基于网络药理学和实验验证的甘麦大枣汤抗抑郁的物质基础及作用机制研究

目的：采用UPLC-Q-TOF-MS/MS技术分析、鉴定甘麦大枣汤的主要化学成分,并在此基础上通过网络药理学及动物实验进一步对甘麦大枣汤抗抑郁的作用机制进行探讨。方法：根据采集到的质谱数据,通过PubChem数据库结合相关参考文献进行化学成分的鉴定。将鉴定出的化学成分输入SwissADME数据库,根据Pharmacokinetics、Druglikeness进行筛选。利用SuperPred和SwissTargetPrediction数据库预测筛选成分的相关靶点,同时在GeneCards、DrugBank等数据库搜索抑郁症相关疾病靶点。利用STRING数据库构建“成分-靶点”及PPI蛋白互作网络,筛选药效作用的核心靶点。采用Metascape数据库进行GO功能富集和KEGG通路富集分析。结果：共分析鉴定了95个化合物,包括黄酮类、萜类、有机酸类、氨基酸类以及其他类。进一步筛选了12个关键活性成分,40个活性成分与疾病交集靶点,通过网络拓扑分析获得TNF、SLC6A3、MAOB等16个核心靶点;富集分析发现甘麦大枣汤抗抑郁作用通路有神经营养相关通路、内分泌相关通路、炎症免疫相关通路等;动物...     

基于外翻肠囊法研究乌蕨醇提物的肠吸收特性

目的 研究乌蕨醇提物在肠道中的吸收特性。方法 采用大鼠外翻肠囊实验模型,收集高、中、低质量浓度乌蕨提取物给药后不同时间的肠囊液;采用HPLC检测肠囊液样品中原儿茶酸、原儿茶醛、牡荆苷3种化学成分含量,计算吸收动力学参数（Q、Ka）,考察各成分肠吸收特征。结果 原儿茶酸、原儿茶醛、牡荆苷3种成分在乌蕨醇提物中能被检测出,但在其肠吸收液中未被检测到。结论 在本研究实验条件下,肠道对乌蕨中原儿茶酸、原儿茶醛、牡荆苷3种指标性成分未有吸收,具体原因还有待实验进一步探究。     

防风止痛功效物质组特征的计算机模拟研究

目的:从分子层面研究防风止痛功效物质组特征,为其临床治疗痹证提供依据。方法:从《中药原植物化学成分手册》和有关防风化学成分的3篇文献,检索防风的化学成分,构建防风的分子数据集;以p38、肿瘤坏死因子α(TNF-α)、诱导型一氧化氮合酶(i NOS)和磷酸二酯酶4A(PDE-4A)为止痛的靶点,借助分子对接技术,从中辨识防风止痛功效物质组;从治疗靶数据库中检索p38、TNF-α、i NOS和PDE-4A的药物/类药分子,比较其和防风止痛功效物质组的化学空间和化合物-靶点作用网络特征,探索防风止痛功效物质组的特征。结果:筛选出防风止痛的药效物质有49个成分,主要为苷类、黄酮类、香豆素类、有机酸等化合物。其在化学空间具有离散的分布,且大部分化合物与药物/类药分子具有相近的化学空间;在化合物-靶点作用网络中,防风化合物和药物/类药分子的平均靶点数分别为1.20和1.05,平均每个靶点分别与12.25和5.50个化合物相关联;防风止痛功效物质组中化合物和治疗靶数据库中药物/类药分子能作用于2个或2个以上靶点的化合物数目分别为8和1。结论:计算机模拟直观显示了防风功效物质组的止痛作用,相对于药物/类药分子,其功效物质组具有较好的多靶点性质,是发现混杂药物的重要来源。     

乌蕨抗炎活性部位研究

目的:比较乌蕨不同浓度乙醇洗脱物的抗炎活性。方法:将乌蕨不同浓度乙醇洗脱物作用于小鼠巨噬细胞RAW264.7,MTT法测定细胞活力;乌蕨醇洗脱物作用于LPS诱导的RAW264.7细胞炎症模型,通过MTT法判断乌蕨醇洗脱物对细胞炎症的影响。结果:在乌蕨(水、30%乙醇、50%乙醇、70%乙醇、95%乙醇)洗脱物作用下,RAW264.7细胞均有较好的存活率;乌蕨(水、30%乙醇、50%乙醇、70%乙醇、95%乙醇)洗脱物对LPS诱导的RAW264.7细胞炎症模型均有保护作用,且乌蕨(50%、70%、95%)乙醇洗脱物具有较强的保护作用。结论:乌蕨(50%、70%、95%)乙醇洗脱物具有显著的抗炎活性,这可为后期开发抗炎单体成分提供依据。     

乌蕨抗炎活性部位的研究

目的 比较乌蕨不同浓度乙醇洗脱物的抗炎活性。方法 乌蕨不同浓度乙醇洗脱物作用于小鼠巨噬细胞RAW264.7,MTT法测定细胞活力;乌蕨醇洗脱物作用于LPS诱导的RAW264.7细胞炎症模型,通过MTT法判断乌蕨醇洗脱物对细胞炎症的影响。结果 在乌蕨(水、30%乙醇、50%乙醇、70%乙醇、95%乙醇)洗脱物作用下,RAW264.7细胞均有较好的存活率;对LPS诱导的RAW264.7细胞炎症模型,均有保护作用,且乌蕨(50%、70%、95%)乙醇洗脱物具有较强的保护作用。结论 乌蕨(50%、70%、90%)乙醇洗脱物具有显著的抗炎活性,为后期开发抗炎单体成分提供依据。     

乌蕨的化学成分、药理作用及质量标准研究进展

<正>乌蕨[Stenoloma chusanum(L.)Ching]又名小叶野鸡尾、细叶凤凰尾等,为多年生草本,系陵齿蕨科乌蕨属植物[1]。根据民间中草药的使用经验,乌蕨具有清热解毒、抗炎、抗菌、抗肿瘤、护肝等作用,主治感冒发热、咽喉炎、毒伤等[2～3]。近十年来,国内外对乌蕨有效成分及药理作用的研究仍然较少,从乌蕨中分离得到的化学成分也比较简单;药理、毒理作用方面的研究大多集中在提取物上,对活性化学成分的研究很少,但近两年对乌蕨抗炎解毒作用的研究较为突出。本文详述了乌蕨的抗氧化、抗菌、抗酪氨     

基于小鼠腹腔毛细管通透性增高模型的三种蕨类的抗炎效果初步比较

目的:采用小鼠腹腔毛细管通透性增高模型对乌蕨、金粉蕨和骨碎补的抗炎效果进行初步比较。方法:将小鼠40只分为空白组、乌蕨组、金粉蕨组和骨碎补组各10只,用生理盐水、乌蕨、金粉蕨和骨碎补含生药1g/ml的水煎煮液分别进行灌胃,连续给药7 d,最后一次给药后,尾静脉注射0.2 ml 0.5%依文思蓝,立即腹腔注射1%醋酸0.2 ml,20 min后处死,再腹腔注射生理盐水6ml,反复轻柔腹部20次,吸出洗液,离心取上清液,测定吸光度,进行比较。结果:与空白组相比较,骨碎补组和乌蕨组有明显的抗毛细管通透性增高的作用,骨碎补组的效果最好,而金粉蕨组的效果不佳。结论:骨碎补和乌蕨水煎液都有一定的抗炎效果,骨碎补水煎液的抗炎效果最佳,而金粉蕨水煎液的抗炎效果不佳。     

基于网络药理学的准噶尔乌头炮制品抗卵巢癌作用机制研究

目的 运用网络药理学探讨准噶尔乌头炮制品抗卵巢癌的作用机制.方法 根据准噶尔乌头与乌头属植物具有化学亲缘性的特点,利用中药系统药理学数据库和分析平台(TCMSP)、中药分子机制的生物信息学分析工具(BATMAN-TCM)等数据库并结合文献收集、筛选准噶尔乌头及其炮制品、乌头属植物有效活性成分.利用Swiss、GeneCards、基因表达数据库(GEO)等数据库预测药物和疾病的靶点.采用Draw Venn Diagram软件识别准噶尔乌头炮制品抗卵巢癌关键靶点,在Cytoscape 3.6.1软件中构建"疾病-药物-成分-靶点"网络.利用String数据库和Cytoscape 3.6.1软件构建关键靶点蛋白互作网络图;利用DAVID和R软件对关键靶点进行富集分析.结果 得到准噶尔乌头炮制品抗卵巢癌的有效活性成分27个,关键靶点152个.准噶尔乌头碱、脱氧乌头碱、次乌头碱等可能是主要活性成分,其作用于PIK3CA、PIK3CB、PIK3CD、PIK3CG、表皮生长因子受体(EGFR)等靶点,参与癌症途径信号通路、PI3 K-Akt信号通路、血管内皮生长因子(VEGF)信号通路、缺氧诱导因子-1(HIF-1)信号通路等多条信号通路,发挥抗卵巢癌作用.结论 准噶尔乌头炮制品抗卵巢癌具有多成分、多靶点、多通路的特点,为开发具有民族特色的抗卵巢癌新药提供了思路.     

射干超临界CO2流体萃取脂溶性成分的GC-MS分析

目的：对射干超临界CO2流体萃取的脂溶性成分进行化学成分鉴定及含量分析。方法：采用超临界CO2流体萃取技术,获得中药射干中的脂溶性成分;运用气相色谱-质谱联用技术对其脂溶性成分进行分离鉴定,并采用峰面积归一化法计算各成分相对百分含量。结果：射干超临界CO2流体萃取脂溶性成分共分离鉴定出11种化合物,所鉴定的成分占总流出峰面积的79.57%。在鉴定组成分中,相对含量在1.00%以上的化合物有7种,含量占总鉴定化合物的98.68%;相对含量在0.05%以上的化合物有3种,含量占总鉴定化合物的1.28%;其余的化学成分较少,在总鉴定化合物中含量不到0.04%。结论：GC-MS法可用于射干超临界CO2流体萃取的脂溶性成分分析,为了解射干化学物质基础和进一步开发利用提供了有益参考依据。     

基于网络药理学探讨芍药甘草汤治疗慢性萎缩性胃炎的作用机制探讨

目的 采用网络药理学探究芍药甘草汤治疗慢性萎缩性胃炎（CAG）的作用机制。方法 利用中药系统药理学数据库与分析平台（TCMSP）数据库、文献挖掘整理芍药甘草汤化学成分;利用GeneCards、OMIM、DrugBank、TTD数据库收集CAG的相关靶点;利用Venn图筛选交集靶点,由Cytoscape软件构建“活性成分-疾病靶点”网络,由String数据库和Cytoscape软件构建蛋白质-蛋白质相互作用（PPI）网络;利用Metascape数据库进行GO功能富集分析和KEGG通路富集分析;利用AutoDock软件进行分子对接。结果 筛选出芍药甘草汤有效活性成分103个,与CAG相关靶点76个,重要活性成分包括槲皮素、山奈酚、柚皮素、甘草查尔酮A,核心靶点包括丝氨酸/苏氨酸蛋白激酶1(AKT1)、肿瘤抑制因子p53(TP53)、肿瘤坏死因子（TNF）等,KEGG通路主要富集于白细胞介素-17(IL-17)、TNF、缺氧诱导因子1(HIF-1)等通路。分子对接结果显示化合物与关键靶点有较好的结合能力。结论 芍药甘草汤可通过多成分、多靶点、多通路发挥对CAG的治疗作用。     

Guns and Knives in New Mexico: Patterns of Penetrating Trauma, 1978–1993

Objective: To identify patterns of nonfatal and fatal penetrating trauma among children and adults in New Mexico using ED and medical examiner data.
Methods: The authors retrospectively sampled in 5-year intervals all victims of penetrating trauma who presented to either the state Level-1 trauma center or the state medical examiner from a 16-year period (1978–1993). Rates of nonfatal and fatal firearm and stabbing injury were compared for children and adults.
Results: Rates of nonfatal injury were similar (firearm, 34.3 per 100,000 person-years; stabbing, 35.1). However, rates of fatal injury were significantly different (firearm, 21.9; stabbing, 2.7; relative risk: 8.2; 95% confidence interval: 5.4, 12.5). From 1978 to 1993, nonfatal injury rates increased for children (p = 0.0043) and adults (p < 0.0001), while fatal penetrating injury remained constant. The increase in nonfatal injury in children resulted from increased firearm injury rates. In adults, both stabbing and firearm nonfatal injury rates increased.
Conclusions: Nonfatal injury data suggest that nonfatal violence has increased; fatal injury data suggest that violent death rates have remained constant. Injury patterns vary by age, mechanism of trauma, and data source. These results suggest that ED and medical examiner data differ and that both are needed to guide injury prevention programs.     

Interprofessional approaches to creating safe,high quality health care

Three supplementary perspectives are presented arguing that interprofessional collaboration is both necessary and desirable. Nonetheless, there are often too many serious intra-professional barriers and obstacles to interprofessional collaboration to make it successful. Some of these barriers, it is argued and illustrated, are found in the multiple ways in which professional identity is tacitly acquired and embodied in the practitioners' habitual, everyday practice. The paper then explores ways in which reflection, especially Second order reflection, can help to elucidate and overcome these obstacles, as well as increasing professional adaptability and competence.     

Systematic Reviews Published in the January 2011 Issue of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly as a DVD and monthly online. The January 2011 issue (first quarterly DVD for 2011) contains 4515 complete reviews, 1985 protocols for reviews in production, and 13,521 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 641,000 randomized controlled trials, and 14,018 cited papers in the Cochrane methodology register. The health technology assessment database contains over 9300 citations. One hundred and seven new reviews have been published in the last 3 months, of which five have potential relevance for practitioners in pain and palliative medicine.     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

手转胎头术失败的原因与分娩结局临床分析

目的 探讨手转胎头术失败的原因与分娩结局.方法 选择2008年1月至2010年12月于我院住院分娩的持续性枕横位、枕后位产妇198例,根据行手转胎头术后结果分为成功组126例、失败组72例.比较两组分娩结局,对比分析失败原因.结果 失败组胎儿体质量≥3500 g的发生率[76.4％(55/72)]明显高于成功组[31.7％(40/126)],差异有统计学意义(x2=30.177,P=0.001)、失败组宫缩乏力发生率[58.3％(42/72)]高于成功组[38.1％ (48/126)],差异有统计学意义(x2=7.569,P=0.006)、失败组骨盆临界或轻度狭窄发生率[38.9％ (28/72)]高于成功组[23.8％(30/126)],差异有统计学意义(x2 =5.030,P=0.002)、失败组手转胎头时机不当(宫口开大＜6 cm、胎头位于坐骨棘上及宫口开大8～10 cm、胎头位于坐骨棘下≥2 cm)发生率[61.1％(44/72)]高于成功组[38.9％(49/126)],差异有统计学意义(x2=9.084,P=0.003).失败组母儿并发症(产后出血、产褥病率、胎儿窘迫、新生儿窒息)发生率高于成功组(x2 =9.586,P=0.002、x2=9.334,P=0.002、x2=5.910,P=0.015、x2=5.240,P=0.022)、失败组剖宫产发生率[72.2％(52/72)]明显高于成功组[34.1 ％(43/126),x2=26.641,P=0.001)].结论 手转胎头术能使难产变顺产,降低剖宫产率,减少母儿并发症,但须积极预防、处理导致手转胎头术失败的原因,对矫正失败后继续矫正及试产应慎重.