Des-Arg(9)bradykinin as a causal metabolite for autism spectrum disorder

BACKGROUND Early diagnosis and therapeutic interventions can greatly enhance the developmental trajectory of children with autism spectrum disorder(ASD).However,the etiology of ASD is not completely understood.The presence of confounding factors from environment and genetics has increased the difficulty of the identification of diagnostic biomarkers for ASD.AIM To estimate and interpret the causal relationship between ASD and metabolite profile,taking into consideration both genetic and environmental influences.METHODS A two-sample Mendelian randomization(MR)analysis was conducted using summarized data from large-scale genome-wide association studies(GWAS)including a metabolite GWAS dataset covering 453 metabolites from 7824 European and an ASD GWAS dataset comprising 18381 ASD cases and 27969 healthy controls.Metabolites in plasma were set as exposures with ASD as the main outcome.The causal relationships were estimated using the inverse variant weight(IVW)algorithm.We also performed leave-one-out sensitivity tests to validate the robustness of the results.Based on the drafted metabolites,enrichment analysis was conducted to interpret the association via constructing a protein-protein interaction network with multi-scale evidence from databases including Infinome,SwissTargetPrediction,STRING,and Metascape.RESULTS Des-Arg(9)-bradykinin was identified as a causal metabolite that increases the risk of ASD(β=0.262,SE=0.064,P_(IVW)=4.64×10^(-5)).The association was robust,with no significant heterogeneity among instrument variables(P_(MR Egger)=0.663,P_(IVW)=0.906)and no evidence of pleiotropy(P=0.949).Neuroinflammation and the response to stimulus were suggested as potential biological processes mediating the association between Des-Arg(9)bradykinin and ASD.CONCLUSION Through the application of MR,this study provides practical insights into the potential causal association between plasma metabolites and ASD.These findings offer perspectives for the discovery of diagnostic or predictive biomarkers to support clinical practice in treating ASD.

Clinical observation on the treatment of severe hand-foot-mouth disease with antelope horn powder combined with auricular point application

Objective:To explore the Clinical observation on the treatment of severe hand-foot-mouth disease with antelope horn powder combined with auricular point application.Methods:From July 2016 to June 2018,90 children were randomly divided into control group(n=30),treatment group(n=30)and control group(n=30).The control group was treated with routine western medicine,the treatment group 1 was treated with oral antelope horn powder on the basis of control group,the second group was treated with auricular point application on the basis of treatment group 1,and the time of symptom relief and clinical cure were observed in each group.Related immune function and related inflammatory factors,serum neuron-specific enolase(NSE),safety index.Results:In treatment group 1,the time of herpes regression,antipyretic,antispasmodic time and clinical cure time were shorter than those of control group,and the time of treatment 2 group was shorter than that of group 1(P<0.05).The levels of CD3,CD4 and CD8 were increased after treatment in the three groups,especially in the treatment group(P<0.05),and the levels of TNF-毩αand IL-2,IL-6,IL-10 were decreased after treatment in the three groups,especially in the treatment group(P<0.05).NSE decreased after treatment in three groups,especially in treatment group 2(P<0.05).Conclusion:The application of antelope horn powder combined with auricular point application can obviously improve the severe hand,foot and mouth disease,and the clinical curative effect is definite.It is worth popularizing and applying in clinical practice.