经典名方地黄饮子的古代文献考究

经典名方地黄饮子现代临床应用广泛,治疗多科疾病,尤其是内科病中的神经系统疾病较多,临床疗效确切,但目前尚未转化成中成药制剂。故笔者采用文献计量学的方法,搜集记载地黄饮子的中医古籍文献,筛选、整理出有效数据254条,涉及中医古籍144部,系统梳理和分析研究了地黄饮子的历史发展源流、主治病证、制方原理、用药剂量、制剂方法、煎服方法等,以期为经典名方的研发和临床应用提供古代文献证据支持。研究发现,地黄饮子出自金代医家刘河间所著《宣明论方》,由熟地黄、巴戟天、山茱萸、肉苁蓉、石斛、附子、五味子、官桂、白茯苓、麦门冬、藏菖蒲、远志12味药物组成,主治喑痱。后世记载的地黄饮子多遵从《宣明论方》中的方剂组成和主治,且临床应用有所扩展,在有主治病证记载的199条文献中,喑痱最多,约占总病证的一半;其次为中风,约占五分之二;亦用于暴喑、痿证、眩晕、遗尿等病证。地黄饮子治疗病证范围较广,但病机总属"肾中水火俱亏"。其制方独特,上下并治,标本兼顾,尤以治下治本为主。在有药物用量记载的56条文献中,约有三分之一继承了《宣明论方》的记载:"等分,上为末,每服3钱。"药物用量总体偏轻。制剂多为汤剂、煮散,在煎服方法上主张"浊药轻投""数滚即服""不计时候"。     

How is safety of dermatology drugs assessed: trials,registries, and spontaneous reporting

ABSTRACT

Introduction: Skin conditions are common and highly varied in their etiology; therefore, a diverse array of therapeutics are utilized. Drug safety studies in dermatology can be challenging as there are over 3000 diagnoses to consider. As a result, dermatologists rely on data from multiple sources including clinical trials and real-world evidence.

Areas covered: In this review, we cover the main sources of safety data available, their strengths and weaknesses and how dermatologists should utilize such data. We use real-world examples of the different types of adverse events reported and how they are best captured by either randomized controlled trials or post-marketing pharmacovigilance methods. With multiple new therapies in dermatology, such as dupilumab for atopic dermatitis and janus-kinase inhibitors for alopecia areata the specialty is awash with evolving high-level evidence for their use. It is important to understand the optimal way to assess safety from trials but also appreciate the need for ongoing capture of safety data in clinical practice.

Expert opinion: In dermatology, there is a plethora of conditions to treat and clinical trials, post-marketing surveillance, such as drug registries and spontaneous reporting, all enable dermatologists to gain a more comprehensive understanding of the safety profiles of drugs being used.     

Posaconazole therapeutic drug monitoring in clinical practice and longitudinal analysis of the effect of routine laboratory measurements on posaconazole concentrations

Posaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimise drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets. Patients who received posaconazole for treatment or prophylaxis of fungal infections were included in the study. The following therapeutic window was defined: if concentration was low (<0.7 mg/L for prophylaxis or < 1.5 mg/L for treatment) or high (>3.75 mg/L), the hospital pharmacist provided the physician with dosage advice, which implementation to patient care was analysed. A longitudinal analysis was performed to analyse if different confounding variables had an effect on posaconazole concentrations. Forty‐seven patients were enrolled resulting in 217 posaconazole trough concentrations. A median of 3 (IQR 1‐7) samples was measured per patient. The median concentration was 1.7 mg/L (IQR 0.8‐2.7) for prophylaxis and 1.76 mg/L (IQR 1.3‐2.3) for treatment. Overall, 78 posaconazole concentrations were out of the therapeutic window. For 45 (54%) of these concentrations, a dosage change was recommended. In the longitudinal analysis, the laboratory markers and patient baseline variables did not have an effect on posaconazole concentrations. Adequate posaconazole exposure was shown in 64% (affected 28 patients) of the measured concentrations. TDM practice of posaconazole can be improved by increasing the implementation rate of dose recommendation by a multidisciplinary antifungal stewardship team.     

Fracture de côte suite à la radiothérapie peropératoire dans le cancer du sein. Cas clinique et expérience locale

Intra-operative radiotherapy for breast cancer has been developed throughout the last two decades. It is already well-established regarding local control and toxicity for intra-operative radiotherapy using electrons as we now have the necessary background knowledge. However, very few data on later toxicity are available for intra-operative radiotherapy using low-energy photons. We report here the case of a 36-year-old woman who experienced rib fracture following intra-operative and external radiotherapy. This patient has been included in the Targit-boost trial. The intra-operative irradiation has been operated with an INTRABEAM device delivering low-energy photons of 50-kV.     

嗜肺军团菌致病性与效应蛋白的研究进展

嗜肺军团菌是一种可以引起军团菌肺炎和庞蒂亚克热的兼性胞内病原菌，主要侵染阿米巴原虫和人类巨噬细胞。该菌在宿主胞内能依靠Dot/Icm IVB型分泌系统产生的效应蛋白成功逃避溶酶体的降解。本文主要对嗜肺军团菌的致病物质、胞内存活与增殖机制及其效应蛋白的生物学功能进行综述，详细介绍嗜肺军团菌的毒力因子与致病机制，为军团病防治的研究提供新思路，也为其他胞内病原菌所致感染性疾病的研究提供重要的借鉴意义。     

Alcance de la implementación en Cataluña de las estrategias de salud reproductiva (2008-2017)

ObjectiveWe analyse how reproductive health strategies have been incorporated into the everyday activities of the services and the resulting transformation of professional and user practices.MethodCartographic research taking a multi-sited ethnographic approach that seeks to reveal the processes of transformation. Data generation techniques featuring participant observation and situated interviews. Discourse analysis of the text corpus using three analytical axes based on three main lines of action promoted by the strategies.ResultsWe identified transformations in: 1) demedicalisation: an increase in midwives’ know-how and autonomy, changes in episiotomy practice and the facilitation of bonding practices; 2) warmth of care: incorporation of women's needs and expectations and improvements in the comfortableness of birth settings, especially in assistance at physiological birth; and 3) participation: actions that foster shared decision-making and the involvement of the persons accompanying women in labour.ConclusionsAbove all, transformation is visible in the incorporation of new attitudes, sensibilities and practices that have developed around the old structures, especially during physiological childbirth. The more technological areas have been less permeable to change. Risk management in decision-making and addressing diversity are identified as areas where transformation is less evident.     

序贯培养体系和单一培养体系对人卵母细胞受精和早期胚胎发育的影响

目的：比较在体外受精/卵胞质内单精子显微注射（IVF/ICSI）治疗周期中序贯培养体系和单一培养体系对人类早期胚胎发育的影响，为人类辅助生殖技术中胚胎培养体系的选择和评估提供参考。方法：选取155例行IVF/ICSI助孕的患者，将同一个患者的卵子分为2组，分别在Vitrolife的序贯培养体系G-IVF/G1/G2培养液（序贯培养组）和Irvine的单一培养体系CSCC培养液（单一培养组）中进行体外受精和胚胎培养，观察2组不同培养体系中胚胎受精和胚胎早期发育情况。结果：与单一培养组比较，序贯培养组受精率、双原核（2PN）受精率和多核受精率差异均无统计学意义（P>0.05）。在IVF患者中，序贯培养组和单一培养组的卵裂率、可用胚胎率、优质胚胎率和囊胚形成率比较差异均无统计学意义（P>0.05）；在ICSI患者中，序贯培养组和单一培养组的卵裂率、可用胚胎率和囊胚形成率比较差异均无统计学意义（P>0.05），但序贯培养组优质胚胎率明显高于单一培养组（P=0.015）。在IVF和ICSI患者中，单一培养组第3天胚胎致密化的比例均明显高于序贯培养组（P=0.001）。在序贯培养组中胚胎形态表面光滑均匀，单一培养组中胚胎表面较为粗糙且有颗粒状。结论：G-IVF/G1/G2序贯培养体系和CSCC单一培养体系对人卵母细胞受精和早期胚胎发育的影响无明显差异。     

The role of exosomes in metastasis and progression of melanoma

The mechanisms of melanoma metastasis have been the subject of extensive research for decades. Improved diagnostic and therapeutic strategies are of increasing importance for the treatment of melanoma due to its high burden of mortality in the advanced stages of the disease. Intercellular communication is a critical event for the progression of cancer. Collective evidence suggests that exosomes, small extracellular membrane vesicles released by the cells, are important facilitators of intercellular communication between the cells and the surrounding environment. Although the emerging field of exosomes is rapidly gaining traction in the scientific community, there is limited knowledge regarding the role of exosomes in melanoma. This review discusses the multifaceted role of melanoma-derived exosomes in promoting the process of metastasis by modulating the invasive and angiogenic capacity of malignant cells. The future implications of exosome research and the therapeutic potential of exosomes are also discussed.     

妇产科住院医师临床技能培训体系构建

妇产科学是一门涉及面广、实践性和操作性均很强的学科,对医生临床操作能力的要求也格外严格。妇产科住院医师临床技能操作水平的高低是评价其岗位胜任力的重要指标,开展全面、规范的临床技能培训,有利于切实提高其临床操作能力,是培养合格妇产科专科医师的必经途径。研究以南京医科大学附属妇产医院为例,讲述了该院从目标体系、过程管理体系、考核评价体系和质量控制体系4个方面出发,探索构建适合专科医院特色的妇产科住院医师临床技能培训体系,并在实践过程中不断完善该体系,以期不断提升妇产科住院医师的临床工作能力,有效增强其岗位胜任力和综合素质。     

左旋肉碱修饰的壳聚糖-硬脂酸协载槲皮素口服紫杉醇纳米胶束的制备、表征及在体肠循环研究

目的 制备左旋肉碱修饰的壳聚糖-硬脂酸（LC-SA/CS-SA）纳米胶束，包载紫杉醇（PTX）且协载槲皮素，考察胶束特性，并以大鼠在体肠循环评估给药系统对PTX口服吸收的促进作用。方法 将硬脂酸（SA）通过酰胺化反应接枝于壳聚糖（CS），形成共聚物CS-SA；采用核磁共振H谱、红外光谱鉴定产物结构；以PTX为主药，槲皮素为辅药，采用激光粒径分析、Zeta电位分析和HPLC分析分别考察了胶束的粒径、Zeta电位、载药量、包封率；透射电子显微镜观察胶束形貌；芘荧光探针法测定LC-SA/CS-SA胶束的临界胶束浓度（critical micelle concentration，CMC）；透析袋法考察胶束的体外释放行为；大鼠在体肠吸收实验评估载药胶束的促吸收作用。结果 红外与核磁结果表明SA通过酰胺键接枝于CS；协载槲皮素的LC-SA/CS-SA载PTX胶束呈类球形，粒径为（148.3±1.7）nm，多分散系数（PDI）为0.16±0.07，Zeta电位为（24.600±0.167）mV，CMC为14.31 μg/mL；体外释放结果表明，与市售紫杉醇注射剂相比，协载槲皮素的LC-SA/CS-SA载PTX胶束、LC-SA/CS-SA载PTX胶束具有明显缓释效应；大鼠在体肠吸收实验表明，协载槲皮素的LC-SA/CS-SA胶束对载药PTX的胃肠吸收具有显著促进作用。结论 构建的协载槲皮素的LC-SA/CS-SA载PTX胶束性能优良，促进了PTX的大鼠肠吸收，具有增强药物口服吸收潜力。