分析

桃红四物汤,活血祛瘀之经典名方。该文对近年来桃红四物汤的化学成分、药理作用以及临床应用研究进展进行总结与分析。目前,桃红四物汤不同提取部位化学成分的研究较为系统,其药理作用研究主要集中在活血化瘀、调经镇痛、促进骨折愈合等方面,临床可应用于多系统、多脏腑疾病的治疗,例如妇科疾病、内科疾病、骨伤科疾病、皮肤科疾病等。在此基础上,依照质量标志物(Q-marker)有效、特有、传递与溯源、可测和处方配伍的"五原则"对桃红四物汤Q-marker进行预测分析,提示阿魏酸、芍药苷、苦杏仁苷、芍药内酯苷、梓醇、没食子酸、羟基红花黄色素A可作为该复方的Q-marker,后续可选择这些Q-marker为指标,根据药材、饮片、中间体、对应实物的量值传递进行桃红四物汤全程质量控制并创建其质量可溯源体系。