The Exploration Of Effective Herbal Combinations Patterns For The Treatment Based On Syndrome Differentiation Of Insomnia Commonly Employed By Many Highly Experienced Chinese Medicine Physicians

1BackgroundAs the main clinical practice form of Chinese medicine, Treatment based on syndrome differentiation is a typical "individualized treatment" approach and it is a complex and flexible progress in which physicians and patients interact with each other while the physicians take the leading role. Meanwhile, it is the fundamental source of new ideas, new theories, and new formulas of Chinese Medicine. The physicians, implemented as the subject of diagnosis and treatment, have differences in academic schools, theoretical level, and other aspects of clinical experience. For the same disease or the same patient, the physicians understand and grasp the characteristics in different aspects, thus there may be differences in terms of the result of treatment based on syndrome differentiation, the syndrome diagnosis, therapies, prescription, etc. which might lead to different clinical effectiveness. The famous highly experienced experts, as the representative of TCM effectiveness, they have their own characteristics in academic background and clinical experience, however, they can achieve good curative effectiveness in the diagnosis and treatment of the same disease. As for the question that whether the individual characteristics of the physician will have an impact on the effect of the diagnosis and treatment, our research group has carried out several studies that taking the physicians that are the implementers of treatment based on syndrome differentiation as the object, taking the different effects of physician’s diagnosis and treatment as the indicators, and exploring the efficacy evaluation protocol design methods of treatment based on syndrome differentiation by different physicians. At present, the appropriate clinical study design methods in evaluating curative effect of treatment based on syndrome differentiation therapy has been initially formed. However, as a system science, there are common features and rules in understanding the disease in TCM theory. Different physician treat the same disease based on syndrome differentiation, in addition to their individual characteristics, perhaps there are some common rules.For instance, the prescription, regularity in herb compatibility, the understanding of pathogenesis of insomnia. However, the inheritance and innovation contained in the process of treatment based on syndrome differentiation is mixed, which is difficult to split and identify.Traditional Chinese medicine is a discipline produced, continuous verified and developed in the clinical practice, the experiences and discoveries came from the clinical practice and applied to guide the clinical practice, which is the basic mode of TCM clinical research."From the clinical practice" is a discovery and formation stage of new prescription, new technologies and new programs. That is accumulated on the basis of clinical practice, with certain scientific and technical methods or tools, gradually generated by refining and sublimation. The clinical research is process of clinical data generation, collection, storage, management, and application. Large amounts of valuable data and literature data accumulated during clinical practice is a valuable asset in medicine. Big data era, using the clinical practical data to conduct scientific research and summarize useful knowledge for the clinical practice or form the theoretical knowledge of significance from large-scale data, it is an effective technology approch to form innovation knowledge and clinical decision.This study selected insomnia cases as the object, fully using the practical insomnia data of treatment based on syndrome differentiation stored in "clinical research information sharing system of TCM", to explore the effective herbal combinations patterns for treatment based on syndrome differentiation of insomnia employed by many highly experienced Chinese medicine physicians via the complex network, that is to conduct the preliminary exploration of common rules or experience treating insomnia by treatment based on syndrome differentiation.2ObjectiveTo explore the core effective herbs combination patterns, the evaluation index, and its indications which laid foundation of a preliminary effective scheme of the treatment based on syndrome differentiation of insomnia by fully using the practical clinical insomnia data of many experienced Chinese medicine physicians stored in "clinical research information sharing system of TCM" and using the complex network method to conduct the data mining.3Content3.1The screening research of effective insomnia casesThe investigation into the effectively evaluation indicators are on the basis of the practical insomnia data of treatment based on syndrome differentiation. Based on the changes of related symptoms, sleep quality or sleep time of the insomnia practical clinical data, taking the insomnia-related scale items as references, we develop the curative effectiveness evaluation index of insomnia and the standards of the incase effectiveness and the overall effectiveness, then complete the effectiveness mark and review. So we form the final effectiveness of qualitative category marked results and screen the effective insomnia cases.3.2The datamation of effective insomnia casesFirst of all, we conduct the preprocessing work of the insomnia data. Applicating the SQL to query and retrieve the data, we respectively extract the original information of insomnia cases related to the topic analysis by correlating the patient ID number; develop the data preprocessing rules of insomnia cases such as the diagnosis, symptoms, syndrome patterns, formula, herbs, and the laboratory information; respectively deal with the data normative approach of the insomnia cases by the ETL (data extraction, transformation, and loading system) tool in "clinical research information sharing system of TCM" and form the structured insomnia data information.Then, we complete the incase effectiveness and the overall effectiveness mark of the insomnia cases through the effectiveness mark platform and form the final insomnia data set for analysis and research.3.3The exploration of effective herbal combinations patterns on the basis of the practical insomnia data of treatment based on syndrome differentiationTo analyze the main constitution of core herbal combinations, appropriate dose, and the indications through the data mining method complex network.The indications include the syndrome differentiation, clinical symptoms and signs, the investigation into the factor affects the efficacy based on practical insomnia data of treatment based on syndrome differentiation.We analyze the complications, symptoms, syndrome patterns, age and other factors by the decision tree model and the support vector machine model of the effective and invalid insomnia data to explore factors influencing the curative effect of treatment based on syndrome differentiation of insomnia.4Methods4.1To develop the evaluation indicators, the effectiveness marking standards and methods based on the development of diagnosis and treatment of insomnia practical data through the literature research of the insomnia evaluation index and screening the evaluation information of insomnia practical data.4.2To load into the target insomnia database after the batch extraction, audit, cleaning, consolidation, and marking the incase and the whole effectiveness of the insomnia data, by applying the SQL Server2008and ETL data processing tools, and to conduct data mining analysis of complex networks through the Liquorice software.5Results5.1Preliminarily developed the evaluation indicators, the effectiveness marking standards, methods and procedures based on the practical insomnia data of treatment based on syndrome differentiation5.1.1The evaluation indicators of practical insomnia data:the primary insomnia symptoms are chosen as the core evaluation indicators, which include as followed: insomnia, short in total sleep time, difficulty in falling asleep, sleep is not deep, fitfully, difficult to sleep after waking, easy to awake, dreams; Evaluation categories are divided into four kinds of circumstances:clinical recovery, improvement, no change, worsening; general medical curative effect evaluation is divided into clinical recovery, effective and invalid.5.1.2Established the effectiveness evaluation marking platform of insomnia suitable for the practical data:according to the evaluation indicators based on the practical insomnia data of diagnosis and treatment, established the effectiveness evaluation marking platform of the treatment effect about insomnia in every visiting time in the data processing software ETL5.1.3Formed the effectiveness evaluation marking methods and procedures based on the practical insomnia data of diagnosis and treatment.5.2The investigation into the effective core herbal combination patterns of insomnia based on the data mining analysis by the complex networks5.2.1The effective core herbal combination patterns are fried zizyphus jujube kernel, polygala, poria cocos, angelica, radix bupleuri, radix paeoniae alba, rhizoma ligustici wallichii, liquorice, rhizoma acori graminei, and keel;5.2.2The effective doses range of the core herbal combination of insomnia:fried zizyphus jujube kernel20-30g, polygala10-12g, poria cocosl0-15g, radix bupleuri10-15g, radix paeoniae alba10-15g, rhizoma ligustici wallichii10-15g, rhizoma acori graminei10-15g, keel20-30g, and liquorice6-10g.5.2.3The indications of the effective core herbal combination of insomnia1) The syndrome patterns are liver depression, blood deficiency, phlegm-heat, and the kidney deficiency;2) The clinical symptoms and signs include difficulty in falling asleep, dreams, upset, irritability, tinnitus, sweating, forgetfulness, fullness feeling in the head, headache, poor spirit, heart palpitations, stiff neck, pale tongue, yellow fur of the tongue, and thin fur of the tongue.3) The factors affecting the effectiveness of treatment based on syndrome differentiation of insomnia on the basis of practical data are as followed:(1)The insomnia patients have the complications including organophosphorus pesticide poisoning, sleep panicdisorder, lacunar infarction, migraine, neurosis, et al, that the curative effectiveness of treating insomnia is not significant; these complications may affect the effectiveness of insomnia.(2)The patients who have the syndrome patterns as follow:the Heart and Kidney is not harmony, the yin and yang of Spleen and Kidney is imbalance, liver yang transformed into wind syndrome, blood deficiency of heart and liver, liver yin deficiency, the fire of heart and liver, liver depression and Yin deficiency, Yin deficiency and transformed into heat of liver and stomach, blood not nourish the heart, internal viscera are deficiency, et al.Maybe these syndrome patterns are factors affect the effectiveness of insomnia. (3)The symptoms and signs which affect the effectiveness of insomnia are divided into several categories:①ain:facial pain, back pain, knee joint pain, breast pain, toothache;②Abnormal urine:urine drops after pee, night urinary frequency, urgent urine, prostatic hyperplasia, prostatic hypertrophy, smelly urine;③Paresthesia: lower extremity muscle atrophy, right limb numbness, cold limbs, the activity of right lower limb is not flexible;④Menstrual abnormalities:early menstruation, late menstruation, premenstrual swelling pain of the breast, menopause;⑤Dysfunction of the digestive system:dawn diarrhea, nausea, abdominal distention, heartburn, acid reflux, big appetite;⑥Bmotional factors:sad and easy to cry, nervousness, fear, Mental fatigue.⑦others:white greasy tongue coating, teeth trace in the tongue, map tongue, spitting, nasal congestion, sneezing, and dizziness,et al.(4) The age factor has no effect on the efficacy of treatment based on syndrome differentiation of insomnia according to the correlation coefficient.5.2.4The rules of adding or subtracting herbs according to the accompanying symptoms or syndrome patterns:phlegm-heat syndrome:rhizoma coptidis, pinellia, pericarpium citri reticulatae, bamboo shavings, poria cocos; liver depression and transformed into fire:cortex moutan, gardenia; kidney Yin deficiency:prepared rehmannia root, cornel, yam, alisma, poria cocos, cortex moutan; Heart and kidney is not harmony:rhizoma coptidis, cinnamon; Liver Yang excessive:gastrodia elata, uncaria, periostracum cicada, batryticated silkworm; hysteria:licorice, wheat, jujube.5.2.5The common herbal combination patternsThe common herbal combination patterns in treatment based on syndrome differentiation of insomnia are as followed:fried zizyphus jujube kernel-polygala, fried zizyphus jujube kernel-poria cocos, fried zizyphus jujube kernel-tuber fleeceflower stem, fried zizyphus jujube kernel-rhizoma anemarrhenae, fried zizyphus jujube kernel-Salvia miltiorrhiza, polygala-rhizoma acori graminei, radix bupleuri-radix paeoniae alba, keel-oysters, radix curcumae-Cortex albiziae, et al.5.3The improvement rate situation of curative effect evaluation index among the insomnia cases1)Signs and symptoms of "clinical recovery" of insomnia cases data is given priority to the accompanying symptoms and signs of insomnia, such as nervous, dry stool, yellow urine, abdominal distension, loose stool, fever, stomachache, stomach distension, diarrhea, edema of the lower limb, etc. But the recovery rate of insomnia, dreams, difficulty in falling asleep, light sleep and other primary symptoms of insomnia are relatively not high, the recovery rate of insomnia is2.94%, the recovery rate of dreams are28.39%, difficulty in falling asleep is20.36%.2) Signs and symptoms of "improved" in insomnia cases data is mainly insomnia, dreams, difficulty in falling asleep, light sleep, poor spirit, anorexia, upset, dizziness, fatigue, bitter mouth, dry stool, thirst, heart palpitations, belching, etc. Among them, the improvement rate of primary symptoms of insomnia is higher, insomnia is82.63%, dreams are60%, difficulty falling asleep is77.25%, and not deep sleep is93.94%.6Conclusions6.1The effectiveness information marking research based on the practical data of diagnosis and treatment is an important part of the data usage and analysis; this study developed the effectiveness evaluation index of insomnia data, the effect information marking platform and method based on practical diagnosis and treatment which lay a foundation for subsequent research.6.2The data mining method complex network analysis can be used to analyze the core herbal combinations of treatment based on syndrome differentiation of insomnia, the rules to add or subtract herbs according to the accompanying symptoms or syndrome patterns and the clinical indications, which will guide the physicians to prescribe medication and lay a foundation for future formula study of insomnia.6.3Using clinical data in combination with data mining analysis, the results reveal that the application of traditional formula and the herbal addition and subtraction rules of treatment based on syndrome differentiation in modern clinical practice.6.4The method exploring the new formulas of traditional Chinese medicine through the complex network analysis based on practical clinical data is feasible, while the quality of data is the key point.