Study On The Distribution Of Syndrome Factors And Sleep Influencing Factors In Patients With Hypertension And Atrial Fibrillation And Network Pharmacology Analysi

Objective:Study 1:Through a cross-sectional study,explore the distribution of TCM syndrome in patients with hypertension and atrial fibrillation,and observe the sleep quality and the association between various factors and sleep.Study 2:The mechanism of the treatment of hypertension combined with atrial fibrillation was discussed through network pharmacology and molecular docking.Methods:Study 1:The common symptoms of atrial fibrillation were sorted out according to ESC2020 Guidelines for Diagnosis and Management of Atrial Fibrillation and Atrial Fibrillation:Current Understanding and Treatment Suggestions 2021,and the scale was designed combined with Zhu Wenfeng’s syndrome differentiation,and the syndrome was recorded through the scale.Analysis by EXCEL,cerensins greater than 20 points were selected.A PSQI score database was established to observe the sleep quality of the patients.Study 2:through the traditional Chinese medicine system pharmacology database and analysis platform(TCMSP)database collection and screening in OB>30%,DL>0.18 ingredients,using GeneCards,OMIM,DrugBank and other database to find out the related targets of hypertension and atrial fibrillation,hypertension and atrial fibrillation targets,and the intersection of drug active targets,through the STRING platform target protein interaction network.The Cytoscape3.9.1 was used to draw the "drug-component-target" network,and conducted GO analysis and KEGG enrichment visualization analysis based on the Metascope database to select the main action pathways.The major macromolecules and major small molecules were selected for molecular docking verification by Autodock.Results:Study 1:(1)General situation statistics ①Population distribution:A total of 164 hypertensive patients with AF were included in this study,including 86 male(52%)and 78 female(48%)women.The mean age of the patients was 71.3±10.8 years,with the minimum being 50 years and the maximum being 93 years.There were 39(23.7%)tobacco smokers and 32(19%)alcohol drinkers.②Medication:105(41%)on CCB,76(30%)on ACEI/ARB,46(18%)onβ blockers,17(7%)on diuretics,5(2%)of other antihypertensive drugs,and 6(2%)untreated.③Distribution of hypertension:51(31%)with grade 1 hypertension,36(22%)with grade 2 hypertension,and 77(47%)with grade 3 hypertension.④ Atrial fibrillation:paroxysmal atrial fibrillation 135(82%),persistent atrial fibrillation 24(14.6%),long-term persistent atrial fibrillation 22(13.5%),permanent atrial fibrillation 5(3%).The number of cases of atrial fibrillation less than 1 year was 40(24%),the duration of 1-3 years was 55(34%),the duration of 4-6 years was 26(16%),the number of patients with 7-10 years was 16(10%),the number of patients with a duration of more than 10 years was 27(16%),and the average duration of illness was 4.2 ± 3.8 years.⑤ Combined diseases:90(18.52%)with hyperlipidemia,76(15.64%),56(11.52%)with diabetes,35(7.20%)with reflux esophagitis,34(7.0%)with old cerebral infarction,29(5.97%)diagnosed with insomnia in outpatient or ward,and 21 with hyperhomocysteine(4.32%).⑥Sleep status:80 patients with sleep disorders and 84 patients without sleep disorders,with an average PSQI of 5.0±3.2 points.⑦Distribution of TCM tongue pulse:patient pulse with string pulse,smooth pulse,fine pulse,pulse pulse is the most common,tongue with dark red tongue,dark tongue,red tongue,light red,purple dark is the most common,moss with thin white moss,white greasy moss,yellow greasy moss,thin yellow moss,less moss is the most common.⑧Distribution of TCM syndrome:the frequency of atrial fibrillation is heart,spleen from high to low,liver,lung and kidney,and the combination of atrial syndrome is the combination of heart and spleen(37 times).The distribution of pathological syndrome elements is mainly qi deficiency,blood stasis,Yin deficiency and phlegm turbidity.In terms of syndrome combination,there were 60 times(36.8%),57 times(35%),38 times(23.3%),and 8 times(4.9%).Among them,the combination of phlegm turbidity+blood stasis+qi deficiency+Yin deficiency(23 times),blood stasis+qi deficiency+Yin deficiency(18 times)and blood stasis+qi deficiency(14 times)appeared the most.On the AF,the number of patients with paroxysmal AF in the lung and kidney was significant compared with persistent AF(P<0.05),while there was no difference.(2)Analysis of sleep disorders and various factors ① relationship between synin and sleep disorders:in hypertensive patients with atrial fibrillation,There was no significant difference in the element distribution between paroxysmal and persistent AF(P>0.05),Except for Yin deficiency syndrome element and disease site syndrome element liver(P<0.05),the relationship between the other syndrome elements and sleep disorders is not very close(P>0.05),Except for the combination of blood stasis+phlegm turbidity+heat+qi deficiency syndrome element(P<0.05),The rest of the pathological and pathological syndrome combinations were not significantly statistically significant,However,the logistic analysis showed that,Yin deficiency was an independent risk factor(OR=1.720,P<0.05)and liver was not an independent risk factor.② Sex and sleep disorders:In patients with hypertension and atrial fibrillation,women were more likely to develop sleep disorders(P<0.01),and gender was an independent influence of sleep disorders(OR=2.288,P<0.05).③Age relationship between sleep quality:There was a significant correlation between age(P<0.01),with Pearson’s correlation was 0.241.④The relationship between hypertension and sleep quality:there was no significant relationship between hypertension or sleep disorders(P>0.05),and drugs and treatment strategies for hypertension had no significant effect on sleep quality(P>0.05).⑤ Association between AF and sleep disturbance:Patients with AF less than 1 year had less sleep disturbance(P<0.05).Long-range persistent AF had a significant relationship with sleep disturbance(P<0.05),while the rest of the AF type had no significant relationship with sleep disturbance(P>0.05),but AF duration and type were not independent risk factors for sleep disturbance.⑥ The relationship between combined diseases and sleep disorders:Patients with hypertension and atrial fibrillation were more likely to develop sleep disorders in patients with cerebrovascular disease or urinary system disease or respiratory disease(P<0.05),with cerebrovascular disease and urinary system disease being independent risk factors for sleep disorders(P<0.05,OR=2.486)and(OR=2.945,P<0.05),and less diabetic patients had sleep disorders.Study 2:1.22 kinds of ginseng active ingredients,5 kinds of active ginger ingredients,23 raw ingredients,4 kinds of hiopogactive ingredients,92 kinds of licorice active ingredients,29 kinds of jujube ingredients,3 kinds of gelatin ingredients,2 kinds of hemp seed ingredients and 8 kinds of cassia branches were obtained.See the table below for details.Finally,469 intersection targets of TCM were obtained.The top 10 most important components were DZ 16(Quercetin),MD4(N-trans-feruoyl tyramine),MD1(The uracil nucleoside),MD3(Oleanolic acid),RS8(Sankaempferol,kaempferol),MD2(Stigmasterol-beta-D-glucoside),GC52(7-Methoxy-2-methyl isoflavone),GC60(Formononetin),GZ 2(β-sitosterol,beta-sitosterol),RS4(Ginsenoside RH2).In the GeneCards database,10685 hypertension,3788 AF targets and 2393 intersection targets were obtained.The genes that intersect with the licorice soup were introduced into String to make JUN,MAPK1,STAT3,AKT1,HSP90AA1,RELA,TNF,MAPK14,CTNNB1,FOS,IL-6,ESR 1,CAV1,MAPK8 were the most important core targets.2.GO analysis can reveal the main involvement of biological effects such as cellular active response to drugs,cellular lipopolysaccharide response,cellular response to bacterial-derived molecules,and response to metal ions.And involved in the cellular response to chemical stress,to alcohol,and to cellular reactive oxygen metabolic processes,oxidative stress.Also is involved in the cellular response to steroid hormone metabolism.It also has effects on cell membrane rafts,vesicle lumen,cytoplasmic capsule lumen,and on postsynaptic membrane components and secreted granules.Also on nuclear receptor activity,ligand activation transcription factor activity,DNA binding transcription factor binding,RNA polymerase 1 specificity,DNA binding transcription cells,and involved in catecholamine binding activity,receptor ligand binding activity,signaling receptor activation,steroid hormone receptor binding activity,cytokine activity is closely related.KEGG showed that the related targets of Zhulicorice decoction were enriched in the age-age signal pathway of diabetic complications,lipid and atherosclerosis,fluid shear stress and atherosclerosis,IL-17 signaling pathway,MAPK signaling pathway,TNF signaling pathway,Th 17 cell differentiation,HIF-1 signaling pathway,etc.3.Molecular docking by AutoDock,docking results showed that quercetin,N-trans-ferulotyramine and uracil nucleoside could bind well to JUN,MAPK1 and STAT3,docking,stable conformation,ideal hydrogen bond connection,ΔG<-5 kJ/mol,strong binding activity.Conclusions:1.In this study,a cross-sectional questionnaire study can conclude that hypertension grade and drugs and medication strategies for hypertension have less impact on sleep quality,which can reduce clinicians’ medication concerns.2.Women,older patients,and patients with cerebrovascular diseases are more likely to develop sleep disorders,so clinicians need to pay attention to them.3.Patients with long-term persistent atrial fibrillation have poor sleep quality,and regardless of atrial fibrillation,the longer the duration,the more likely to cause sleep disturbance.4.The patients with atrial fibrillation and hypertension are heart,spleen,liver,qi deficiency,blood stasis,Yin deficiency and phlegm turbidity.The incidence of paroxysmal atrial fibrillation is more significant in the number of lung and kidney.In terms of TCM syndrome,Yin deficiency and the liver are more prone to sleep disorders.Therefore,in the treatment of traditional Chinese medicine,the methods of nourishing qi and Yin,relieving liver and qi,activating blood stasis and removing phlegm and turbidity can be targeted for treatment.5.Using network pharmacology and molecular docking technology,we can verify various active ingredients,such as quercetin,N-trans-ferlooyriramine and uracil nucleoside,which can affect the occurrence and development of hypertension and atrial fibrillation through a variety of signaling pathways and biological processes,such as alleviating the hardening of arterial vessels and reducing myocardial remodeling.