复方薰衣草颗粒镇静催眠及改善认知障碍作用研究

目的 观察复方薰衣草颗粒（CLG）镇静催眠及对轻度认知功能障碍（MCI）模型小鼠的治疗作用。方法 （1）CLG镇静催眠和抗抑郁、抗疲劳作用研究：以旷场训练结果为主要条件、体质量为次要条件，随机将79只ICR小鼠分为对照组、地西泮（3 mg·kg^-1，化药阳性药）组、复方枣仁胶囊（12.3 mg·kg^-1，中药阳性药）组和CLG低、中、高剂量（2.36、4.72、9.44 g·kg^-1）组。采用戊巴比妥钠阈下剂量催眠、旷场和转棒实验，观察CLG对小鼠的一般状态、睡眠潜伏期、30 min内入睡比例和总睡眠时间以及行为学的影响。（2）CLG改善MCI作用研究：将60只昆明小鼠以Y迷宫实验训练结果为主要条件、体质量为次要条件随机分为对照组、模型组、多奈哌齐（3 mg·kg^-1，阳性药）组和CLG低、中、高剂量（2.36、4.72、9.44 g·kg^-1）组，每天1次，连续ig给药14 d，给药第9天起，给药1 h后，除对照组外，ip 3 mg·kg^-1东莨菪碱制备MCI模型。于末次给药20 min后进行Y迷宫实验；第15天进行跳台实验；解剖取脑，称取脑质量并计算脑系数；HE染色后观察脑组织病理改变；取海马，ELISA法测定乙酰胆碱（Ach）、乙酰胆碱酯酶（AchE）、超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽（GSH）水平。结果 （1）与对照组比较，CLG各剂量对体质量无明显影响；地西泮组和CLG各剂量组入睡率有增高趋势，但无显著性差异；地西泮组和CLG高剂量组入睡潜伏期明显缩短（P<0.05） ；各给药组睡眠时间均显著延长（P<0.01）。（2）与模型组比较，多奈哌齐组和CLG各剂量组跳台次数均显著减少（P<0.05）；CLG各剂量组Ach有升高趋势，多奈哌齐组和CLG中、高剂量组AchE有降低趋势；CLG各剂量组SOD显著增加，MDA显著降低（P<0.05）；CLG中、高剂量组小鼠皮层和海马病理改变明显减轻。结论 CLG具有镇静催眠作用，其改善MCI的作用可能与调节胆碱能系统和抗氧化应激有关。     

The reproducibility issue and preclinical academic drug discovery: educational and institutional initiatives fostering translation success

ABSTRACT

Introduction: Drug discovery depends critically upon published results from the academy. The reproducibility of preclinical research findings reported by academia in the peer-reviewed literature has been called into question, seriously jeopardizing the value of academic science for inventing therapeutics.

Areas covered: The corrosive effects of the reproducibility issue on drug discovery are considered. Purported correctives imposed upon academia from the outside deal mainly with expunging fraudulent literature and imposing punitive sanctions on the responsible authors. The salutary influence of such post facto actions on the reproducibility of discovery-relevant preclinical research data from academia appears limited. Rather, intentional doctoral-scientist education focused on data replicability and translationally-meaningful science and active participation of university entities charged with research innovation and asset commercialization toward ensuring data quality are advocated as key academic initiatives for addressing the reproducibility issue.

Expert opinion: A mindset shift on the part of both senior university faculty and the academy to take responsibility for the data reproducibility crisis and commit proactively to positive educational, incentivization, and risk- and reward-sharing practices will be fundamental for improving the value of published preclinical academic research to drug discovery.     

Dental age estimation of Omani children using Demirjian's method

Dental age plays a significant role in forensic dentistry, orthodontics and paediatric dentistry, as well as in general diagnosis and treatment planning. Different methods have been developed to determine dental age. One of the most commonly used methods is Demirjian’s method, which was developed in 1973 from research on a large number of French-Canadian children. It is based on the degree of tooth mineralisation by examining the radiological appearance of the lower mandibular left quadrant. The purpose of this study was to assess the dental age of Omani children using Demirjian's method and evaluate the applicability of the method in dental age estimation for Omani children. The sample consisted of 485 digital panoramic radiographs of children (264 males, 221 females) aged between 4.6?years and 16.5?years, and obtained from the records of the Military Dental Centre in Oman. The data were analysed using SPSS. Paired t-tests, intraclass correlation coefficients (ICC) and difference-against-mean plots were used to compare the dental age calculated by Demirjian's method with chronological age. A single examiner scored the radiographs, and intra-observer reliability was evaluated using Cronbach's alpha on data from rescoring one out of every 20 radiographs. For boys, the mean difference between chronological age and dental age for all age groups was 0.10 (95% CI ?0.03 to 0.24). For girls, the mean difference between chronological age and dental age for all age groups was 0.05 (95% CI ?0.11 to 0.22). Difference-against-mean plots showed no evidence of differential bias by age. For boys, the ICC was 0.896 (95% CI 0.869–0.917); for girls, it was 0.886 (95% CI 0.854–0.911). Difference-against-mean plots for boys (Fig. 1) and girls (Fig. 2) showed some evidence of differential bias by age. In conclusion, the extent of the observed differences was sufficient for doubt to be cast upon the utility of Demirjian’s method for Oman, particularly when it is considered that the method’s most likely application would be in age determination for minors in the workforce.     

Treatment development: Can we find a better way?

The present paper argues that traditional approaches to treatment development, including a technological approach, a stage model, and existing inductive approaches such as functional analysis are inadequate in various ways. Treatment developing needs to focus more on theoretical development, practicality, and the fit with clients and practitioners. We argue that progress requires greater philosophical clarity, and steps to ensure a connection between philosophy of science assumptions and an analytic agenda which fits naturally with applied psychology. Theoretical progress requires distinguishing between clinical and basic models and harmonizing their relationship, and more focus on the manipulable context of action. Applied psychology needs to join in a common cause with basic psychology in domains of mutual interest, and develop basic analyses and mid-level terms that can be both scientifically progressive and clinically useful. Issues of practicality, capacity for dissemination, and public health impact need to be considered at the beginning and throughout treatment development. Issues of effectiveness, change processes, mediation, moderation, training, active components, and similar issues should be part of the evaluation system from the beginning. It is time to create a more coherent approach to treatment innovation.     

人文社科期刊国际化研究综述

【目的】 人文社科期刊国际化是全球人文思想传播和文化交流的重要方式,随着中国特色哲学社会科学“三大体系”工作的推进,人文社科期刊国际化成为新文科建设理念下一个紧迫的研究课题。【方法】 以CNKI、WoS、Google Scholar为文献来源,结合计量方法获取相关文献,通过文献阅读法,构建“抽象化—具体化—标准化”的研究思路。【结果】 对人文社科期刊国际化的基础研究、特征标准、评价指标“三方内容”进行综述,分析人文社科期刊国际化研究存在的“四个挑战”:发展进程缓慢、意识形态差异、评价体系构建难题、期刊自身制约。【结论】 对未来人文社科期刊研究提出了加强基础研究、解决国际本土之争、深化区域合作、推动数据驱动、创新评价方法的“五大展望”。     

The persistence of illicit drug smoke residues and their recovery from common household surfaces

Third‐hand smoke is the residue remaining on surfaces during smoking events. It is composed of particles and vapours that form upon heating. The phrase ‘third‐hand smoke’ is primarily used to describe nicotine and other chemicals from cigarettes, but any residues formed from the smoking of various substances could be classified similarly. There has been an increasing body of research on third‐hand smoke from cigarettes in the last decade, but little has been done in regards to understanding the persistence of particles and vapours from illicit drugs. In this work, small samples of cocaine and methamphetamine were volatilized to produce an illicit drug smoke that was collected onto various surface materials and left exposed to ambient conditions over 672 h (four weeks). Chemical analyses by electrospray ionization‐mass spectrometry of residues on silicon, plastic, laminate, and artificial leather surfaces indicated a rapid decrease in recovery of the parent molecule, with varied formation of decomposition products over the first 168 h of exposure. Measurable amounts of the parent molecule were still present after 672 h, exhibiting a strong persistence of these drugs on various household materials. This is important in a forensic science context, as third‐hand smoke residues could provide a viable source of trace evidence previously not utilized. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.     

Graft-versus-host disease after liver transplantation is associated with bone marrow failure,hemophagocytosis, and DNMT3A mutations

Graft-versus-host disease after liver transplantation (LT-GVHD) is rare, frequently fatal, and associated with bone marrow failure (BMF), cytopenias, and hyperferritinemia. Given hyperferritinemia and cytopenias are present in hemophagocytic lymphohistiocytosis (HLH), and somatic mutations in hematopoietic cells are associated with hyperinflammatory responses (clonal hematopoiesis of indeterminate potential, CHIP), we identified the frequency of hemophagocytosis and CHIP mutations in LT-GVHD. We reviewed bone marrow aspirates and biopsies, quantified blood/marrow chimerism, and performed next-generation sequencing (NGS) with a targeted panel of genes relevant to myeloid malignancies, CHIP, and BMF. In all, 12 marrows were reviewed from 9 LT-GVHD patients. In all, 10 aspirates were evaluable for hemophagocytosis; 7 had adequate DNA for NGS. NGS was also performed on marrow from an LT cohort (n = 6) without GVHD. Nine of 10 aspirates in LT-GVHD patients showed increased hemophagocytosis. Five (71%) of 7 with LT-GVHD had DNMT3A mutations; only 1 of 6 in the non-GVHD LT cohort demonstrated DNMT3A mutation (p = .04). Only 1 LT-GVHD patient survived. BMF with HLH features was associated with poor hematopoietic recovery, and DNMT3A mutations were over-represented, in LT-GVHD patients. Identification of HLH features may guide prognosis and therapeutics. Further studies are needed to clarify the origin and impact of CHIP mutations on the hyperinflammatory state.

     

以胜任力为核心的“二经四纬”医学类研究生培养模式构建及实践——以滨州医学院为例

“大健康”背景下，对医学人才提出了更高的要求，为提高医学研究生岗位胜任力，滨州医学院紧紧围绕“岗位胜任力”的核心，从研究生导师队伍建设和研究生培养两个“经度”入手，在创新能力、实践能力、学科交叉思维和国际视野4个“纬度”，实施培养模式改革。在研究生导师队伍建设经度，建立健全研究生导师分类遴选考核体系，构建“四位一体” +“思政贯通”的导师培训体系，开展“医学+X”交叉融合工程，组建国际化导师队伍，全面提高研究生导师岗位胜任力。在研究生培养经度，构建科学学位科研素养全周期覆盖、专业学位 “产学研”一体化的研究生分类培养体系，建立“医学+X”医学研究生交叉培养体系和“S-P-R-I国际化培养模式”，提高研究生学科交叉能力，拓宽国际视野，提升研究生岗位胜任力。自新模式实施以来，切实提升了研究生的创新能力、实践能力、学科交叉思维和国际视野，岗位胜任力显著提高，深受就业单位欢迎，就业率近100%，均从事医学科研或临床工作。     

Die Hitler in UNS (The Hitler in US): Evil and the Psychoanalytic Situation

In exploring egregious behavior on the part of psychoanalysts, this article attempts to redefine the traditionally ecclesiastical, moralistic notion of evil. Referencing the “Nazification” of the famed Berlin Institute, the vociferous “controversial discussions” at the British Psychoanalytic Society during the London Blitz, and more recent events involving psychologists condoning torture, the author considers evil as a universal potential in context, rather than a fixed social or psychiatric aberration. As such, the dynamic stance of participant observation is put forth as a safeguard against the analyst's loss of self-reflexivity.