Experiences In Diagnosis And Treatment Of Vertigo By Xin’an Physicians In The Ming-qing Period And Research On Data Mining As Well As Network Pharmacology Of Banxia Baizhu Tianma Decoction In Treating Vertigo

Objective This study mainly summarizes the overall characteristics of Xin’an physicians in the treatment of vertigo during the Ming-Qing period,based on their relevant academic works and medical records.Using data mining technology to study the prescription medication rule of Xin’an physicians for the treatment of vertigo,this research is expected to inherit Xin’an medicine and provide reference for clinical treatment.Based on data mining technology,this paper explores the clinical medication rule of Banxia Baizhu Tianma Decoction in treating vertigo in recent 30 years,which is the famous prescription of Xin’an physician Cheng Guopeng.The paper studies the material basis of pharmacodynamics and molecular mechanism of Banxia Baizhu Tianma Decoction in the treatment of vertigo by using network pharmacology and molecular docking technology to explore its multi-component,multi-target and multi-channel mechanism.MethodsUsing literature research methods such as literature tracing,classification,vertical horizontal connection to sort and analyze the relevant academic works and medical records,this paper studies the experiences of Xin’an physicians in treating vertigo to summarizes the general characteristics.These physicians include Wang Ji,Sun Yikui,Yu Cong,Ye Gui,Wang Wenqi,Cheng Guopeng,Cheng Wenqi,Fang Zhaoquan and Cheng Yougong,etc.IBM SPSS Modeler 18.0,SPSS Statistics 22.0 and Chinese Medicine Inheritance Assistant System Platform(V2.5)were used for frequency statistics,association rule analysis,complex network analysis,system clustering,entropy hierarchical clustering new formula and principal component factor analysis on the prescription.SPSS Statistics 22.0 and IBM SPSS Modeler 18.0 were performed to analysis frequency statistics,principal component factor,systematic clustering and association rule on the symptoms and medications of vertigo treated with modified Banxia Baizhu Tianma Decoction in the past 30 years.TCMSP,TCMID,SEA were used to screen effective ingredients and target proteins.The targets of vertigo-related diseases were screened by Genecards,OMIM,Drug Bank,TTD,etc.The common targets were obtained by Venn online software,and the network diagram of "drug-disease-target" was constructed by Cytoscape 3.7.2 software.STRING was used to draw the protein interaction(PPI)network,Cyto NCA was used for screening,Mcode was performed for PPI networks.GO function enrichment and KEGG pathway analysis were carried out by using David database and cluster profile package in R language 3.6.3.Auto Dock Vina performed semi-flexible molecular docking of ligand and receptor.Finally,three-dimensional and two-dimensional visualization analysis were carried out by using Py MOL,Lig Plot ++and MOE software.ResultsXin ’an physicians in Ming-Qing period hold the view that vertigo is different in deficiency,excess,inside and outside.The excess pathological factors are phlegm,fire,wind and blood stasis.It is believed that phlegm is the most important by Sun Yikui,Sun Wenyin,Fang Guang,Yu Wuting,Xu Chunfu,Hong Shenqi,Cheng Guopeng,Wang Wenqi,Wang Ang,Wu Mai and Wang Qixian.There are often phlegm in upper Energizer,phlegm turbidity in the obstruction,phlegm heat on the disturbance,liver fire with phlegm,wind phlegm on the disturbance,liver-Yang hyperactivity,phlegm and blood stasis mutual obstruction,etc.The deficiency pathological is mostly due to the deficiency of qi,blood,yin and yang in viscera.Lost of Physicians pay special attention to dizziness caused by the shortage of qi and blood,for example,Wang Ji,Wu Zhenglun,Cheng Jingtong,Wang Huan,Wu Chu,Wu Yang,Luo Zhouyan,Wu Kun,Fang Zhaoquan,Zheng Zhongguang and so on.Qi deficiency includes insignificance of middle qi(spleen and stomach qi),deficiency of yuan qi,and lack of inter-kidney qi.Blood deficiency includes scarcity of liver and camp blood,etc.The dizziness due to the deficiency of kidney-yang is also valued by Sun Yikui,Cheng Guopeng,Wang Wenqi,Luo Zhouyan,Wang Rulin and Zheng Chongguang et al.Yang deficiency includes spleen and kidney yang reduction.With deficiency as the foundation and excess as the outward manifestation,deficiency and excess can be affected separately,and often influence and transform each other so that form the syndrome of deficiency and excess inclusions.Both external and internal wind can be felt.It is considered that yin deficiency and yang hyperactive active wind were dominant by Ye Tianshi,Cheng Xingxuan,Cheng Yougong,Hong Gui and Wang Zhongqi.Yin deficiency included liver,kidney and heart Yin deficiency.Xin ’an physicians believe that the location of vertigo lies in the brain(mind),lesions in the viscera are mainly responsible for the liver(gallbladder),spleen(stomach),kidney.The five elements of the heart and lungs are also related to each other.In terms of syndrome differentiation and treatment,for people with insufficient of qi and blood,Xin ’an doctors are good at cultivating qi and blood with Ginseng,Astragalus membranaceus,Angelica sinensis and Bighead atractylodes.For those with deficiency of yin and hyperactive of yang,Xin ’an doctors like nourishing liver and kidney to reconcile yang and calm wind.For those with turbid phlegm,Xin ’an doctors commonly use flexible modification Erchen decoction to replenish spleen qi and dispel phlegm.For those with kidney deficiency,warm and nourish the yang of the spleen and kidney in order to improve its function.For those with Kan and Li out of touch,nourishing water and fire is the foundation to cultivate the spirit.For people who are concerned about their illnesses and emotions,it is very important to pay attention to the idea of vipassana and rest treatment.In terms of medication,Xin ’an doctors inherited the classic prescription of ancient doctors,used them flexibly and boldly created new prescriptions,such as Gai Zheng Si Jun Zi Decoction,Gai Zheng Si Wu Decoction,Shi Tang Decoction,Xue Xu Xuan Yun Decoction,Qi Xu Xuan Yun Decoction,Qing Shang Pill,Zhuang Yuan Decoction,Xiang Sha Liu Jun Zi Decoction,Banxia Baizhu Tianma Decoction,etc.In addition,they are also good at the compatibility of medicines,such as Ginseng,Astragalus membranaceus,Tortoise shell,Oysters,Pinellia,Dried tangerine or orange peel,Pinellia tuber and rhizoma gastrodiae,Radix paeoniae alba,Radix rehmanniae,Mother-of-pearl,Oysters,Bitter butyl tea,Selfheal,etc.The 203 prescriptions involved 239 kinds of traditional Chinese medicines.The cumulative frequency of medication was 2120,and the average frequency was 9 times.There were 137 traditional Chinese medicines with a frequency of less than 9 times(470times),accounting for 22.17%,and 66 traditional Chinese medicines were used ≧9times(1650 times),accounting for 77.83%.There are 18 categories of traditional Chinese medicines,mainly 10 categories,among which tonic drugs,heat-clearing drugs,liver and wind-relieving drugs,anti-surface drugs,and diuretic and dampening drugs are among the top five.In the aspect of four qi,cold drugs and warm drugs appear and use most frequently.Among the five flavors,sweet drugs,bitter drugs and pungent drugs are used most frequently.Regarding the meridian,liver meridian tropism,lung meridian tropism,spleen meridian tropism,kidney meridian tropism and stomach meridian tropism appeared most frequently,whille liver meridian tropism,lung meridian tropism and spleen meridian tropism are used most frequently.A total of 7 location syndrome elements and 12 disease syndrome elements are involved.The more frequent location syndrome elements are liver,spleen and kidney,while the more frequent disease syndrome elements are phlegm(dampness),wind-moving,hyperactivity of yang,fire(heat)and yin deficiency.31 groups of two related drug combinations,32 groups of three related drug combinations and 29 groups of four related drug combinations were obtained.The core prescription consists of Pinellia ternata,Poria cocos,Dried tangerine peel,Licorice,Atractylodes macrocephala koidz,Ginseng,Gastrodia elata and White peony root.19 groups of drugs were clustered.15 new prescriptions for vertigo were obtained by entropy hierarchical clustering,and 22 common factors of traditional Chinese medicine were extracted.180 medical records include 1673 symptom records and 2527 Chinese medicine records,which correspond to 144 symptoms and 187 Chinese medicines.The top six symptoms are dizziness,nausea,anorexia,fatigue,vomiting and white and greasy fur.The top six traditional Chinese medicines are Pinellia ternata,Atractylodes macrocephala Koidz,Gastrodia elata Blume,Poria cocos,Pericarpium Citri Tangerinae and Glycyrrhiza uralensis Fisch.A total of 15 symptom common factors were extracted by principal component factor analysis,with a cumulative contribution rate of 68.004%.A total of 11 groups of cluster combinations of traditional Chinese medicines were obtained by systematic clustering.32 association combinations of two,three and four items were obtained by association rules,and 28 association combinations of two,three and four items between symptoms and traditional Chinese medicines were obtained.A total of 193 compounds of the active ingredients of Banxia Baizhu Tianma Decoction were screened out,and 330 targets were sorted out.There were 149 common targets for vertigo-related diseases.According to PPI network,STAT3,CXCL8,EGFR,VEGFA,MAPK14,EP300,MAPK3,CTNNB1,JUN,AKT1,MAPK8,CCND1 may be key therapeutic targets.GO analysis contained 2827 enrichment results,including 2480 biological processes,203 molecular functions and 144 cell components.KEGG pathway analysis found 176 items,involving AGE-RAGE signal pathway,fluid shear stress and atherosclerosis signal pathway,endocrine resistance signal pathway and so on.The results of molecular docking showed that the components with good docking with key targets were stigmasterol,quercetin,β-carotene,kaempferol,gastrodin,and sitosterol.Conclusion1.In Ming-Qing period,Xin ’an physicians thought that the etiology of vertigo was due to deficiency and solidity,deficiency in origin and excess in superficiality,deficiency and excess mixed.The excess pathological factors include phlegm,fire,wind and blood stasis,especially the phlegm.The deficiency is mainly due to the shortage of qi,blood,yin and yang in the viscera.Deficiency and excess can cause disease alone,and also influence and transform each other.2.In terms of syndrome differentiation and treatment,Xin ’an physicians have unique characteristics.They inherited classic prescriptions from previous generations of physicians,used them flexibly,boldly created new prescriptions,and were good at the compatibility of medicines,which is worthy of further research and inheritance.3.The data mining method is used to analyze the prescription of vertigo cases of Xin’an doctors from multiple dimensions.On the one hand,it confirms the results of theoretical research,on the other hand,it further expands the breadth and depth of research,and makes up for the limitations of literature theoretical research.4.8 Chinese medicines of Xin’an Chengguo Peng Banxia Baizhu Tianma Decoction are simple and powerful,which are closely related to the pathogenesis of spleen deficiency and phlegm generation,liver wind acting internally,and wind-phlegm disturbance.So the prescription is widely used in clinical practice.The causes of vertigo treated by Banxia Baizhu Tianma Decoction by famous Chinese medicine practitioners are often wind-phlegm,liver-wind,liver-fire,phlegm turbidity,spleen deficiency,blood stasis,etc.Combined with this recipe,it can treat different syndromes and stages of vertigo such as hyperactivity of liver-yang,turbid phlegm,deficiency of qi and blood,obstruction of orifices by blood stasis,etc.5.Through the method of network pharmacology,it is speculated that Banxia Baizhu Tianma Decoction acts synergistically on STAT3,CXCL8,EGFR,VEGFA,MAPK14,EP300,MAPK3,CTNNB1,AKT1 and other targets affected by potential pharmacodynamic components such as quercetin,kaempferol,stigmasterol,β-sitosterol,gastrodin and β-carotene.Banxia Baizhu Tianma Decoction may play a role in treating vertigo by participating in tube diameter adjustment,vascular processes in the circulatory system,reactive oxygen metabolism processes,oxidative stress reactions,etc.This effect may be related to fluid shear stress and atherosclerosis signaling pathway,IL-17 signaling pathway,TNF signaling pathway and other signaling pathways.The above research results preliminarily revealed the mechanism of the synergistic of Banxia Baizhu Tianma Decoction through multi-components,multi-targets and multi-channels.