The TCM Pattern And Treatment Protocols For Xiao Ke Bi Zheng Based On The Real World Study

BackgroundThe pathogenesis of Xiaoke Bi Zheng (Diabetic Peripheral Neuropathy, DPN) is deficiency in origin and excess in superficiality,where deficiency is the core. It is found that the long term of "Xiaoke" would result into the Bi Zheng/Xue Bi/Wei Zheng. Prevention and treatment of Xiaoke Bi Wei,also known as DPN,matters in the studies of modern medicine and traditional Chinese medicine. Even though a lot of progress has been achieved in the fields of etiology and pathogenesis theory, clinical research and experiment research, little evidence supports due to the lack of large sample, multi center, and prospective researches.Real World Study (RWS), also called as the outcome research, is boomingto measure and evaluate the effectiveness of drugs or interventions in the real clinical environment. RWS is usually applied to assess the intervention safety, seldom reported for the effectiveness of intervention. The core characteristics of RWS requires the real world sample in the studies, responding to the real world. Therefore, the subjects needs large sample but less restriction; and the interventions have less restrictionand,been more like the clinical practice;long-term follow-up for evaluation is needed.The key point for the RWS is how to ensure the sample size to reflect the general population, and the sample records achieve the real world requirements.In order to solve these problems,the data processing system, professional data entry,and data analysis staff are needed for the multi-center, large sample,RWS clinical studies’ evidence.In such background,this research combining the TCM theory and modern techniques has been administrated base on theprogram"based on clinical diagnosis and treatment of clinical research integration technology platform to diseases such as stroke of traditional Chinese medicine"(supported bythe national administration of traditional Chinese medicine, No.200707001).The TCM clinical information sharing system was employed to establish a databaseby collecting the massive clinical information of real world Xiaoke Bi Zheng patients. Based on the database, data mining methods were used to analyze TCM basic elements "TCM disease-Symptoms-TCM pattern-Formula-Herbs".TCM pattern differentiation and comprehensive treatment protocol for Xiaoke Bi Zheng were summarized and optimized to provide evidence for the standardization of Xiaoke Bi Zheng.ObjectiveTo explore The TCM pattern and treatment protocols for Xiao ke Bi zheng based on the real world study.Content1Real World Study of Xiaoke Bi Zheng pattern differentiation and treatment based on the TCM clinical information sharing systemSharing structured clinical information acquisition system and DS01-A diagnosis system of tongue and pulse instrument were developed by using the TCM clinical information sharing system.Besides,the database of Xiaoke Bi Zheng was established according to the characteristics of Xiaoke Bi Zheng and its complications.The TCM pattern differentiation and treatment protocol rule of Xiaoke Bi Zheng were data mined and analyzed by topic model method as to the TCM elements"disease-Symptoms-TCM pattern-Formula-Herbs", after data selection,the first verification, analysis and the second verification.2Real World Study of Xiaoke Bi Zheng comprehensive treatment protocol based on the TCM pattern differentiationFive main TCM patterns have been abstracted from the topic model analysis results for the further excavation and analyses of core symptoms and integrated traditional Chinese and Western medicine treatment protocol by using complex network software as to the basic elements"symptom-TCM pattern-herbs". The methods includes the multilayer network, computing node degree, degree distribution and intensity equivalent.3Tutor’s academic thoughts and clinical experience of Xiaoke and Xiaoke Bi ZhengTutor’s academic thoughts and clinical experience of Xiaoke and Xiaoke Bi Zheng were summarized by literature reviews and cases analysis of typical clinical cases. More than that, the result of above was compared with and used to verify the results from data mining.Method1The casesDuring January2008to March2012,1021patients with a total of1073visits were recorded in the8clinical centers, which included the basic information1073items and the mainclinicalinformation (chief complaints, present illness, past medical history, family history, personalhistory, physical examination, TCM pattern differentiation)276706items.2Inclusion criteriaCases should meet the criteria of the1999WHO type2diabetes mellitus, the diabetic peripheral neuropathy, and the Xiaoke Bi Zheng.3Thedata processing3.1Clinical information collectionsSharing structured clinical information acquisition system and DS01-A diagnosis system of tongue and pulse instrument were developed by using the TCM clinical information sharing system. Besides,the database of Xiaoke Bi Zheng was established according to the characteristics of Xiaoke Bi Zheng and its complications.3.2The data processingLog data warehouse,classifying the data by ID and SQL screening,and then export the data backup. The data was verifiedby ETL software,and the items which failed to meet the conditionswere deleted.3.3Data analyses and processingData processing was an overloaded and time-consuming job due to the large. Meanwhile,the task was important due to thathigh quality of was the promise for analysis.4Data analysesData analyses were done by the data mining methods,topic model and complex network,and then the results was compared with and used to verify the results from literature reviews.Result1Xiaoke Bi Zheng pattern differentiation and treatment The topic model analyses of the Xiaoke Bi Zheng main symptoms were:limb numb pain,weight loss,blurred vision,limb hair is cool,sexual dysfunction,insomnia,pain,pee not free, easy to hunger,fatigue,dizziness,chest intermittent,claudication, itch of skin. The main TCM patternswere:blood stasis,phlegm be filled,deficiency of both qi and Yin, deficiency of Qi and blood stasis,deficiency of yin and heat inside. The tongues were dark redtongue with thin and white fur, dark redtongue with thick greasy fur. The pulses werewiry with thin, thin with rapid, deep with thin. According to the "symptom-TCM pattern-tongue-pulse", patients with Xiaoke Bi Zheng had high probability of using herbs as follows:white atractylodes rhizome, glossy privet fruit,Eclipta,pollen Typhae,tree peony bark,Radix Paeoniae Alba, radix rehmanniae,radix paeoniae rubra, Gallus gallus domesticus, myrrh,perilla leaf, Cortex LyciiRadicis, GeGen, Anemarrhenarhizome, figwort, ophiopogon root, Rhizoma Chuanxiong, Rhizoma Polygonati, Sichuan Achyranthes root, safflower, peach seed, coix seed, earthworm, Salvia miltiorrhiza, leech, stir fried with bran, phellodendron bark, tangerine peel, citrus aurantium Guizhi, yam, Poria, Alisma, dogwood, bitter almond, mulberry leaf, snakegourdfruit, Chinese angelica, Plantago, Zeeland, heterophylla, astragalusrhubarb, gardenia, Shi Wei, Schisandra chinensis, Rhizoma Atractylodis, hemp seed, Eucommia ulmoides Oliv.2Xiaoke Bi Zheng comprehensive treatment protocol2.1Treatment protocolfor the patients with Xiaoke Bi Zheng Qi deficiency patternThe high probability of herb application were:Poria,Radix Astragali, salvia, Atractylodes, angelica, radix rehmanniae, Radix Paeoniae Alba, Radix Paeoniae Rubra.The high frequencies of combination of herbs were:Radix Paeoniae Rubra and Radix Paeoniae Alba:, Ligustrum lucidum, Poria, Atractylodes, Eclipta, keel, oysters, Rhizoma Chuanxiong, angelica, peach kernel, safflower, Oriental waterplantain rhizome, poria.The high frequencies of combined western medicine were:insulin, blood pressure lowering drugs, oral hypoglycemic agents, anti-angina drugs, anti-platelet drugs, anti-atherosclerosis drugs. The main symptoms were:fatigue, dry mouth, more drink, blurred vision, dizziness, insomnia, constipation.The main complications were:hypertension, coronary heart disease, diabetic nephropathy, diabetic retinopathy, metabolic syndrome.2.2Treatment protocolfor the patients with Xiaoke Bi Zheng Yin deficiency patternThe high probability of herb application were:Poria, angelica, Atractylodes, radix rehmanniae, Radix Astragali.The high frequencies of combination of herbs were:Radix Paeoniae Rubra and Radix Paeoniae Alba:, Ligustrum lucidum, Poria, Atractylodes, Eclipta alba, Rhizoma alismatis, tuckahoe, peach kernel, safflower, keel oyster, Rhizoma Chuanxiong, angelica, dried tangerine peel, pinellia tuber, red peony root, angelica, Schisandra chinensis, Radix ophiopogonis.The high frequencies ofcombined western medicine were:insulin, blood pressure lowering drugs, anti angina drugs, antiplatelet agents, vasoactive drugs, oral hypoglycemic agents, anti atherosclerosis drugs. The main symptoms were:fatigue, polydipsia, dry mouth, blurred vision, dizziness, insomnia, constipation, chest tightness.The main complications were:hypertension, coronary heart disease, diabetic retinopathy, diabetic nephropathy, metabolic syndrome.The main existence of yin deficiency syndrome in populations of complications including Carved symptoms include:Yin deficiency syndrome in population combined with western medicine of the highest frequency respectively, Traditional Chinese medicine are:Poria cocos, salvia, angelica, astragalus, Atractylodes, radix rehmanniae, radix paeoniae rubra. Traditional Chinese medicine combination of relatively strong correlation with.2.3Treatment protocolfor the patients with Xiaoke Bi Zheng Blood stasis patternThe high probability of herb application were:Poria, Radix Astragali, Radix Paeoniae Alba, Radix Angelicae sinensis, radix rehmanniae, radix paeoniae rubra, radix salvia miltiorrhizae, Pericarpium Citri Reticulatae.The high frequencies of combination of herbs were:peach kernel,safflower, Radix Paeoniae Rubra:Rhizoma Chuanxiong, radix paeoniae rubra, Radix Paeoniae Alba, peach kernel, earthworm, keel, oysters safflower, radix paeoniae rubra, safflower and earthworm. The high frequencies of combined western medicine were:insulin, antiplatelet agents, anti angina drugs, antihypertensive drugs, oral hypoglycemic agents, vasodilator, anti atherosclerosis drugs. The main symptoms were:fatigue, blurred vision, dry mouth, drink, constipation, insomnia, dizziness, chest tightness. The main complications were:hypertension, coronary heart disease, diabetic nephropathy, diabetic retinopathy, diabetic peripheral vascular disease, metabolic syndrome.syndrome mainly exist in the crowd complications including:Carved symptoms include,Blood stasis syndrome combined with western medicine in the highest frequency respectively, Traditional Chinese medicine are etc.Traditional Chinese medicine combination of relatively strong correlation with.2.4Treatment protocol for the patients with Xiaoke Bi Zheng dampness patternThe high probability of herb application were:Poria, Atractylodes, licorice, dried orange peel, dried rehmannia root, Chinese angelica, astragalus root, Rhizoma Chuanxiong, Radix cyathulae. The high frequencies of combination of herbs were: Cornus-yam, Atractylodes Poria, Rhizoma Corydalis, Radix Linderae, papaya- Rhizoma cibotii, dogwood, tree peony bark, Radix Linderae, Gallus gallus domesticus, Rhizoma Corydalis,Gallus gallus domesticus. The high probability of combined western medicine were:insulin, antiplatelet drug, blood pressure lowering drugs, anti angina drugs,oral hypoglycemic agents,anti atherosclerosis drugs. The main symptoms were:fatigue,polydipsia, dry mouth, blurred vision, dizziness, insomnia, dizziness. The main complications were:diabetic nephropathy, diabetic retinopathy, coronary heart disease, and hypertension.The main existing syndrome in the crowd:complications including and so on. Carved symptoms include, Dampness syndrome combined with western medicine in the highest frequency respectively, Traditional Chinese medicine are etc. Traditional Chinese medicine combination of relatively strong correlation.2.5Treatment protocol for the patients with Xiaoke Bi Zheng phlegm patternThe high probability of herb application were:Poria, Atractylodes, Radix Paeoniae Alba, tangerine peel, salvia,chuanxiong, radix paeoniae rubra, Radix Glycyrrhizae, radix rehmanniae, Rhizoma Pinelliae, snakegourd. The high frequencies of combination of herbs were:Poria, tangerine peel, pinellia, dried orange peel, Fructus Ligustri Lucidi radix paeoniae rubra, Radix Paeoniae Alba, Han Liancao, glossy privet fruit, Acorus and Curcuma Han Liancao, Rhizoma Atractylodis, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae-red,Traditional Chinese medicine are:Poria, Atractylodes, Radix Paeoniae Alba, tangerine peel, salvia, chuanxiong, radix paeoniae rubra, Radix Glycyrrhizae, radix rehmanniae, Rhizoma Pinelliae, snakegourd. Traditional Chinese medicine combination of relatively strong correlation:Poria, tangerine peel, pinellia, dried orange peel, Fructus Ligustri Lucidi radix paeoniae rubra, Radix Paeoniae Alba, Han Liancao,glossy privet fruit, Acorus and Curcuma Han Liancao,Rhizoma Atractylodis, radix paeoniae rubra, Radix Paeoniae Alba, Rhizoma Atractylodis Macrocephalae Rhizoma Pinelliae, Poria. The high frequencies of combined western medicine were:insulin, antiplatelet agents, oral hypoglycemic drugs, blood pressure lowering drugs, anti angina drugs, anti atherosclerosis drugs, vasoactive drugs. The main symptoms were:insomnia, fatigue, dry mouth, blurred vision, chest tightness, polydipsia, anorexia, heart palpitations. The main complications were:coronary atherosclerotic heart disease, hypertensive, diabetic nephropathy, diabetic retinopathy, diabetic peripheral vascular disease, heart failure.The main existing syndrome in complications including Carved disease includes In phlegm syndrome group combined with western medicine of the highest frequency respectively.Conclusion1Real world data were collected by the TCM clinical information sharing system.The rule of the disease and some micro-details were analyzed and explored from the real world data. Only in this way could the convincing results be drawn from the data.2Each properties of the topic model method, such as symptoms, TCM patterns and herbs, were described by the probability to represent the sample reflecting the overall population, whose data were convincing and meant a lot to the TCM pattern differentiation and treatment evidence. The complex network could conclude the valuable rules from the complicated phenomena, and its network diagram showed the XiaoKeBi Zheng symptom-pattern-herbs laws. It provided visual effect of the core treatment principle, clinical usual drugs and its corresponding pathology. Meanwhile, thisconclusion has been proved validated and reliable by comparing withthe clinical practice.3Medical conclusions3.1Xiaoke Bi ZhengTCM patterns were drawn as follows:blood stasis, deficiency of qi and Yin, deficiency of yin and yang, phlegm stasis, phlegm and blood stasis, Qi deficiency and blood stasis. The result was basically consistency with the tutor’s experience; on the other hand, it provided a new idea for clinical TCM patter differentiation.3.2With35model sanalyzed from the topic model, blood stasis was proved to be the core pathogenesis in the Xiaoke Bi Zheng.3.3Based on the complex network analysis, the patients with DPN, above all, took oral hypoglycemic agents or insulin to control and stablethe blood sugar withthe blood pressure lowering and lipid-lowering drugs for the concurrent diseases. Secondly, the treatment was to relief the symptoms, such asnerve nutrition agent, antioxidant and other painkillers. However, TCM differentiated the patterns and applied the basic treatment principle, nourish Qi, Yin and activate blood, for the patients with Xiaoke Bi Zheng. The results suggested that the TCM pattern differentiation and Western medical diagnosis should be combined for the early prevention, early treatment. 3.4According to literature reviews and clinical records, Professor Lin Lan carried out that there were four TCM patterns differentiation for DPN. In the treatment and drug commonly the result here was consistency with those from data mining.The innovation1Database of the Xiaoke Bi Zheng was established based on the TCM clinical information sharing system. During the process, the terminology of Xiaoke Bi Zheng has been standardized.2Apply the instruments of the tongue and pulse to collect the data and establish a database about the tongue and pulse.3Apply thedata mining methods, topic model and complex network to analyze and summarize the Xiaoke Bi Zheng TCM pattern differentiation and comprehensive treatment protocol.