His-234是毛白杨对香豆酸 ∶ CoA连接酶的重要酶催化活性残基

对香豆酸∶CoA连接酶(4-coumarate: coenzyme A ligase,4CL)是植物苯丙烷类代谢途径中的一个重要的酶．4CL以肉桂酸衍生物(香豆酸、咖啡酸、阿魏酸等)、ATP和CoA为底物合成相应的酰基-CoA酯,这些酰基-CoA酯是一系列重要化合物(如木质素)的前体．4CL的酶催化反应分两步进行：第一步以肉桂酸衍生物和Mg² -ATP为底物合成酰基-AMP,第二步用CoA取代AMP,产生酰基-CoA酯,催化过程中酶的构象产生明显的变化．因为4CL在木质素的合成中所起的作用,这个酶是通过蛋白质工程方法改进林产品质量的重要靶标．我们通过X射线衍射技术,解析了毛白杨对香豆酸∶CoA连接酶1(Pt4CL1)与其中间产物对香豆酰-AMP的复合物晶体结构,与同家族成员结构比对,确定所获得的蛋白质结构为Pt4CL1催化第二步反应,即酰基-CoA酯合成的构象．结构分析表明：His-234残基在Pt4CL1的酶催化机理中起着多重作用,即通过侧链与AMP磷酸基团形成氢键,降低磷酸基团的负电荷,催化CoA的亲核取代反应;侧链可以采取两种不同的构象以调节CoA进入Pt4CL1的催化中心;His-234的侧链还可能夺取CoA巯基的质子,从而增强CoA的亲核反应活性．突变体酶活数据结果也显示His-234对Pt4CL1的活性非常重要,是Pt4CL1催化中心的活性残基．     

高寒草地狼毒与阴山扁蓿豆种群的空间格局

不同的格局类型和空间关联性可以反映出干扰状态下天然草地植物种群的资源环境适应对策.采用草地群落学调查与点格局分析方法,分析了祁连山北坡高寒草地优势种群更替过程中狼毒和阴山扁蓿豆种群的空间格局及其种间关联关系.结果表明:随着草地退化程度加剧,狼毒种群地上生物量、密度、植株高度持续增加,空间分布类型由聚集分布转变为非聚集分布,阴山扁蓿豆种群高度逐渐降低,种群密度和地上生物量先增大后减小,空间分布类型由均匀或聚集分布转为随机分布;狼毒和阴山扁蓿豆的空间关联性由显著正关联区间不断增大转为关联性不显著.草地退化过程中群落上层禾草西北针茅种群的衰退以及狼毒和阴山扁蓿豆的植株高度差异,导致了植物对光资源的非对称性竞争,使二者的资源分配策略发生了调整,并影响了空间分布格局和种间关联性.     

Inhibition of Fe-induced colon oxidative stress by lactobacilli in mice

Iron (Fe) can promote hydrogen peroxide (H₂O₂) and hydroxyl radical generation in the colonic surface and promote growth of Fe-dependent bacteria. Some Lactobacillus strains are resistant to oxygen free-radicals, allowing them to survive in a Fe-modulated mucosal environment and influence colon microbial ecology and redox state. Here, we investigated the capacity of lactobacilli with different antioxidant abilities to modify the bacterial profile and prevent oxidative stress in the colon of Fe-overloaded mice. Survival time of Lactobacillus rhamnosus LGG (LGG) in the presence of H₂O₂ and hydroxyl radical was significantly longer compared with the mid- and non-antioxidative strains, Lactobacillus paracasei Fn032 and Lactobacillus plantarum Fn001, respectively. Different Lactobacillus strains are specific in free-radical scavenging activities of their cell-free extracts, which increased to varying extent depending on strains when bacteria were exposed to simulated gastric and pancreatic juice. Fe-overloaded mice showed increased colonic luminal ferrous Fe content, Enterococcus and Escherichia coli concentrations, mucosal malondialdehyde and free-radicals, and decreased mucosal total antioxidative capacity and oxidative enzymatic activity. Translocation of endotoxin to the liver was also significantly increased (P < 0.05). Lactobacilli inhibited ferrous Fe accumulation, especially in LGG and Fn032. LGG significantly inhibited the increase of colonic mucosal free-radicals and malondialdehyde content (P < 0.05). Fn032 only inhibited malondialdehyde (P < 0.05). LGG and Fn032 significantly inhibited increases in colonic Enterococcus (P < 0.05). Fn001 showed no significant antioxidative ability in vivo. The difference of these effects in vivo were well agreed with scavenging activities against reactive oxygen species (ROS) of simulated gastrointestinals fluid pretreated cells in vitro. In conclusion, ROS scavenging activities was essential for Lactobacillus to prevent oxidative stress in vivo and inhibition of ROS-producing bacterial growth and mucosal barrier injury.     

中国橐吾属(菊科-千里光族)的分类学研究(二)：植夫橐吾的名实订正

通过文献和标本考证,发现《中国植物志》第77卷第2分册和《Flora of China》第20~21卷中均误将黑穗橐吾(Ligularia melanothyrsa Hand.-Mazz.)鉴定为植夫橐吾(L. fangiana Hand.-Mazz.),而真正的植夫橐吾应处理为川鄂橐吾[L. wilsoniana (Hemsl.) Greenm.]的异名。     

凝结芽孢杆菌活菌片预防先兆流产保胎妇女胃肠功能紊乱的临床观察

目的观察凝结芽孢杆菌活菌片（商品名：爽舒宝）预防先兆流产保胎妇女胃肠功能紊乱的临床疗效。方法将60例先兆流产保胎妇女随机分为爽舒宝预防组和对照组,预防组30例,对照组30例,两组均给予常规服用保胎药物,出现顽固性便秘后用开塞露通便,其中预防组在此基础上同时口服凝结芽孢杆菌活菌片首次2. 1 g,以后1.05 g/次,3次/d,温水送服,疗程2-4周。观察保胎期间孕妇胃肠功能紊乱情况和使用开塞露的通便次数。结果预防组患者胃肠功能紊乱的发生率显著低于对照组,差异有统计学意义（P〈0.05 ）。结论凝结芽孢杆菌活菌片预防先兆流产保胎妇女胃肠功能紊乱疗效显著,值得临床推广。     

耶氏肺孢子菌与宿主免疫防御相互作用

肺孢子菌肺炎(Pneumocystis pneumonia,PCP)是由酵母样真菌耶氏肺孢子菌(Pneumocystis jirovecii,Pj)引起的肺炎,是免疫缺陷患者重要的致死原因。Pj一般不导致系统性感染,仅在肺部繁殖,引发严重损害肺换气功能的间质性肺炎。Pj通过主要表面糖蛋白(major surface glycoprotein,MSG)的抗原转换,逃避宿主免疫系统清除,而宿主利用dectin-1识别β-(1,3)-D-葡聚糖(beta-1,3-D-glucan,BG)、甘露糖受体识别MSG,启动天然免疫反应,继而CD4+T细胞聚集活化,调控细胞免疫和体液免疫。分泌干扰素γ的细胞毒型CD8+Tc1细胞有助于控制Pj感染,特异性抗体有助于调理加强吞噬细胞清除Pj,而聚集的中性粒细胞和非Tc1CD8+T细胞与肺损伤有关。血浆BG水平可以辅助诊断PCP,而支气管肺泡灌洗液中白介素8的水平与肺损伤及死亡预后有关。     

舒芬太尼、曲马多用于小儿鼾症手术苏醒期躁动的临床研究

目的：探究舒芬太尼与曲马多对用于小儿鼾症手术苏醒期躁动的作用与影响。方法：60例ASAI或II级扁桃体肥大或腺样体肥大的鼾症手术患儿,年龄6-14岁,无呼吸系统,循环系统等疾病,一般状态良好。随机分为舒芬太尼组（s组）和曲马多（T组）,每组各30例。常规监测各项生命体征。于手术结束前20分钟（min）,S组缓慢静脉输入0．15μg／kg舒芬太尼,T组静脉输入1．2mg／kg曲马多。观察各组的：平均动脉压 （MAP）、心率（HR）、血氧饱和度（SpO2）,进行各组的镇静评分（RSS）、躁动评分（RS）、镇痛评分（VRS）、意识状态评分（OAAS）。记录拔管前（T0）、拔管时（T1）、拔管后5min（T2）、拔管后10min（T3）、拔管后20min（T4）各时间点各参数的变化。记录各组的恶心呕吐、呼吸抑制、烦躁等的发生率。结果：SpO2各组间无显著差异。MAP,HR在各时间点的变化T组大于S组,P〈0．05,有显著差异。T组在RS,RSS,VRS评分与S组有显著差异,P〈0．05。结论：0．15μg／kg的舒芬太尼在小儿鼾症手术的苏醒期可以维持稳定的血流动力学,副作用小,镇痛效果良好,可以有效减少小儿苏醒期的躁动。     

帕罗西汀血药浓度检测方法研究进展

帕罗西汀为5-羟色胺（5-HT）阻断药,具有起效快、疗效好、不良反应低等优点,为目前临床上常用抗抑郁症药物。帕罗西汀疗效和不良反应与该药血药浓度密切相关,并且个体差异性较大。因此,研究开发专一性强、灵敏度高的血药浓度检测方法十分必要,具有重要的临床和实践意义。本文综述帕罗西汀血药浓度检测时血样的前处理方法,同时对高效液相色谱法和气相色谱法检测帕罗西汀血药浓度进展进行论述,为该领域的临床合理用药和相关领域的研究提供借鉴。     

我国现行医疗卫生政策的相关问题分析

医疗卫生是构建和谐社会的重要因素之一,也是关乎百姓切身利益的重大问题之一,近年来,医疗体制的不断改革,医疗卫生的相关政策的不断出台,已经大大地改善了我国广大人民群众的“看病难,看病贵”等问题,增加了医保的覆盖人群,减轻了城市低收入人群及农村的医疗负担,但是,我们仍面临着巨大的挑战,新的问题也不断涌现,医疗卫生政策不适应现在的医疗需求发展、经济发展不均衡、不同层次群众的医疗需求有差异等,都是医疗卫生改革中面临的问题,医疗改革的不断推进势在必行。我国的医疗保障制度覆盖率已经达到95％,但是,现行的医疗保障制度的还不能从根本上解决人民群众的“就医难,治病贵”的问题,其他医疗保险不能与现行的医疗保障制度相适应,从而,影响了我国整体的医疗水平的提高。     

Patients with Nipple-Areola Paget’s Disease and Underlying Invasive Breast Carcinoma Have Very Poor Survival: A Matched Cohort Study

Paget’s disease (PD) of the breast is a rare disease. The survival rate of PD was reported to depend on the characteristics of the underlying carcinoma. This study aimed to investigate the characteristics and survival rate of PD patients with underlying invasive breast carcinoma (IBC). Fifty-two patients were diagnosed with PD and an associated IBC from 2001 to 2005 in Fudan University Shanghai Cancer Center. Twenty-four (46.2%) had no clinical manifestation of PD and were diagnosed unexpectedly by a histologic examination. The 52 patients were all recruited in this study as the PD group. They tended to have greater chances of lymph node involvement (53.8% vs. 35.7%), lower hormone receptor expression (34.6% vs. 69.7%), higher human epidermal growth factor receptor 2 (HER2) expression (76.9% vs. 21.3%), and worse survival (5-year relapse-free survival (RFS) 52.2% vs. 86.7%, P<0.01; breast cancer-specific overall survival (OS) 62.1% vs. 91.8%, P<0.01) when compared with patients diagnosed with IBC. A matched study was then performed to investigate whether the poor survival of patients in the PD group was due to the unfavorable prognosis of the underlying IBC. One hundred and fifty-six (3∶1 ratio of controls to PD patients) patients diagnosed with IBC only were recruited into the matched group. The match was conducted according to four variables: dimension of IBC, lymph node status, hormone receptor status and HER2 status. The 5-year RFS (52.2% vs. 81.4%, P<0.01) and OS (62.1% vs. 85.9%, P<0.01) were both lower for patients in the PD group than those in the matched group. Patients with PD and underlying IBC had poor survival. Their survival was worse than that of patients with IBC of similar stage and characteristics. For patients with no clinical PD manifestation who were histologically diagnosed as PD, survival might be worse compared to patients with clinically diagnosed PD.