Clinical Research of Kangshi Kangxian Recipe Treating on Hepatic Fibrosis of Chronic Hepatitis B

目的观察康氏抗纤方治疗慢性乙型肝炎肝纤维化的临床疗效,探讨其对肝组织N-花生四烯酸氨基乙醇(; arachidonoylethanolamine,AEA) 、2-花生四烯酸甘油( 2-arachidonoylglycerol,2-AG); 、大麻素受体1( cannabinoid receptor 1,CBR1) mRNA、大麻素受体2( cannabinoid receptor; 1,CBR2); mRNA含量变化的影响。方法将110例慢性乙型肝炎肝纤维化患者按随机数字表法分为治疗组和对照组,每组55例。治疗组予中药康氏抗纤方联合恩替卡韦分; 散片治疗,对照组用恩替卡韦分散片单药治疗,两组均治疗48周。判定两组临床疗效,检测血清ALT水平,HBV; DNA、HBsAg、HBsAb定量,肝组织病理、肝硬度变化,肝组织AEA、 2-AG含量和CBR1、CBR2; mRNA表达水平。结果与对照组比较,治疗组的临床总有效率、HBsAg阴转率、肝组织纤维化分期疗效有效率均高于对照组(chi~2 =; 4.453,4.152,6.364,均P < 0.05); 。与本组治疗前比较,治疗后两组患者肝纤维化瞬时弹性测定值、AEA、2-AG含量及CBR1、CBR2 mRNA表达均降低(均P <; 0.05),且治疗组降低更明显(均P < 0.05); 。肝组织病理显示:治疗后治疗组肝小叶结构基本完整,肝细胞轻度水样变性,汇管区纤维组织无增生,局部少量淋巴细胞浸润,炎症及纤维化较对照组明显改善。; 结论康氏抗纤方具有提高慢性乙型肝炎肝纤维化患者的临床总有效率、HBsAg阴转率、肝组织纤维化分期疗效有效率,其作用机制可能与调节内源性大麻素系统; 有关。Objective To observe the clinical effect of Kangshi Kangxian Decoction (; KSKXD) in treating on patients of hepatic fibrosis of chronic hepatitis; B ( CHB),and to explore the mechanisms of KSKXD by regulating the; contents of arachidonoylethanolamine ( AEA),2-arachidonoylglycerol (; 2-AG),cannabinoid receptor 1 ( CBR1 mRNA) and cannabinoid receptor 2 (; CBR2 mRNA) in the liver tissue. Methods Totally 110 patients with; hepatic fibrosis of CHB were assigned to the treatment group and the; control group according to random digit table,55 cases in each group.; The treatment group was treated with Chinese herb KSKXD combined with; Entecavir,and the control group was treated with Entecavir. Both of the; two groups were treated for 48 weeks. The clinical efficacy of the two; groups was determined. The serum ALT levels,HBV DNA, HBsAg and HBsAb; quantification,liver pathological changes,liver stiffness; changes,contents of AEA and 2-AG,mRNA expression of CBR1 and CBR2 in the; liver tissue were detected. Results The total effective rate,HBsAg; negative conversion rate,hepatic fibrosis staging and curative effect; rate of the treatment group were higher than those of the control group; (chi~2 = 4.453,4.152,6.364,allP <0.05). After treatment,the; instantaneous elasticity of liver fibrosis,the contents of AEA and; 2-AG,the mRNA expressions of CBR1 and CBR2 in the liver tissue in the; two groups were decreased compared to those of the same group before; treatment (P < 0.05),and the treatment group had better effect than that; of the control group (P < 0.05). The pathological changes in the; treatment group after treatment indicated the liver lobules; integrity,mild hydropic degeneration of liver cells,periportal fibrous; tissue hyperplasia,local small lymphocytic infiltration,which fibrosis; and inflammation were better than those of the control group.; Conclusions KSKXD was effective in the treatment of hepatic fibrosis of; CHB, which improved total effective rate,HBsAg seroconversion rate and; liver fibrosis stage efficiency. And its mechanism maybe related to the; regulation of the endocannabinoid system.国家自然科学基金资助项目; 福建省科技计划引导性项目; 厦门市科技惠民项目; 福建中医药大学临床专项校管课题基

菖郁逍遥方治疗慢性乙型肝炎伴抑郁症的临床疗效及作用机制探讨

目的观察菖郁逍遥方治疗慢性乙型肝炎（chronic hepatitis B,CHB）伴抑郁症的临床疗效,并探讨其作用机制。方法 90例慢性CHB伴抑郁症患者,采用随机数字表法分为治疗组45例,对照组45例。在恩替卡韦治疗的基础上,对照组服用氟哌噻吨美利曲辛片;治疗组服用中药复方菖郁逍遥方,疗程12周。以汉密尔顿抑郁量表17项(Hamilton depression scale,HAMD17)评分观察治疗前、治疗中（治疗4周）、治疗后（治疗12周）两组患者的抑郁状态变化;以副反应量表（treatment emergent symptom scale,TESS）观察两组治疗后副反应;观察治疗前后血清ALT活性、乙型肝炎病毒DNA（hepatitis B virus DNA,HBV DNA）定量、5-羟色胺（5-hydroxytryptamine, 5-HT）、去甲肾腺上素（norepinephrine, NE）、脑源性神经营养因子（brain derived neurotrophic factor,BDNF）水平及内源性大麻素:N-花生四烯酸氨基乙醇（Arachidonoylethanolamine,AEA）、2-花生四烯酸甘油（2-arachidonoylglycerol,2-AG）及其受体（cannabinoid receptor,CBR）1、2指标变化。结果两组治疗中、治疗后的HAMD17评分较治疗前均明显降低（P0.05）。结论菖郁逍遥方具有显著改善CHB患者抑郁状态的临床疗效,作用机制与通过调控内源性大麻素水平来升高单胺类神经递质、BDNF相关。国家自然科学基金资助项目(No.81503529,No.81673660,No.81873242);;福建省科技计划引导性项目(No.2015D0007,No.2016D012);;厦门市科技计划项目(No.3502Z20174028);;厦门市重要重大疾病联合攻关项目(No.3502Z20179047);;福建省卫生计生医学创新科研人才培养项目(No.2018-CXB-28

非酒精性脂肪肝同病异证与肝活检病理学的相关性研究

目的:观察非酒精性脂肪肝(NAFLD)患者不同中医证型与临床指标、肝活检病理学的关系。方法:选择312例NAFLD患者进行辨证分型,均进行肝组织活检,常规判定NAFLD活动度积分(NAS)和肝纤维化分期。结果:NAFLD患者的中医证型频数分布为痰湿内阻证>肝郁脾虚证>湿热蕴结证>肝郁气滞证>痰瘀互结证。NAFLD患者性别、年龄、病程、血生化、体质量指数、肝硬度值、NAS积分等指标在不同中医证型的分布差异具有统计学意义(P<0.05)。结论:NAFLD患者痰湿内阻证、痰瘀互结证、湿热蕴结证三型NAS积分较高,故NAFLD的治疗应着重于健脾化痰、清热利湿、活血化瘀。国家自然科学基金项目(No.81503529,No.81673660,No.81873242);;福建省科技计划引导性项目(No.2015D007,No.2016D012);;厦门市科技计划项目(No.3502Z20174028);;厦门市重要重大疾病联合攻关项目(No.3502Z20179047);;福建省卫生计生医学创新科研人才培养项目(No.2018-CXB-28);;福建中医药大学基金项目(No.XB2016080);;陈国良名老中医传承工作室(厦门市卫生局资助项目);;全国第六批老中医药专家学术经验继承工作(2017年)~

慢性乙型肝炎患者肝组织HBcAg表达模式与中医证型的关系

目的:观察慢性乙型肝炎(CHB)患者肝组织乙型肝炎核心抗原(HBcAg)表达模式与中医证型及肝组织炎症、纤维化等指标的关系并进一步探讨相应的机制。方法:选择CHB患者556例,均进行中医辨证分型及肝组织活检,测定肝组织HBcAg表达模式、炎症、纤维化程度及ALT、AST、HBV DNA水平。结果:(1)556例患者按中医辨证标准分为6组:瘀血阻络证44例、肝肾阴虚证42例、肝郁气滞证48例、肝郁脾虚证282例、湿热蕴结证140例、脾肾阳虚证0例;按HBcAg表达模式分HBcAg阴性组42例、胞浆型HBcAg组186例、胞浆优势型HBcAg组290例、浆核各半型HBcAg组38例。(2)经Spearman秩相关分析,肝组织HBcAg表达模式与肝组织炎症活动度、纤维化程度均呈负相关;经Fisher确切概率检验,肝组织HBcAg表达模式与中医证型分布具有相关性。结论:肝组织HBcAg表达模式与中医证型、肝组织炎症、纤维化程度均有相关性;HBcAg阴性组、胞浆型HBcAg组及肝郁脾虚证、湿热蕴结证多处于慢性乙型肝炎活动期,正气未伤,免疫功能较强,为抗病毒治疗的较佳时机。国家自然科学基金项目(No.81503529,No.81673660);;福建省科技计划引导性项目(No.2015D007,No.2016D012);;厦门市科技惠民项目(No.3502Z20174028);;厦门市重要重大疾病联合攻关项目(No.3502Z20179047);;福建中医药大学基金项目(No.XB2016080)~

高速列车空气动力学优化设计及评估技术

建成了高速列车数值仿真平台和高速列车动模型试验平台。 利用高速列车数值仿真平台完成对改进型头部气动特性的综合评估，提供了运行安全评估的气动载荷数据。评估了CRH2-300、CRH3等型高速列车不同速度等级明线单车运行场景的阻力、升力、力矩等气动特性。完成了基于空气动力学的CRH380A和CRH380B等型高速列车头型设计，形成了满足不同设计需求的高速列车“头型”族。完成了基于空气动力学的高速列车连接部件设计，形成了满足不同设计需求的高速列车连接部件集。完成了基于空气动力学的高速列车车体设计，形成了满足不同设计需求的高速列车车体族。完成了基于空气动力学的高速列车顶部装置设计，形成了满足不同设计需求的高速列车顶部装置设计技术。 完成了CRH2和CRH3等型高速列车头型、列车连接部、列车顶部主要部件如进排气装置、受电弓装置、支架及整流罩等的噪声测试，为高速列车头型和关键部件的外形优化和降噪提出建议。 完成了高速列车列车不同车型、不同速度等级交会场景分析，总结了复杂工况下高速列车交会压力波的基本特征及其与列车运行速度的关系特征，建立了线间距和车体宽度对上述关系的影响。 完成了高速列车隧道通过和隧道交会的数值模拟。建立了高速列车通过隧道时运行安全评估参数。 完成了横风对高速列车空气动力学性能影响、在横风时高速列车交会过程中列车表面压力、空气阻力、升力、横向力及力矩的变化规律的数值分析研究。总结了列车横风对高速列车空气动力学性能影响、在横风时高速列车交会过程中列车表面压力、空气阻力、升力、横向力及力矩的变化规律的数值模拟结果，建立了高速列车在横风条件下相关的安全运行参数。 发展了有效的、准确的列车风对高速铁路旁建筑物和高速铁路旁站台人员影响的数值模拟软件，完成了列车风对高速铁路旁建筑物和高速铁路旁站台人员影响的数值模拟，为高速铁路旁的建筑物和站台人员和高速铁路的安全距离随列车速度的关系提供可靠的数据基础

山东省淡水小型甲壳动物新亚种和新记录

本文记述了山东省首次记录的28种淡水小型甲壳动物。其中包括一新亚种微齿大尾溞Leydigia acanthocercoides denticulatus和4个中国新记录种和亚种

A new mutation pattern of hepatitis B virus X gene

目的:证实乙型肝炎病毒(hepatitis Bvirus,HBV)X基因一种新的变异方式.方法:从HBV慢性感染患者血清中提取HBVDNA,扩增X基因序列,克隆入pMD19T载体,选择阳性克隆进行DNA测序,与已知HBV基因相应序列比较该患者体内HBV基因变异位点以及变异形式.结果:从21例患者中共挑选74个克隆测序,测序结果提示54个克隆X基因下游大段缺失突变,长度达234nt,位于1601-1834nt处,另有1个克隆发生245nt缺失突变.发生缺失变异的病毒株同时存在G/A1515C、G1518C和A1585T替换突变,这两种突变具有联动特征.缺失突变株HBx仅编码76aa,其第44和45位编码为LL,具有特异性.结论:观察到一种X蛋白变异方式,这种大段缺失突变导致X蛋白下游编码序列丢失,其为X因子还是X蛋白以及这种变异是否为常态形式尚需进一步研究.AIM: To identify a novel X gene mutation pattern of hepatitis B virus (HBV) in patients with chronic HBV infection.METHODS: A pair of primers was designed on the basis of nucleotide sequences of X gene. Polymerase chain reaction (PCR) was used to amplify the target region from HBV DNA sam- ples extracted from chronic hepatitis B patients in Xiamen city. After electrophoresis of the PCR products in 9 g/L agarose gel, the target regions were cut, re-purified and TA-cloned into pMD19 T vector. The inserted regions in positive clones were sequenced. Sequence comparison with HBV genome submitted in GenBank was made to find the mutation sites. RESULTS: Totally 74 strains from 21 patients with chronic HBV infection were sequenced, and the results showed that there was a charac- teristic deletion region, with a length of 234 nt (nt 1601-1834) in 54 clones, and a length of 245 nt in 1 clone. There were 3 replacement mutations bounding to deletion mutation: G/A1515C, G1518C and A1585T, which caused substitutions in the 44th and 45th amino acid site to LL. These mutant strains only coded 76 aa of up-stream HBx. CONCLUSION: A novel deletion mutation in HBV X gene is observed in patients with chronic HBV infection. The deletion mutants encode 76-aa X factor instead of X protein.厦门市首批重大疾病科研攻关资助项目,No.WKZ0501;; 厦门市卫生局医学科研立项资助项目,No.WSK0506;; 厦门大学引进人才科研启动基金资助项目,No.Z03109;; 福建省青年科技人才创新资助项目,No.2006F3127~