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.

A clinical pathway for integrative medicine in the treatment of functional constipation in Hong Kong,China

Objective:Functional constipation(FC)is a common intestinal disease worldwide.Despite the presence of criteria such as Roman IV,there is no standardized diagnosis and treatment algorithm in Hong Kong that combines both Western and Chinese medicine approaches.This study integrates current effective and safe diagnosis and treatment methods for FC and provides a clear and scientific pathway for clinical professionals and patients.Methods:A systematic search of the PubMed,Cochrane Library,and China National Knowledge Infrastructure databases was performed from their inception to June 30th,2022,collecting the current evidence about the efficacious integrative management for FC.We organized a meeting of professionals in fields relevant to treatment and management of FC to develop a consensus agreement on clinical pathway process.Results:We developed a clinical pathway for the treatment of FC based on the most recent published guidelines and consultation with experts.This pathway includes a hierarchy of recommendations for every step of the clinical process,including clinical intake,diagnostic examination,recommended labs,diagnostic flowchart,and guidance for selection of therapeutic drugs.Conclusion:This pathway establishes clinical standards for the diagnosis and treatment of FC using Chinese medicine and Western medicine;it will help to provide high-quality medical services in Hong Kong for patients with FC.