Application Of Metabolomics In Children With Short Stature And Hand-foot-mouth Disease

Pediatric diseases are related to the health problems of children and adolescents in their growth and development.Early detection,dearly intervention and early treatment are very important for the healthy growth of children.In this thesis,two typical pediatric diseases,short stature and hand-foot-mouth disease,were chosen,and nuclear magnetic resonance(NMR)-based metabolomic technique was used to analyze the metabolic changes during the pediatric diseases to understand the underlying biochemical mechanism and provide new diagnostic methods.Firstly,1H NMR spectra of all serum samples from the patients and the healthy controls were acquired.Next,principal component analysis and orthogonal partial least squares-discriminant analysis were performed on the spectral data to identify the significant differences in metabolic profiles between the two groups.Finally,volcano plot based on the univariate and multivariate statistical analysis was constructed to summarize and identify potential biomarkers,and the corresponding disturbed metabolic pathways related to the diseases were obtained,so as to further understand the pathogenesis and recommend possible intervention strategies.Short stature is defined as a condition in which a child's height is 2 standard deviations below the average height of the children in the same sex,age,and race.Studies have shown that the pathogenesis of short stature is divided into disease type and non-disease type,among which the growth retardation caused by endocrine and metabolic diseases as growth hormone deficiency accounts for a large proportion.It is essential for short stature parents and doctors to understand the cause and the metabolic characteristics to determine the possibility of treatments.The metabolomic analysis of serum revealed that the disburbed glucose metabolilsm and metabolism and biosynthesis of amino acids are typical metabolic features of short stature,and the growth axes and stress state of short stature children were also affected.Accordingly,supplemental betaine in dietary pattern,the improvement of glycometabolism,and endogenous replenishment of lysine and glutamine allow the possible treatment strategy for short stature.Hand-foot-mouth disease(HFMD)is an infectious disease caused by intestinal viruses.This disease,which affects children under five years old,has become a public health threat across the Asia-Pacific region.The incubation period of hand-foot-mouth disease can be up to 2-10 days.Most common cases are accompanied with acute onset of illness,and severe cases can cause nervous system,respiratory system,circulatory system complications,even lead to death.At present,the diagnosis of hand-foot-mouth disease mainly depends on clinical symptoms,easy to miss isolation infection source and the best period of treatment.Serum levels of myo-inositol,valine,leucine,lysine,isoleucine and 3-hydroxybutyrate were higher,while serum levels of glycerophosphorylcholine,phosphocholine,glutamine and alanine were significantly lower in HFMD children than than in healthy controls.A total of 7 metabolic pathways are affected to varying degrees,including valine,leucine and isoleucine decomposition,glycosylation,alanine,aspartate and glutamate metabolism,glutamate and glutamine metabolism,ketone body synthesis and decomposition,fat digestion and absorption,and lysine decomposition,which are mainly related to inflammation,impaired intestinal absorptive function and immune response.Our results shed light on the underlying pathogenesis of this disease,and could provide potential solutions for early prevention,early diagnosis,intermediate intervention and late treatment of the disease.