INAUGURAL ARTICLE by a Recently Elected Academy Member:Lexical shifts,substantive changes,and continuity in State of the Union discourse, 1790–2014

This study reveals that the entry into World War I in 1917 indexed the decisive transition to the modern period in American political consciousness, ushering in new objects of political discourse, a more rapid pace of change of those objects, and a fundamental reframing of the main tasks of governance. We develop a strategy for identifying meaningful categories in textual corpora that span long historic durées, where terms, concepts, and language use changes. Our approach is able to account for the fluidity of discursive categories over time, and to analyze their continuity by identifying the discursive stream as the object of interest.When did modern political discourse emerge in the United States? What is distinctive of basic understandings of the tasks of governance today, in contrast to those that organized the politics of an earlier period? Can the origins of contemporary political understandings be located in the discourse of the past? The annual State of the Union address (hereafter, SoU), in which the US president reports broadly on the progress and challenges of his administration, provides a singular standpoint from which to address the evolution of the tasks of governance. It can thus be used to investigate old questions like those above using network-based text analysis strategies.This study reveals that the entry into World War I (WWI) in 1917 indexed the decisive transition to the modern period in American political consciousness, ushering in new objects of political discourse, a more rapid pace of change of those objects, and a fundamental reframing of the main tasks of governance. At the same time, this study demonstrates that discourse distinctive to modern politics, although it later crystalized around the liberal welfare state, in fact emerged before the transition to the modern period.We offer a unique view of American political history, which tracks the articulation of the major tasks of governance in American political and social discourse. To do so, we develop a strategy for identifying meaningful categories in textual corpora that span long historic durées. We are able to account for the fluidity of discursive categories over time, and to analyze their continuity by identifying the discursive stream as the object of interest. The methodological approach developed in this article can be used to meaningfully analyze texts produced over very long historical periods, where terms, concepts, and language use changes—to our knowledge, a problem not satisfactorily solved.     

虎杖苷药理作用及机制研究进展

虎杖苷是从传统中药虎杖中分离出的一种多酚类单体化合物，是虎杖的主要有效成分，具有多种药理活性。近年来，有关虎杖苷药理作用及机制的研究日益增多。现代药理学研究表明，虎杖苷对神经系统，心脑血管系统，呼吸系统等均有保护作用，对肝、肾、肺等器官亦作用明显，其调节血糖血脂的作用对抗动脉粥样硬化效果显著；其抗纤维化的作用对肝、肾保护效果明显。虎杖苷对多种肿瘤细胞均有抑制作用，可抑制肿瘤细胞增殖并诱导肿瘤细胞凋亡。虎杖苷还具有抗炎，保护骨髓，促进创面愈合，抗辐射等药理活性。笔者查阅有关虎杖苷的药理作用文献发现其单个药理作用机制往往受多靶点蛋白、多条通路调控，但大多还未明确其作用靶点，有待深入研究。该文就近5年来有关虎杖苷的药理作用及机制研究进展进行归纳总结，并对其研究现状及未来研究方向提出相关建议，以期拓宽科研者的研究思路，加快明确其发挥药效作用的靶点，为虎杖苷的进一步开发利用提供科学的理论依据。     

基于“整体观”探讨中药的研究思维和方法

中药源于自然，治疗疾病有自身的优势和特点，其作用方式一直是中药研究者们不断研究和探索的重要内容。本文从中医的“整体观”对中药起效机制进行深入思考，认为中药成分多样可契合生物多靶，而生物靶标之间的协同作用是中药起效机制的重要补充；此外，中药对情志及肠道菌群稳态的调节作用也不容忽视，或许可为今后开展中药作用机制的研究提供新的思维和方法。     

生物黏附辅料对葛根总黄酮类化合物在Caco-2细胞模型中转运的影响

目的:葛根总黄酮（PTF）可治疗心脑血管疾病，但膜通透性差，口服生物利用度低。一些辅料如卡波姆、壳聚糖和羟丙基甲基纤维素可以提高口服生物利用度。传统的体外评价技术，包括大鼠肠灌流和细胞模型，不能评价PTF整体的吸收机制。方法:本研究评价辅料的黏附性及对PTF在Caco-2细胞单层模型中转运的影响。采用cDNA微阵列测定PTF和PTF+辅料给药后的Caco-2细胞的基因表达变化，从基因水平揭示辅料对PTF整体吸收的影响机制。结果:体外黏附和Caco-2细胞转运实验表明，与单独PTF相比，加入辅料后对胃黏膜具有更高的黏附性，且在Caco-2细胞模型中的转运效率更高。PTF与辅料的相互作用显著改变了某些基因的表达，可能影响PTF的吸收效率。结论:不同的生物黏附聚合物能提高PTF的肠道吸收，可能与ATP结合盒(ABC)和溶质载体转运体(SLC)的表达基因有关。     

SOS应答对质粒介导的qnr耐药基因表达调控机制的研究进展

SOS应答是普遍存在于细菌中的一种低保真度的DNA修复方式。当细菌DNA受损时，大量的DNA单链堆积，SOS应答启动并诱导远距离基因表达参与DNA修复。此修复过程缺失了DNA复制的校正功能，因此SOS应答会大大增加细菌的基因突变频率从而使细菌能够更快的适应不利环境。另一方面，随着细菌耐药的日益严峻，qnr基因家族成为质粒介导的喹诺酮耐药(plasmid-mediated quinolone resistanc PMQR)研究热点。有报道发现细菌的SOS应答会对菌株的qnr耐药水平造成明显的差异性，完整的SOS应答能够使菌株MIC成倍增加。由此可以怀疑SOS应答对qnr基因的表达存在相应的调控机制，但是相关机制尚未阐明。基于此本文就SOS应答机制和qnr耐药机制二者之间的关系进行试探性的综述。     

Adrenomedullin: an important participant in neurological diseases

Adrenomedullin,a peptide with multiple physiological functions in nervous system injury and disease,has aroused the interest of researchers.This review summarizes the role of adrenomedullin in neuropathological disorders,including pathological pain,brain injury and nerve regeneration,and their treatment.As a newly characterized pronociceptive mediator,adrenomedullin has been shown to act as an upstream factor in the transmission of noxious information for various types of pathological pain including acute and chronic inflammatory pain,cancer pain,neuropathic pain induced by spinal nerve injury and diabetic neuropathy.Initiation of glia-neuron signaling networks in the peripheral and central nervous system by adrenomedullin is involved in the formation and maintenance of morphine tolerance.Adrenomedullin has been shown to exert a facilitated or neuroprotective effect against brain injury including hemorrhagic or ischemic stroke and traumatic brain injury.Additionally,adrenomedullin can serve as a regulator to promote nerve regeneration in pathological conditions.Therefore,adrenomedullin is an important participant in nervous system diseases.     

Ketamine in the Treatment of Major Depressive Disorder

Major depressive disorder (MDD) is a prevalent and highly debilitating psychiatric condition that affects many young adults worldwide. This brief review summarizes the current available data about the use of ketamine as a treatment for MDD. We describe pharmacological mechanisms, dose considerations, drug interactions, side effects, and the relevancy of ketamine in the treatment of MDD.