Study On The Distribution Pattern Of TCM Syndromes And Characteristics Of Medication In Patients With Common Tachyarrhythmia

Background:Tachyarrhythmia is a common clinical disease,which is often secondary to cardiovascular related diseases such as coronary heart disease and myocardial infarction.It can also be idiopathic,and the common types can include atrial fibrillation,frequent premature contraction,short-circuit ventricular tachycardia,and paroxysmal supraventricular tachycardia.Its incidence has long affected the quality of life of patients,and brought mental pressure to patients.Severe symptoms can lead to transient somnolence,syncope and even death,which is detrimental to the physical and mental health of human beings.It has become an urgent problem to be solved in the field of cardiovascular disease.The introduction and rapid development of radio frequency ablation technology have helped patients to solve this problem to a great extent.However,due to the limitations of surgical complications and postoperative recurrence,some patient groups are still unwilling to receive surgical treatment in clinic.As antiarrhythmic drugs are the cornerstone of treatment,its disadvantages such as adverse reactions and arrhythmia are difficult to overcome in a short period of time.Treatment of tachyarrhythmia based on syndrome differentiation of Traditional Chinese Medicine(TCM)has been proved to be effective in alleviating clinical symptoms and reducing adverse reactions,showing a good development prospect.Based on the major health problem of common clinical tachyarrhythmia,we conducted a cross-sectional survey of TCM syndromes,data mining of clinical medication patterns,and network pharmacology research.Therefore,in this study,firstly,from the perspective of TCM syndrome factors,we investigated the general situation of common tachyarrhythmia and explored the distribution characteristics of palpitation syndrome through cross-sectional investigation.Second,the literature study in recent years in the treatment of common tachyarrhythmia disease medication law,through the data mining method to analyze the clinical medication of tachyarrhythmia treatment,explore the physicians in the treatment of this disease medication and prescription rules;Finally,based on the above clinical and literature research,we further explored the potential action mechanism of commonly used drugs using network pharmacology,in order to provide an evidence-based basis for clinical treatment and guidance on treatment thinking,and provide a basic research direction for in-depth study of Chinese medicine components.Objective:1.Based on the clinical cross-sectional study,understand the general situation of patients with common tachyarrhythmia,and analyze the distribution law and characteristics of TCM syndrome.2.Based on the literature research,we digs out the laws of medication and prescription of various physicians in treating common tachyarrhythmia with Chinese medicine.3.Explore the potential mechanism of drugs’ therapeutic effects based on network pharmacology.Methods:1.Cross-sectional study:A continuous sampling cross-sectional study was used.After informed consent was obtained from patients,face-to-face questionnaire was filled out and patient information was collected on site.One part was for basic information collection,including the patient’s age,gender,BMI,history of tobacco and alcohol use,as well as echocardiography and blood lipid.The other part was conducted under the supervision of senior physicians with high-level professional title in cardiovascular department with high seniority,to complete the collection of syndrome element data related to the four TCM diagnoses of the patient.Summarize and describe that characteristics of syndrome distribution law.2.Data mining part:With the keywords of "tachyarrhythmia","premature beat","atrial fibrillation","atrial flutter","tachycardia","traditional Chinese medicine and western medicine","Chinese medicine","Chinese medicine" and so on as the theme of the search term,the published Chinese and English literatures in CNKI database,Wanfang database,VIP database,China Biomedical Literature database and PubMed database are searched professionally,and the literatures that meet the inclusion criteria are screened out,from which the high-frequency drug use and drug taste tropism are summarized,and the association rules are used.3.The part of network pharmacology:Based on the first two parts of research,three herbs,Codonopsis radix,Sal viae miltiorrhizae radix et rhizoma and Coptidis rhizoma,were selected,and the main active components of "Codonopsis radix-Sal viae miltiorrhizae radix et rhizoma-Coptidis rhizoma" were obtained from TCMSP and HERB databases,and the corresponding targets of the active compounds were predicted by SwissTargetPrediction.DisGeNET,GeneCards,DRUGBANK and OMIM databases were used to collect target disease targets after merging and de-duplication.The target of active compound of traditional Chinese medicine is intersected with the target of disease,which is the potential intersection target of traditional Chinese medicine in treating diseases.The intersecting targets were imported into the STRING database,and a protein-protein interaction network(PPI)was constructed.The network was visualized by Cytoscape 3.7.2 software,that is,the network of"traditional Chinese medicine-active ingredient-target-disease",and the core targets in the PPI network were further extracted by plug-ins.GO function enrichment and KEGG pathway enrichment of intersection targets were analyzed by Metascape.Molecular docking was used to verify the results of core components and key targets.Results:1.clinical cross-sectional study part① Basic information:A total of 304 patients were included in this study,including 141 males(46.4%)and 163 females(53.6%).The middle-aged and elderly patients were the main attack groups.The disease types involved single or multiple coexisting tachyarrhythmias,among which the largest number was atrial fibrillation(231 cases(78.0%),and the course of disease was one year or less.Patients with previous history of smoking and drinking alcohol were less,accounting for 29.9%and 25.7%,respectively.BMI was mainly overweight(48%)and normal(38%),and the overall sleep quality of patients was poor.40.5%of patients indicated that they had no obvious dietary preference,and some of them preferred meat and salty/pickled food,accounting for 28%and 19.4%,respectively.Hypertension was more common in family history and comorbidity.② Distribution of TCM syndromes:from high to low,the syndromes are blood stasis syndrome>qi deficiency syndrome>phlegm turbidity syndrome>heat accumulation syndrome>yin deficiency syndrome>water stagnation syndrome>yang deficiency syndrome>qi stagnation syndrome>blood deficiency syndrome.The distribution of syndrome combinations is mainly 2-4 combinations.Qi deficiency syndrome and yin deficiency syndrome are common in deficiency syndrome,while blood stasis syndrome and phlegm turbidity syndrome are common in solid syndrome.2.data mining research part① The 282 prescriptions in the network literature database were ultimately included in this study,involving a total of 212 traditional Chinese medicines.The most used traditional Chinese medicine was Gl ycyrrhizae radix et rhizoma praeparata cum melle,and the ones with the appearance frequency≥50 times were high-frequency drugs,including Gl ycyrrhizae radix et rhizoma praeparata cum melle,Sal viae miltiorrhizae radix et rhizoma,Ophiopogonis radix,Ziziphi spinosae semen,Astragali radix,Angelicae sinensis radix,Poria and Codonopsis radix.According to the statistical analysis of four gases and five flavors,the cold drugs were most used in the prescription,with the sweet and bitter flavors common,followed by the pungent drugs.Meridian tropism of drugs is closely related to liver meridian,lung meridian and spleen meridian.② Apriori algorithm was used for high-frequency medication to analyze the association rules between drugs.With the confidence≥80%and support≥10%,a total of 74 association rules were obtained,and the combination of Ophiopogonis radix and Schisandrae chinensis fructus showed the highest support and occurrence frequency.The high-frequency medication association was visualized using Cytoscape 3.7.2 software.The Gl ycyrrhizae radix et rhizoma praeparata cum melle was strongly associated with Sal viae miltiorrhizae radix et rhizoma,Ziziphi spinosae semen,Ophiopogonis radix and Astragali radix,and it was analyzed that Ophiopogonis radix-Schisandrae chinensis fructus,Gl ycyrrhizae radix et rhizoma praeparata cum melle-Cinnamomi ramulus,and Gl ycyrrhizae radix et rhizoma praeparata cum melle-Rehmanniae radix were the core drug combination in the literature database prescriptions.③ The prescription traditional Chinese medicine could be divided into seven types by clustering:The first type comprise Os draconis,Ostreae concha,Gl ycyrrhizae radix et rhizoma praeparata cum melle,and Cinnamomi ramulus;The second type:Codonopsis radix;The third type:Poria,Pinelliae rhizoma praeparatum,Ziziphi spinosae semen,and Pol ygalae radix;The fourth type:Ophiopogonis radix,Schisandrae chinensis fructus,and Rehmanniae radix;Fifth type:Sophorae fla vescentis radix,Ardostachyos radix et rhizoma,and Sal viae miltiorrhizae radix et rhizoma;Sixth type:Coptidis rhizoma;Seventh type:Astragali radix,Angelicae sinensis radix,Paeoniae radix alba,and Chuanxiong rhizoma.3.network pharmacology research part① In this study,the network of "Codonopsis radix-Sal viae miltiorrhizae radix et rhizoma-Coptidis rhizoma" for the treatment of patients with tachyarrhythmia was constructed by network pharmacology method,involving 178 active compounds of traditional Chinese medicine,47 intersecting targets of traditional Chinese medicine and diseases and 11 core targets.② Core active compounds:Quercetin,luteolin,stigmasterol and other compounds play an important role in the whole network,which may be the core components of "Codonopsis radix-Sal viae miltiorrhizae radix et rhizoma-Coptidis rhizoma" in the treatment of tachyarrhythmia.③Core targets:core gene targets such as IL6,TNF,ACE,NOS3,EDN1,NPPA,CAV1,ADRB2,KCNH2 play an important role in the treatment.④Enrichment analysis:67 molecular functions,67 cell components and 701 biological processes were obtained by GO function enrichment analysis(P<0.01).Sixty-six signaling pathways(P<0.01)were screened by KEGG pathway enrichment analysis,which involves mainly enriched in cGMP-PKG signaling pathway,adrenergic signaling pathway in cardiomyocytes,calcium signaling pathway and cAMP signaling pathway,etc.⑤ Molecular docking:The average docking affinity of the top three components after molecular docking with key targets was-7.49 kcal/mol,indicating that the components had strong binding energy to the targets.Conclusion:1.Cross-sectional study has revealed that the syndrome distribution of common tachyarrhythmia diseases is dominated by the qi deficiency and blood stasis syndrome composed of two syndromes,with more phlegm and heat accumulation.2.In the literature database,the main prescription drugs that benefit qi,nourish yin and tranquilize mind were Gl ycyrrhizae radix et rhizoma praeparata cum melle,Ophiopogonis radix and Ziziphi spinosae semen,and attention was paid to the regulation of liver,lung and spleen.3."Codonopsis radix-Sal viae miltiorrhizae radix et rhizoma-Coptidis rhizoma" may act on core targets such as IL-6,TNF,ACE through core components such as quercetin,luteolin and stigmasterol,and regulate cGMP-PKG signaling pathway,adrenergic signaling pathway in cardiomyocytes,calcium signaling pathway and cAMP signaling pathway to exert biological functions such as gate channel activity,neurotransmitter receptor activity,and G protein-coupled receptor binding,and intervene in biological processes such as inflammation,oxidative stress and ion transport,thereby directly or indirectly achieving the purpose of treating tachyarrhythmia.