苯并二氢吡喃腙衍生物的合成及其初步药理活性

为进一步筛选活性更强、副作用更小的抗绝经后骨质疏松症药物 ,在综合考察雷洛昔芬和异丙氧基异黄酮的基础上 ,设计合成一系列苯并二氢吡喃腙化合物 .化合物的结构均经波谱鉴定 ,并通过研究其对幼年小鼠子宫增重和血碱性磷酸酶活性的影响 ,初步考察化合物的药理活性 .结果表明 ,XY990 2具有较弱的雌激素受体激动作用和一定的雌激素受体拮抗作用 ,并有助于成骨细胞增殖 ,对治疗骨质疏松症是有利的 .     

诸子蜂起 百家争鸣(二)——英国中医药的现状与展望

中医药面临着"诸子蜂起,百家争鸣"的国际医药保健时代,处于有机会又有曲折的局面.故从1)中医药在国外的发展.2)中医药在英国的现状.3)英国推动中医教育的经验.4)英国偶尔发生的中医事故影响中医界整体形象.5)英国中医的立法过程与国际影响.6)建立中医药企业文化和品牌标准--英国的经验.7)中医药发展展望.8)中医药的宣传和外交等方面论述.指出在"诸子蜂起,百家争鸣"的新"全球医学"时代,中医界人士需团结一致,既往开来,为把中医真正纳入世界主流医学,并能恩泽于全人类而全心全力、努力不懈!     

同病异证H22肝癌小鼠肿瘤组织细胞凋亡通路基因差异表达的特征

目的:观察昆明种H22肝癌小鼠邪毒壅盛证与气虚证肿瘤组织细胞凋亡通路基因表达特征,探讨中医同病异证发生的物质基础。方法:采用小鼠计量化辨证方法,筛选出瘤早期邪毒壅盛证与气虚证同病异证H22肝癌小鼠,采用Affymetrix GeneChip Mouse Exon 1.0 ST Array检测肿瘤组织细胞凋亡通路相关基因表达的特征。结果:依据KEGG数据库细胞凋亡通路,筛选出芯片数据中匹配的33个基因,发现(1)TNF-α和IL-1依赖的细胞凋亡信号通路总体上不利于邪毒壅盛证小鼠肿瘤细胞的凋亡;(2)IL-3依赖的细胞凋亡信号通路总体上反似有利于邪毒壅盛证小鼠肿瘤细胞凋亡;而(3)线粒体介导的细胞凋亡信号通路,邪毒壅盛证小鼠一致表达下调,提示不利于其细胞凋亡。结论:邪毒壅盛肝癌小鼠肿瘤细胞恶性增殖程度高,可能与线粒体介导的细胞凋亡信号通路系列相关基因表达轻度抑制有关。     

大黄清胃冲剂活性成分提取工艺的均匀设计优化选择

目的 探讨大黄清胃冲剂活性成分提取分离的优化工艺条件。方法 以游离蒽醌提取率为定量指标,通过４种生长黄煎煮方法的初步筛选,确定浸渍溶剂、浸渍时间、回流溶剂及回流时间为考察因素,并为Ｕ９（９＾６）均匀表设计试验。结果 大黄提取优化工艺条件为７０％乙醇浸润１４ｈ和回流提取８０ｍｉｎ。结论 工艺条件可以用于大黄清胃冲剂的生产制备。     

可逆性后部白质脑病综合征患者临床表现与磁共振影像学特点分析

目的分析可逆性后部白质脑病综合征(RPLS)患者的临床表现及磁共振(MRI)影像学特点。方法回顾性分析115例RPLS患者的临床及影像学资料。结果 115例RPLS患者表现为血压升高(89.56%)、痫性发作(74.78%)、头痛(59.13%)、视觉障碍(32.17%)、神经系统体征(20.00%)和意识改变(15.65%),其中101例(87.83%)患者头颅MRI异常,累及枕叶(71.29%)、顶叶(59.40%)、额叶(49.50%)、颞叶(38.26%)、侧室脑旁(1.98%)、脑干(3.96%)、小脑(3.96%)、皮质(3.96%)、丘脑(0.99%)、基底节区(0.99%),病灶为等或低T1WI信号,高T2WI信号,等或低DWI信号,高ADC及FLAIR信号。治疗后随访3～60月,81例预后良好,21例预后不良,5例死亡。预后不良组头痛发生率、住院期间m RS评分≥3分及并发症比例高于预后良好组(P<0.05)。结论 RPLS的MRI表现具有特征性,结合临床表现可作出正确判断,及时治疗,改善预后。     

强心冲剂对充血性心力哀竭家兔模型心钠素、血管紧张素Ⅱ的影响

目的观察强心冲剂干预后充血性心力衰竭(CHF)家兔模型心钠素(ANP)、血管紧张素Ⅱ(AngⅡ)的变化,探讨强心冲剂对神经内分泌活性的影响.方法将40只家兔随机分为4组,假手术组、模型组、地高辛组、强心冲剂组,每组10只.采用腹主动脉缩窄术建立家兔CHF模型,予强心冲剂和地高辛灌胃,检测并比较ANP、AngⅡ的活性.结果CHF家兔模型ANP、AngⅡ活性显著升高,神经内分泌激素释放失衡,强心冲剂干预后,可以纠正其失衡状态,明显降低ANP、AngⅡ水平.结论强心冲剂能显著纠正神经内分泌激素释放失衡状态,改善神经内分泌激素的激活,可以防止CHF的进一步恶化.     

五味沙棘散对卵清蛋白诱导的过敏性支气管哮喘大鼠的保护作用及机制

目的 探究五味沙棘散对卵清蛋白（ovalbumin,OVA）诱导的过敏性哮喘大鼠的保护作用及机制。方法 SD大鼠随机分为对照组、模型组、地塞米松（0.5 mg/kg）组和五味沙棘散（0.5、2.0 g/kg）组,建立OVA诱导的大鼠早期支气管哮喘模型,苏木素-伊红（HE）和Masson染色观察支气管病理情况及纤维化程度;免疫组化检测支气管间隙连接蛋白43（connexin 43,Cx43）的表达和分布;ELISA检测血清中免疫球蛋白E（immunoglobulin E,IgE）和白细胞介素-13（interleukin-13,IL-13）水平;亚甲基蓝法和WSP-1荧光探针法测定血清中硫化氢（hydrogen sulfide,H₂S）水平。建立CdCl₂诱导的支气管上皮BEAS-2B细胞损伤模型,MTT法检测细胞活性;Hoechest 33342染色法观察细胞核形态变化;MitoSOX染色检测细胞线粒体活性氧（mitochondrial reactive oxygen species,mtROS）水平;Western blotting检测半胱氨酸天冬氨酸蛋白酶-3（cystein-asparate protease-3,Caspase-3）、核因子红细胞系2相关因子（nuclear factor erythroid 2-related factor,Nrf2）和Kelch样ECH关联蛋白1（Kelch like ECH associated protein 1,Keap1）蛋白表达。结果 五味沙棘散能够减少支气管黏膜上皮细胞脱落和黏液分泌（P＜0.001）,降低胶原纤维的沉积和Cx43的表达及分布（P＜0.05、0.01、0.001）,降低血清中IgE、IL-13水平（P＜0.05）,升高血清中H₂S水平（P＜0.05、0.01）。五味沙棘散含药血清呈剂量相关性地抑制CdCl₂诱导的BEAS-2B细胞凋亡及mtROS水平（P＜0.01、0.001）,上调Caspase-3和Nrf2蛋白表达（P＜0.05、0.01）,下调Keap1蛋白表达（P＜0.01）。结论 五味沙棘散对OVA诱导的哮喘大鼠和CdCl₂诱导的支气管上皮细胞凋亡均具有保护作用,其机制可能与调控Nrf2/Keap1信号通路有关。     

Avian IRF1 and IRF7 Play Overlapping and Distinct Roles in Regulating IFN-Dependent and -Independent Antiviral Responses to Duck Tembusu Virus Infection

Avian interferon regulatory factors 1 and 7 (IRF1 and IRF7) play important roles in the host’s innate immunity against viral infection. Our previous study revealed that duck tembusu virus (DTMUV) infection of chicken fibroblasts (DF1) and duck embryo fibroblasts (DEFs) induced the expression of a variety of IFN-stimulated genes (ISGs), including VIPERIN, IFIT5, CMPK2, IRF1, and IRF7. IRF1 was further shown to play a significant role in regulating the up-expression of VIPERIN, IFIT5, and CMPK2 and inhibiting DTMUV replication. In this study, we confirm, through overexpression and knockout approaches, that both IRF1 and IRF7 inhibit DTMUV replication, mainly via regulation of type I IFN expression, as well as the induction of IRF1, VIPERIN, IFIT5, CMPK2, and MX1. In addition, IRF1 directly promoted the expression of VIPERIN and CMPK2 in an IFN-independent manner when IRF7 and type I IFN signaling were undermined. We also found that non-structural protein 2B (NS2B) of DTMUV was able to inhibit the induction of IFN-β mRNA triggered by Newcastle disease virus (NDV) infection or poly(I:C) treatment, revealing a strategy employed by DTMUV to evade host’s immunosurveillance. This study demonstrates that avian IRF7 and IRF1 play distinct roles in the regulation of type I IFN response during DTMUV infection.     

A new isoquinolinone derivative with noble vasorelaxation activity

The pharmacological effects of BDPBI (7-bromo-1,4-dihydro-2-phenyl-4,4-bis(4-pyridinylmethyl)2H-isoquinolin-3-one dihydrochloride) were tested on isolated endothelium-containing or denuded aorta of the guinea pig. BDPBI with the formula C(27)H(24)BrCl(2)N(3)O was synthesized starting with 3-isochromanone. In the endothelium-containing preparations of the aortic rings, phenylephrine (PHE; 10 micromol/l) elicited contracture and acetylcholine (ACh; 10 micromol/l) or BDPBI (0.01-10 micromol/l) elicited relaxation effects on the PHE-precontracted preparations. The BDPBI-elicited effect on the PHE-precontracted aortic rings was not altered in the presence of adrenergic blockers (propranolol or yohimbine; 1 micromol/l) or pretreated preparations with aspirin, indomethacin (10 micromol/l) or L-NAME (1 mmol/l). However, the relaxation effects of BDPBI were blocked if the preparations were pretreated with diphenhydramine (10 micromol/l) or chloropheniramine maleate (10 micromol/l). In contrast to lower concentrations of atropine (1 micromol/l), higher concentrations of atropine (30 micromol/l) did block the effects of BDPBI on the PHE-precontracted aortic rings. HTMT dimaleate (0.01-10 micromol/l), a histamine H(1) receptor agonist, also elicited relaxation effects on the PHE-precontracted preparation, and the effects were blocked if the preparations were pretreated with diphenhydramine or chloropheniramine maleate. On isolated denuded aorta of the guinea pig, BDPBI did not elicit relaxation effects on the PHE-precontracted aortic rings. These results demonstrated that the vasorelaxation effect of BDPBI on PHE-precontracted aortic rings is partly dependent on the activation of a histaminergic receptor from the vascular endothelium. We suggested that BDPBI would be an effective vasorelaxant for cardiovascular systems.