【作者】 郭明星；

【导师】 盛国光；

【作者基本信息】 湖北中医药大学 ， 中医内科学， 2014， 博士

【摘要】 背景和目的我国是慢性乙型肝炎高发区，其流行性广，难于彻底根治,预计我国有乙肝病毒携带者0.93亿以上,现症慢性乙型肝炎患者约2千万以上,其中10-20%可发展为肝硬化，1-5%可演变为肝癌，不仅造成巨大的经济损失和资源消耗，也给人们的身体健康和社会生产力造成严重威胁，是我国目前面临的最严重的公共卫生问题之一。中医药是我国人民的宝贵财富，是古代人民智慧的结晶，是我国最具原创性的领域。加强中医药防治慢性乙型肝炎的研究，对提高我国慢性乙型肝炎防治能力和水平具有十分重要的意义。中医治疗传统中医肝病有系统的中医理论基础、悠久的历史，积累了大量的临床经验，自从上世纪60年开始中医药就广泛的运用于乙肝病毒引起的相关疾病的临床治疗，并进行了大量的临床与实验研究。当今世界正向大数据时代迈进，数据作为一种巨大的资源，通过数据来解决问题的创新模式已越来越得到重视。将大数据理论及其研究方法应用到中医药的临床与科研中，将会给中医学带来革命性的变化。本研究通过构建肝病临床科研信息共享系统，形成临床科研一体化的基础信息平台，以海量临床信息为基础，开展基于真实世界的临床实际数据的科学研究，可以从中发现中医临床的经验、规律和问题，验证中医临床疗效，发现中医临床疗效相关的规律。本研究以慢性乙型肝炎为研究对象，分析探讨慢性乙型肝炎中医证候分布特点及辨治用药规律，为建立标准化规范化的中医诊疗模式提供参考，为规范慢性乙型肝炎中医辨证论治提供依据，提高临床诊疗水平。方法本研究分为三个部分。第一部分：肝病临床科研信息共享系统构建研究首先从教材、标准、文献三个方面为基础进行临床术语收集，建立中医肝病临床基本术语集，再基于临床基本术语和肝病中医诊疗方案制定结构化电子病历模板，形成肝病结构化电子病历模板集，并充分整合医院的信息化资源，利用现代信息与网络技术，构建数字化、信息化、网络化的中医药临床数据支撑平台与管理服务共享体系，即临床科研信息共享系统，使其具备临床诊疗信息全程收集、整理和分析能力，实现基于临床实际数据的科学研究。第二部分：基于共享系统的慢性乙型肝炎证候规律研究基于临床科研信息共享系统，应用结构化电子病历采集慢性乙型肝炎患者的住院信息。采集数据来源于2002年-2013年诊断为慢性乙型肝炎的住院患者，共1200例。对采集的数据进行解析、转换、清洗、处理，抽取所需要的数据导入数据仓库。利用临床科研一体化技术平台及复杂网络技术，对基本信息、舌象、脉象、症状、中医证候的分布进行聚类分析，对常见证型与症状、舌象、脉象之间进行关联分析，利用SPSS17.0软件进行统计分析，探讨慢性乙型肝炎中医证候分布规律。第三部分：基于共享系统的慢性乙型肝炎用药规律研究在第二部分的数据采集的基础上将采集的中药数据进行分析处理，利用临床科研一体化技术平台及复杂网络技术，对中药使用频率、药物性味归经等进行了统计分析，并分析中药与中医证候的关联性，利用SPSS17.0软件进行统计分析，探讨慢性乙型肝炎中药用药规律。结果第一部分：肝病临床科研信息共享系统构建研究1形成了标准规范的中医肝病临床基本术语集，包括主体临床术语26种，属性术语10种，其中肝病常见症状类术语69个。2基于中医肝病诊疗方案及中医肝病临床基本术语集，制定肝病结构化电子病历模板集，包括结构化电子病历模板107个，并形成了肝病模板体系表。3以结构化电子病历为核心，并充分整合医院的信息化资源，包括HIS、LIS、PACS等信息，构建了数字化、信息化、网络化肝病临床科研信息共享系统平台。第二部分：基于共享系统的慢性乙型肝炎证候规律研究1慢性乙型肝炎患者基本情况的统计分析，在临床采集的1200例病例中，男性患者922例，占76.8％，女性患者278例，占23.3％，男女比例3.32∶1，说明慢性乙型肝炎患病率男性患者高于女性。年龄分布其中<40岁的患者714例，占59.5％，40-60岁的患者362例，占30.2％，>60岁的患者124例，占10.3％，患病年龄以40岁以下为主。2慢性乙型肝炎患者中医症状分布，在1200例临床采集病例中，共提取5278个症状，经统计分析，慢性乙型肝炎患者主要症状集中在乏力、烦躁易怒、胁痛、胁胀、口干、口苦、食欲不振、便溏、腹胀、黄疸、小便黄赤等，其中乏力在所有症状中所占比重最高，为65.50％。3慢性乙型肝炎患者舌脉分布，舌象分布中常见舌质有舌红、舌淡红、舌暗红，其中舌红、舌淡红为主，合计所占比重90％；常见舌苔有苔薄白、苔白、苔薄黄、苔白腻、苔黄腻、苔黄，以苔薄白、苔白为主，所占比重分别为49.83％、21.08％；常见脉象有脉弦、脉缓、脉滑、脉弦细、脉细、脉弦滑、脉数、脉滑数、脉濡，以脉弦最为常见，所占比重68.42％。4慢性乙型肝炎中医证型分布，共提取慢性乙型肝炎中医证型64个，1200频次，经规范化处理，得出慢性乙型肝炎主要中医证型有：肝郁脾虚证、湿热蕴结证、肝郁气滞证、脾虚湿阻证、瘀血阻络证、肝肾阴虚证、脾肾阳虚证。其中肝郁脾虚证和湿热蕴结证所占比重最大，分别为占53.41％、28.33％。说明肝郁脾虚证和湿热蕴结证是慢性乙型肝炎常见证型。经分析，慢性乙型肝炎中医证型与性别无明显相关性，肝郁脾虚证、湿热蕴结证、肝郁气滞证、脾虚湿阻证与年龄无明显相关性，而瘀血阻络证、肝肾阴虚证、脾肾阳虚证与年龄有一定的相关性。5对慢性乙型肝炎常见证型肝郁脾虚证和湿热蕴结证进行中医辨证规范化研究，将证型与症状、舌脉进行关联性分析，并结合辨证标准，分析其中医辨证的规范性、准确性，将结果与辨证标准相比较，基本符合规范。第三部分：基于共享系统的慢性乙型肝炎用药规律研究1对慢性乙型肝炎总体用药规律分析，得出慢性乙型肝炎最常用的5味中药是茯苓、茵陈、白术、丹参、郁金，其中茯苓应用687频次，占总中药处方比例57.25%；茵陈585频次，占48.75%；白术547频次，占45.58%；丹参488频次，占40.67%；郁金407频次，占33.92%。前20味中药为：茯苓、茵陈、白术、丹参、郁金、白花蛇舌草、连翘、麦芽、甘草、半夏、陈皮、谷芽、柴胡、黄芩、车前草、枳实、薏苡仁、厚朴、赤芍、太子参。从中可以看出慢性乙型肝炎的用药思路是扶正解毒、祛瘀化痰。2对慢性乙型肝炎中药性味归经的研究，发现常用中药药味以苦味药和甘味药为主，其次是辛味药；中药药性多为性寒、性微寒、性温、性平的中药，并无明显大寒大热竣猛之品，体现了中医“平调阴阳，以平为期”辨证治疗思想；中药归经以归脾经、肝经的中药为主，体现了慢性乙型肝炎从肝脾论治的思想。3通过对慢性乙型肝炎用药演变规律的分析，显示慢性乙型肝炎的辨证思想从“毒”到“毒痰瘀”再到“毒痰瘀虚”的转变，体现了扶正解毒、祛瘀化痰的治疗思路的形成。结论本研究构建的肝病临床科研信息共享系统，经过临床应用，能满足临床科研的需求，能提高临床医生的工作效率和工作质量，通过对临床数据的结构化标准化存储，能够满足数据挖掘的需求，能够以海量临床信息为基础，开展基于真实世界的临床实际数据的科学研究。初步体现了“以人为中心，以临床数据为导向，从临床中来、到临床中去”临床科研一体化科研范式。基于共享系统对慢性乙型肝炎临床数据进行结构化采集，通过对慢性乙型肝炎中医证候分布特点及辨治用药规律研究，为建立标准化规范化的中医诊疗模式提供参考，为规范慢性乙型肝炎中医辨证论治提供依据。更多还原

【Abstract】 Background and0bjectiveOur country is a high incidence of chronic hepatitis B, whichis widely epidemic and difficult to completely cure, it is estimatedthat more than93,000,000hepatitis B virus carrier in our country,and over20,000,000people has chronic hepatitis B.In which10-20%may develop into hepatic cirrhosis,1-5%can evolve intohepatocellular carcinoma, it is caused huge economic losses and theconsumption of resources, but also posed a serious threat topeople’s health and social productivity, it is one of the mostserious public health problems faced by our country. Chinesemedicine is the precious wealth of Chinese people, is thecrystallization of the wisdom of the ancient, is Chinnese mostoriginal field. Strengthen the research on traditional Chinesemedicine in the treatment of chronic hepatitis B, is of greatsignificance to improve our ability of prevention and treatment ofchronic hepatitis B. Chinese medicine treatment in hepatic diseasehas its Chinese medicine theory, and a system with long history,accumulated a large amount of clinical experience. Since60yearsof the last century clinical treatment of Chinese medicine is widely used in the related diseases of hepatitis B virus, and get a lotof the clinical and experimental study with it. The world today isthe age of big data, that is as a great resource, innovation modelto solve the problem by data has been paid attention to more andmore. The large data theory and research method is applied to theclinical and scientific research of TCM, will bring revolutionarychange to traditional Chinese Medicine. In this study, through theconstruction of hepatic disease clinical research informationsharing system,to form the basic information platform ofintegration of clinical research, based on the massive clinicalinformation, to carry out scientific research and clinicalpractice on the data of the real world, then we can find TCMclinical experience, rules and problems, verify the clinical effectof traditional Chinese medicine, find the clinical curative effectof TCM related rules.In this study, chronic hepatitis B as the research object,analysis of chronic hepatitis B distribution characteristics of TCMsyndromes and syndrome differentiation and treatment of drug rules,to provide reference for the establishment of standardization ofTCM diagnosis and treatment mode, also to provide the basis theoryfor regulating the differentiation of chronic hepatitis B treatment,improving the level of diagnosis and treatment.Methods: Our study is divided into three partes.Part one:the study on construction of hepatic disease clinicalresearch information sharing systemFirst, we collect the clinical term from the three basic aspectsof teaching materials, standard, literature, then establish TCMhepatic disease clinical basic term set, formulat structured electronic medical record based on the clinical basic terminologyand hepatic disease in TCM diagnosis and treatment scheme, formatof liver structured electronic medical record template set, fullyintegrated hospital information resources, we use the moderninformation and network technology, to construct the system ofsharing digital, information, network of Chinese medicine clinicaldata supporting platform and management services, called clinicalresearch information sharing system,which has the ability ofwhole clinical information collection, collation and analysis,achieve clinical research based on the real data.Part two: Study on chronic hepatitis B syndrome rule based onsharing systemBased on clinical research information sharing system, wecollect the information of inpatients with chronic hepatitis B byapplicating of structured electronic medical records. The data iscollecting from patients with diagnosis of chronic hepatitis B whoinpatient in the year of2002to2013,a total of1200cases.Analysising, conversing, cleaning, processing the collecting data,and import data that we need into Data warehous. Using theintegration of clinical research technology platform and complexnetwork technology. Analysising the basic information, tongue,pulse and symptoms, TCM syndrome, and the correlation between TCMsyndromes and symptoms, tongue, pulse. SPSS17software is used forstatistical analysis, investigating the regularity of TCMSyndromes of chronic hepatitis B.Part three: Study on chronic hepatitis B syndrome treatment rulebased on sharing systemBased on the information in part two, we analysis the traditional Chinese medicine data, use the clinical researchtechnology integration platform and complex network technology, tostatistical analysis Chinese medicine usage frequency, flavor andmeridian tropism, and analysis the correlation between traditionalChinese medicine and TCM Syndrome. SPSS17software is used forstatistical analysis, investigating the regularity of traditionalChinese medicine of chronic hepatitis B.ResultsPart one:the study on construction of hepatic disease clinicalresearch information sharing system1.We format criterion standard of TCM hepatic disease clinicalbasic terminology, including26main clinical terms,10propertyterms, in which the common symptoms of hepatic disease terms are69.2. Base on the hepatic disease in TCM diagnosis and treatmentscheme and TCM hepatic disease clinical basic terminology,we makehepatic structured electronic medical record template set,including107structured electronic medical record template, andformating hepatic template system table.3. Make structured electronic medical record as the core, wefully integrated hospital information resources, including HIS、LIS、PACS, to construct the digital, information, network ofhepatic disease clinical research information sharing system.Part two: Study on chronic hepatitis B syndrome rule based onsharing system1.Statistically analysis the basic situation of patients withchronic hepatitis B, in the1200cases from clinical collecting,there is922of male patients, accounted for76.8%;there is278 cases of female patients, accounted for23.3%, male to female ratiois3.32:1, this shows that the rate of male patients of chronichepatitis B was higher than that of female.The age distributionis that aged under40years old patients has714cases, accountedfor59.5%, aged40-60years old patients has362cases, accountedfor30.2%, over60years old patients were124cases, accounted for10.3%, this shows that the age of40years is main.2.The distribution of TCM symptoms in patients with Chronichepatitis B, in the1200cases from clinical collecting, There were5278symptoms. After statistical analysis, the main symptoms ofpatients with chronic hepatitis B are weakness, irritability, chestpain, flank pain, thirstiness, bitterness, poor appetite, loosestools, jaundice, abdominal distention, yellow urine, et. Theweakness is in the highest proportion of all symptoms, accountedfor65.50%.3. The distribution of tongue and pulse in patients with Chronichepatitis B, the common tongue of tongue distribution is redtongue, pale tongue, dark red tongue, and red tongue, pale tongueas the main, the total proportion is90%; the common coat of thetongue is thin white fur, white fur, thin yellow fur, white andgreasy fur, yellow greasy fur, yellow fur, and thin white fur, whitefur as the main, the total proportion is49.83%,21.08%; the commonpulse is taut pulse, slow pulse, slippery pulse, wiry pulse, threadypulse, taut and slippery pulse, rapid pulse, slippery and rapidpulse, moisten pulse,and taut pulse as the main.4. The distribution of TCM syndrome in patients with Chronichepatitis B, we totally extract64TCM Syndrome of chronichepatitis B,1200rates, with standard processing, get the main TCM Syndrome of chronic hepatitis B: syndrome of liver depressionand spleen deficiency, endoretention of damp heat, qi stagnation,spleen deficiency and dampness, blood stasis, liver kidney yindeficiency, spleen kidney yang deficiency syndrome. Among that thebiggest proportion is syndrome of liver depression and spleendeficiency, endoretention of damp heat,each accountedfor53.41%,28.33%.It is show that he main TCM Syndrome is syndromeof liver depression and spleen deficiency, endoretention of dampheat.Through analysising, there is no significant correlationbetween TCM Syndrome patterns of chronic hepatitis B and gender,there is no significant correlation between age and syndrome ofliver depression and spleen deficiency, endoretention of damp heat,qi stagnation, spleen deficiency and dampness,but blood stasis,liver kidney yin deficiency, spleen kidney yang deficiency syndromehas a certain significant correlation with age.5. We make TCM syndrome differentiation standardization studyon chronic hepatitis B in syndrome of liver depression and spleendeficiency, endoretention of damp heat, do correlated analysis onsyndrome and symptoms, tongue and pulse, combined with syndromedifferentiation standardization,to analysis the standard andaccuracy of TCM syndrome differentiation, comparing the resultswith the standardization, it is basicly specification.Part three: Study on chronic hepatitis B syndrome treatment rulebased on sharing system1. Analysis of drug rule in chronic hepatitis B, the five mostcommonly used chinese herb for chronic hepatitis B are poria, yinchen, white atractylodes rhizome, radix salviae miltiorrhizae,radix curcumae, and the usage rate of poria is678, accounted for57.25%; yin chen is585, accounted for48.75%, whiteatractylodes rhizome is547, accounted for45.58%, radix salviaemiltiorrhizae is488,accounted for40.67%, radix curcumae is407,accounted for33.92%. The first20using chinese medicinal herbs areporia, yin chen, white atractylodes rhizome, radix salviaemiltiorrhizae, radix curcumae, hedyotis diffusa, forsythia, malt,licorice root, pinellia, dried orange peel, gu ya, bupleurum,scutellaria, plantain, citrus fruit, coix seed, magnolia bark,radix paeoniae rubra, Radix pseudostellariae.We can find thatmedication idea of chronic hepatitis b is the centralizerdetoxification, remove blood stasis phlegm.2. Study on the tropism and flavour of chinese herb using forchronic hepatitis B, we discover that the common used chinese herbis bitter and sweet, the second is pungent. The property of Chineseherb is cold, slightly cold, warm, flat, but no colder, hot,ferocious medicine, which show the differential treatment thoughtof traditional Chinese medicine "flat to flat-yin and Yang,".Channel tropism in traditional herb is mainly in liver and spleen,it shows the treatment ideas from the liver and spleen in chronichepatitis B.3. By analyzing the evolution of chronic hepatitis B treatment,shows that the dialectical thought of chronic hepatitis B is fromthe "toxic" to "toxic phlegm and blood stasis" even to "toxic phlegmstasis virtual". Reflecting that the treatment ideas of " thecentralizer detoxification, remove blood stasis phlegm" isformatted.ConclusionsThe construction of hepatic disease clinical research information sharing system in this study,using in clinic, can meetthe demand of clinical research, and can improve the work efficiencyand quality of clinicians. Through structured standardized storagefor clinical data,we can meet the demand of data mining, can makethe massive clinical information as basic, to carry out scientificresearch and clinical practice based on the data of the real world.It is initial manifestation of the "people-centered, clinicaldata-oriented, from clinic to clinic" clinic researchintegration paradigm in clinical research. Sharing system isstructured to collect the clinical data of patients with chronichepatitis B,the distribution regularity of TCM syndromes,differentiation treatment characteristics and drug research inchronic hepatitis B, providing reference for the establishment ofstandardization of TCM diagnosis and treatment mode of chronichepatitis B,providing the basis theory standardization for TCMsyndrome differentiation treatment.更多还原