In vitro dissolution and oral bioavailability study of fenofibrate nanomatrix system prepared by hot-melt extrusion

Solvent evaporation method for preparation of nanomatrix has the disadvantages, such as residual organic solvent, environmental pollution, explosion-proofing and so on. To overcome these shortcomings, a series of fenofibrate nanomatrix drug delivery system (NDDS) consisting of nano-porous silica Sylysia^®350 (S350) and pH sensitive material Eudragit^® L100-55 (EL100-55) were prepared using hot-melt extrusion (HME), and their in vitro dissolution and in vivo bioavailability were compared. Finally, the formulation with the highest in vivo bioavailability was selected as the optimized formulation for DSC and PXRD characterization. The results showed that the optimized NDDS showed a higher bioavailability than the reference formulation, although there was crystalline form drug remaining in NDDS. The relative bioavailability of the optimized formulation was 157.1% compared with the commercial product Lipanthyl^®. In addition, the relative bioavailability of the optimized formulation was 124.8% in comparison with the formulation prepared by solvent evaporation method, showing that the NDDS prepared by the HME method was effective in improving the bioavailability of fenofibrate. In conclusion, HME was a promising method to prepare NDDS.     

The diagnostic significance of repeat ultrasound-guided biopsy of musculoskeletal soft-tissue lesions with initially inconclusive biopsy results

IntroductionTo determine the diagnostic yield of repeat ultrasound (US)-guided biopsy of musculoskeletal soft-tissue lesions with initially inconclusive biopsy results, and to explore predictive factors for success of repeat biopsy.Materials and methodsThis retrospective study included 42 patients who underwent a repeat (second) US-guided biopsy session to target a musculoskeletal soft-tissue lesion because an initial US-guided biopsy session provided inconclusive results. Both biopsy sessions were performed in a tertiary referral center for soft-tissue sarcomas.ResultsThe diagnostic yield of repeat US-guided biopsy was 47.6%. Malignant nature of the lesion (P = 0.031), sharp lesion borders on US (P = 0.011), and good to very good lesion visibility on US (P = 0.017) were significantly associated with a diagnostic repeat US-guided biopsy. There was also a trend towards significance (P = 0.073) for a higher number of biopsy passes through the lesion. Other patient characteristics (age and gender), magnetic resonance imaging features (lesion homogeneity on T1-weighted, T2-weighted, and gadolinium chelate enhanced sequences, borders, enhancement pattern, depth and size), US features (lesion appearance, vascular flow, and depth), biopsy-related factors (days between initial and repeat US-guided biopsy, needle diameter, maximum length of acquired samples), and operator-related factors (same or different radiologists/pathologists for initial and repeat biopsies), were not associated with the diagnostic success of the repeat US-guided biopsy.ConclusionsRepeat US-guided biopsy of a musculoskeletal soft-tissue lesion with initially inconclusive biopsy results can be useful to establish a final diagnosis. Lesion features on US (borders and visibility) may be used to prospectively determine the utility of a repeat US-guided biopsy.     

Developmental validation of the ANDE™ rapid DNA system with FlexPlex™ assay for arrestee and reference buccal swab processing and database searching

A developmental validation was performed to demonstrate reliability, reproducibility and robustness of the ANDE System with the FlexPlex assay, including an integrated Expert System, across a number of laboratories and buccal sample variations. Previously, the related DNAscan™/ANDE 4C Rapid DNA System using the PowerPlex^®16 assay and integrated Expert System Software received NDIS approval in March 2016. The enhanced ANDE instrument, referred to as ANDE 6C, and the accompanying 6-dye, 27-locus STR assay, referred to as FlexPlex, have been developed to be compatible with all widely used global loci, including the expanded set of the CODIS core 20 loci.Six forensic and research laboratories participated in the FlexPlex Rapid DNA developmental validation experiments, testing a total of 2045 swabs, including those obtained from 1387 unique individuals. The goal of this extensive and comprehensive validation was to thoroughly evaluate and document the ANDE System and its internal Expert System to reliably genotype reference buccal swab samples in a manner compliant with the FBI’s Quality Assurance Standards and the NDIS Operational Procedures.The ANDE System, including automated Expert System analysis, generated reproducible and concordant results for buccal swabs when testing various instruments at different laboratories by a number of different operators. When testing a number of non-human DNAs, including oral bacteria, the ANDE System and FlexPlex assay demonstrated limited cross-reactivity. Potential PCR inhibitors were evaluated as part of the validation and no inhibition was detected. Reproducible and concordant profiles were generated from buccal swab samples collected with a limit of detection appropriate for buccal swab collections from arrestees. The precision and resolution of the System met industry standards for detection of microvariants and single base resolution.The integrated Expert System appropriately demonstrated the ability to correctly pass or fail profiles for CODIS upload without human review. During this comprehensive developmental validation, the ANDE System successfully interpreted over 2000 samples tested with over 99.99% concordant alleles. The data package described herein led to the ANDE System with the FlexPlex assay receiving NDIS approval in June 2018.     

住院医师规范化培训中科研能力的同质化培养

住院医师规范化培训是提高我国临床医师队伍整体素质和水平的重要举措。培训内容和培训方式也需要与时俱进才能培养出真正适应快速发展的医学事业人才。当前住院医师的培养多局限于理论知识灌输及临床操作技能的训练,忽视了科研能力的提高。特别是社会学员的科研能力训练往往被忽视,不符合目前住院医师规范化培训对同质化的要求。本文结合既往研究和自身从事规培管理工作的实践,从多角度对规培中针对科研能力培养存在的问题进行梳理,主要包括:带教教师的科研培训、学生自身提高、考核标准完善和基地配套保障四个方面。先提出各方面存在问题,再深入分析出现上述问题的原因,最后结合既往研究及自身实践,对上述各问题的解决方法进行分析和讨论,最后得出相应的具有可行性的解决方案。     

虚实结合的翻转课堂在解剖实验教学中的应用

目的评价虚实相结合的翻转课堂在系统解剖学实验教学中的应用。方法选取齐齐哈尔医学院2018级临床专业和医学影像学专业学生共107名,在系统解剖学实验课中,对某些章节采用部分翻转课堂的教学模式,对照章节则采用传统的教学方法。教学结束后进行考核,比较前后章节的课堂测验成绩,另外采用调查问卷,分析学生对两种教学方法的满意度。结果临床医学和医学影像学专业的学生第二次课堂测试的成绩均高于第一次课堂测试的成绩(P <0.01),同时学生对翻转课堂教学模式的满意度高于传统教学法。结论在系统解剖学实验教学中实行翻转课堂教学模式,同时讲解实物标本并应用数字人解剖学系统进行知识内化,不仅能提高学生的学习成绩,也能调动学生学习系统解剖学的热情,增加教学效果满意度,并为其他解剖学专业课的教学模式改革提供参考和借鉴。     

康复治疗配合化痰祛瘀汤对脑梗死患者纤溶系统、神经功能及血液流变学的影响

目的:探究康复治疗配合化痰祛瘀汤对脑梗死患者纤溶系统、神经功能恢复及血液流变学的影响。方法:选取收治的150例脑梗死患者作为研究对象并分为2组,对照组75例行康复治疗,观察组75例在对照组基础上联合化痰祛瘀汤治疗。比较2组治疗效果及纤溶系统指标、神经功能缺损评分、血液流变学指标。结果:观察组总有效率高达93.33%,高于对照组的77.33%(P<0.05)。2组治疗后纤溶系统指标、神经功能评分及血液流变学指标均有所改善(P<0.05);治疗后组间比较,观察组纤溶酶原激活物(t-PA)及血小板聚集率(PAR)均高于对照组(P<0.05),组织纤溶酶原抑制物(PAI)、血浆黏度(PV)、全血黏度(WBV)均低于对照组(P<0.05)。结论:化痰祛瘀汤联合康复治疗有利于维持脑梗死患者纤溶系统动态平衡,促进神经功能恢复及改善血液流变学。     

Colitis following the use of immune checkpoint inhibitors: A real-world analysis of spontaneous reports submitted to the FDA adverse event reporting system

BackgroundAlthough colitis has been reported in patients treated with immune checkpoint inhibitors (ICIs), associations between colitis and ICIs had not been thoroughly assessed in real-world studies. Here, we identified and characterized significant colitis-associated with ICIs.MethodsBased on the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 2004 to December 2019, the disproportionality analysis and Bayesian analysis, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN) and the multi-item gamma Poisson shrinker (MGPS) algorithms were adopted to data mining of the suspected adverse events of colitis after ICIs administrating. Clinical characteristics of patients with ICIs-associated colitis and the time to onset of colitis following different ICI regimens were collected.ResultsA total of 3786 reports of colitis adverse events were identified with ICIs. Seven ICI monotherapies were associated with the reporting of colitis. Statistically significant ROR, PRR, information component (IC), and empirical Bayesian geometric mean (EBGM) emerged for all ICI monotherapies and combination therapies. ICIs-associated colitis affected mostly male (53.51%), with a wide mean age range (60.65 to 72 years). Colitis adverse events were commonly reported in patients with melanoma and lung cancer. Adverse outcomes of colitis concerning ICI were mainly outcomes of hospitalization-initiated or prolonged and other serious. Among colitis cases, 17.43% cases of colitis concerning ICI lead to death. The adverse event of colitis occurred earliest in ipilimumab monotherapy with a median time to onset of 64.21 days (IQR: 27–69 days) among all monotherapies.ConclusionsICI may lead to severe and disabling ICIs-associated colitis during therapy. Analysis of FAERS data identified signals for adverse events of colitis with ICI regimens. Practitioners should consider the factors that may increase the likelihood of colitis. The findings support a continued surveillance and risk factor identification studies.     

基于肥厚型心肌病临床数据管理系统的设计与应用

目的设计一款简单易操作的数据管理系统,解决目前零散的肥厚型心肌病临床数据,将临床信息科学有效地进行整合管理,便于医生及科研人员查询、统计。方法采用Foxtable搭建一个数据库管理软件框架,并建立局域网外部数据源,实现数据的存储、查询、共享、导出。结果基于肥厚型心肌病数据管理系统的设计与应用能够满足临床医生和科研人员的基本工作需求,很大程度上节省了数据整理时间。结论该系统操作简单、移植性高、实用性强,广泛适用于各临床科室有科研项目的小型数据库管理。     

Horloge interne,sommeil et médias électroniques : le comportement à risque des adolescents

The internal clock located in the suprachiasmatic nuclei of the hypothalamus is controlled by genetic factors (clock genes) and environmental factors (light-dark and sleep-wake alternations). Light is the major component of the clock control. Clock desynchronization occurs when the internal clock is no longer in phase with the environment resulting in a phase shift (phase advance or phase delay depending of the time of exposure to light). An increasing number of children and adolescents are experiencing chronic exposure to light at night due to misuse, including late at night, of electronic media. This results in a clock desynchronization, i.e. a shift of the clock circadian phase (which is delayed with exposure to light at night) with concomitant health issues: disturbances of sleep which is both shortened and delayed, mood alterations, fatigue etc. This risky behavior of children and adolescents is becoming a public health issue.