高忠英教授学术思想与经验总结及运用数据挖掘方法对慢性胃炎用药规律的研究
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摘要
高忠英教授,出身中医世家,自幼习医,精通内、妇、儿科,是卫生部认定的全国500名老中医药专家之一,第二、三、四批国家级继承人导师。从事中医临床、教学、科研工作58年,历任首都医科大学中医药学院中医内科学、中药方剂学教研室主任,研习医理,精通经典医籍,创立“五脏补益法”。精心临证,处方精当,方简效宏。尤其对脾胃病的治疗有独到的见解,疗效显著,在运用中药辨证治疗慢性胃炎方面积累了丰富的临床经验。本研究分为三大部分：
第一部分高忠英教授学术思想渊源。用访谈法和分析归纳法对高忠英教授学术思想渊源进行了总结,梳理了高忠英教授传承谱系及传承现状,探寻了高忠英教授学术思想及其临床经验的形成过程,明晰了高忠英教授脾胃专业相关的中医各家学派的关系,并对高忠英教授脾胃学术思想中医经典古籍渊薮进行了挖掘整理。包括高忠英教授成才之路以及家传师承情况及北京中医药“薪火传承3+3工程”高忠英老中医药专家继承工作站的传承情况,对高忠英教授脾胃学术思想的形成有重大影响的经典古籍的介绍,如《内经》的脾胃论、张仲景的脾胃论、李东垣的脾胃论、叶天士的脾胃论,与脾胃相关的中医各家学派的关系,如施今墨、魏舒和.、董建华、关幼波、李乾构及其继承与创新的具体体现。
第二部分高忠英教授学术思想和临床经验的整理与研究。高忠英教授学术思想集中体现在五脏补益法的学术思想和1临床用药配伍规律的研究,本部分从五方面分别叙述了五脏补益法的学术思想、临床用药配伍规律的研究、关于方剂学的独特学术观点、高忠英教授脾胃学术思想以及治疗呼吸系统疾病学术思想的整理与研究。
首先将高忠英教授理论学术思想研究——“五脏补益”学术思想深入挖掘,五脏补益法确切地体现了补益气、血、阴、阳选药组方的配伍规律,是补益五脏虚证必须遵守的治疗法则。从高忠英教授的五脏补益理论中,我们提炼出：五脏虚并非气血阴阳俱虚,是按五脏的生理特点、病理特征有所侧重,补脾、肺、肾重在补气、阴、阳；补心、肝则气、血、阴、阳均可补益。
高忠英教授在长期的方剂学教学中,潜心研究经典古籍,积累了丰富的教学经验,指出了现在方剂学教学的不足,提出了自己独到的见解和观点。教学之余,勤于临证,理论与实际相结合,努力达到方剂学研究的最高境界,即找寻出临床用药的配伍规律。
高忠英教授在脾胃病方面,不仅在理论上博采众长,而且在实践中有所创新。高忠英教授认为脾胃理论源于《内经》,辨证法于仲景,集大成者则系李东垣,而清代叶天士关于脾胃分治的认识和甘润养胃阴的学术观点,弥补了东垣详于治脾,略于治胃,重在温补,不及养阴的不足。高忠英教授师古而不泥古,在对脾胃病的临床诊治中,提出了自己独到的见解,认为胃阴的产生源于中焦气化,脾阳代表整个消化功能,脾阴则包涵上下消化道的消化液、润滑液(唾液,食道润滑液,胃液、肠液等)。胃阴(液)是脾阴的一部分,是脾阳升华水液所产生的消化液。当胃粘膜的腺体萎缩,胃阴生化无源时,应以补脾助生化之源为本。逐渐形成了自己独特的理论体系。在治疗慢性胃炎方面,从脾胃的生理、病理及慢性胃炎的病因病机角度,提出慢性胃炎多为本虚标实之证,脾虚胃燥是其核心病机,治疗当以健脾益气、养阴润燥为法,辨证与辨病相结合进行治疗。其核心思想为：①脾虚胃燥是慢性胃炎的基本病机；②脾虚是消化功能减弱的必然趋势；③胃燥是慢性胃炎病变实体的特征；④脾虚胃燥是慢性胃炎阳虚阴亏的根源；⑤补脾润燥是治疗慢性胃炎的基本治法。辨证分型是治疗慢性胃炎的基础,同时强调注意脾虚胃燥的病理归属,结合胃镜下黏膜红肿、糜烂、萎缩等状态,正确地选药组方,定会取得理想效果。
高忠英教授诊疗经验相当丰富,经治病人涉及内、外、妇、儿各科,尤其在消化系统和呼吸系统疾病方面有非常独到的临床疗效,譬如慢性萎缩性胃炎、胃食管反流病、溃疡性结肠炎、慢性顽固性咳嗽、过敏性鼻炎和过敏性哮喘都是高忠英教授的善治病种。在妇科用药方面也匠心独到,突出特点为“强调冲任,兼顾阳明”“突出调经,重在化瘀”.“和降阳明,兼以调经”“喜用温药,暖宫为先”。另外在用温热药治疗高血压病和复发性口腔溃疡及应用古方葶苈丸加减治疗小儿咳喘方面均具有非常好的临床疗效。
第三部分高忠英教授学术经验的临床研究
本研究利用复杂系统熵聚类技术,在治疗有效的前提下,对高忠英教授的处方数据进行挖掘,并在临床实践中验证,探讨治疗慢性胃炎的处方用药的规律。
研究方法：
首先,采用Epidata数据库平台进行熵聚类等方法对数据库的处理,得出结论。主要从三个层面挖掘隐含在数据库背后的处方用药规律,一个层面是单味药的,主要通过频次法实现；第二个层面是药对的分析,主要通过互信息,关联规则等,探讨在脾胃病证下常用的药对,初步揭示处方用药规律；最后一个层面是多个药物之间的组合规律,通过复杂系统熵聚类,聚类分析,主成份分析和因子分析等。这三个层面相互印证,互为补充,共同揭示高忠英教授的处方用药规律。
同时应用复杂网络Pajek软件,不仅提供了一整套快速有效的用来分析复杂网络的算法,而且还提供了一个可视化的界面,可以从视觉的角度更加直观地了解复杂网络的结构特性。通过对高忠英教授处方集的共性网络结构分析,能够发现体现其处方思维和临床特点的核心处方配伍结构,从而辅助进行高忠英教授经验的传承和整理研究。
结果：
通过上述方法,分析筛选了数据库中730首处方,得到治疗慢性胃炎中使用频率较高的30味药物,应用改进的互信息法,分析得到了94个常用药对；应用复杂系统熵聚类方法,得到核心组合11个。采用复杂熵聚类的方法构建80味治疗慢性胃炎常用中药之间的关联关系,获得122项关联。绘制出了慢性胃炎常用中药复杂网络节点分类图。经过统计得出的频次规律最高为海螵蛸355,天花粉347,太子参324,浙贝300,白术296,半夏曲244,莪术201,鸡内金196,砂仁144,莱菔子142,白芍126,黄连125,吴茱萸116,炮姜94,连翘80。这一结果与临床实际完全符合,基本上是高忠英教授治疗慢性胃炎的常用药物,根据上述复杂网络的结果,再与临床实际相结合,可得到如下
结论：
复杂网络节点分类图位于最核心的药物组合有太子参(或党参),白术,天花粉,浙贝(或川贝),海螵蛸。太子参(或党参),白术主要是健脾为主；天花粉,浙贝(或川贝),海螵蛸主要针对胃体本身,修复糜烂,以润燥为主。核心组合的配伍,正切中慢性胃炎脾虚胃燥的核心病机,所以无论是慢性浅表性胃炎还是慢性萎缩性胃炎,这个核心组合均可使用。
根据网络提供的数据,结合临证实践观察,总结出经验方如下：慢性浅表性胃炎基本方：太子参(或党参)、白术、海螵蛸、浙贝(或川贝)、天花粉、鸡内金、连翘、半夏曲。慢性萎缩性胃炎基本方：太子参(或党参)、白术、海螵蛸、浙贝(或川贝)、天花粉、沙参、麦冬、玉竹、山药、石斛、黄芪。
创新点：
在总结老师的经验的同时,逐渐形成自己的新观点,征得老师的认可后,归纳为：
治疗慢性胃炎在理论方面的创新思路
将高忠英教授提出的慢性胃炎的核心病机脾虚胃燥的观点,进一步细化,结合慢性胃炎的发展演变过程,我认为,脾虚是始终存在的,胃燥可分为两个阶段,第一阶段为胃燥偏实热的慢性浅表性胃炎,第二阶段是胃燥偏虚热的慢性萎缩性胃炎。有关基础研究已与清华信息科学与技术国家实验室(筹)生物信息学研究部合作,开展“基于生物信息学和代谢组学的慢性萎缩性胃炎寒热证的标记物网络研究”并已立项。
治疗慢性胃炎在临床用药方面的新突破
将高忠英教授慢性胃炎的经验方广泛地应用于临床实践,在基本方的基础上,根据患者情况随症加减。譬如,粘膜红肿或Hp感染阳性可酌加清热药物,如黄芩、蒲公英等；寒热错杂患者,也可选用仲景的半夏泻心汤加减。中重度浅表性胃炎或萎缩性胃炎,可多用些活血化瘀药丹参、莪术等,促进胃粘膜血液循环,改善血供,有助于胃粘膜萎缩的逆转。伴有中重度异型增生者,除用活血化瘀药外,可加重天花粉和浙贝的用量,再配伍软坚散结药物,如生牡蛎、生薏米等加强疗效；且可早用抗癌药物提前干预,如白花蛇舌草,半枝莲等,“未病先防”,防止胃癌的发生。借鉴高忠英教授的慢性胃炎基本方,并结合自己的临床经验,自拟健脾益胃汤加减观察治疗慢性萎缩性胃炎46例,与对照组西药常规治疗相比,总有效率、主要症状和胃镜病理的改善情况均有显著性差异(P<0.05,P<0.01)。相关学术论文已发表在《中国中西医结合消化杂志》(见附录)。
第三部分运用数据挖掘方法对高忠英教授治疗慢性胃炎用药规律的研究
为了能更好的学习和继承高忠英教授的脾胃学术思想,提高临床治疗水平,本研究试从多个角度总结、挖掘高忠英教授治疗慢性胃炎的临床用药规律。利用复杂系统熵聚类技术,对高忠英教授的处方数据进行挖掘,在治疗有效的前提下,探讨治疗慢性胃炎的处方用药的规律。
研究方法：
首先,采用Epidata数据库平台进行熵聚类等方法对数据库的处理,得出结论。主要从三个层面挖掘隐含在数据库背后的处方用药规律,一个层面是单味药的,主要通过频次法实现；第二个层面是药对的分析,主要通过互信息,关联规则等,探讨在脾胃病证下常用的药对,初步揭示处方用药规律；最后一个层面是多个药物之间的组合规律,通过复杂系统熵聚类,聚类分析,主成份分析和因子分析等。这三个层面相互印证,互为补充,共同揭示高忠英教授的处方用药规律。
同时应用复杂网络Pajek软件,不仅提供了一整套快速有效的用来分析复杂网络的算法,而且还提供了一个可视化的界面,可以从视觉的角度更加直观地了解复杂网络的结构特性。通过对高忠英教授处方集的共性网络结构分析,能够发现体现其处方思维和临床特点的核心处方配伍结构,从而辅助进行高忠英教授经验的传承和整理研究。
结果：
通过上述方法,分析筛选了数据库中730首处方,得到治疗慢性胃炎中使用频率较高的30味药物,应用改进的互信息法,分析得到了94个常用药对,其关联系数均在0.05以上；应用复杂系统熵聚类方法,得到核心组合11个。采用复杂熵聚类的方法构建80味治疗慢性胃炎常用中药之间的关联关系,获得122项关联。绘制出了慢性胃炎常用中药复杂网络节点分类图。经过统计得出的频次规律最高为海螵蛸355,天花粉347,太子参324,浙贝300,白术296,半夏曲244,莪术201,鸡内金196,砂仁144,菜菔子142,白芍126,黄连125,吴茱萸116,炮姜94,连翘80。这一结果与临床实际完全符合,基本上是高忠英教授治疗慢性胃炎的常用药物,根据上述复杂网络的结果,再与临床实际相结合,可得到如下结论：
复杂网络节点分类图位于最核心的药物组合有太子参(或党参),白术,天花粉,浙贝(或川贝),海螵蛸。太子参(或党参),白术主要是健脾为主；天花粉,浙贝(或川贝),海螵蛸主要针对胃体本身,修复糜烂,以润燥为主。核心组合的配伍,正切中慢性胃炎脾虚胃燥的核心病机,所以无论是慢性浅表性胃炎还是慢性萎缩性胃炎,这个核心组合均可使用。
根据网络提供的数据,结合临证实践观察,总结出经验方如下：慢性浅表性胃炎基本方：太子参(或党参)、白术、海螵蛸、浙贝(或川贝)、天花粉、鸡内金、连翘、半夏曲。慢性萎缩性胃炎基本方：太子参(或党参)、白术、海螵蛸、浙贝(或川贝)天花粉、沙参、麦冬、玉竹、山药、石斛、黄芪。
创新点：
在总结老师的经验的同时,逐渐形成自己的新观点,征得老师的认可后,归纳为：
治疗慢性胃炎在理论方面的创新思路
将高忠英教授提出的慢性胃炎的核心病机脾虚胃燥的观点,进一步细化,结合慢性胃炎的发展演变过程,我认为,脾虚是始终存在的,胃燥可分为两个阶段,第一阶段为胃燥偏实热的慢性浅表性胃炎,第二阶段是胃燥偏虚热的慢性萎缩性胃炎。有关基础研究已与清华信息科学与技术国家实验室(筹)生物信息学研究部合作,开展“基于生物信息学和代谢组学的慢性萎缩性胃炎寒热证的标记物网络研究”并已立项。
治疗慢性胃炎在临床用药方面的新突破
将高忠英教授慢性胃炎的经验方广泛地应用于临床实践,在基本方的基础上,根据患者情况随症加减。譬如,粘膜红肿或Hp感染阳性可酌加清热药物,如黄芩、蒲公英等；寒热错杂患者,也可选用仲景的半夏泻心汤加减。中重度浅表性胃炎或萎缩性胃炎,可多用些活血化瘀药丹参、莪术等,促进胃粘膜血液循环,改善血供,有助于胃粘膜萎缩的逆转。伴有中重度异型增生者,除用活血化瘀药外,可加重天花粉和浙贝的用量,再配伍软坚散结药物,如生牡蛎、生薏米等加强疗效；且可早用抗癌药物提前干预,如白花蛇舌草,半枝莲等,“未病先防”,防止胃癌的发生。借鉴高忠英教授的慢性胃炎基本方,并结合自己的临床经验,自拟健脾益胃汤加减观察治疗慢性萎缩性胃炎46例,与对照组西药常规治疗相比,总有效率、主要症状和胃镜病理的改善情况均有显著性差异(P<0.05,P<0.01)。相关学术论文已发表在《中国中西医结合消化杂志》(见附录)。
Professor Gao Zhongying, born in a family specializing in traditional Chinese medicine (TCM), has studied medication since his childhood and acquired the proficiency in internal medicine, gynecology and pediatrics. As one of 500 eminent TCM experts identified by the National Ministry of Health, he is also among the second, the third and fourth batch of national successor mentors. With 58 years of experiences in clinical medicine, teaching and research work, he has served as the director successively in the Research Departments of Traditional Chinese Internal Medicine and TCM Formulas in the TCM School of Capital Medical University. By studying the principles of medical science, Professor Gao has became a master on classical medical books, and created the "five-organ reinforcing method", which breaks traditional theoretical concepts and expands the meaning of reinforcing method. Clinical evidences have shown that, Professor Gao can achieve effective treatment with precise and appropriate prescription. He has rich clinical experiences in applying pure Chinese medicine to treat chronic gastritis. This study consists of three parts.
PartⅠreviews origins of Professor Gao Zhongying's academic thoughts. Based on methods of interview and analytical induction, origins of Professor Gao's academic thoughts are summarized, finishing his heritage genealogy and heritage status, while excavating the formation process of his academic thoughts and clinical experiences, clearing the relationship of each professional school of TCM related to Professor Gao Zhongying's the spleen and stomach field, excavating and finishing Professor Gao's academic thoughts of spleen and stomach in the TCM classic works. The study included Professor Gao's road to success, medical family tradition, Beijing traditional Chinese medicine project "Passing Heritage 3+3" and his workstation of Chinese traditional medicine experts are presented. Introducing such medical ancient classics as Nei Jing from which Professor Gao has derives the academic thoughts concerning spleen and stomach are exhaustively researched, and the well-know ancient medical scholars such as Zhang Zhongjing, Li Dongyuan, and Ye Tianshi. The relationship of various TCM schools specialized in stomach and spleen, including Shi Jinmo, Wei Shuhe, Dong Jianhua, Guan Youbo, Li Qiangou. Their different ways to inherit tradition and make creation are clearly defined..
PartⅡ, Gao Zhongying's academic thoughts and clinical experiences are finished and studied. His academic thoughts embodied in the study of the clinical formula rules, this part from five aspects describes the "five-organ reinforcing method" respectively, the rules of Clinical formula, special viewpoints of formula, his spleen and stomach theory, and his therapy on respiratory diseases
Firstly, a deep analysis is made on Professor Gao's theoretical and academic thoughts of reinforcing five internal organs, which exactly reflects the compatibility rule in combining herbs to reinforce the Qi, blood, Yin and Yang and is an essential and compliance principle for replenishing the deficiency of five internal organs. The followings are extracted from Professor Gao's theory:the deficiency of five internal organs doesn't mean the deficiency of blood, Yin and Yang, but means different emphasis according to the physiological characteristics of the five internal organs and their pathological features. The reinforcing of spleen, lung and kidney focuses on Qi, Yang and Yin. The reinforcing of heart and liver can also strengthen the Qi, blood, Yin and Yang.
In his years of pharmacology teaching, Gao Zhongying, based on his extensive reading of medical classics and rich teaching experiences, points out the disadvantage of the present formula teaching and puts forward his unique views. Apart from teaching, he did lots of clinical works combining with the theories, and makes great efforts to reach the top level of formula study which refers to find out the rules of clinical medicine.
Professor Gao Zhongying not only absorbed many insights in the theories but also makes innovation in dealing with spleen and stomach diseases. His spleen and stomach academic thoughts originated from the Nei Jing, and differentiation form Zhang Zhongjing, and Li Dongyuan summarized all of them. In the Qing Dynasty, Ye Tianshi proposed the academic concept of separately treating the spleen and stomach with an emphasis on nourishing the stomach Yin, making a supplementary to Li Dongheng's theory of focusing more on treating spleen than on treating stomach and focusing on warming than on nourishing Yin. Professor Gao concentrates on studying ancient theories on the spleen and stomach but doesn't blindly obey them. He has put forward his own insights that the production of stomach Yin originates from the Qi transformation of middle burner. Spleen Yang represents the entire digestive function, while the spleen Yin includes the digestive fluid and lubricating fluid (saliva, esophagus lubricating fluid, gastric juice, intestinal juice, etc.) in upper and lower digestive tracts. As a part of the spleen Yin, stomach Yin (fluid) is the digestive fluid sublimated from body fluid by spleen Yang. When the gland of gastric mucosa atrophies, the stomach yin is short of production, the essential way is that the spleen should be reinforced to promote the source. Professor Gao has gradually formed his own unique theoretical system. In the treatment of chronic gastritis, he also has unique insights and clinical experience. From the physiology & pathology of spleen and stomach as well as the etiology & pathogenesis of chronic gastritis, he proposes the theory that most chronic gastritis are the deficiency of the root and the excess of the branch, its core pathogenesis lies in the spleen insufficiency and stomach dryness, so the treatment should focuses on reinforcing the spleen Qi, nourishing Yin and moistening the dryness, and combining the differentiation of syndromes and diseases. Its core ideas:(1) the spleen deficiency and stomach dryness are the basic pathogenesis of chronic gastritis; (2) the spleen deficiency is the inevitable result of weakening digestive function; (3) the stomach dryness is the characteristics of chronic gastritis; (4) the spleen deficiency and stomach dryness are the reasons for Yang and Yin deficit of chronic gastritis; (5) reinforcing the spleen and moistening the stomach are the basic treatments to chronic gastritis. Syndrome Differentiation Classification is the basis of treating chronic gastritis. It also emphasizes attribution of spleen deficiency and stomach dryness, combined with endoscopic mucosal swelling, ulceration, atrophy observed, so as to make correct herbs selection to obtain good effect.
Professor Gao Zhongying has quite rich diagnosis and treatment experiences, covering internal medicine, surgery, gynecology and Pediatrics, especially specialized in various digestive system and respiratory system diseases such as chronic atrophic gastritis, gastro-esophageal reflux disease, ulcerative colitis, chronic intractable cough, allergic rhinitis and allergic asthma. He also shows originality in gynecological medicine, with the outstanding characteristics of "emphasizing Chong, Ren while thinking about Yangming", "stressing to regulate menstruation and removing blood stasis", "descending Yangming in harmony and regulating menstruation" and "preferring warm herbs and keeping uterus warm first". Besides, he has achieved very good clinical effect with warm herbs in the treatment of hypertensive disease and recurrent oral ulcer and with Tingli pill in children cough and asthma.
PartⅢClinical research on Professor Gao's academic experiences In order to better study and inherit Professor Gao's academic thinking of spleen and stomach, and improve the level of clinical treatment, this research has summed up and mined his clinical medication rules in treating chronic gastritis from multiple perspectives. By entropy clustering technology of complex systems, mine Professor Gao's formula data, and discuss the rules of formula which have good effects in the treatment of chronic gastritis.
Methods:
First, apply entropy clustering methods with Epidata 3.1 database platform to deal with formula data, and draw conclusions. Search for the formula laws behind the database mainly from the three aspects. The first aspect referred to the single herb, and it was mainly achieved through the frequency method; the second aspect referred to the analysis on couplet herbs, mainly through mutual information and association rules, etc., to discuss the commonly used couplet herbs for spleen & stomach diseases and initially reveal the formula rules; and the last aspect referred to the combination laws of many herbs, which were discussed through the entropy clustering of complex systems, clustering analysis, principal component analysis and factor analysis. These three aspects mutually supplemented and corresponded with each other, revealing Professor Gao Zhongying's formula laws together.
Meanwhile, the software Pajek for complex networks was applied in the process. It not only provided a set of fast and efficient algorithms for analyzing complex networks, but also presented a visual interface to facilitate the understanding on the structural characteristics of complex networks from a visual point of view. Through an analysis on the commonness of Professor Gao's formula, we found the compatibility structure that reflected formula thinking and core clinical features, thus supporting the arrangement of Professor Gao's experiences.
Results:
Through the above-mentioned methods, we analyzed and screened 730 formulas in the database, and found 30 herbs most frequently used in the treatment of chronic gastritis. By applying the method of modified mutual information, we got 94 commonly-used herbs with correlation coefficients of above 0.05; and through entropy clustering method of complex systems, we found 11 core combinations. Entropy clustering method of complex systems was used to build the association among 80 herbs commonly used for treating chronic gastritis, and 122 associations were obtained. We draw out the classified graph of complex network nodes of herbs commonly used for chronic gastritis. According to statistics, cuttlebone had the highest frequency of 355, trichosanthin 347, heterophylla 324, bulbus fritilariae 300, atractylis ovata 296, pinellia rhizome fermented mass 244, rhizoma zedoariae 201, endothelium corneum gigeriae galli 196, amomum villosum 144, radish seed 142, paeonia lactiflora pallas 126, rhizoma coptidis 125, evodia rutaecarpa 116, baked ginger 94, forsythia 80. This result is completely in line with clinical practice, and they are essentially Professor Gao's commonly used herbs for chronic gastritis. Combining the above result of complex network with clinical practice, we can draw the following conclusions:
We have summed up the following prescriptions by combining the network data with clinical observations:the basic formula for chronic superficial gastritis:heterophylla (or codonopsis), atractylis ovata, cuttlebone, thunbery fritillary bulb (or fritillary), trichosanthin, endothelium corneum gigeriae galli, forsythia and pinellia rhizome fermented mass. The basic formula for chronic atrophic gastritis:heterophylla (or codonopsis), atractylis ovata, cuttlebone, thunbery fritillary bulb (or fritillary), trichosanthin, root of straight ladybell, ophiopogon root, polygonatum, yam, dendrobium and astragalus.
Innovative concept:
In summing up the professor's experiences, we have gradually formed our own ideas and introduced innovative concept to the theory of chronic gastritis treatment, namely, we proposed a further subdivision based on Professor Gao's theory that the core pathogenesis of chronic gastritis lies in the deficiency of spleen and dryness of stomach. According to the development and evolution of chronic gastritis, the deficiency of spleen is always there, and the dryness of stomach can be divided into two phases, the first of which is chronic superficial gastritis with excess heat of stomach dryness, and the second phase is the chronic atrophic gastritis with deficiency heat of stomach dryness.
The related basic research has been with Tsinghua Information Science and Technology (raise) National Laboratory the Ministry of bioinformatics research, to carry out "Based on Bioinformatics and Metabolomics of Cold and Heat Syndrome of Chronic Atrophic Gastritis Markers of Network Research," and has been approved.
Based on Professor Gao Zhongying's basic formula for treating chronic gastritis, we have made breakthroughs in clinical medication by modifying the formula according to patients' different symtoms.
For instance, herbs for reducing fever (such as skullcap, dandelion, etc.) can be appropriately added to treat reddening and swelling of mucosa or Hp infection; and patients with cold-heat jumble can also use appropriate dose of Zhang Zhongjing's decoction of tuber pinellia for removing the heart-fire. Moderate to severe superficial gastritis or atrophic gastritis can adopt more herbs for invigorating blood circulation and eliminating stasis such as salvia miltiorrhiza and rhizoma zedoariae, etc. to contribute to the reversion of gastric atrophy. For patients with moderate to severe dysplasia, more forsythia and fritillaria should be additionally added with herbs for softening hard lumps and dispelling nodes, such as raw oysters, spina gleditsiae, selfheal, etc. to enhance efficacy; and anti-cancer drugs (such as Herba Oldenlandiae, Herba Scutellariae Barbatae, etc.) can be early used for intervention to prevent gastric cancer.
Applying the reinforcing spleen and tonifying the stomach decoction we made to treat 46 cases of the chronic superficial gastritis comparing to the control group treated by conventional western medicine drugs, the total effect rate, main symptoms, the pathological changing condition under gatroscopy are obvious difference between two groups (P＜0.05,P＜0.01.) The related academic paper already have been published Chinese Journal of Integrated Traditional and Western Medicine on Digestion
In order to better study and inherit Professor Gao's academic thinking of spleen and stomach, and improve the level of clinical treatment, this research has summed up and mined his clinical medication rules in treating chronic gastritis from multiple perspectives. By entropy clustering technology of complex systems, mine Professor Gao's formula data, and discuss the rules of formula which have good effects in the treatment of chronic gastritis. Methods:
First, apply entropy clustering methods with Epidata 3.1 database platform to deal with formula data, and draw conclusions. Search for the formula laws behind the database mainly from the three aspects. The first aspect referred to the single herb, and it was mainly achieved through the frequency method; the second aspect referred to the analysis on couplet herbs, mainly through mutual information and association rules, etc., to discuss the commonly used couplet herbs for spleen & stomach diseases and initially reveal the formula rules; and the last aspect referred to the combination laws of many herbs, which were discussed through the entropy clustering of complex systems, clustering analysis, principal component analysis and factor analysis. These three aspects mutually supplemented and corresponded with each other, revealing Professor Gao Zhongying's formula laws together.
Meanwhile, the software Pajek for complex networks was applied in the process. It not only provided a set of fast and efficient algorithms for analyzing complex networks, but also presented a visual interface to facilitate the understanding on the structural characteristics of complex networks from a visual point of view. Through an analysis on the commonness of Professor Gao's formula, we found the compatibility structure that reflected formula thinking and core clinical features, thus supporting the arrangement of Professor Gao's experiences.
Results:
Through the above-mentioned methods, we analyzed and screened 730 formulas in the database, and found 30 herbs most frequently used in the treatment of chronic gastritis. By applying the method of modified mutual information, we got 94 commonly-used herbs with correlation coefficients of above 0.05; and through entropy clustering method of complex systems, we found 11 core combinations. Entropy clustering method of complex systems was used to build the association among 80 herbs commonly used for treating chronic gastritis, and 122 associations were obtained. We draw out the classified graph of complex network nodes of herbs commonly used for chronic gastritis. According to statistics, cuttlebone had the highest frequency of 355, trichosanthin 347, heterophylla 324, bulbus fritilariae 300, atractylis ovata 296, pinellia rhizome fermented mass 244, rhizoma zedoariae 201, endothelium corneum gigeriae galli 196, amomum villosum 144, radish seed 142, paeonia lactiflora pallas 126, rhizoma coptidis 125, evodia rutaecarpa 116, baked ginger 94, forsythia 80. This result is completely in line with clinical practice, and they are essentially Professor Gao's commonly used herbs for chronic gastritis. Combining the above result of complex network with clinical practice, we can draw the following conclusions:
We have summed up the following prescriptions by combining the network data with clinical observations:the basic formula for chronic superficial gastritis:heterophylla (or codonopsis), atractylis ovata, cuttlebone, thunbery fritillary bulb (or fritillary), trichosanthin, endothelium corneum gigeriae galli, forsythia and pinellia rhizome fermented mass. The basic formula for chronic atrophic gastritis:heterophylla (or codonopsis), atractylis ovata, cuttlebone, thunbery fritillary bulb (or fritillary), trichosanthin, root of straight ladybell, ophiopogon root, polygonatum, yam, dendrobium and astragalus.
Innovative concept:
In summing up the professor's experiences, we have gradually formed our own ideas and introduced innovative concept to the theory of chronic gastritis treatment, namely, we proposed a further subdivision based on Professor Gao's theory that the core pathogenesis of chronic gastritis lies in the deficiency of spleen and dryness of stomach. According to the development and evolution of chronic gastritis, the deficiency of spleen is always there, and the dryness of stomach can be divided into two phases, the first of which is chronic superficial gastritis with excess heat of stomach dryness, and the second phase is the chronic atrophic gastritis with deficiency heat of stomach dryness.
The related basic research has been with Tsinghua Information Science and Technology (raise) National Laboratory the Ministry of bioinformatics research, to carry out "Based on Bioinformatics and Metabolomics of Cold and Heat Syndrome of Chronic Atrophic Gastritis Markers of Network Research," and has been approved.
Based on Professor Gao Zhongying's basic formula for treating chronic gastritis, we have made breakthroughs in clinical medication by modifying the formula according to patients' different symtoms.
For instance, herbs for reducing fever (such as skullcap, dandelion, etc.) can be appropriately added to treat reddening and swelling of mucosa or Hp infection; and patients with cold-heat jumble can also use appropriate dose of Zhang Zhongjing's decoction of tuber pinellia for removing the heart-fire. Moderate to severe superficial gastritis or atrophic gastritis can adopt more herbs for invigorating blood circulation and eliminating stasis such as salvia miltiorrhiza and rhizoma zedoariae, etc. to contribute to the reversion of gastric atrophy. For patients with moderate to severe dysplasia, more forsythia and fritillaria should be additionally added with herbs for softening hard lumps and dispelling nodes, such as raw oysters, spina gleditsiae, selfheal, etc. to enhance efficacy; and anti-cancer drugs (such as Herba Oldenlandiae, Herba Scutellariae Barbatae, etc.) can be early used for intervention to prevent gastric cancer. Applying the reinforcing spleen and tonifying the stomach decoction we made to treat 46 cases of the chronic superficial gastritis comparing to the control group treated by conventional western medicine drugs, the total effect rate, main symptoms, the pathological changing condition under gatroscopy are obvious difference between two groups (P＜0.05,P＜0.01) The related academic paper already have been published Chinese Journal of Integrated Traditional and Western Medicine on Digestion
第一部分高忠英教授学术思想渊源。用访谈法和分析归纳法对高忠英教授学术思想渊源进行了总结,梳理了高忠英教授传承谱系及传承现状,探寻了高忠英教授学术思想及其临床经验的形成过程,明晰了高忠英教授脾胃专业相关的中医各家学派的关系,并对高忠英教授脾胃学术思想中医经典古籍渊薮进行了挖掘整理。包括高忠英教授成才之路以及家传师承情况及北京中医药“薪火传承3+3工程”高忠英老中医药专家继承工作站的传承情况,对高忠英教授脾胃学术思想的形成有重大影响的经典古籍的介绍,如《内经》的脾胃论、张仲景的脾胃论、李东垣的脾胃论、叶天士的脾胃论,与脾胃相关的中医各家学派的关系,如施今墨、魏舒和.、董建华、关幼波、李乾构及其继承与创新的具体体现。
第二部分高忠英教授学术思想和临床经验的整理与研究。高忠英教授学术思想集中体现在五脏补益法的学术思想和1临床用药配伍规律的研究,本部分从五方面分别叙述了五脏补益法的学术思想、临床用药配伍规律的研究、关于方剂学的独特学术观点、高忠英教授脾胃学术思想以及治疗呼吸系统疾病学术思想的整理与研究。
首先将高忠英教授理论学术思想研究——“五脏补益”学术思想深入挖掘,五脏补益法确切地体现了补益气、血、阴、阳选药组方的配伍规律,是补益五脏虚证必须遵守的治疗法则。从高忠英教授的五脏补益理论中,我们提炼出：五脏虚并非气血阴阳俱虚,是按五脏的生理特点、病理特征有所侧重,补脾、肺、肾重在补气、阴、阳；补心、肝则气、血、阴、阳均可补益。
高忠英教授在长期的方剂学教学中,潜心研究经典古籍,积累了丰富的教学经验,指出了现在方剂学教学的不足,提出了自己独到的见解和观点。教学之余,勤于临证,理论与实际相结合,努力达到方剂学研究的最高境界,即找寻出临床用药的配伍规律。
高忠英教授在脾胃病方面,不仅在理论上博采众长,而且在实践中有所创新。高忠英教授认为脾胃理论源于《内经》,辨证法于仲景,集大成者则系李东垣,而清代叶天士关于脾胃分治的认识和甘润养胃阴的学术观点,弥补了东垣详于治脾,略于治胃,重在温补,不及养阴的不足。高忠英教授师古而不泥古,在对脾胃病的临床诊治中,提出了自己独到的见解,认为胃阴的产生源于中焦气化,脾阳代表整个消化功能,脾阴则包涵上下消化道的消化液、润滑液(唾液,食道润滑液,胃液、肠液等)。胃阴(液)是脾阴的一部分,是脾阳升华水液所产生的消化液。当胃粘膜的腺体萎缩,胃阴生化无源时,应以补脾助生化之源为本。逐渐形成了自己独特的理论体系。在治疗慢性胃炎方面,从脾胃的生理、病理及慢性胃炎的病因病机角度,提出慢性胃炎多为本虚标实之证,脾虚胃燥是其核心病机,治疗当以健脾益气、养阴润燥为法,辨证与辨病相结合进行治疗。其核心思想为：①脾虚胃燥是慢性胃炎的基本病机；②脾虚是消化功能减弱的必然趋势；③胃燥是慢性胃炎病变实体的特征；④脾虚胃燥是慢性胃炎阳虚阴亏的根源；⑤补脾润燥是治疗慢性胃炎的基本治法。辨证分型是治疗慢性胃炎的基础,同时强调注意脾虚胃燥的病理归属,结合胃镜下黏膜红肿、糜烂、萎缩等状态,正确地选药组方,定会取得理想效果。
高忠英教授诊疗经验相当丰富,经治病人涉及内、外、妇、儿各科,尤其在消化系统和呼吸系统疾病方面有非常独到的临床疗效,譬如慢性萎缩性胃炎、胃食管反流病、溃疡性结肠炎、慢性顽固性咳嗽、过敏性鼻炎和过敏性哮喘都是高忠英教授的善治病种。在妇科用药方面也匠心独到,突出特点为“强调冲任,兼顾阳明”“突出调经,重在化瘀”.“和降阳明,兼以调经”“喜用温药,暖宫为先”。另外在用温热药治疗高血压病和复发性口腔溃疡及应用古方葶苈丸加减治疗小儿咳喘方面均具有非常好的临床疗效。
第三部分高忠英教授学术经验的临床研究
本研究利用复杂系统熵聚类技术,在治疗有效的前提下,对高忠英教授的处方数据进行挖掘,并在临床实践中验证,探讨治疗慢性胃炎的处方用药的规律。
研究方法：
首先,采用Epidata数据库平台进行熵聚类等方法对数据库的处理,得出结论。主要从三个层面挖掘隐含在数据库背后的处方用药规律,一个层面是单味药的,主要通过频次法实现；第二个层面是药对的分析,主要通过互信息,关联规则等,探讨在脾胃病证下常用的药对,初步揭示处方用药规律；最后一个层面是多个药物之间的组合规律,通过复杂系统熵聚类,聚类分析,主成份分析和因子分析等。这三个层面相互印证,互为补充,共同揭示高忠英教授的处方用药规律。
同时应用复杂网络Pajek软件,不仅提供了一整套快速有效的用来分析复杂网络的算法,而且还提供了一个可视化的界面,可以从视觉的角度更加直观地了解复杂网络的结构特性。通过对高忠英教授处方集的共性网络结构分析,能够发现体现其处方思维和临床特点的核心处方配伍结构,从而辅助进行高忠英教授经验的传承和整理研究。
结果：
通过上述方法,分析筛选了数据库中730首处方,得到治疗慢性胃炎中使用频率较高的30味药物,应用改进的互信息法,分析得到了94个常用药对；应用复杂系统熵聚类方法,得到核心组合11个。采用复杂熵聚类的方法构建80味治疗慢性胃炎常用中药之间的关联关系,获得122项关联。绘制出了慢性胃炎常用中药复杂网络节点分类图。经过统计得出的频次规律最高为海螵蛸355,天花粉347,太子参324,浙贝300,白术296,半夏曲244,莪术201,鸡内金196,砂仁144,莱菔子142,白芍126,黄连125,吴茱萸116,炮姜94,连翘80。这一结果与临床实际完全符合,基本上是高忠英教授治疗慢性胃炎的常用药物,根据上述复杂网络的结果,再与临床实际相结合,可得到如下
结论：
复杂网络节点分类图位于最核心的药物组合有太子参(或党参),白术,天花粉,浙贝(或川贝),海螵蛸。太子参(或党参),白术主要是健脾为主；天花粉,浙贝(或川贝),海螵蛸主要针对胃体本身,修复糜烂,以润燥为主。核心组合的配伍,正切中慢性胃炎脾虚胃燥的核心病机,所以无论是慢性浅表性胃炎还是慢性萎缩性胃炎,这个核心组合均可使用。
根据网络提供的数据,结合临证实践观察,总结出经验方如下：慢性浅表性胃炎基本方：太子参(或党参)、白术、海螵蛸、浙贝(或川贝)、天花粉、鸡内金、连翘、半夏曲。慢性萎缩性胃炎基本方：太子参(或党参)、白术、海螵蛸、浙贝(或川贝)、天花粉、沙参、麦冬、玉竹、山药、石斛、黄芪。
创新点：
在总结老师的经验的同时,逐渐形成自己的新观点,征得老师的认可后,归纳为：
治疗慢性胃炎在理论方面的创新思路
将高忠英教授提出的慢性胃炎的核心病机脾虚胃燥的观点,进一步细化,结合慢性胃炎的发展演变过程,我认为,脾虚是始终存在的,胃燥可分为两个阶段,第一阶段为胃燥偏实热的慢性浅表性胃炎,第二阶段是胃燥偏虚热的慢性萎缩性胃炎。有关基础研究已与清华信息科学与技术国家实验室(筹)生物信息学研究部合作,开展“基于生物信息学和代谢组学的慢性萎缩性胃炎寒热证的标记物网络研究”并已立项。
治疗慢性胃炎在临床用药方面的新突破
将高忠英教授慢性胃炎的经验方广泛地应用于临床实践,在基本方的基础上,根据患者情况随症加减。譬如,粘膜红肿或Hp感染阳性可酌加清热药物,如黄芩、蒲公英等；寒热错杂患者,也可选用仲景的半夏泻心汤加减。中重度浅表性胃炎或萎缩性胃炎,可多用些活血化瘀药丹参、莪术等,促进胃粘膜血液循环,改善血供,有助于胃粘膜萎缩的逆转。伴有中重度异型增生者,除用活血化瘀药外,可加重天花粉和浙贝的用量,再配伍软坚散结药物,如生牡蛎、生薏米等加强疗效；且可早用抗癌药物提前干预,如白花蛇舌草,半枝莲等,“未病先防”,防止胃癌的发生。借鉴高忠英教授的慢性胃炎基本方,并结合自己的临床经验,自拟健脾益胃汤加减观察治疗慢性萎缩性胃炎46例,与对照组西药常规治疗相比,总有效率、主要症状和胃镜病理的改善情况均有显著性差异(P<0.05,P<0.01)。相关学术论文已发表在《中国中西医结合消化杂志》(见附录)。
第三部分运用数据挖掘方法对高忠英教授治疗慢性胃炎用药规律的研究
为了能更好的学习和继承高忠英教授的脾胃学术思想,提高临床治疗水平,本研究试从多个角度总结、挖掘高忠英教授治疗慢性胃炎的临床用药规律。利用复杂系统熵聚类技术,对高忠英教授的处方数据进行挖掘,在治疗有效的前提下,探讨治疗慢性胃炎的处方用药的规律。
研究方法：
首先,采用Epidata数据库平台进行熵聚类等方法对数据库的处理,得出结论。主要从三个层面挖掘隐含在数据库背后的处方用药规律,一个层面是单味药的,主要通过频次法实现；第二个层面是药对的分析,主要通过互信息,关联规则等,探讨在脾胃病证下常用的药对,初步揭示处方用药规律；最后一个层面是多个药物之间的组合规律,通过复杂系统熵聚类,聚类分析,主成份分析和因子分析等。这三个层面相互印证,互为补充,共同揭示高忠英教授的处方用药规律。
同时应用复杂网络Pajek软件,不仅提供了一整套快速有效的用来分析复杂网络的算法,而且还提供了一个可视化的界面,可以从视觉的角度更加直观地了解复杂网络的结构特性。通过对高忠英教授处方集的共性网络结构分析,能够发现体现其处方思维和临床特点的核心处方配伍结构,从而辅助进行高忠英教授经验的传承和整理研究。
结果：
通过上述方法,分析筛选了数据库中730首处方,得到治疗慢性胃炎中使用频率较高的30味药物,应用改进的互信息法,分析得到了94个常用药对,其关联系数均在0.05以上；应用复杂系统熵聚类方法,得到核心组合11个。采用复杂熵聚类的方法构建80味治疗慢性胃炎常用中药之间的关联关系,获得122项关联。绘制出了慢性胃炎常用中药复杂网络节点分类图。经过统计得出的频次规律最高为海螵蛸355,天花粉347,太子参324,浙贝300,白术296,半夏曲244,莪术201,鸡内金196,砂仁144,菜菔子142,白芍126,黄连125,吴茱萸116,炮姜94,连翘80。这一结果与临床实际完全符合,基本上是高忠英教授治疗慢性胃炎的常用药物,根据上述复杂网络的结果,再与临床实际相结合,可得到如下结论：
复杂网络节点分类图位于最核心的药物组合有太子参(或党参),白术,天花粉,浙贝(或川贝),海螵蛸。太子参(或党参),白术主要是健脾为主；天花粉,浙贝(或川贝),海螵蛸主要针对胃体本身,修复糜烂,以润燥为主。核心组合的配伍,正切中慢性胃炎脾虚胃燥的核心病机,所以无论是慢性浅表性胃炎还是慢性萎缩性胃炎,这个核心组合均可使用。
根据网络提供的数据,结合临证实践观察,总结出经验方如下：慢性浅表性胃炎基本方：太子参(或党参)、白术、海螵蛸、浙贝(或川贝)、天花粉、鸡内金、连翘、半夏曲。慢性萎缩性胃炎基本方：太子参(或党参)、白术、海螵蛸、浙贝(或川贝)天花粉、沙参、麦冬、玉竹、山药、石斛、黄芪。
创新点：
在总结老师的经验的同时,逐渐形成自己的新观点,征得老师的认可后,归纳为：
治疗慢性胃炎在理论方面的创新思路
将高忠英教授提出的慢性胃炎的核心病机脾虚胃燥的观点,进一步细化,结合慢性胃炎的发展演变过程,我认为,脾虚是始终存在的,胃燥可分为两个阶段,第一阶段为胃燥偏实热的慢性浅表性胃炎,第二阶段是胃燥偏虚热的慢性萎缩性胃炎。有关基础研究已与清华信息科学与技术国家实验室(筹)生物信息学研究部合作,开展“基于生物信息学和代谢组学的慢性萎缩性胃炎寒热证的标记物网络研究”并已立项。
治疗慢性胃炎在临床用药方面的新突破
将高忠英教授慢性胃炎的经验方广泛地应用于临床实践,在基本方的基础上,根据患者情况随症加减。譬如,粘膜红肿或Hp感染阳性可酌加清热药物,如黄芩、蒲公英等；寒热错杂患者,也可选用仲景的半夏泻心汤加减。中重度浅表性胃炎或萎缩性胃炎,可多用些活血化瘀药丹参、莪术等,促进胃粘膜血液循环,改善血供,有助于胃粘膜萎缩的逆转。伴有中重度异型增生者,除用活血化瘀药外,可加重天花粉和浙贝的用量,再配伍软坚散结药物,如生牡蛎、生薏米等加强疗效；且可早用抗癌药物提前干预,如白花蛇舌草,半枝莲等,“未病先防”,防止胃癌的发生。借鉴高忠英教授的慢性胃炎基本方,并结合自己的临床经验,自拟健脾益胃汤加减观察治疗慢性萎缩性胃炎46例,与对照组西药常规治疗相比,总有效率、主要症状和胃镜病理的改善情况均有显著性差异(P<0.05,P<0.01)。相关学术论文已发表在《中国中西医结合消化杂志》(见附录)。
Professor Gao Zhongying, born in a family specializing in traditional Chinese medicine (TCM), has studied medication since his childhood and acquired the proficiency in internal medicine, gynecology and pediatrics. As one of 500 eminent TCM experts identified by the National Ministry of Health, he is also among the second, the third and fourth batch of national successor mentors. With 58 years of experiences in clinical medicine, teaching and research work, he has served as the director successively in the Research Departments of Traditional Chinese Internal Medicine and TCM Formulas in the TCM School of Capital Medical University. By studying the principles of medical science, Professor Gao has became a master on classical medical books, and created the "five-organ reinforcing method", which breaks traditional theoretical concepts and expands the meaning of reinforcing method. Clinical evidences have shown that, Professor Gao can achieve effective treatment with precise and appropriate prescription. He has rich clinical experiences in applying pure Chinese medicine to treat chronic gastritis. This study consists of three parts.
PartⅠreviews origins of Professor Gao Zhongying's academic thoughts. Based on methods of interview and analytical induction, origins of Professor Gao's academic thoughts are summarized, finishing his heritage genealogy and heritage status, while excavating the formation process of his academic thoughts and clinical experiences, clearing the relationship of each professional school of TCM related to Professor Gao Zhongying's the spleen and stomach field, excavating and finishing Professor Gao's academic thoughts of spleen and stomach in the TCM classic works. The study included Professor Gao's road to success, medical family tradition, Beijing traditional Chinese medicine project "Passing Heritage 3+3" and his workstation of Chinese traditional medicine experts are presented. Introducing such medical ancient classics as Nei Jing from which Professor Gao has derives the academic thoughts concerning spleen and stomach are exhaustively researched, and the well-know ancient medical scholars such as Zhang Zhongjing, Li Dongyuan, and Ye Tianshi. The relationship of various TCM schools specialized in stomach and spleen, including Shi Jinmo, Wei Shuhe, Dong Jianhua, Guan Youbo, Li Qiangou. Their different ways to inherit tradition and make creation are clearly defined..
PartⅡ, Gao Zhongying's academic thoughts and clinical experiences are finished and studied. His academic thoughts embodied in the study of the clinical formula rules, this part from five aspects describes the "five-organ reinforcing method" respectively, the rules of Clinical formula, special viewpoints of formula, his spleen and stomach theory, and his therapy on respiratory diseases
Firstly, a deep analysis is made on Professor Gao's theoretical and academic thoughts of reinforcing five internal organs, which exactly reflects the compatibility rule in combining herbs to reinforce the Qi, blood, Yin and Yang and is an essential and compliance principle for replenishing the deficiency of five internal organs. The followings are extracted from Professor Gao's theory:the deficiency of five internal organs doesn't mean the deficiency of blood, Yin and Yang, but means different emphasis according to the physiological characteristics of the five internal organs and their pathological features. The reinforcing of spleen, lung and kidney focuses on Qi, Yang and Yin. The reinforcing of heart and liver can also strengthen the Qi, blood, Yin and Yang.
In his years of pharmacology teaching, Gao Zhongying, based on his extensive reading of medical classics and rich teaching experiences, points out the disadvantage of the present formula teaching and puts forward his unique views. Apart from teaching, he did lots of clinical works combining with the theories, and makes great efforts to reach the top level of formula study which refers to find out the rules of clinical medicine.
Professor Gao Zhongying not only absorbed many insights in the theories but also makes innovation in dealing with spleen and stomach diseases. His spleen and stomach academic thoughts originated from the Nei Jing, and differentiation form Zhang Zhongjing, and Li Dongyuan summarized all of them. In the Qing Dynasty, Ye Tianshi proposed the academic concept of separately treating the spleen and stomach with an emphasis on nourishing the stomach Yin, making a supplementary to Li Dongheng's theory of focusing more on treating spleen than on treating stomach and focusing on warming than on nourishing Yin. Professor Gao concentrates on studying ancient theories on the spleen and stomach but doesn't blindly obey them. He has put forward his own insights that the production of stomach Yin originates from the Qi transformation of middle burner. Spleen Yang represents the entire digestive function, while the spleen Yin includes the digestive fluid and lubricating fluid (saliva, esophagus lubricating fluid, gastric juice, intestinal juice, etc.) in upper and lower digestive tracts. As a part of the spleen Yin, stomach Yin (fluid) is the digestive fluid sublimated from body fluid by spleen Yang. When the gland of gastric mucosa atrophies, the stomach yin is short of production, the essential way is that the spleen should be reinforced to promote the source. Professor Gao has gradually formed his own unique theoretical system. In the treatment of chronic gastritis, he also has unique insights and clinical experience. From the physiology & pathology of spleen and stomach as well as the etiology & pathogenesis of chronic gastritis, he proposes the theory that most chronic gastritis are the deficiency of the root and the excess of the branch, its core pathogenesis lies in the spleen insufficiency and stomach dryness, so the treatment should focuses on reinforcing the spleen Qi, nourishing Yin and moistening the dryness, and combining the differentiation of syndromes and diseases. Its core ideas:(1) the spleen deficiency and stomach dryness are the basic pathogenesis of chronic gastritis; (2) the spleen deficiency is the inevitable result of weakening digestive function; (3) the stomach dryness is the characteristics of chronic gastritis; (4) the spleen deficiency and stomach dryness are the reasons for Yang and Yin deficit of chronic gastritis; (5) reinforcing the spleen and moistening the stomach are the basic treatments to chronic gastritis. Syndrome Differentiation Classification is the basis of treating chronic gastritis. It also emphasizes attribution of spleen deficiency and stomach dryness, combined with endoscopic mucosal swelling, ulceration, atrophy observed, so as to make correct herbs selection to obtain good effect.
Professor Gao Zhongying has quite rich diagnosis and treatment experiences, covering internal medicine, surgery, gynecology and Pediatrics, especially specialized in various digestive system and respiratory system diseases such as chronic atrophic gastritis, gastro-esophageal reflux disease, ulcerative colitis, chronic intractable cough, allergic rhinitis and allergic asthma. He also shows originality in gynecological medicine, with the outstanding characteristics of "emphasizing Chong, Ren while thinking about Yangming", "stressing to regulate menstruation and removing blood stasis", "descending Yangming in harmony and regulating menstruation" and "preferring warm herbs and keeping uterus warm first". Besides, he has achieved very good clinical effect with warm herbs in the treatment of hypertensive disease and recurrent oral ulcer and with Tingli pill in children cough and asthma.
PartⅢClinical research on Professor Gao's academic experiences In order to better study and inherit Professor Gao's academic thinking of spleen and stomach, and improve the level of clinical treatment, this research has summed up and mined his clinical medication rules in treating chronic gastritis from multiple perspectives. By entropy clustering technology of complex systems, mine Professor Gao's formula data, and discuss the rules of formula which have good effects in the treatment of chronic gastritis.
Methods:
First, apply entropy clustering methods with Epidata 3.1 database platform to deal with formula data, and draw conclusions. Search for the formula laws behind the database mainly from the three aspects. The first aspect referred to the single herb, and it was mainly achieved through the frequency method; the second aspect referred to the analysis on couplet herbs, mainly through mutual information and association rules, etc., to discuss the commonly used couplet herbs for spleen & stomach diseases and initially reveal the formula rules; and the last aspect referred to the combination laws of many herbs, which were discussed through the entropy clustering of complex systems, clustering analysis, principal component analysis and factor analysis. These three aspects mutually supplemented and corresponded with each other, revealing Professor Gao Zhongying's formula laws together.
Meanwhile, the software Pajek for complex networks was applied in the process. It not only provided a set of fast and efficient algorithms for analyzing complex networks, but also presented a visual interface to facilitate the understanding on the structural characteristics of complex networks from a visual point of view. Through an analysis on the commonness of Professor Gao's formula, we found the compatibility structure that reflected formula thinking and core clinical features, thus supporting the arrangement of Professor Gao's experiences.
Results:
Through the above-mentioned methods, we analyzed and screened 730 formulas in the database, and found 30 herbs most frequently used in the treatment of chronic gastritis. By applying the method of modified mutual information, we got 94 commonly-used herbs with correlation coefficients of above 0.05; and through entropy clustering method of complex systems, we found 11 core combinations. Entropy clustering method of complex systems was used to build the association among 80 herbs commonly used for treating chronic gastritis, and 122 associations were obtained. We draw out the classified graph of complex network nodes of herbs commonly used for chronic gastritis. According to statistics, cuttlebone had the highest frequency of 355, trichosanthin 347, heterophylla 324, bulbus fritilariae 300, atractylis ovata 296, pinellia rhizome fermented mass 244, rhizoma zedoariae 201, endothelium corneum gigeriae galli 196, amomum villosum 144, radish seed 142, paeonia lactiflora pallas 126, rhizoma coptidis 125, evodia rutaecarpa 116, baked ginger 94, forsythia 80. This result is completely in line with clinical practice, and they are essentially Professor Gao's commonly used herbs for chronic gastritis. Combining the above result of complex network with clinical practice, we can draw the following conclusions:
We have summed up the following prescriptions by combining the network data with clinical observations:the basic formula for chronic superficial gastritis:heterophylla (or codonopsis), atractylis ovata, cuttlebone, thunbery fritillary bulb (or fritillary), trichosanthin, endothelium corneum gigeriae galli, forsythia and pinellia rhizome fermented mass. The basic formula for chronic atrophic gastritis:heterophylla (or codonopsis), atractylis ovata, cuttlebone, thunbery fritillary bulb (or fritillary), trichosanthin, root of straight ladybell, ophiopogon root, polygonatum, yam, dendrobium and astragalus.
Innovative concept:
In summing up the professor's experiences, we have gradually formed our own ideas and introduced innovative concept to the theory of chronic gastritis treatment, namely, we proposed a further subdivision based on Professor Gao's theory that the core pathogenesis of chronic gastritis lies in the deficiency of spleen and dryness of stomach. According to the development and evolution of chronic gastritis, the deficiency of spleen is always there, and the dryness of stomach can be divided into two phases, the first of which is chronic superficial gastritis with excess heat of stomach dryness, and the second phase is the chronic atrophic gastritis with deficiency heat of stomach dryness.
The related basic research has been with Tsinghua Information Science and Technology (raise) National Laboratory the Ministry of bioinformatics research, to carry out "Based on Bioinformatics and Metabolomics of Cold and Heat Syndrome of Chronic Atrophic Gastritis Markers of Network Research," and has been approved.
Based on Professor Gao Zhongying's basic formula for treating chronic gastritis, we have made breakthroughs in clinical medication by modifying the formula according to patients' different symtoms.
For instance, herbs for reducing fever (such as skullcap, dandelion, etc.) can be appropriately added to treat reddening and swelling of mucosa or Hp infection; and patients with cold-heat jumble can also use appropriate dose of Zhang Zhongjing's decoction of tuber pinellia for removing the heart-fire. Moderate to severe superficial gastritis or atrophic gastritis can adopt more herbs for invigorating blood circulation and eliminating stasis such as salvia miltiorrhiza and rhizoma zedoariae, etc. to contribute to the reversion of gastric atrophy. For patients with moderate to severe dysplasia, more forsythia and fritillaria should be additionally added with herbs for softening hard lumps and dispelling nodes, such as raw oysters, spina gleditsiae, selfheal, etc. to enhance efficacy; and anti-cancer drugs (such as Herba Oldenlandiae, Herba Scutellariae Barbatae, etc.) can be early used for intervention to prevent gastric cancer.
Applying the reinforcing spleen and tonifying the stomach decoction we made to treat 46 cases of the chronic superficial gastritis comparing to the control group treated by conventional western medicine drugs, the total effect rate, main symptoms, the pathological changing condition under gatroscopy are obvious difference between two groups (P＜0.05,P＜0.01.) The related academic paper already have been published Chinese Journal of Integrated Traditional and Western Medicine on Digestion
In order to better study and inherit Professor Gao's academic thinking of spleen and stomach, and improve the level of clinical treatment, this research has summed up and mined his clinical medication rules in treating chronic gastritis from multiple perspectives. By entropy clustering technology of complex systems, mine Professor Gao's formula data, and discuss the rules of formula which have good effects in the treatment of chronic gastritis. Methods:
First, apply entropy clustering methods with Epidata 3.1 database platform to deal with formula data, and draw conclusions. Search for the formula laws behind the database mainly from the three aspects. The first aspect referred to the single herb, and it was mainly achieved through the frequency method; the second aspect referred to the analysis on couplet herbs, mainly through mutual information and association rules, etc., to discuss the commonly used couplet herbs for spleen & stomach diseases and initially reveal the formula rules; and the last aspect referred to the combination laws of many herbs, which were discussed through the entropy clustering of complex systems, clustering analysis, principal component analysis and factor analysis. These three aspects mutually supplemented and corresponded with each other, revealing Professor Gao Zhongying's formula laws together.
Meanwhile, the software Pajek for complex networks was applied in the process. It not only provided a set of fast and efficient algorithms for analyzing complex networks, but also presented a visual interface to facilitate the understanding on the structural characteristics of complex networks from a visual point of view. Through an analysis on the commonness of Professor Gao's formula, we found the compatibility structure that reflected formula thinking and core clinical features, thus supporting the arrangement of Professor Gao's experiences.
Results:
Through the above-mentioned methods, we analyzed and screened 730 formulas in the database, and found 30 herbs most frequently used in the treatment of chronic gastritis. By applying the method of modified mutual information, we got 94 commonly-used herbs with correlation coefficients of above 0.05; and through entropy clustering method of complex systems, we found 11 core combinations. Entropy clustering method of complex systems was used to build the association among 80 herbs commonly used for treating chronic gastritis, and 122 associations were obtained. We draw out the classified graph of complex network nodes of herbs commonly used for chronic gastritis. According to statistics, cuttlebone had the highest frequency of 355, trichosanthin 347, heterophylla 324, bulbus fritilariae 300, atractylis ovata 296, pinellia rhizome fermented mass 244, rhizoma zedoariae 201, endothelium corneum gigeriae galli 196, amomum villosum 144, radish seed 142, paeonia lactiflora pallas 126, rhizoma coptidis 125, evodia rutaecarpa 116, baked ginger 94, forsythia 80. This result is completely in line with clinical practice, and they are essentially Professor Gao's commonly used herbs for chronic gastritis. Combining the above result of complex network with clinical practice, we can draw the following conclusions:
We have summed up the following prescriptions by combining the network data with clinical observations:the basic formula for chronic superficial gastritis:heterophylla (or codonopsis), atractylis ovata, cuttlebone, thunbery fritillary bulb (or fritillary), trichosanthin, endothelium corneum gigeriae galli, forsythia and pinellia rhizome fermented mass. The basic formula for chronic atrophic gastritis:heterophylla (or codonopsis), atractylis ovata, cuttlebone, thunbery fritillary bulb (or fritillary), trichosanthin, root of straight ladybell, ophiopogon root, polygonatum, yam, dendrobium and astragalus.
Innovative concept:
In summing up the professor's experiences, we have gradually formed our own ideas and introduced innovative concept to the theory of chronic gastritis treatment, namely, we proposed a further subdivision based on Professor Gao's theory that the core pathogenesis of chronic gastritis lies in the deficiency of spleen and dryness of stomach. According to the development and evolution of chronic gastritis, the deficiency of spleen is always there, and the dryness of stomach can be divided into two phases, the first of which is chronic superficial gastritis with excess heat of stomach dryness, and the second phase is the chronic atrophic gastritis with deficiency heat of stomach dryness.
The related basic research has been with Tsinghua Information Science and Technology (raise) National Laboratory the Ministry of bioinformatics research, to carry out "Based on Bioinformatics and Metabolomics of Cold and Heat Syndrome of Chronic Atrophic Gastritis Markers of Network Research," and has been approved.
Based on Professor Gao Zhongying's basic formula for treating chronic gastritis, we have made breakthroughs in clinical medication by modifying the formula according to patients' different symtoms.
For instance, herbs for reducing fever (such as skullcap, dandelion, etc.) can be appropriately added to treat reddening and swelling of mucosa or Hp infection; and patients with cold-heat jumble can also use appropriate dose of Zhang Zhongjing's decoction of tuber pinellia for removing the heart-fire. Moderate to severe superficial gastritis or atrophic gastritis can adopt more herbs for invigorating blood circulation and eliminating stasis such as salvia miltiorrhiza and rhizoma zedoariae, etc. to contribute to the reversion of gastric atrophy. For patients with moderate to severe dysplasia, more forsythia and fritillaria should be additionally added with herbs for softening hard lumps and dispelling nodes, such as raw oysters, spina gleditsiae, selfheal, etc. to enhance efficacy; and anti-cancer drugs (such as Herba Oldenlandiae, Herba Scutellariae Barbatae, etc.) can be early used for intervention to prevent gastric cancer. Applying the reinforcing spleen and tonifying the stomach decoction we made to treat 46 cases of the chronic superficial gastritis comparing to the control group treated by conventional western medicine drugs, the total effect rate, main symptoms, the pathological changing condition under gatroscopy are obvious difference between two groups (P＜0.05,P＜0.01) The related academic paper already have been published Chinese Journal of Integrated Traditional and Western Medicine on Digestion
引文
[1]王仲霞,陈秀玉.论顾护脾胃观念在《金匾要略》制剂及服法中的应用.中医研究,2005,18(9)：9-10
[2]郝丽莉,李欣育.李东垣脾胃学说浅识.中医药学报.1999,1：3-4
[3]严世芸.中医各家学说.北京：中国中医药出版社.2003：137-145
[4]董振华.李东垣对脾胃学说的贡献.现代远程教育.2005,3(11)：19-21
[5]徐寿生.李杲脾胃阴阳升降理论探讨.安徽中医学院学报,1999,18(4)：9-10
[6]杨慧清.浅谈叶天士对脾胃学说的贡献.新中医,2006,38(6)：82-83
[7]郑星.叶天士胃阴学说探析.上海中医药杂志,2002,12：34-35
[8]黄英志主编.叶天士医学全书.中国中医药出版社,1999,85-87
[9]王永炎,张志斌,张志强等,关于加强中医学派研究的建议.[J]中医杂志.2011,14(52)：1171-1172
[10]杨晋翔.董建华诊治胃痛的学术经验探讨[J].北京中医杂志,1991,1：8-9.
[1]陈颧珠,丁训杰,廖履坦,等.实用内科学,人民卫生出版社.2003年,11版：1737.
[2]中华医学会消化病学分会.中国慢性胃炎共识意见[J].胃肠病学,2006(11)：674-679.
[3]刘为纹.Hp与胃癌.中华消化杂志.1993,13(2)：100.
[4]李兆申.全国慢性胃炎诊治研讨会纪要.中华消化内镜杂志,2004；21(2)：99
[5]Zhang C, Yamada N, Wu YL, Matsuhisa T, Matsukura N. Comparison of Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients. World Gastroenterol.2005 Feb 21;11(7):976-81
[6]Park DI, Park SH, Kim SH,Kim JW, Cho YK, Kim HJ, Sohn CI, Jeon WK, Kim BI, Cho EY, Kim EJ, Chae SW, Sohn JH, Sung IK, Sepulveda AR, Kim JJ.Effect ofHelicobacter pylori infection on the expression of DNA mismatch repair protein.Helicobacter.2005 Jun; 10(3):179-84.
[7]郭昱,郭霞.慢性萎缩性胃炎胃泌素、生长抑素、表皮生长因子、血管性肠肽的测定及临床意义[J].中华消化杂志,2003,11(5)：531-534.
[8]吕农华,杨桢.幽门螺杆菌临床检验方法评价及选择[J]中国实用内科杂志,2008,28(9)：720-722.
[9]张虹雨,周曾芬,董树强,等.幽门螺杆菌抗体检测分析[J].胃肠病学和肝病学杂志,2008,17(2)：133-135.
[10]Tucci A, Bisceglia M, Rugge M, et al.Clinical usefulness of gastric-juice analysis in 2007:the stone that the builders rejected has become the cornerstone[J].Clinical Endoscopy, 2007,5:881-890.
[11]江汉龙,金峰,郑国凡,等.含泮托拉唑、左氧氟沙星的三联方案治疗幽门螺杆菌102例[J].中国实用医药,2009,4(9)：23-24.
[12]刘志为.左氧氟沙星三联疗法根除幽门螺杆菌临床观察[J].胃肠病学和肝病学,2009,18(5)：481-482.
[13]TONG JL,RAN ZH,SHEN J,etal.Sequential thera-py vs.standard triple therapies forHelicobacter pyloriinfection:a meta-analysis[J].J Clin Pharm Ther,2009,34 (1):41-53.
[14]张慧等.10日序贯疗法与标准三联疗法根除幽门螺杆菌的疗效比较.临床荟萃.2011,17,(26)：1538-1540
[15]张万岱,陈治水,危沈海,李道本.慢性胃炎的中西医结合诊治方案(草案).中国中西医结合消化杂志,2004,10,12(5)；314-317
[16]贺红魁.中医治疗慢性浅表性胃炎88例疗效观察[J].北京中医学院学报,2008,12(15)：19.
[17]吴俊良.中药治疗慢性浅表性胃炎200例[J].辽宁中医杂志,2007,21(9)：405
[18]李有田,等.慢性萎缩性胃炎49例治疗探讨[J].白求恩医科大学学报,2009,15(2)：216.
[19]李翠竹.辨证分型治疗慢性萎缩性胃炎34例疗效观察[J].中国社区医师,2008,24(2)：36.
[20]路娣,顾洁.养胃化浊汤治疗慢性萎缩性胃炎60例[J].河北中医,2009,29(1)：63.
[21]张文卿.六味地黄汤加减治疗萎缩性胃炎50例[J].新疆中医药,2007(4)：13
[22]王顺华.半夏泻心汤治疗慢性萎缩性胃炎的临床观察[J].湖北中医杂志,2008,30(3)：30.
[23]杨印坤.加味二陈汤治疗慢性萎缩性肠炎120例[J].四川中医,1995,13(8)：38
[24]王秋生.活血化瘀汤加味治疗慢性萎缩性胃炎32例[J].四川中医,2007,25(11)：63.
[25]王立新,缪卫华,崔恒德,等.针药结合治疗萎缩性胃炎48例[J].吉林中医药,2008,28(2)：131.
[26]宋建宁,陈庆龄.穴位注射、针刺治疗慢性浅表性胃炎70例疗效比较.福建医学.2002,24(5)：16.
[27]黄配宜.和胃法治疗幽门螺杆菌相关性胃炎120例疗效观察[J].新中医.2009,3,(41)：47-48
[28]刘晓芳,全成,贾浩.中西医结合治疗萎缩性胃炎40例[J].陕西中医,2008,29(5)：63.
[29]陈建新,陈静,等.复杂系统熵聚堆算法及其在中风病临床的应用.系统仿真学报,2008,20(15)：4155-4162
[30](意)paoloGiudcici著.袁方,等译.实用数据挖掘.北京：电子工业出版社.2004.1
[31]田文敬.中医特色研究应借助现代数据挖掘技术.中医研究,2005,(8)：7-8
[32]田琳,等.数据挖掘及其在中医药领域中的应用.中国中医基础医学杂志,2005,11(9)：710-712
[33]王映辉,姜在肠等.基于信息和数据挖掘技术的名老中医临床诊疗经验研究思路.世界科学技术--中医药现代化*数字人体,2005,7(1)：98-105
[34]王阶,邢雁伟,陈建新,等.复杂系统熵聚堆方法对1069例冠心病心绞痛证候要素提取和应证组合规律研究.中国中医基础医学杂志,2008,14(3)：211-213
[35]李文泉,权红,等.方和谦经验方“和肝汤”临床应用数据的挖掘研究.中国中医基础医学杂志,2008,14(11)：855-857
[36]唐仕欢,陈建新,杨洪军,等.基于复杂系统熵聚类方法的中药新药处方发现研究思路.世界科学技术——中医药现代化,2009,11(2)：225-228.
[37]吴荣,王阶.数据挖掘在中医药领域中的应用进展.辽宁中医杂志,2009,36(2)：314-315
[1]史成和.高忠英教授治疗慢性萎缩性胃炎临床经验.浙江中医药大学学报,2008,6：753-754
[2]陈建新,陈静,等.复杂系统熵聚堆算法及其在中风病临床的应用.系统仿真学报,2008,20(15)：4155-4162
[3](意)paoloGiudcici著.袁方,等译.实用数据挖掘.北京：电子工业出版社.2004.1
[4]田文敬.中医特色研究应借助现代数据挖掘技术.中医研究,2005,(8)：7-8
[5]田琳,等.数据挖掘及其在中医药领域中的应用.中国中医基础医学杂志,2005,11(9)：710-712
[6]国家中医药管理局.中医病证诊断疗效标准.南京大学出版社,1994年第1版：9
[7]郑筱萸,主编.中药新药临床研究指导原则(第2辑).中国医药科技出版社.2002：124-127.
[8]中华医学会消化分会.中华消化杂志.2006,20(3),199-201.
[9]陈建新,陈静等,复杂系统熵聚堆算法及其在中风病临床的应用,系统仿真学报,2008,20(15)：4155-4162
[10]陈建新,陈静等,复杂系统熵聚堆算法及其在中风病临床的应用,系统仿真学报,2008,20(15)：4155-4162
[11]王阶,邢雁伟,陈建新等,复杂系统熵聚堆方法对1069例冠心病心绞痛证候要素提取和应证组合规律研究,中国中医基础医学杂志2008,14(3)：211-213
[12]唐仕欢,陈建新,杨洪军,王波,基于复杂系统熵聚类方法的中药新药处方发现研究思路,世界科学技术冲医药现代化,2009,11(2)：225-228
[13]史成和,王秀娟.韩爱庆.健脾益胃汤加减治疗慢性萎缩性胃炎46例.《中国中西医结合消化杂志》2009,17(6)：396-397
[2]郝丽莉,李欣育.李东垣脾胃学说浅识.中医药学报.1999,1：3-4
[3]严世芸.中医各家学说.北京：中国中医药出版社.2003：137-145
[4]董振华.李东垣对脾胃学说的贡献.现代远程教育.2005,3(11)：19-21
[5]徐寿生.李杲脾胃阴阳升降理论探讨.安徽中医学院学报,1999,18(4)：9-10
[6]杨慧清.浅谈叶天士对脾胃学说的贡献.新中医,2006,38(6)：82-83
[7]郑星.叶天士胃阴学说探析.上海中医药杂志,2002,12：34-35
[8]黄英志主编.叶天士医学全书.中国中医药出版社,1999,85-87
[9]王永炎,张志斌,张志强等,关于加强中医学派研究的建议.[J]中医杂志.2011,14(52)：1171-1172
[10]杨晋翔.董建华诊治胃痛的学术经验探讨[J].北京中医杂志,1991,1：8-9.
[1]陈颧珠,丁训杰,廖履坦,等.实用内科学,人民卫生出版社.2003年,11版：1737.
[2]中华医学会消化病学分会.中国慢性胃炎共识意见[J].胃肠病学,2006(11)：674-679.
[3]刘为纹.Hp与胃癌.中华消化杂志.1993,13(2)：100.
[4]李兆申.全国慢性胃炎诊治研讨会纪要.中华消化内镜杂志,2004；21(2)：99
[5]Zhang C, Yamada N, Wu YL, Matsuhisa T, Matsukura N. Comparison of Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients. World Gastroenterol.2005 Feb 21;11(7):976-81
[6]Park DI, Park SH, Kim SH,Kim JW, Cho YK, Kim HJ, Sohn CI, Jeon WK, Kim BI, Cho EY, Kim EJ, Chae SW, Sohn JH, Sung IK, Sepulveda AR, Kim JJ.Effect ofHelicobacter pylori infection on the expression of DNA mismatch repair protein.Helicobacter.2005 Jun; 10(3):179-84.
[7]郭昱,郭霞.慢性萎缩性胃炎胃泌素、生长抑素、表皮生长因子、血管性肠肽的测定及临床意义[J].中华消化杂志,2003,11(5)：531-534.
[8]吕农华,杨桢.幽门螺杆菌临床检验方法评价及选择[J]中国实用内科杂志,2008,28(9)：720-722.
[9]张虹雨,周曾芬,董树强,等.幽门螺杆菌抗体检测分析[J].胃肠病学和肝病学杂志,2008,17(2)：133-135.
[10]Tucci A, Bisceglia M, Rugge M, et al.Clinical usefulness of gastric-juice analysis in 2007:the stone that the builders rejected has become the cornerstone[J].Clinical Endoscopy, 2007,5:881-890.
[11]江汉龙,金峰,郑国凡,等.含泮托拉唑、左氧氟沙星的三联方案治疗幽门螺杆菌102例[J].中国实用医药,2009,4(9)：23-24.
[12]刘志为.左氧氟沙星三联疗法根除幽门螺杆菌临床观察[J].胃肠病学和肝病学,2009,18(5)：481-482.
[13]TONG JL,RAN ZH,SHEN J,etal.Sequential thera-py vs.standard triple therapies forHelicobacter pyloriinfection:a meta-analysis[J].J Clin Pharm Ther,2009,34 (1):41-53.
[14]张慧等.10日序贯疗法与标准三联疗法根除幽门螺杆菌的疗效比较.临床荟萃.2011,17,(26)：1538-1540
[15]张万岱,陈治水,危沈海,李道本.慢性胃炎的中西医结合诊治方案(草案).中国中西医结合消化杂志,2004,10,12(5)；314-317
[16]贺红魁.中医治疗慢性浅表性胃炎88例疗效观察[J].北京中医学院学报,2008,12(15)：19.
[17]吴俊良.中药治疗慢性浅表性胃炎200例[J].辽宁中医杂志,2007,21(9)：405
[18]李有田,等.慢性萎缩性胃炎49例治疗探讨[J].白求恩医科大学学报,2009,15(2)：216.
[19]李翠竹.辨证分型治疗慢性萎缩性胃炎34例疗效观察[J].中国社区医师,2008,24(2)：36.
[20]路娣,顾洁.养胃化浊汤治疗慢性萎缩性胃炎60例[J].河北中医,2009,29(1)：63.
[21]张文卿.六味地黄汤加减治疗萎缩性胃炎50例[J].新疆中医药,2007(4)：13
[22]王顺华.半夏泻心汤治疗慢性萎缩性胃炎的临床观察[J].湖北中医杂志,2008,30(3)：30.
[23]杨印坤.加味二陈汤治疗慢性萎缩性肠炎120例[J].四川中医,1995,13(8)：38
[24]王秋生.活血化瘀汤加味治疗慢性萎缩性胃炎32例[J].四川中医,2007,25(11)：63.
[25]王立新,缪卫华,崔恒德,等.针药结合治疗萎缩性胃炎48例[J].吉林中医药,2008,28(2)：131.
[26]宋建宁,陈庆龄.穴位注射、针刺治疗慢性浅表性胃炎70例疗效比较.福建医学.2002,24(5)：16.
[27]黄配宜.和胃法治疗幽门螺杆菌相关性胃炎120例疗效观察[J].新中医.2009,3,(41)：47-48
[28]刘晓芳,全成,贾浩.中西医结合治疗萎缩性胃炎40例[J].陕西中医,2008,29(5)：63.
[29]陈建新,陈静,等.复杂系统熵聚堆算法及其在中风病临床的应用.系统仿真学报,2008,20(15)：4155-4162
[30](意)paoloGiudcici著.袁方,等译.实用数据挖掘.北京：电子工业出版社.2004.1
[31]田文敬.中医特色研究应借助现代数据挖掘技术.中医研究,2005,(8)：7-8
[32]田琳,等.数据挖掘及其在中医药领域中的应用.中国中医基础医学杂志,2005,11(9)：710-712
[33]王映辉,姜在肠等.基于信息和数据挖掘技术的名老中医临床诊疗经验研究思路.世界科学技术--中医药现代化*数字人体,2005,7(1)：98-105
[34]王阶,邢雁伟,陈建新,等.复杂系统熵聚堆方法对1069例冠心病心绞痛证候要素提取和应证组合规律研究.中国中医基础医学杂志,2008,14(3)：211-213
[35]李文泉,权红,等.方和谦经验方“和肝汤”临床应用数据的挖掘研究.中国中医基础医学杂志,2008,14(11)：855-857
[36]唐仕欢,陈建新,杨洪军,等.基于复杂系统熵聚类方法的中药新药处方发现研究思路.世界科学技术——中医药现代化,2009,11(2)：225-228.
[37]吴荣,王阶.数据挖掘在中医药领域中的应用进展.辽宁中医杂志,2009,36(2)：314-315
[1]史成和.高忠英教授治疗慢性萎缩性胃炎临床经验.浙江中医药大学学报,2008,6：753-754
[2]陈建新,陈静,等.复杂系统熵聚堆算法及其在中风病临床的应用.系统仿真学报,2008,20(15)：4155-4162
[3](意)paoloGiudcici著.袁方,等译.实用数据挖掘.北京：电子工业出版社.2004.1
[4]田文敬.中医特色研究应借助现代数据挖掘技术.中医研究,2005,(8)：7-8
[5]田琳,等.数据挖掘及其在中医药领域中的应用.中国中医基础医学杂志,2005,11(9)：710-712
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