大黄素的高效提取及其NMR结构探索研究

目的通过NMR定性研究大黄素的结构以及大黄素结构中的活泼性部位,为大黄素的化学结构修饰提供依据。方法从虎杖中高效提取了蒽醌类化合物大黄素,采用1D和2D-NMR的分析方法对大黄素结构进行鉴定,通过NMR变温技术及NOESY技术研究活泼性部位。结果以DMSO为溶剂、TMS作内标,采用1HNMR,13CNMR,DEPT,1H-1H COSY,NOESY,HSQC,HMBC等多种核磁共振方法对大黄素氢谱、碳谱进行完整归属,并通过NMR变温技术及NOESY的研究确定了其结构的活泼性部位。结论大黄素的3位羟基为其活泼性部位,该信息为大黄素的结构修饰以及衍生物的设计与抗肿瘤活性研究提供了物质基础。     

SARS相关冠状病毒M基因片段的克隆及其DNA疫苗诱导的体液免疫

目的：构建含有SARS相关冠状病毒(severe acute respiratory syndrome coronavirus，SARS—CoV)M基因片段的核酸疫苗，观察其免疫小鼠后病毒特异性抗体产生情况。方法：将合成的M基因片段克隆到核酸疫苗真核表达载体pVAX1中，免疫小鼠后，用SARS—CoV抗体ELISA检测试剂盒定期检测免疫小鼠血清中抗SARS—CoV的病毒特异性抗体水平。结果：构建了重组核酸疫苗质粒pVCo—M，免疫小鼠后可诱导产生出病毒特异性抗体。结论：以M为抗原基因的DNA疫苗能诱导SARS病毒特异性抗体，为进一步改进或探索同类DNA疫苗提供有益启示。     

肝细胞生长因子对实验性急性胰腺炎细胞凋亡作用的研究

目的:观察外源性肝细胞生长因子(HGF)对小鼠轻症实验性急性胰腺炎的炎症反应及胰腺细胞凋亡的作用。方法:以雨蛙肽腹腔注射诱发小鼠轻症实验性急性胰腺炎。第1组以盐水腹腔注射作为对照,第2、3及4组每小时腹腔注射雨蛙肽诱发急性胰腺炎;第3组在造模前及造模中两次皮下注射重组人肝细胞生长因子(rhHGF);第4组同时皮下注射rhHGF及其单抗。观察HGF对炎症反应的干预作用及对腺泡细胞凋亡的影响。结果:炎症小鼠予每公斤体重4、20μgrhHGF时,与单纯炎症组相比,血清淀粉酶、脂肪酶下降,胰腺组织学炎症评分减少,胰腺腺泡细胞TUNEL凋亡指数增加,caspase3活性增强。予每公斤体重4或20μgrhHGF时,其效应无显著性差异。同时予rhHGF单抗的小鼠,上述指标与单纯炎症组相比差异无显著性。结论:HGF能减轻雨蛙肽诱导的小鼠轻症实验性急性胰腺炎。HGF单抗能消除HGF的生物学作用。HGF可以促进急性胰腺炎时腺泡细胞的凋亡,这可能是其保护胰腺的作用机制之一。     

五行学说的方法论价值

五行学说的价值主要在于其方法论意义。五行模型是对人体自我调节机制的一种表达,反映了机体调节和防卫反应的“自组织原则”、“自主性原则”、“目的性原则”。调整阴阳是典型的矛盾调节,五行调节是典型的反馈调节,五行学说是对阴阳学说必然的补充,有不同于阴阳调节的特点,主要是:多体关系、多种作用、反馈控制、不可逆性、整体稳定等。五行学说不仅符合人体实际,而且符合数学的一些严格规则,取了奇素数中的“5”,五行学说面临的不是存废问题,而是如何发展,一方面要使传统五行学说更加完备,另方面应发展“七行”、“十一行”、“十三行”等新模型,可概称为“N行”。     

生物材料人工气管的设计与动物实验研究

目的：通过筛选适宜的生物材料和选用特殊的成型工艺自行研制新型人工气管假体，探讨其用于长段气管缺损重建的可行性。方法：根据理想化气管替代物的要求，设计出I型人工气管：由聚丙烯单丝、聚乙丙交酯纤维纺织成直管状网管，内壁涂以聚氨酯薄膜和胶原蛋白，涂层材料不能透过外壁网孔，外壁采用胶原蛋白-羟基磷灰石多孔状海绵覆盖。作为对照的II型人工气管，网管结构与I型相同，内外壁均涂以聚氨酯。分别将I型、II型人工气管用于实验组（8只）和对照组（4只）动物，构建犬颈部气管置换与重建的动物模型。结果：实验组犬术后人工气管假体能迅速被宿主气管周围组织包绕而达到生物学固定，假体在位良好，吻合口肉芽生长不明显；假体内腔可见不规则黏膜上皮生长，色较苍白，未铺覆内腔全长；包绕假体的周围组织中可扪及散在的大小不等的硬质骨性结构；动物存活时间长。而对照组术后均出现不同程度的假体松脱现象，并发生局部漏气、感染及狭窄等并发症。结论：该生物材料人工气管可用于长段气管置换重建手术，具有一定的开发利用价值和临床应用前景。     

Multimodal investigation of dopamine D2/D3 receptors,default mode network suppression,and cognitive control in cocaine-use disorder

Stimulant-use disorders have been associated with lower availability of dopamine type-2 receptors (D2R) and greater availability of type-3 receptors (D3R). Links between D2R levels, cognitive performance, and suppression of the default mode network (DMN) during executive functioning have been observed in healthy and addicted populations; however, there is limited evidence regarding a potential role of elevated D3R in influencing cognitive control processes in groups with and without addictions. Sixteen individuals with cocaine-use disorder (CUD) and 16 healthy comparison (HC) participants completed [¹¹C]-(+)-PHNO PET imaging of D2R and D3R availability and fMRI during a Stroop task of cognitive control. Independent component analysis was performed on fMRI data to assess DMN suppression during Stroop performance. In HC individuals, lower D2R-related binding in the dorsal putamen was associated with improved task performance and greater DMN suppression. By comparison, in individuals with CUD, greater D3R-related binding in the substantia nigra was associated with improved performance and greater DMN suppression. Exploratory moderated-mediation analyses indicated that DMN suppression was associated with Stroop performance indirectly through D2R in HC and D3R in CUD participants, and these indirect effects were different between groups. To our knowledge, this is the first evidence of a dissociative and potentially beneficial role of elevated D3R availability in executive functioning in cocaine-use disorder.Subject terms: Addiction, Cognitive control     

Weight-of-evidence evaluation of long-term ozone exposure and cardiovascular effects

We conducted a weight-of-evidence (WoE) analysis to assess whether the current body of research supports a causal relationship between long-term ozone exposure (defined by EPA as at least 30 days in duration) at ambient levels and cardiovascular (CV) effects. We used a novel WoE framework based on the United States Environmental Protection Agency's National Ambient Air Quality Standards causal framework for this analysis. Specifically, we critically evaluated and integrated the relevant epidemiology and experimental animal data and classified a causal determination based on categories proposed by the Institute of Medicine's 2008 report, Improving the Presumptive Disability Decision-making Process for Veterans. We found that the risks of CV effects are largely null across human and experimental animal studies. The few positive associations reported in studies of CV morbidity and mortality are very small in magnitude, mainly reported in single-pollutant models, and likely attributable to bias, chance, or confounding. The few positive effects in experimental animal studies were observed mainly in ex vivo studies at high exposures, and even the in vivo findings are not likely relevant to humans. The available data also do not support a biologically plausible mechanism for the effects of ozone on the CV system. Overall, the current WoE provides no convincing case for a causal relationship between long-term exposure to ambient ozone and adverse effects on the CV system in humans, but the limitations of the available studies preclude definitive conclusions regarding a lack of causation; thus, we categorize the strength of evidence for a causal relationship between long-term exposure to ozone and CV effects as “below equipoise.”     

Psychological dysregulation during adolescence mediates the association of parent-child attachment in childhood and substance use disorder in adulthood

Objective: This prospective study tested the hypothesis that psychological dysregulation in mid-adolescence (age 16) mediates the association between parent-child attachment in late childhood (age 10–12) and development of substance use disorder (SUD) in adulthood (age 22). Method: The Youth Attachment to Parents Scale (YAPS) was developed in 10–12-year-old boys and girls (N?=?694) at baseline residing in western Pennsylvania. Psychological dysregulation was measured by the neurobehavior disinhibition trait. Substance use was assessed at ages 10–12, 12–14, 16 and 19. SUD was diagnosed at age 22 using the Structured Clinical Interview for DSM Disorders. The mediation of parent-child attachment and SUD by neurobehavior disinhibition was tested separately for mothers and fathers while controlling for baseline substance use. Results: Psychological dysregulation mediates the association between attachment to mothers and SUD, and partially mediates the association between attachment to fathers and SUD. Significant mediation effects remains after controlling for baseline substance use. Conclusion: Optimal prevention of SUD should include ameliorating both psychological dysregulation predisposing to SUD and quality of the parent-child relationship.