Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.     

上海市黄浦区社会办医疗美容机构《医疗美容管理办法》知晓情况调查

目的了解上海市黄浦区社会办医疗美容机构的管理人员和医师对《医疗美容管理办法》相关内容的掌握情况,发现存在的问题并提出改善建议.方法采用现场调查与现场问卷调查相结合的方式,对在上海市黄浦区开展医疗美容科目的所有社会办医疗机构(共计38家)进行全覆盖现场调查,并对其中的管理人员41人、相关医师31人进行问卷调查.结果38家社会办医疗美容机构中,美容外科和美容皮肤科的开展率较高,分别为96.8%和97.2%,而美容牙科开展率为52.4%,美容中医科开展率最低(25.0%).管理人员关于非主诊医师可在主诊医师指导下工作的知晓率仅68.3%.关于美容外科、皮肤科、中医科、牙科主诊医师应具备的工作年限,管理人员答对率为90.2%,医师答对率为72.0%,二者有显著性差异(P<0.05).结论社会办医疗美容机构中的二级科目设置需进一步优化,以减少资源空置.应加强对医疗机构管理人员和医师的法律培训,改变经营模式,制定明确的准入与退出机制,从而减少违法违规行为的发生.     

Multidimensional Ultrasound Doppler Signal Analysis for Fetal Activity Monitoring

Fetal activity parameters such as movements, heart rate and the related parameters are essential indicators of fetal wellbeing, and no device provides simultaneous access to and sufficient estimation of all of these parameters to evaluate fetal health. This work was aimed at collecting these parameters to automatically separate healthy from compromised fetuses. To achieve this goal, we first developed a multi-sensor–multi-gate Doppler system. Then we recorded multidimensional Doppler signals and estimated the fetal activity parameters via dedicated signal processing techniques. Finally, we combined these parameters into four sets of parameters (or four hyper-parameters) to determine the set of parameters that is able to separate healthy from other fetuses. To validate our system, a data set consisting of two groups of fetal signals (normal and compromised) was established and provided by physicians. From the estimated parameters, an instantaneous Manning-like score, referred to as the ultrasonic score, was calculated and was used together with movements, heart rate and the associated parameters in a classification process employing the support vector machine method. We investigated the influence of the sets of parameters and evaluated the performance of the support vector machine using the computation of sensibility, specificity, percentage of support vectors and total classification error. The sensitivity of the four sets ranged from 79% to 100%. Specificity was 100% for all sets. The total classification error ranged from 0% to 20%. The percentage of support vectors ranged from 33% to 49%. Overall, the best results were obtained with the set of parameters consisting of fetal movement, short-term variability, long-term variability, deceleration and ultrasound score. The sensitivity, specificity, percentage of support vectors and total classification error of this set were respectively 100%, 100%, 35% and 0%. This indicated our ability to separate the data into two sets (normal fetuses and pathologic fetuses), and the results highlight the excellent match with the clinical classification performed by the physicians. This work indicates the feasibility of detecting compromised fetuses and also represents an interesting method of close fetal monitoring during the entire pregnancy.     

PBL教学法在临床心肺复苏术教学中的应用分析

目的 分析重症医学科PBL教学法在临床心肺复苏术教学中的应用效果.方法 本次实验的开展基础数据选择2016年9月—2018年7月进入医院重症医学科实习学生64例,按照学生自身意愿以及学校安排将参与实验学生分为均数相同的两个小组(对照组、观察组),每组实验人数均为32例,其中对照组(n=32)采用传统教学方法 ,观察组(n=32)则应用PBL教学法教学,对比两组学生在学期结束后整体的学习质量情况和教学满意率.结果 观察组学生经过测试后理论知识和专业技能得分均对比对照组更高,教学效果更加理想,观察组学生对于教学的满意率评价更高,P<0.05.结论 重症医学科临床心肺复苏术教学中应用PBL教学法,将理论与实践进行结合,对教学方法 进行改进,全面提升学生的思维理解能力,培养良好的动手能力,促进理论教学与实践的结合,为学生以后的职业生涯提供更加理想的条件.     

Multicentric Analytical and Inter-observer Comparability of Four Clinically Developed Programmed Death-ligand 1 Immunohistochemistry Assays in Advanced Clear-cell Renal Cell Carcinoma

BackgroundPrevious studies have suggested increased clinical benefit with inhibition of programmed death-ligand 1 (PD-L1)/programmed death-1 in patients with PD-L1–positive locally advanced/metastatic renal cell carcinoma (RCC). We examined the analytical and inter-observer comparability of PD-L1–positivity across 4 clinically developed immunohistochemistry assays in clear-cell RCC (CCRCC).Materials and MethodsRandomly selected archived, formalin-fixed, paraffin-embedded nephrectomy specimens from 201 patients with locally advanced CCRCC were screened using VENTANA SP142. From these, 30 cases were selected based on their tumor-infiltrating immune cell (IC) PD-L1 status (PD-L1-IC–positivity of < 1%, 1%-5%, or > 5%; 10 cases each). These cases were stained for PD-L1 using VENTANA SP142 and SP263, and DAKO 22C3 and 28-8, and scored for PD-L1 expression on IC and tumor cells (TC) by trained readers at 5 sites.ResultsAdjusted mean percentages of PD-L1-IC–positivity and PD-L1-TC–positivity varied from 4.0% to 4.9% and from 1.3% to 10.7%, respectively, between assays. Inter-assay differences in PD-L1-IC–positivity were small and non-significant (P = .1938 to .9963); for PD-L1-TC–positivity, significant differences were observed between VENTANA SP142 and the other assays (P ≤ .0001) and between VENTANA SP263 and DAKO 28-8 (P = .0248). Intra-class correlation values showed moderate-to-high inter-reader agreement for each assay for PD-L1-IC–positivity and for 3 assays for PD-L1-TC–positivity.ConclusionsIn this first multicenter analytical comparison study of PD-L1 assays in CCRCC, PD-L1–positivity could be assessed reproducibly using all 4 assays for IC and for 3 of the 4 assays for TC.     

参麦注射液联合米力农治疗难治性心力衰竭疗效观察

目的探讨参麦注射液联合米力农治疗难治性心力衰竭的临床效果。方法选择难治性心力衰竭患者92例,依据随机数字的方法分为对照组46例和观察组46例,患者入院后均常规治疗,对照组给予米利农治疗,观察组在对照组治疗方法基础上给予参麦注射液。对两组治疗前后的心型脂肪酸结合蛋白(H-FABP),血浆心肌肌钙蛋白Ⅰ(cTnⅠ),氨基末端B型钠尿肽原(NT-proBNP),心率(HR),左心室射血分数(LVEF),每搏输出量(SV)进行对比。对两组的临床治疗效果进行对比。对两组治疗过程中的不良反应对比。结果经过治疗后,对照组的H-FABP从(17.23±3.51)ng/L降低到(15.11±3.12)ng/L,NT-proBNP从(8.13±2.32)μg/L降低到(6.51±1.45)μg/L,cTnⅠ从(31.25±5.01)ng/L降低到(23.81±4.25)ng/L,观察组的H-FABP从(16.97±3.78)ng/L降低到(9.91±3.01)ng/L,NT-proBNP从(8.21±1.98)μg/L降低到(4.13±1.34)μg/L,cTnⅠ从(32.07±5.23)ng/L降低到(18.81±5.12)ng/L,观察组的变化幅度大于对照组,数据差异均具有统计学意义(t=8.135,8.176,5.096,P<0.05),经过治疗后,对照组的HR从(135.26±10.51)次/min降低到(103.81±9.81)次/min,LVEF从(32.41±5.41)%升高到(38.31±4.87)%,SV从(37.91±2.71)mL升高到(43.23±3.47)mL,观察组的HR从(134.81±11.28)次/min降低到(95.31±9.97)次/min,LVEF从(31.87±5.37)%升高到(43.21±4.25)%,SV从(38.11±3.13)mL升高到(50.91±3.68)mL,观察组的变化幅度大于对照组,数据差异均具有统计学意义(t=4.122,-5.142,-10.298,P<0.05),观察组的治疗效果优于对照组,数据差异具有统计学意义(z=-4.994,P<0.05),两组的恶心[4.35%(2/46)VS. 2.17%(1/46)],血压低[6.52%(3/46)VS. 4.35%(2/46)],头晕[8.70%(4/46)VS. 13.04%(6/46)],乏力[15.22%(7/46)VS. 8.70%(4/46)],呕吐[4.35%(2/46)VS. 6.52%(3/46)],室性早搏[2.17%(1/46)VS. 4.35%(2/46)],发生率数据差异均不具有统计学意义(χ^2=0.000,0.000,0.449,0.929,0.000,0.000,P>0.05)。结论利用参麦注射液联合米力农治疗难治性心力衰竭,可以改善心肌功能,提升治疗效果,安全性良好。     

Effectiveness of a nurse-led multidisciplinary self-management program for patients with coronary heart disease in communities: A randomized controlled trial

ObjectiveTo examine the effectiveness of a nurse-led multidisciplinary self-management program (NMSP) on self-management behaviors, self-efficacy, health-related quality of life (HRQoL) and unplanned health service utilization (HSU) among Chinese patients with coronary heart disease (CHD) in communities.MethodsA randomized controlled trial with repeated measurements was used. A convenience sample of 144 participants was recruited from a community health center in China. All participants were randomly assigned to an intervention group (n = 72) in the newly developed NMSP or a control group (n = 72) in routine care. Outcome measurement was performed at baseline, 3 months and 6 months using Coronary Artery Disease Self-Management Scale (CADSs), Self-efficacy for Chronic Disease 6-item Scale (SECD6), and Short Form-12 health survey questionnaire (SF-12).ResultsOver the six months, the two groups reported significant differences in disease medical and emotional management of CADSs, confidence in symptom and disease management of SECD6, physical and mental component summary of SF-12, as well as emergency and outpatient visits of unplanned HSU.ConclusionsThe NMSP improves self-management behaviors, self-efficacy, HRQoL and reduces unplanned HSU among CHD patients in communities.Practice implicationsThis study provides an effective approach to empower CHD patients with emphasizing on collaboration support of health professionals in communities.