融合基于案例教学法与二维四阶教学法的精髓,将基于案例教学法的二维四阶教学法引入到中医血液学的教学中,使学生更好地理解和掌握中医血液学的基础理论知识,提高学生的临床技能和临床诊疗思维,探索一种有效的临床教学模式.

目的:分析柴胡"推陈致新"作用的中医内涵,并运用网络药理学方法探讨柴胡干预肝纤维化的可能机制.方法:通过查阅文献分析柴胡"推陈致新"含义,并检索TCMSP、OMIM、GeneCards数据库,筛选柴胡干预肝纤维化的活性成分和作用靶点,在Cytoscape中构建"化合物-靶点-疾病"网络,STRING数据库中构建靶点蛋白互作网络,通过拓扑学分析筛选核心靶点.运用Autodock vina软件对核心靶点蛋白进行分子对接.基于R语言对作用靶点进行GO和KEGG富集分析.结果:筛选出146个柴胡干预肝纤维化的作用靶点,其中,AKT1、MAPK8、IL-6、MYC、EGF、CCND1等27个靶点为其核心靶点,分子对接结果显示,度值前10的核心靶点能与柴胡的主要活性成分形成较稳定的构象,具有良好的结合活性.GO和KEGG结果主要涉及炎症、氧化应激、细胞增殖与凋亡、肝再生等生物学过程及TLR、TNF、PI3K/Akt、MAPK等信号通路.结论:柴胡"推陈致新"作用蕴含再生理念,柴胡或通过槲皮素、山奈酚、异鼠李素等作用于AKT1、MAPK8/1、IL-6等核心靶点及TLR、TNF、PI3K/Akt、MAPK等信号通路,参与调节炎症反应、氧化应激、细胞增殖、肝再生等生物学过程,起到抑制肝纤维化的同时,促进肝细胞再生的作用.

目的:挖掘整理中药治疗免疫性血小板减少症的相关文献,为中药治疗免疫性血小板减少症提供治疗和科研思路.方法:分别在中国知网、万方数据知识服务平台、维普期刊资源整合服务平台进行高级检索,采用Bibexcel软件提取文献关键词,使用VOSviewer软件绘制关键词共现图谱.结果:从经典中药复方角度,中药治疗免疫性血小板减少症以益气养血、清热凉血为核心,注意和解少阳的应用,代表方剂有归脾汤、犀角地黄汤、茜根散、小柴胡汤等;从现代中药复方角度,以补益、凉血、活血为原则,但研究较为分散,出现频数较高的方剂有紫癜汤、生血散、益肾活血方等;从单味中药角度,以收敛止血和清热凉血为主导,核心药物有仙鹤草、水牛角、墨旱莲等.结论:中药复方治疗免疫性血小板减少症主要从补法、清法、和法入手,其中补法以健脾益气为主,清法需注意辨别热之虚实,和法以扶正达邪;单味中药治疗,需注意收敛止血和凉血止血中药的应用.

目的:从肝气虚证角度并通过网络药理学探讨黄芪-柴胡干预肝炎的作用机制.方法:检索中药系统药理学数据库与分析平台(TCMSP)等数据库,筛选黄芪-柴胡干预肝炎的活性成分和作用靶点.构建化合物-靶点-疾病网络和蛋白质-蛋白质相互作用(PPI)网络,进行拓扑学分析,筛选关键药效分子和核心靶点.对作用靶点进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析,并用Cytoscape软件构建化合物-靶点-通路网络.结果:黄芪-柴胡通过升补肝气治疗肝炎患者肝气虚证.经网络药理学分析,筛选出黄芪-柴胡14个关键药效分子,19个核心作用靶点与其干预肝炎密切相关.分子对接结果显示,度值前10的核心靶点能与黄芪-柴胡的关键活性成分形成较稳定的构象,具有良好的结合活性.GO和KE GG结果主要涉及炎症、氧化应激、细胞增殖等生物学过程.结论:黄芪-柴胡或通过槲皮素、山柰酚、芒柄花素等活性成分作用于Toll样受体、Th17细胞分化、Th1和Th2细胞分化、PI3K/AKT、MAPK、IL-17等信号通路,参与调节氧化应激反应、肝脏炎症反应、细胞增殖等生物学过程,发挥干预肝炎的作用.

目的 探究再障膏方对再生障碍性贫血小鼠免疫细胞、脾脏形态及功能的影响.方法 将SPF级BALB/c雌性小鼠随机分为空白组8只、模型组18只、中西医结合组10只、再障膏方组10只、环孢素组10只.除空白组外,其余组均连续灌胃5d白消安片悬液建立再生障碍性贫血模型.自实验第11天开始,模型组与空白组灌胃无菌注射用水0.1 mL,早晚各1次;再障膏方组早上灌胃820 mg/mL再障膏方溶液0.1 mL,晚上灌胃无菌注射用水0.1 mL;环孢素组早上灌胃无菌注射用水0.1 mL,晚上灌胃5 mg/mL环孢素溶液0.1 mL;中西医结合组早上灌胃820 mg/mL再障膏方溶液0.1 mL,晚上灌胃5 mg/mL环孢素溶液0.1 mL.各组均连续干预10 d后摘眼球取血,检测外周血细胞,采用流式细胞仪检测外周血Treg、Th17细胞占比;摘取脾脏,计算脾脏指数,HE染色观察脾脏形态.结果 模型组外周血中WBC、RBC、Hb、Plt及Treg细胞占比、Treg/Th17均明显低于空白组(P均<0.05),Th17细胞占比明显高于空白组(P<0.05);中西医结合组WBC、RBC、Hb、Plt、Treg细胞占比、Treg/Th17和再障膏方组Plt及环孢素组RBC、Plt均明显高于模型组(P均<0.05);中西医结合组Plt明显高于环孢素组(P<0.05),WBC、Plt均明显高于再障膏方组(P均<0.05).实验第11天和实验第21天,中西医结合组、再障膏方组、环孢素组小鼠体重比较差异均无统计学意义(P均>0.05),均明显低于空白组(P均<0.05);模型组小鼠脾脏指数明显低于空白组(P<0.05),中西医结合组、环孢素组脾脏指数明显高于模型组和再障膏方组(P均<0.05),再障膏方组与模型组比较差异无统计学意义(P>0.05).HE染色显示模型组小鼠红白髓界限消失,中西医结合组红白髓界基本可见,再障膏方组红白髓界限模糊,环孢素组红白髓界限隐约可见.结论 环孢素联合再障膏方较单用环孢素能更好地促进再生障碍性贫血小鼠血象恢复,改善Treg/Th17细胞比值异常及脾脏功能.

近年现代医学研究表明,肠-肝轴参与脂肪肝的发病机制.胡世平教授将肠-肝轴和中医肝病实脾理论相结合,探讨脂肪肝的中医发病机理与治疗,指出脂肪肝主要责之肝脾同病,以脾虚调节脂代谢失常为本,肠道菌群失衡属脾虚的微观表现,肠-肝轴或为肝脾同病的病理基础;肝病实脾理论指导脂肪肝治疗的核心在于调脾,其机理或通过调节肠-肝轴,促进恢复肠道菌群稳态和肝功能,以延缓、阻止疾病发展.

目的:验证健脾益气摄血方缓解ITP乏力症状与改善线粒体功能的相关性.方法:通过被动免疫造模法建立ITP小鼠模型,分为正常组、模型组、强的松组、健脾益气摄血(JPYQSX)中、高剂量组.通过光谱法检测小鼠脾脏组织活性氧含量;通过实时荧光定量PCR(qPCR)检测线粒体DNA相对拷贝数;通过免疫荧光法检测结肠ATP含量.结果:与正常组比较,模型组(P<0.01)、强的松组(P<0.05)、健脾益气摄血各剂量组(P<0.01)小鼠脾脏组织ROS含量增多,脾脏组织线粒体DNA相对拷贝数明显下调(P<0.01),结肠组织ATP含量明显下调(P<0.01);与模型组比较,强的松组、健脾益气摄血各剂量组小鼠脾脏组织ROS含量减少,脾脏组织线粒体DNA相对拷贝数比较无统计学意义(P>0.05),结肠组织ATP含量均显著升高(P<0.01).结论:健脾益气摄血方可通过改善线粒体功能来有效缓解ITP乏力症状.

目的 观察再障膏方联合环孢素对再生障碍性贫血模型小鼠脾脏叉头状转录因子3(forkhead box protein 3,FOXP3)、GATA结合蛋白3(GATA binding protein 3,GATA-3)、T细胞特异性转录因子(transcription factor T-bet,T-bet)、Notch1蛋白表达及外周血调节性T细胞(regulatory T cell,Treg)/辅助性T细胞17(helper T type 17,Th17)的影响.方法 使用白消安灌胃制作再生障碍性贫血小鼠模型,造模成功后随机分为空白组、模型组、中药组、西药组、中+西药组.中药组予再障膏方溶液灌胃,西药组予CsA溶液灌胃,中+西药组予再障膏方+CsA溶液灌胃,连续给药10天.采用流式细胞术检测小鼠外周血Treg、Th17细胞表达;采用蛋白免疫印迹法检测小鼠脾脏FOXP3、GATA-3、T-bet、Notch1蛋白表达水平.结果 再障膏方联合环孢素能明显增加再生障碍性贫血小鼠外周血Treg/Th17及脾脏FOXP3、GATA-3、Notch1蛋白表达、降低T-bet蛋白表达(P<0.05),且疗效优于单纯西药组及中药组(P<0.05).结论 再障膏方联合环孢素治疗能显著改善AA模型小鼠脾脏转录因子FOXP3、GATA-3、T-bet的表达,促进外周血Treg/Th17细胞比例恢复平衡,但是否与Notch1信号通路相关有待进一步研究.

目的 基于生物分子网络研究柴芪益肝方治疗肝纤维化的作用机制.方法 检索TCMSP、TCMID、Swiss Target Prediction数据库,挖掘柴芪益肝方的潜在活性成分及其作用靶点,并基于OMIM和Gene Cards数据库筛选肝纤维化的相关靶点.运用String数据库和Cytoscape软件对PPI进行可视化及拓扑学分析.借助clusterpro-file对交集靶点行GO分析以及KEGG富集分析,运用Autodckvina软件进行分子对接.结果 筛选出柴芪益肝方137种潜在活性成分以及257个对应靶点,肝纤维化相关靶点6807个,其抗纤维化作用可能与丝裂原激活蛋白激酶MAPK1/3/8、原癌基因酪氨酸激酶Src、激活子蛋白c-Jun、热休克蛋白HSP90α、表皮生长因子受体、p53抑癌基因、血管内皮生长因子、连环蛋白β1、肝细胞生长因子等靶点有关.柴芪益肝方抗纤维化的靶点显著富集于PI3K-Akt、TNF、IL-17、MAPK/NF-κB、HIF-1α/VEGF等信号通路中.分子对接结果表明,柴芪益肝方的主要活性成分槲皮素、白藜芦醇、山柰酚、木犀草素、丹参酮ⅡA等对丝裂原激活蛋白激酶MAPK1/3/8、原癌基因酪氨酸激酶Src、激活子蛋白c-Jun、热休克蛋白HSP90α、表皮生长因子受体、p53抑癌基因、血管内皮生长因子、连环蛋白β1等靶点表现出显著性亲和作用.结论 柴芪益肝方中槲皮素、白藜芦醇、山柰酚、木犀草素、丹参酮ⅡA等活性成分可能作用于丝裂原激活蛋白激酶MAPK1/3/8、原癌基因酪氨酸激酶Src、激活子蛋白c-Jun、热休克蛋白HSP90α、表皮生长因子受体、连环蛋白β1、肝细胞生长因子等靶点,参与PI3K-Akt、TNF、IL-17、MAPK/NF-κB、HIF-1α/VEGF等信号通路,调控氧化应激反应、肝脏炎症反应、肝再生等生物过程,最终发挥治疗肝纤维化的作用.

目的 探讨柴芪益肝方抗肝纤维化的作用机制.方法 选取50只无特定病原体级C57BL/6雄性小鼠通过随机数字表法分成空白对照组、模型组、柴芪益肝方低、高剂量组、水飞蓟素阳性对照组,各10只.除空白对照组外,各组小鼠腹腔注射15％的四氯化碳橄榄油诱导肝纤维化模型.从造模第1天起,空白对照组和模型组以等体积的0.5％羧甲基纤维素钠溶液灌胃,其余3组每天分别灌胃低、高剂量柴芪益肝方和水飞蓟素.小鼠处死后,观察肝脏形态,苏木精-伊红、Masson、天狼星红染色观察肝组织和胶原纤维变化,生化法分析血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平,酶联免疫吸附试验法检测肝组织中丙二醛、超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GSH-Px)和羟脯氨酸的含量,蛋白质印迹法检测肝组织中α-平滑肌激动蛋白(α-SMA)、Ⅰ型胶原蛋白(CollagenⅠ)、转化生长因子β(TGF-β)、基质金属蛋白酶9(MMP-9)及MMP组织抑制因子1(TIMP-1)蛋白表达水平.结果 水飞蓟素阳性对照组和柴芪益肝方低、高剂量组小鼠肝细胞变性、坏死及纤维化组织增生程度均较模型组明显减轻.柴芪益肝方低、高剂量组血清ALT、AST水平,肝组织中丙二醛、羟脯氨酸、α-SMA、CollagenⅠ、TGF-β及TIMP-1蛋白表达较模型组呈现剂量依赖性降低,而柴芪益肝方高剂量组SOD、GSH-Px、MMP-9的蛋白表达水平显著高于模型组,差异均有统计学意义[(125±14)U/mg比(41±11)U/mg、(267±19)U/g比(82±22)U/g、(0.43±0.04)比(0.12±0.01)](P<0.01或P<0.05).结论 柴芪益肝方对肝纤维化小鼠有一定的抗肝纤维化及肝脏保护作用,其机制可能与其调节脂质代谢、抗氧化应激反应、抑制TGF-β蛋白表达,促进细胞外基质降解等相关.

目的:观察中西医结合治疗骨髓增生异常综合征(Myelodysplastic Syndromes,MDS)的中位生存期,探究影响MDS患者生存期的因素.方法:选取2009年12月至2018年5月北京中医药大学东方医院收治的自愿接受益髓浓煎方联合西药治疗的MDS患者57例作为研究对象,随访至死亡或观察截止,记录其中医证型及血液、骨髓等检查,分析评估生存期的影响因素.结果:57例患者中位生存期30个月,其中65周岁以下较高危组患者中位生存期30个月,长于国内报道的27个月以下.8例接受地西他滨联合中药治疗的较高危组患者中位生存期17个月,长于文献报道的单纯西药治疗的13个月.津液内停、实热的出现影响患者生存.结论:部分分组MDS患者生存期较单纯西药治疗延长,提示没有异基因造血干细胞移植条件的MDS患者进行中西医结合治疗可在生存期上获益.中医证型与MDS危险分层存在相关性,实邪的出现提示预后不良,生存期缩短,因此,中医药参与MDS治疗不能单纯采用"补益"中药治疗,还应该根据患者的危险分层,对较高危组患者采用一定"祛邪"药物治疗.

目的 分析骨髓增生异常综合征(myelodysplastic syndrome,MDS)患者的危险分层与中医证候的关系,初步探究MDS中医证候与分子遗传学特点的关系.方法 综合MDS国际预后积分系统(IPSS、IPSS-R和IPSS-R-M)将72例MDS患者分为相对低危组和相对高危组,检测患者外周血、肝肾功、骨髓细胞形态学、突变基因等指标,收集中医四诊进行辨证并计算证候积分,制定并填写《病例报告表》,整理数据,分析MDS危险分层和中医证候分型、证候积分、基因突变的关系.结果 中医辨证为气血两虚证的患者相对低危组(67.5％)多于相对高危组(25％)(P＜0.05),辨证为瘀血内阻证的患者相对高危组(56.25％)多于相对低危组(15％)(P＜0.05),差异有统计学意义;脾肾不足证相对低危组(17.5％)与相对高危组(18.75％)比较(P＞0.05),差异无统计学意义.相对低危组与相对高危组均为气血两虚证证候积分最低,脾肾不足证证候积分稍高,瘀血内阻证证候积分最高.相对低危组的3个证型证候积分相比较,差异有统计学意义(P＜0.05),两两比较,脾肾不足证与气血两虚证、气血两虚证与瘀血内阻证证候积分差异有统计学意义(P＜0.05),脾肾不足证与瘀血内阻证证候积分差异无统计学意义(P＞0.05);相对高危组的3个证型证候积分比较,差异有统计学意义(P＜0.05),两两比较,气血两虚证与瘀血内阻证积分差异有统计学意义(P＜0.05),脾肾不足证与气血两虚证、脾肾不足证与瘀血内阻证积分差异均无统计学意义(P＞0.05).就3个证型而言,无论哪种证型的证候积分,均是相对低危组较相对高危组低,P＜0.05,差异有统计学意义.相对高危组基因突变率高于相对低危组(P＜0.05).3个中医证型中,脾肾不足证所检出最多的基因为TET2(3例,30％),气血两虚证为SF3B1(8例,57.14％),瘀血内阻证为TET2(9例,45％).在各个常见突变基因中,SF3B1检出率最高的证型是气血两虚证(8例,57.14％),且3个证型的检出率相比较差异有统计学意义(P＜0.05),SRSF2检出率最高的证型是瘀血内阻证(7例,35％),3个证型检出率比较差异有统计学意义(P＜0.05),其余常见突变基因在3个证型中的检出率均无统计学差异(P＞0.05).结论 MDS危险分层与中医证候分型、中医证候积分、基因突变之间存在着一定的规律性.

目的 观察通痹降浊汤对高尿酸血症大鼠模型的药效学影响.方法 通痹降浊汤由北京中医药大学深圳医院制剂室制备,将60只雄性SD大鼠按体质量随机分为空白对照组、模型组、低剂量中药组、高剂量中药组和别嘌醇组,每组12只.实验周期14 d,药物组大鼠预先灌胃给药7 d,第8天开始使用酵母膏15 g/kg+腺嘌呤100 mg/kg灌胃,连续7 d,最后1 d灌胃氧嗪酸钾300 mg/kg造模.检测大鼠血尿酸、尿素氮,苏木素-伊红染色(HE染色)法检测肾组织病理.结果 与空白对照组相比,模型组大鼠血清尿酸、尿素氮含量显著升高,且肾脏病理组织有一定程度损害,两个剂量中药均具有降低高尿酸血症大鼠血清尿酸的作用,且可显著降低大鼠血清尿素氮水平,减轻肾脏病理改变,其作用无明显剂量依赖性.结论 通痹降浊汤对于高尿酸血症大鼠具有明显治疗作用.

Objective To explore the mechanism of Yiqi Yangxue Bushen preparation combined with Stanozolol in the treatment of severe aplastic anemia. Methods The patients with severe aplastic anemia in our hospital from 2014 to 2017 are divided into the treatment group and the control group according to the treatment methods. The two groups are all included in 31 cases. The control group is treated with stanozolol and cyclosporine A, while the treatment group is treated with traditional Chinese medicine Qi Yangxue Bushen decoction the basis of the control group. Both groups are treated with the same adjuvant therapy during the treatment period. The course of treatment is 6 months. The changes in the number of T lymphocyte subsets (CD3+, CD4+, CD8+), Th1 and Th2 in the auxiliary T lymphocyte, the positive and negative regulatory factors of the hematopoiesis (IL-4, IFN-α) are observed before and after treatment. Results The total effective rate of the treatment group is 90.32 ％, significantly higher than that of the control group (P < 0.05); the CD8+ in each group is lower than that before the treatment, the CD4+/CD8+ ratio is higher, the difference between the two groups is statistically significant (P < 0.05), there is no statistical difference before and after treatment with CD3+ and CD4+ (P> 0.05). After treatment, the two groups of Th1 and the ratio of Th1/Th2 decreased, and the reduction of the treatment group is greater than that of the control group (P < 0.05). There is no significant change in Th2 after treatment. The number of IFN-γ decreased after treatment and the degree of change in the treatment group is greater than that of the control group (P < 0.05). The number of IL-4 increased and the difference is not obvious.Conclusion The effect of Yiqi Yangxue Bushen recipe combined with stanozolol in the treatment of severe aplastic anemia is significant, and its mechanism may be related to the regulation of the number of T lymphocyte subsets and related hematopoietic regulation factors.

胡世平教授为北京中医药大学教授,博士研究生导师,广东省名中医,广东省首批名中医师承项目指导老师,全国基层名老中医师承项目指导老师,南粤最美中医,深圳市劳动模范.胡教授从医33年来,注重临床经验积累总结,熟读中医各家经典著作,先后师从唐祖宣、王琦等国医大师,广纳各家所长,形成了一系列独特的中医治疗五脏疾病及疑难病症的学术思想及治疗方法,尤以治疗肝病、调治脾胃见长.胡教授认为岭南地区因其独特的地理、气候、饮食生活习惯及人群体质差异,该地区患者的脾胃疾病较常见,且具有一定的特点,基于“脾胃乃后天之本”“内伤脾胃,百病由生”“善治病者唯在调理脾胃”等学术思想,胡教授在临床中强调脾胃的调理,并根据多年临证体会,提出一系列脾胃病学术观点.笔者有幸跟诊,现将胡教授诊治岭南地区脾胃疾病的经验总结如下.

OBJECTIVE:The present study aimed to evaluate the pregestational body mass index (preBMI) and initial fasting plasma glucose (FPG) in predicting gestational diabetes mellitus (GDM) in southern Chinese women.STUDY DESIGN:A total of 327 pregnant women were recruited from the third affiliated hospital of Sun Yat-Sen University, Guangzhou, China. The preBMI and initial FPG at 16-18 weeks' gestation were measured. Oral glucose tolerance test was performed at 24-28 weeks' gestation. The sensitivity and specificity of preBMI and initial FPG as predictors for GDM were evaluated by receiver-operator characteristic curve analysis.RESULTS:Both preBMI and initial FPG correlated with the 0-hour, 1-hour and 2-hour plasma glucose during oral glucose tolerance test (P < 0.05). The area under receiver-operator characteristic curve was 0.63 (95% CI: 0.57-0.68) for preBMI and 0.68 (95% CI: 0.61-0.72) for initial FPG in diagnosing GDM. The optimal cutoff for preBMI was 21.5 kg/m(2) (sensitivity 52.1% and specificity 69.2%) and 4.6 mmol/L (sensitivity 64.6% and specificity 65.2%) for initial FPG. Interestingly, the initial FPG had a better sensitivity compared to preBMI when the specificity was the same. Multivariate logistic regression analysis showed that initial FPG but not preBMI was the independent risk factor for the later development of GDM. After adjustment for the preBMI and the maternal age, the odds ratios of initial FPG and parity were 3.57 (95% CI: 1.72-7.45) and 2.11 (95% CI: 1.20-3.72).CONCLUSIONS:Although both preBMI and initial FPG could be used as indicators for GDM, the initial FPG may be more suitable for predicting GDM in southern Chinese women.

BACKGROUND:Apolipoprotein A-I (apoA-I), the major protein for high density lipoprotein, is essential for reverse cholesterol transport. Decreased serum levels of apoA-I have been reported to correlate with subcortical infarction and dementia, both of which are highly related to white matter lesions (WMLs). However, the association between apoA-I and WMLs has never been investigated. In this study, we sought to investigate the association between apoA-I and the presence of WMLs in middle-aged and elderly subjects.METHODS:Consecutive patients aged 50 years and older of our department were prospectively enrolled in this study (n = 1282, 606 men and 676 women, 65.9 ± 9.4 years). All participants underwent MRI scans to assess the presence and severity of WMLs. Multivariate logistic regression analyses were performed to examine the association of apoA-I with WMLs.RESULTS:Patients with WMLs were older and showed significantly higher proportion of male sex, hypertension, diabetes mellitus, previous stroke, and coronary heart disease whereas levels of total cholesterol, high density lipoprotein cholesterol, and apoA-I were lower. After adjustment for potential confounders, the lowest apoA-I quartile was independently associated with an increased risk of WMLs (odds ratio: 1.87, 95% confidence interval: 1.29-2.72). In sex-specific analyses, this relationship was observed only in women.CONCLUSIONS:Our findings demonstrated that apoA-I was inversely associated with the presence of WMLs in middle-aged and elderly subjects. This results suggest that therapies which increase apoA-I concentration may be beneficial to reduce the risk of WMLs, dementia and stroke.

Objective To assess the efficacy and safety of dl-3-n-butylphthalide injection in acute ischemic stroke patients. Methods A randomized, double-blind, double-dummy trial enrolled 552 patients in China, if they were within 48 hours of onset of ischemic stroke, and had a score from 6 to 25 on the National Institutes of Health Stroke Scale (NIHSS). Three hundred and seventy patients were randomly assigned to receive infusion of dl-3-n-butylphthalide and 182 patients received infusion of ozagrel. Results In dl-3-n-butylphthalide group, NIHSS score at baseline, on the 8th and 15th days were 8.64±3.03,6.45±3.88 and 4.71±3.90 respectively, whereas Barthel index score were 45.42±20.82,55.60±25.64 and 65.39±26.85 respectively. The difference of NIHSS score between the 15th day and baseline was significantly higher in dl-3-n-butylphthalide group as compared with ozagrel group (Wilcoxon rank sum test, z=2.21, P=0.027). Similar result was found when Barthel index was evaluated（z=2.50，P=0.012）, suggesting a favorable outcome of dl-3-n-butylphthalide treatment. Among the 515 subjects included in the efficacy analysis, 14 days of treatment with dl-3-n-butylphthalide was significantly associated with a favorable outcome than that in 14-day treatment with ozagrel as measured by NIHSS（z=2.21, P=0.027）and Barthel index (z=2.50, P=0.012). The effective rate on the 15th day was significantly higher in dl-3-n-butylphthalide group as compared with that in ozagrel group. The rate of adverse events was similar between two groups (2.74% vs 4.44%，P=0.34). Elevated alanine aminotransferase was the most common adverse event. Conclusion This trial suggested that the 14-day treatment with dl-3-n-butylphthalide could improve outcomes on the 15th day after stroke, and intravenous administration of dl-3-n-butylphthalide was safety. (Trial registration:Chinese Clinical Trial Registry (ChiCTR-TRC-09000483)). Key words: Brain infarction; Benzofurans; Randomized controlled trial

Objective:To research the effects of Wuyu decoction drug-containing serum on expression of P38 MAPK of ovarian granulosa cells (GC) of rats by serum pharmacological method. Methods:25 SD rats were randomly divided into normal con-trol group,western medicine group,low,middle and high dosage of Wuyu decoction group. Blood was taken from femoral artery of rats and serums were separated 4 d after administration. Serum in each group was added into ovarian granulose cell medium system of rats,then 48 h later relative expression of P38 MAPK phosphorylated protein was measured by Western blot. Results:Compared with blank control group,relative expression of P38 MAPK phosphorylated protein was significantly increased in treatment groups (P<0.01). Effect of middle dosage group of Wuyu decoction was better than that of western medicine group (P<0.01). Conclusion:Wuyu decoction drug-containing serum could promote the proliferation of ovarian granulosa cells through enhancing P38 MAPK protein phosphorylation. It is indicated that Wuyu decoction cou ld promote development,maturation and ovulation of ovarian follicle through adjusting P38 MAPK signal transduction pathway.