Prediction of skin sensitization potency using machine learning approaches

The replacement of animal use in testing for regulatory classification of skin sensitizers is a priority for US federal agencies that use data from such testing. Machine learning models that classify substances as sensitizers or non‐sensitizers without using animal data have been developed and evaluated. Because some regulatory agencies require that sensitizers be further classified into potency categories, we developed statistical models to predict skin sensitization potency for murine local lymph node assay (LLNA) and human outcomes. Input variables for our models included six physicochemical properties and data from three non‐animal test methods: direct peptide reactivity assay; human cell line activation test; and KeratinoSens™ assay. Models were built to predict three potency categories using four machine learning approaches and were validated using external test sets and leave‐one‐out cross‐validation. A one‐tiered strategy modeled all three categories of response together while a two‐tiered strategy modeled sensitizer/non‐sensitizer responses and then classified the sensitizers as strong or weak sensitizers. The two‐tiered model using the support vector machine with all assay and physicochemical data inputs provided the best performance, yielding accuracy of 88% for prediction of LLNA outcomes (120 substances) and 81% for prediction of human test outcomes (87 substances). The best one‐tiered model predicted LLNA outcomes with 78% accuracy and human outcomes with 75% accuracy. By comparison, the LLNA predicts human potency categories with 69% accuracy (60 of 87 substances correctly categorized). These results suggest that computational models using non‐animal methods may provide valuable information for assessing skin sensitization potency. Copyright © 2017 John Wiley & Sons, Ltd.     

从2型糖尿病的发病机制谈糖尿病治疗的新策略

目的探讨对2型糖尿病患者的发病机制进行分析和总结,制定新的糖尿病治疗策略。方法对该院2012年—2013年收治的94例2型糖尿病患者的临床资料进行回顾分析,从其发病机制实现对糖尿病治疗新策略的探讨。结果患者胆固醇数值超过6.6 mmol/L,空腹状态的血糖数值超过6.8 mmol/L,尿白蛋白超过20.3 mg,尿酸超过479.98μmol/L。结论全面认识2型糖尿病的发病机制,并采取相应的处理措施,提出新的糖尿病治疗策略,可实现对糖尿病治疗的有效控制和治疗。     

Nanomedicine for acute respiratory distress syndrome: The latest application,targeting strategy,and rational design

Acute respiratory distress syndrome (ARDS) is characterized by the severe inflammation and destruction of the lung air–blood barrier, leading to irreversible and substantial respiratory function damage. Patients with coronavirus disease 2019 (COVID-19) have been encountered with a high risk of ARDS, underscoring the urgency for exploiting effective therapy. However, proper medications for ARDS are still lacking due to poor pharmacokinetics, non-specific side effects, inability to surmount pulmonary barrier, and inadequate management of heterogeneity. The increased lung permeability in the pathological environment of ARDS may contribute to nanoparticle-mediated passive targeting delivery. Nanomedicine has demonstrated unique advantages in solving the dilemma of ARDS drug therapy, which can address the shortcomings and limitations of traditional anti-inflammatory or antioxidant drug treatment. Through passive, active, or physicochemical targeting, nanocarriers can interact with lung epithelium/endothelium and inflammatory cells to reverse abnormal changes and restore homeostasis of the pulmonary environment, thereby showing good therapeutic activity and reduced toxicity. This article reviews the latest applications of nanomedicine in pre-clinical ARDS therapy, highlights the strategies for targeted treatment of lung inflammation, presents the innovative drug delivery systems, and provides inspiration for strengthening the therapeutic effect of nanomedicine-based treatment.     

Retrieval of overviews of systematic reviews in MEDLINE was improved by the development of an objectively derived and validated search strategy

ObjectivesLocating overviews of systematic reviews is difficult because of an absence of appropriate indexing terms and inconsistent terminology used to describe overviews. Our objective was to develop a validated search strategy to retrieve overviews in MEDLINE.Study Design and SettingWe derived a test set of overviews from the references of two method articles on overviews. Two population sets were used to identify discriminating terms, that is, terms that appear frequently in the test set but infrequently in two population sets of references found in MEDLINE. We used text mining to conduct a frequency analysis of terms appearing in the titles and abstracts. Candidate terms were combined and tested in MEDLINE in various permutations, and the performance of strategies measured using sensitivity and precision.ResultsTwo search strategies were developed: a sensitivity-maximizing strategy, achieving 93% sensitivity (95% confidence interval [CI]: 87, 96) and 7% precision (95% CI: 6, 8), and a sensitivity-and-precision–maximizing strategy, achieving 66% sensitivity (95% CI: 58, 74) and 21% precision (95% CI: 17, 25).ConclusionThe developed search strategies enable users to more efficiently identify overviews of reviews compared to current strategies. Consistent language in describing overviews would aid in their identification, as would a specific MEDLINE Publication Type.     

急诊护士心理健康状况调查分析及对策

【摘要】 目的 了解急诊科护士的心理健康状况，分析影响因素，提出相应护理对策，以指导护理管理工作。 方法 采用症状自评量表（SCL-90）对我院的急危重症科的护士进行问卷调查。 结果 急诊科护士的心理健康状况不良，不同学历、职称、年龄的护士存在差异，尤其是在人际关系、焦虑、抑郁方面。结论 应采取切实措施，避免长期紧张源的刺激，缓解急诊科护士心理压力，维护急诊科护士的身心健康，培养和造就一批具有合格心理素质的急诊护理队伍。     

东兴区2003-2011年丙型病毒性肝炎流行特征及趋势分析

目的总结东兴区9年丙型病毒性肝炎(简称丙肝)的发病趋势及其流行病学特征,为今后制定防控策略和措施提供参考依据.方法采用描述性流行病学方法分析2003-2011年东兴区丙型病毒性肝炎的发病特点,数据分析采用X2检测.结果2003-2011年东兴区丙肝发病率在0.24/10万~8.17/10万之间,年均病发率为3.24/10万,2003年最低为2例,随后上升;东兴区绝大部分乡镇均有病例报告,少数乡镇发病率较高,但乡镇间差别无统计学意义(X2=1.087,P=0.297,P>0.05);丙肝发病在30-49岁的青壮年人居多,占总病例的47.48%;男性与女性发病率无统计学差别(P>0.05);病例以农民居多,占总病例的44.96%.结论东兴区的丙肝发病率2003年较低,但呈现上升趋势.今后要加强病情控制工作,以切断传播途径的方式为主,逐步建立起综合防范措施.     

Normalization as a barometer: Recreational drug use and the consumption of leisure by younger Britons

This article discusses the development of the normalization thesis in respect of monitoring sustained increases in young Britons’ consumption of illicit drugs and alcohol over the past decade. It describes five dimensions of normalization which have been applied in a cluster of studies undertaken by the author, highlighting results from the N.W. England Longitudinal Study showing easy accessibility, high rates of drug trying (76% at 22 years) and long-term recreational drugs careers involving both alcohol and illicit drugs. The social accommodation of ‘sensible’ substance use was apparent amongst most drug abstainers in the cohort who routinely had close friends who used drugs ‘recreationally’. Further cultural acceptance of recreational drug use is described. A sixth dimension – state or government responses to widespread recreational drug use – is introduced and illustrated. The article concludes by emphasizing the negative outcomes associated with recreational poly substance use in terms of personal and public health highlighting the ‘slippage’ from recreational to problem drug use as a growing phenomenon. It calls for a more integrative national strategy to address negative aspects of normalization.     

大学生抗挫折能力现状及培养策略

挫折是大学生不得不面对的问题，抗挫折能力是大学生必备的素质之一，挫折教育也成为当代大学生重要的必修课程。本文简述了挫折的概念及挫折教育的意义，重点分析了大学生抗挫折能力的现状、影响因素及培养策略，旨在为提高大学生的心理素质，促进其健康成长提供依据。     

实施职业卫生分类分级监管的实践体会

流行性乙型脑炎（乙脑）是由乙脑病毒感染所致的中枢神经系统急性传染病，患者有高热、呼吸衰竭、意识障碍、抽搐等神经系统明显受损的表现。目前，该病缺乏特效治疗药物，临床主要依靠积极对症治疗和支持治疗。近年来，依靠先进的器官支持技术和优质的护理措施最大限度提高了流行性乙脑整体救治成功率，但极重型流行性乙脑患者会导致严重神经系统后遗症，其致残率仍然居高不下。本文就流行性乙脑后遗症处理中面临的诸多非医学问题，从生理、心理、社会、伦理等多方面进行探讨，分析其原因和对策，为提高患者生存质量提供参考。