The Clinical Study On The Efficacy Of Chuanhuo Xingshen Nasal Drops On The Patients With Severe Coma

Objective:(1)To explore the mechanism of Chuanhuo Xingshen Nasal Drops in intervening coma by using network pharmacology tools,and to establish the theoretical basis for further clinical study of its efficacy.(2)By observing the effect of Chuanhuo Xingshen Nasal Drops on patients with severe coma,to evaluate the wakening effect of Chuanhuo Xingshen Nasal Drops,and to provide new methods and new ideas for the treatment of coma with Traditional Chinese Medicine.Methods:(1)In order to clarify the targets and pathways of Chuanhuo Xingshen Nasal Drops in the treatment of coma,the chemical compositions of the volatile oil of four traditional Chinese medicines in Chuanhuo Xingshen Nasal Drops were collected through CNKI and PubMed.The targets of the compositions were predicted through SwissTargetPrediction database,and the targets of coma were screen through GeneCards database.The Venn diagram,drug-composition-target-disease network diagram,and protein-protein interaction(PPI)network diagram were respectively drawn by Venny 2.1.0,Cytoscape 3.7.2,and STRING 11.0.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed through DAVID 6.8.(2)A total of 40 patients with severe coma admitted to the Affiliated Hospital of Nanjing University of traditional Chinese medicine from November 2019 to January 2021 were randomly divided into the experimental group(Chuanhuo Xingshen Nasal Drops group)and the control group(routine group).The control group was given conventional western medicine treatment,and the experimental group was combined with Chuanhuo Xingshen Nasal Drops on the basis of conventional treatment.The course of treatment was 14 days.Glasgow Coma Score,amplitude integrated electroencephalogram score and relative alpha variability score before and after treatment,and Glasgow Outcome Score after treatment were statistically analyzed.Results:(1)Network pharmacology:A total of 44 main components were obtained,including neocnidilide,senkyunlide A,(z)-ligustilide,3-butylidenephthalide,4-vinylguaiacol,butylphthalide,gamma-terpinene,terpinen-4-ol,terpinolene,etc.328 drug targets were obtained,and 108 potential action targets were obtained for the treatment of coma.There are 20 key pathways involved in the development of coma,such as neuroactive ligand receptor interaction,serotonergic synapse,HIF-1 signaling pathway,etc.(2)The clinical study:①The Glasgow Coma Score of the 7th day and the 14th day in the control group and the experimental group was significantly higher than that before treatment(P<0.01),and the experimental group was significantly better than the control group(P<0.01).② The score of amplitude integrated electroencephalogram of the 7th day and the 14th day in the experimental group was significantly higher than that before treatment(P<0.01).The score of amplitude integrated electroencephalogram of the 7th day in the control group was better than that before treatment(P<0.05),and the score of amplitude integrated electroencephalogram of the 14th day in the control group was significantly higher than that before treatment(P<0.01).The score of amplitude integrated electroencephalogram of the 7th day and the 14th day in the experimental group was better than that in the control group(P<0.05).③ The relative alpha variability of the 7th day and the 14th day in the experimental group was significantly better than that before treatment(P<0.01).The relative alpha variability of the 7th day in the control group had no significant improvement compared with that before treatment,and the 14th day in the control group was significantly better than that before treatment(P<0.01).The relative alpha variability of the 7th day and the 14th day in the experimental group was better than that in the control group(P<0.05).④ After 14 days of treatment,the curative effect was evaluated according to Glasgow Outcome Score.Compared with the control group,the curative effect of the experimental group was better than that of the control group(P<0.05).⑤ The recovery rate of the experimental group was 80%,and that of the control group was 50%.The recovery rate of the experimental group was higher than that of the control group(P<0.05).⑥ There were 3 all-cause deaths in the experimental group and 6 all-cause deaths in the control group.There was no significant difference in 28-day mortality between the two groups(P>0.05).Conclusions:(1)Network pharmacology suggests that Chuanhuo Xingshen Nasal Drops may treat coma by interfering with AKT1,MAPK3,APP,CASP3,SRC and other key targets,regulating important pathways such as neuroactive ligand receptor interaction,serotonergic synapse,HIF-1 signaling pathway and so on.(2)The clinical study suggests that:① Chuanhuo Xingshen Nasal Drops can improve the Glasgow Coma Score,improve the state of consciousness,and increase the recovery rate of patients.② Chuanhuo Xingshen Nasal Drops can improve the amplitude integrated electroencephalogram score,relative alpha variability,electrical activity of the brain and cerebral blood flow,and improve the brain function of patients.③ There was no significant difference in the 28-day mortality between the two groups,which suggests that Chuanhuo Xingshen Nose Drops is reasonable,can be safely applied to patients with severe coma,which is worthy of wide clinical promotion.