半夏厚朴汤抗抑郁作用——改善脑内氧化应激水平

目的：通过观察半夏厚朴汤对慢性应激抑郁模型大鼠行为学和氧化应激的影响,研究半夏厚朴汤抗抑郁的机制。方法：采用强迫游泳实验、开野实验、糖水偏好实验,研究半夏厚朴汤对慢性应激抑郁模型大鼠的抗抑郁作用,并通过UPLC-T-QMS系统检测其大鼠脑内单胺类神经递质的含量,部分动物取其海马制备海马匀浆,Western blotting检测超氧化物歧化酶（SOD）、丙二醛（MDA）。结果：与空白组相比,模型组大鼠糖水消耗量显著下降,强迫游泳不动时间显著延长,交叉次数、直立次数显著减少;海马内去甲肾上腺素、5-羟色胺含量显著降低。与模型组相比,半夏厚朴汤组糖水消耗量显著升高,强迫游泳不动时间显著缩短。半夏厚朴汤组显著增加大鼠脑内去甲肾上腺素和5-羟色胺含量。Western blotting检测结果显示,与模型组比较,半夏厚朴汤组显著升高SOD水平,显著降低MDA水平。结论：半夏厚朴汤能明显改善慢性应激所致的大鼠抑郁行为,其机制可能与上调海马内去甲肾上腺素、5-羟色胺水平,增强机体抗氧化应激能力有关。     

鹧鸪花果实trichilin-type柠檬苦素化学成分研究

通过常压硅胶、凝胶、反相柱色谱和高压反相柱色谱等色谱技术对楝科植物鹧鸪花果实的化学成分进行研究,从鹧鸪花(Trichilia connaroides)果实乙醇提取物中分离获得4个trichilin-type柠檬苦素,包括2个新化合物和2个已知化合物3α-deacetylamoorastatin (3)和mesendanins K (4)。通过综合运用HR-ESI-MS、1H NMR、13C NMR、HSQC、HMBC和ROESY等多种光谱分析方法确定了新化合物1、2的平面结构和相对构型。通过对分离获得的化合物进行肿瘤细胞毒活性研究,结果表明新化合物1、2和已知化合物4对宫颈癌细胞(HeLa)具有微弱的细胞毒活性。     

珠芽蓼止泻颗粒联合布拉氏酵母菌散治疗小儿功能性腹泻的临床研究

目的 建立枳实薤白桂枝汤HPLC指纹图谱分析方法和复方中10种指标成分（辛弗林、槲皮素、桂皮酸、厚朴酚、柚皮苷、腺苷、香豆素、橙皮苷、和厚朴酚、新橙皮苷）含量测定方法,开展相关评价分析。方法 采用HPLC法建立枳实薤白桂枝汤指纹图谱,开展相似度评价研究;测定复方中10个指标成分,分析复方中药材不同配伍对其量的变化影响;采用聚类分析等化学计量学方法,对获取相关数据进行分析,评价枳实薤白桂枝汤的质量控制相关指标的影响和价值。结果 10批样品的相似度在0.376～0.990,部分批次相似度大于0.9（5批）,说明10批样品相似度差异较大。10批样品中S1～S3、S5、S6、S8、S10为一组,S4、S9为一组,S7单独为一组。共标定了30个特征峰,经主成分分析,主成分1～6是影响药材样品质量评价的主要因子;30个特征峰中对样品分组起关键作用的成分为21（新橙皮苷）、26、29（和厚朴酚）、3、23、17、30（厚朴酚）、5、24（香豆素）、28和7。含量测定结果显示,除槲皮素外,其余9种成分在测定的质量浓度范围内线性关系、精密度、稳定性和重复性良好;不同配伍会对药材中相关成分产生增加或抑制溶出的作用。结论 所建立的HPLC方法可用于同时测定枳实薤白桂枝汤中10种化学成分的含量,该方法高效、准确、重复性好,可用于枳实薤白桂枝汤的质量控制和评价。     

自噬信号通路与心血管疾病的研究进展

自噬是指自噬溶酶体将自身的细胞器分解并回收利用的一种细胞降解过程,广泛存在于机体组织中。在正常情况下,自噬活动水平在维持细胞的稳态和功能中发挥着重要作用;过量或不足的自噬通量水平都可能导致疾病的发生。在本文中,我们讨论了自噬的概念分类以及自噬信号通路的研究进展,并阐述了自噬对心血管疾病的影响。     

Early life exposure to extended general anesthesia with isoflurane and nitrous oxide reduces responsivity on a cognitive test battery in the nonhuman primate

Despite the widespread use of general anesthesia, a growing body of research suggests that anesthesia exposure early in life may be associated with acute neurotoxicity and lasting behavioral changes. To better evaluate the risk posed by early life anesthesia on cognitive development, infant rhesus monkeys were exposed to an anesthesia regimen previously shown to be neurotoxic and their cognitive development was subsequently measured using a translational operant test battery. On postnatal day 5 or 6, animals were exposed to 8 h of isoflurane (n = 6, 1% isoflurane in a vehicle gas of 70% nitrous oxide and 30% oxygen) or a control condition (n = 8). Starting at 7 months of age, the monkeys were continuously trained and assessed on the NCTR Operant Test Battery (OTB). The OTB consists of cognitive tests which also exist in near identical forms for use in rats and humans, and includes tests of learning, memory, color discrimination, and motivation. Monkeys previously exposed to anesthesia showed a clear decrease in responding in a measure of motivation, as well as a lower response rate in a learning task. These data further support the hypothesis that prolonged anesthesia early in life may increase the risk of developing cognitive impairments later in life.     

Formation of Hemihydrate Crystal form Overcomes Milling Issue Induced by Exposed Functional Groups on Cleavage Plane for a Y5 Receptor Antagonist of Neuropeptide Y

This study aimed to investigate the crystal forms of an originally designed Y5 receptor antagonist of neuropeptide Y. Polymorphic screening was performed via solvent evaporation and slurry conversion using various solvents. The obtained crystal forms α, β, and γ were characterized by X-ray powder diffraction analysis. Thermal analysis determined that forms α, β, and γ were hemihydrate, metastable and stable forms, respectively; the hemihydrate and the stable forms were candidates. To arrange the particle size, forms α and γ were subjected to jet milling. However, form γ could not be milled because of powder stiction to the apparatus, whereas form α could be. To investigate this mechanism, single-crystal X-ray diffraction analysis was performed. The crystal structure of form γ was characterized by two-dimensional hydrogen bonding between neighboring molecules. This revealed that the functional groups forming hydrogen bonds were exposed on the cleavage plane of form γ. The three-dimensional hydrogen-bonding network with water stabilized the hemihydrate form, α. These results indicate that the hydrogen bondable groups exposed on the cleavage plane of form γ should result in stiction of the powder and adherence to the apparatus. It was concluded that crystal conversion is a method to overcome the milling issue.     

中药两面针的化学成分及细胞毒活性成分研究

采用硅胶、凝胶、RP-18中压柱色谱、HPLC等分离方法,结合NMR,MS等波谱技术,从中药两面针的甲醇提取物中分离鉴定了10个化合物,分别为zanthonitidine B(1)、cyclo-(Leu-Leu-Leu-Leu-Ile)(2)、6S-10-O-demethylbocconoline(3)、鹅掌楸碱(liriodenine,4)、异阔果芸香碱(isoplatydesmine,5)、5,5′-二甲氧基落叶松脂醇(5, 5′-dimethoxylariciresinol,6)、丁香树脂醇(syringaresinol,7)、表丁香脂素(episyringaresinol,8)、异紫花前胡内酯(marmesin,9)、丁香醛(syringaldehyde,10)。其中化合物1为新的生物碱类化合物,化合物2为首次从植物界发现的环五肽,化合物3为首次从花椒属植物中分离得到的生物碱。化合物3和4对人结肠癌细胞HT29、人非小细胞肺癌细胞A549和人乳腺癌细胞MDA-MB-231均具有一定的细胞毒活性,其IC50分别为27.37, 24.10, 33.58μmol·L-1和9.12, 6.05, 11.35μmol·L^-1。     

基于多数据平台探讨桂枝茯苓丸对乳腺癌的干预机制

目的 利用多数据平台与生物信息分析技术探讨桂枝茯苓丸对乳腺癌的干预机制,并通过细胞试验对分析结果进行验证。方法 从GEO数据库下载乳腺癌相关数据集,分析乳腺癌差异基因;从TCMSP数据库中筛选出桂枝茯苓丸的主要有效成分及作用靶基因;2组靶基因映射出桂枝茯苓丸治疗乳腺癌的关键靶基因。通过TCGA数据平台分析关键靶基因在乳腺癌中的表达,并通过TIMER、CPTAC Data Portal、Kaplan-Meier plotter、TISIDB、SangerBox等数据平台分析该表达与乳腺癌免疫微环境、免疫浸润水平、基因组异质性、免疫亚型和分子亚型以及不良预后的关系。通过Metascape分析平台对关键靶基因进行KEGG通路富集,寻找可能信号通路。最后采用血清药理学方法通过CCK-8试验、细胞划痕试验、Transwell小室试验及Westernblotting技术在体外对分析结果进行验证。结果 桂枝茯苓丸中有效成分42个,对应靶点185个,与GEO数据库映射得到与乳腺癌治疗相关的关键靶点14个,经与TCGA中乳腺癌差异基因比对,得到桂枝茯苓丸治疗乳腺癌的6个关键靶基因。这6个靶基因表达与乳腺...