Loss of Hrh2 on dopaminergic neurons leads to mania-like behavior in mice

OBJECTIVE Dysfunction of the dopaminergic(DA)neurons is implicated in the pathogenesis of bipolar disorder(BPD).Hista⁃mine receptor 2(Hrh2)is highly expressed in DA neurons,and its antagonists have been reported to induce mania phase of BPD.However,whether Hrh2 on DA neurons contributes to BPD patho⁃genesis is unclear.The present study aims to explore the role of hrh2 on DA neurons in the pathology of BPD.METHODS AAV-FLEX-shHrh2 was injected into a targeted brain area of DAT-Cre mice,leading to a selective brain-regional loss of Hrh2 on DA neurons.A series of behavior tests were used to measure the sponta⁃neous activity,anxiety and depression level of Hrh2-deficient mice.RESULTS①In the open field test and home-cage activity test,Hrh2-defi⁃cient mice displayed increased spontaneous activity.②Hrh2-deficient mice showed reduced depression level in the tail suspension test,forced swimming test and sucrose preference test.③The anxiety level of Hrh2-deficient mice was decreased in the open field test.CONCLU⁃SION Hrh2 on DA neurons is closely related with mania-like behavior.

基于双前沿面交叉效率模型的中国科技创新资源配置效率研究

为克服乐观视角评价问题的片面性,首先从悲观视角出发,构建基于悲观视角的改进交叉效率模型,然后综合乐观和悲观交叉效率模型对中国31个省市区的科技创新资源配置效率进行研究,利用综合交叉效率得分作为对31个省市区的科技创新资源进行配置的依据,并深入分析了区域内部和外部省份科技创新能力的差异及其产生的根源,最后对改善区域省份科技创新能力提出政策性建议。

酪氨酸激酶抑制剂类小分子抗肿瘤药物的研究进展

酪氨酸激酶在肿瘤发生发展过程中扮演着重要的角色,以其为导向的分子靶向药物研发已成为现代抗肿瘤药物发展的主流趋势之一,近年来已取得重大进展。本文总结并综述了近年来30余种已上市的酪氨酸激酶抑制剂类小分子抗肿瘤靶向药物,同时概述了相关类似物结构改造的研究进展和趋势。

一种基于区间信度结构的混合型多属性决策方法

考虑决策者对语言评估的不确定性,用区间值表示语言评价等级,并将证据理论(DST)和数据包络分析(DEA)两种方法相结合,提出一种基于区间信度结构的混合型多属性决策方法.首先,通过区间型交叉效率模型构造决策单元定量指标的区间信度结构,利用证据推理非线性优化模型对区间信度结构进行集结,并将集结后的区间信度结构进行效用等价转换,得到一个信度为区间型的分布式等级评估向量;然后,通过证据推理非线性优化模型对定量指标和定性指标的区间信度结构进行融合,得到决策单元总的区间信度结构分布式评估向量,并结合期望效用理论对决策单元进行排序;最后,通过具体算例进行比较分析,结果验证了所提出方法的有效性和合理性.

Identification of constituents in Gui-Zhi-Jia-Ge-Gen-Tang by LC-IT-MS combined with LC-Q-TOF-MS and elucidation of their metabolic networks in rat plasma after oral administration

Gui-Zhi-Jia-Ge-Gen-Tang(GZJGGT) is a traditional Chinese medicine(TCM) prescription commonly used to treat cervical spondylopathy, scapulohumeral periarthritis, etc. Though it is widely applied in clinical practice, the effective constituents of GZJGGT remain unclear. This was the first report on the identification of the chemical constituents from GZJGGT in vitro and in vivo using LC-IT-MS combined with LC-Q-TOF-MS. A total of 141 constituents were detected in GZJGGT, and 77 were identified. These compounds mainly included flavonoid glycosides, triterpene saponins, monoterpene glycosides, puerosides, and organic acids. Among them, 12 compounds were unequivocally identified in comparison with reference substances. Additionally, a diagnostic base peak ion filtering strategy for rapid classification of flavonoid O-glycosides and C-glycosides was proposed. After gastrointestinal administration of GZJGGT to rats, 45 prototypes and 48 metabolites in rat plasma were speculated. In addition, the metabolic profile of GZJGGT was portrayed to understand interrelationship between metabolites.

两性霉素B阴道用纳米泡沫剂的制备及评价

目的制备两性霉素B阴道用纳米泡沫剂并进行基本理化性质和体内药效学评价。方法采用单因素法,分别优化处方中的蛋黄磷脂用量和起泡剂参数,制备两性霉素B纳米泡沫剂;进一步考察制剂的药物粒径、泡沫形态、发泡性能等基本理化性质;构建白假丝酵母菌阴道炎小鼠模型,评价药物对阴道炎症的治疗效果。结果两性霉素B纳米泡沫剂的优化处方中需在5mg·m L^-1的药物量中加入60 mg·m L^-1的蛋黄磷脂和30 mg·m L^-1的烷基糖苷APG0810,制剂的药物粒径约240 nm,微泡沫直径约200~400μm,泡沫半衰期约为43. 5 min,对小鼠阴道炎症感染有显著治疗效果。结论采用磷脂纳米粒和起泡剂制备的两性霉素B纳米泡沫剂基本理化性质和体内治疗效果良好,有望成为具有潜力的治疗外阴阴道白色念珠菌感染的药物新剂型。

十八种清热中药特征性挥发性成分分析

目的:采用顶空固相微萃取-气相色谱-质谱法(HS-SPME-GC-MS)探究18种清热中药特征性挥发性成分。方法:采用HS-SPME萃取药材粉末样品,结合GC-MS对挥发性成分进行定性和定量分析。GC进样口温度为250℃,程序升温,以高纯氦气为载气,柱流量1.0 mL·min^-1,不分流进样,溶剂延时3 min。MS条件为电子轰击离子源,电子轰击能量70 eV,离子源温度230℃,四极杆温度150℃,扫描范围m/z 29~370。将质谱数据进行谱库NIST2013检索,初步鉴定各中药材的挥发性成分,采用面积归一法计算各组分相对含量,并通过主成分分析(PCA)方法进行数据分析,探讨清热类中药材的挥发性成分特征。结果:在18种清热药中共检测到了328种挥发性化合物,主要包括烷烃类、不饱和烃类、醇类、醛类、酮类、酯类、呋喃等。不同清热中药的挥发性成分数量和相对含量差异较大。主成分分析表明,18种清热中药存在一些特征性挥发成分,如左旋樟脑、香榧醇、氧化石竹烯、蓝桉醇和优葛缕酮等。结论:清热类中药中含有较为丰富的挥发性成分,既有形成药材特有香气的主要贡献者,又有发挥药效作用的主要活性物质。