关键词： antiretroviral   chemical exchange saturation transfer   HIV-1   lamivudine   theranostics  

摘要： Objective: Antiretroviral drug theranostics facilitates the monitoring of biodistribution and efficacy of therapies designed to target HIV type-1 (HIV-1) reservoirs. To this end, we have now deployed intrinsic drug chemical exchange saturation transfer (CEST) contrasts to detect antiretroviral drugs within the central nervous system (CNS). Design and methods: CEST effects for lamivudine (3TC) and emtricitabine (FTC) were measured by asymmetric magnetization transfer ratio analyses. The biodistribution of 3TC in different brain sub-regions of C57BL/6 mice treated with lipopolysaccharides was determined using MRI. CEST effects of 3TC protons were quantitated by Lorentzian fitting analysis. 3TC levels in plasma and brain regions were measured using ultraperformance liquid chromatography tandem mass spectrometry to affirm the CEST test results. Results: CEST effects of the hydroxyl and amino protons in 3TC and FTC linearly correlated to drug concentrations. 3TC was successfully detected in vivo in brain sub-regions by MRI. The imaging results were validated by measurements of CNS drug concentrations. Conclusion: CEST contrasts can be used to detect antiretroviral drugs using MRI. Such detection can be used to assess spatial--temporal drug biodistribution. This is most notable within the CNS where drug biodistribution may be more limited with the final goal of better understanding antiretroviral drug-associated efficacy and potential toxicity.

关键词： adolescents   Africa   biomarkers   HIV   lung disease   pathogenesis  

摘要： Objective: HIV-associated chronic lung disease (HCLD) is a common comorbidity in children and adolescents in sub-Saharan Africa (SSA). The pathogenesis of HCLD is unclear and may be driven by underlying dysregulated systemic immune activation and inflammation. We investigated the association between 26 plasma soluble biomarkers and HCLD. Design: Case--control analysis of baseline biomarker data from 336 children and adolescents (6-19 years old) with perinatal HIV infection (PHIV) and HCLD (cases) and 74 age-matched and sex-matched controls with PHIV but no CLD. HCLD was defined as having a forced expiratory volume in one second (FEV1) z score less than -1 with no reversibility. Methods: Cryopreserved plasma collected at recruitment was used in a multiplex bead assay (Luminex) to measure baseline levels of soluble biomarkers. Logistic regression alongside data-reduction and techniques quantifying the interconnectedness of biomarkers were used to identify biomarkers associated with odds of HCLD. Results: Biomarkers of general immune activation and inflammation (beta 2M, CRP, sCCL5, GCSF, IFN-gamma, IP-10), T-cell activation (sCD25, sCD27), platelet activation (sCD40-L), monocyte activation (sCD14), coagulation (D-Dimer), cellular adhesion (E-selectin), and extracellular matrix degradation (MMP-1, MMP-7, MMP-10) were associated with increased odds of HCLD. Exploratory PCA and assessment of biomarker interconnectedness identified T-cell and platelet activation as centrally important to this association. Conclusion: HCLD was associated with a large number of soluble biomarkers representing a range of different pathways. Our findings suggest a prominent role for T-cell and platelet activation in HCLD.

关键词： 敦煌书写   新神话   新历史   新叙事   《野马,尘埃》  

摘要： 冯玉雷是一位学者型作家,其“丝绸之路(敦煌)文学书写”特别是最新力作《野马,尘埃》,在神话、历史、叙事等层面彰显出丰富的创新性。民间文化、敦煌文化和丝路文化,是冯玉雷小说的创造性得以发生的“素材”。“新神话”表征小说的灵动之美,“新历史”表征小说的同情之心,而"新叙事"表征自觉的文体意识,三者彼此交融,融合会通,开拓了独特的审美意蕴和文化价值。

关键词： 穴位埋线   单纯性肥胖   Meta分析  

摘要： 目的:评价穴位埋线与其他针灸疗法治疗单纯性肥胖症临床效果的差异。方法:计算机检索中国知网、维普、万方、SinoMed、PubMed、Cochrane Library数据库,收集2015年1月至2020年4月穴位埋线治疗单纯性肥胖的临床随机对照试验文献,由两名评价者按照Cochrane系统评价手册的要求单独提取资料并相互探讨核验,采用RevMan5.3软件对数据进行系统分析。结果:最终纳入12篇符合要求的文献,涉及897例单纯性肥胖患者。Meta分析结果显示:穴位埋线治疗单纯性肥胖症的总有效率高于其他针灸疗法,其合并效应量为(RR=1.13,95%CI[1.06,1.20],P<0.0001),而且在减轻患者的体质量(MD=-2.55,95%CI[-3.64,-1.46],P<0.00001)、降低BMI指数(MD=-0.39,95%CI[-0.67,-0.11],P=0.006)方面均优于其他针灸疗法。结论:穴位埋线治疗单纯性肥胖症的临床疗效优于其他针灸疗法,病人在临床治疗中获益更多,有望提供单纯性肥胖症的优先替代疗法的理论支撑。

关键词： 新陈代谢   细菌感染   烹调   猪  

摘要： 猪与狗,都只要好吃的东西就下嘴,全然没有人类那样先洗一下,乃至烧煮烹调过后才食用,以免细菌感染的作法。我在塞上时,那里老乡养的猪往往以人的消化物为食,也不听说有生病的。其实动物躯体中,哪里可能没有细菌?细菌参予寄主的新陈代谢,彼此相安而共存。它对后者通常不会有祸害之心,否则不等于害自己?如此愚蠢的生物在进化长途上绝没有生存下来的可能。

关键词： 糖尿病   患病率   新诊断糖尿病   慢性代谢性疾病  

摘要： 目的调查海南省城乡居民糖尿病患病率及合并其他慢性代谢性疾病情况。方法于2018—2020年采用多阶段分层整体抽样方法调查海南省≥18岁城市和乡村常住居民,通过问卷方式记录调查对象的社会人口学信息、生活方式和疾病史,测量身高、体重、腰围、血压,检测空腹血糖、OGTT-2h血糖、糖化血红蛋白、尿酸、血脂等生化指标。结果共选择2136名≥18岁居民,总糖尿病、新诊断糖尿病、既往确诊糖尿病和糖尿病前期患病率分别为16.0%、11.8%、4.2%和25.0%。城市和乡村新诊断患病率分别为为10.1%和13.4%,差异有统计学意义(P<0.05)。糖尿病知晓率、治疗率和控制率分别为25.8%、15.2%和42.3%。男性、受教育程度低、超重和肥胖、有糖尿病家族史人群总糖尿病、新诊断糖尿病和糖尿病前期的患病率较高。糖尿病及糖尿病前期的患病率均随着年龄的增长而增加。所有糖尿病人群中有40.2%合并高血压,51.6%合并血脂异常,40.5%合并超重,13.2%合并肥胖,26.1%合并高尿酸血症,87.4%合并代谢综合征,均高于非糖尿病人群(P<0.01)。新诊断糖尿病人群中有44.3%合并高血压,56.5%合并血脂异常,29.2%合并高尿酸血症,90.9%合并代谢综合征,明显高于既往确诊糖尿病人群(P<0.01)。结论海南省成人糖尿病防控形势严峻,尤其在农村,糖尿病患病率明显上升,新诊断糖尿病占比高,合并更高比例的慢性代谢性疾病。亟需普及糖尿病的科普知识,重视健康宣教,提倡健康的生活方式。同时,还要加强糖尿病及其他慢性代谢性疾病的筛查和管控。

关键词： epiGenetic algorithm   Smart mobility   LED panel   Travel time   Greenhouse gas emissions   Fuel consumption  

摘要： Traffic congestion is one of the main concerns of citizens living in big cities. In this article we propose a novel system, called Yellow Swarm, with the aim of improving road traffic at a low cost and easy implementation by using a set of LED panels placed throughout the city in order to spread road traffic over its streets. The system is optimally configured by a new epigenetic algorithm which calculates the time slots for each suggested detour shown in the panels. Yellow Swarm was tested on three scenarios of the city of Malaga, Spain, using the real city layout and actual traffic flows calculated by our flow generator algorithm with data published by the city's authorities. Our results show shorter average travel times (up to 19 s) and a reduction of greenhouse gas emissions (up to 4.5%) and fuel consumption (up to 1.6%), which have been achieved without increasing the maximum travel times (reduced by 205 s). Yellow Swarm, as a distributed traffic management system in the city, represents a major improvement that benefits drivers on long trips by reducing travel times and preventing traffic jams. (C) 2021 Elsevier B.V. All rights reserved.

关键词： renal cell carcinoma   alternative splicing   subtype classification   pathway   immune  

摘要： Irregular splicing was associated with tumor formation and progression in renal cell carcinoma (RCC) and many other cancers. By using splicing data in the TCGA SpliceSeq database, RCC subtype classification was performed and splicing features and their correlations with clinical course, genetic variants, splicing factors, pathways activation and immune heterogeneity were systemically analyzed. In this research, alternative splicing was found useful for classifying RCC subtypes. Splicing inefficiency with upregulated intron retention and cassette exon was associated with advanced conditions and unfavorable overall survival of patients with RCC. Splicing characteristics like splice site strength, guanine and cytosine content and exon length may be important factors disrupting splicing balance in RCC. Other than cis-acting and trans-acting regulation, alternative splicing also differed in races and tissue types and is also affected by mutation conditions, pathway settings and the response to environmental changes. Severe irregular splicing in tumor not only indicated terrible intra-cellular homeostasis, but also changed the activity of cancer-associated pathways by different splicing effects including isoforms switching and expression regulation. Moreover, irregular splicing and splicing-associated antigens were involved in immune reprograming and formation of immunosuppressive tumor microenvironment. Overall, we have described several clinical and molecular features in RCC splicing subtypes, which may be important for patient management and targeting treatment.