Research Of Metabolic Characteristic Of Child Viral Pneumonia With Syndrome Of Obstruction Of The Lung By Phlegm Heat Based On UPLC-MS Technology

Background:Pneumonia is a common disease of infants and young children. As a major cause of infant death was listed as one of the world’s three important pediatric diseases by World Health Organization. With social development viral pneumonia shows a clear upward trend in China. Viral pneumonia common pathogens in children are:Respiratory syncytial virus(RSV) Adenovirus (ADV)、Influenza virus (IFV).. Parainfluenza virus (PIV) and so on. The disease belongs to Traditional Chinese Medicine "fei yan chuan sou" category, of which the obstruction of the lung by phlegm heat is most likely to be present and the most important syndrome. There is no direct causal link between syndromes of traditional Chinese medicine and modern medicine, and it is difficult to prove a syndrome with one or several indicators. Scientific and comprehensive exploration of the material basis of syndromes are key issues in the process of modernization of traditional Chinese medicine, and need to be resolved.Correlation is no clear evidence that Western medicine for children with viral pneumonia targeted treatment, currently only "ribavirin" was recommended by the American Academy of Pediatrics with the commentary:"Maybe you can use." Compared to Western medicine treatment of viral pneumonia in children is obviously insufficient, Chinese medicine has obvious advantages, and has been confirmed by many clinical and experimental studies. The research group leading by Nanjing University of Chinese Medicine Professor Wang Shouchuan has been committing to research in the TCM treatment of childhood viral pneumonia for 20 years, developed the effective JinXin oral liquid. There are also many injections such as Yanhuning, Qingkailing, Xiyanping and so on and many kinds of traditional Chinese medicine oral dosage play an important role in the clinical treatment of children with viral pneumonia.As an emerging discipline of systems biology, metabolomics focuses on the types, quantity and variation biological endogenous metabolites. Endogenous metabolites organisms are the real and sensitive final products of gene and protein activitys. Instead of focusings on a certain substance, metabolomics study of all endogenous metabolites organisms. Therefore, not like the traditional research methods, the application of metabolomics has the adavantge of avoiding to pay too much attention to a lack of one or several indicators change. Metabolomics has integrity, dynamic and comprehensive holistic features in the methodology. This feature is consistent with the most important and basic overall concept of traditional Chinese medicine theory. In the philosophical sense, the forefront of modern technology metabonomics and the ancient Chinese medicine have a language can communicate for the first time. Using metabonomics our group study plasma samples of 4 kinds childhood viral pneumonia of the syndrome of obstructionof the lung by phlegm heat, try to clarify the scientific essence of the syndrome of obstructionof the lung by phlegm heat, looking for the marker-metabolic-group of syndrome of obstructionof the lung by phlegm heat.Objective:In metabolomics technology platform were studied plasma samples of pneumonia of syndrome of obstructionof the lung by phlegm heat which caused by respiratory syncytial virus, adenovirus, influenza virus, parainfluenza virus, and explored the scientific essence of syndrome of obstructionof the lung by phlegm heat and its changes laws and metabolic pathway.Methords:Clinical experiment of metabolomics sthudy on viral pneumonia in children with syndrome of obstruction of the lung by phlegm heat:Based on traditional Chinese medicine, Western medicine diagnostic criteria exclude unsuitable, plasma samples were collected of each virus pneumonia in children with the syndrome of obstruction of the lung by phlegm heat. We collected and actual selected 35 cases of RSV pneumonia group,31 cases of ADV pneumonia group,11 cases of IFV pneumonia group,32 cases of PIV pneumonia group, and 30 healthy children as normal group.Using UPLC-LTQ/Orbitrap-MS test samples and acquisition chromatogram mass spectrum. Based on the XCMS Online platform with the PCA, OPLS-DA, NMMDS analytical methods and connecting online HMDB database, UMDB database, LIPID MAPs database, METLIN databases, analysed the result-matrix data, analysis the metabolic pathways and metabolic model, explored the typical metabolites group difference between viral pneumonia and normal children.In this study we had no animal experiments and comparative experiments medications. Subsequent to those findings, we compared the 4 groups results under real-world research paradigm, find out the common metabolomics with the exactly same trends among the same syndrome caused by 4 different viruses and formed into a password table of children viral pneumonia with the syndrome of obstruction of the lung by phlegm heat.Results:1.ADV pneumonia with the syndrome of obstruction of the lung by phlegm heat had a sicanifcently difference with the normal children and could be completely separated from the normal group.The main different metabolic pathways are Vitamin B9 metabolism,Vitamin B12 metabolism,Bile acid biosynthesis,Dynorphin metabolism,Carnitine shuttle, Biopterin metabolism,Alanine and Aspartate Metabolism,Arginine and Proline Metabolism,Carnitine shuttle,Tyrosine metabolism,Lysine metabolism,Ascorbate (Vitamin C) and Aldarate Metabolism,Propanoate metabolism, Pyrimidine metabolism,Beta-Alanine metabolism,Nitrogen metabolism, Carbon fixation, Purine metabolism, Glycerophospholipid metabolism, Glycosphingolipid metabolism, Tryptophan metabolism, Dynorphin metabolism,Squalene and cholesterol biosynthesis,Urea cycle/amino group metabolism,Fatty Acid Metabolism,De novo fatty acid biosynthesis.2. RSV pneumonia with the syndrome of obstruction of the lung by phlegm heat had a sicanifcently difference with the normal children and could be completely separated from the normal group.The main different metabolic pathways are Tryptophan metabolism,Ascorbate (Vitamin C) and Aldarate Metabolism,Porphyrin metabolism,Tyrosine metabolism,Aspartate and asparagine metabolism,Lysine metabolism,Purine metabolism, Saturated fatty acids beta-oxidation, Vitamin A (retinol) metabolism,Vitamin B9 (folate) metabolism,Lysine metabolism, Dynorphin metabolism, Biopterin metabolism, Vitamin E metabolism, Urea cycle/amino group metabolism.3. IFV pneumonia with the syndrome of obstruction of the lung by phlegm heat had a sicanifcently difference with the normal children and could be completely separated from the normal group.The main different metabolic pathways are Carnitine shuttle,Vitamin E metabolism,Sialic acid metabolism,Glycosphingolipid metabolism,Prostaglandin formation from arachidonate,Aspartate and asparagine metabolism,Glutamate metabolism,Arginine and Proline Metabolism,Glycine, serine, alanine and threonine metabolism,Vitamin B9 (folate) metabolism,Biopterin metabolism,Fatty Acid Metabolism,Tyrosine metabolism,De novo fatty acid biosynthesis,Alanine and Aspartate Metabolism,Vitamin A (retinol) metabolism.4. PIV pneumonia with the syndrome of obstruction of the lung by phlegm heat had a sicanifcently difference with the normal children and could be completely separated from the normal group.The main different metabolic pathways arePurine metabolism,Porphyrin metabolism,Saturated fatty acids beta-oxidation,Urea cycle/amino group metabolism,Tryptophan metabolism,Lysine metabolism,Hexose phosphorylation,Vitamin B9 (folate) metabolism,Glycine, serine, alanine and threonine metabolism,Sialic acid metabolism,Starch and Sucrose Metabolism,Aspartate and asparagine metabolism,Ascorbate (Vitamin C) and Aldarate Metabolism,Galactose metabolism,Tyrosine metabolism,Fatty Acid Metabolism,Androgen and estrogen biosynthesis and metabolism,C21-steroid hormone biosynthesis and metabolism,Prostaglandin formation from arachidonate,Carnitine shuttle,Glycosphingolipid metabolism,Carnitine shuttle,Biopterin metabolism, Vitamin E metabolism,Vitamin D3 (cholecalciferol) metabolism,Dynorphin metabolism,Vitamin B9 (folate) metabolism,Squalene and cholesterol biosynthesis,Lysine metabolism,Bile acid biosynthesis,Glycosphingolipid metabolism,Butanoate metabolism.5. In real-world paradigm investigated 4 different viral pneumonia in children with normal group plasma to identify its upper phase of plasma 313 core plasma metabolites and lower phase of plasma 128 core metabolites.And then screen out trend fully consistent iconic core material, which up-regulated 71 metabolites, down-regulated 349 metabolites and total 420 metabolites.And then we formed into a password table of children viral pneumonia with the syndrome of obstruction of the lung by phlegm heat.Conclusion:1. Using XCMS Online platform "cloud storage" "cloud computing" technology, using metabolomic analysis metabonomics changes in plasma among different viral pneumonia with the syndrome of obstruction of the lung by phlegm heat. It came to a conclusion that large data methodology interpreted the material basis of Chinese medicine syndrome was practical, reliable.2. Starting from 4 different virus pneumonia, in the UPLC-LTQ/Orbitrap-MS experimental technology platform, using the metabolomic analysis show different pneumonia had the different metabolic disorders. We ccould distinguish different metabolic patterns among the ADV, RSV, IFV, PIV pneumonia and healthy children.3. Effect of viral pneumonia in children was to reduce the main endogenous metabolite levels such as amino acid and energy metabolism, and increase the metabolite accounts for a lower proportion of the whole.4. Through horizontal analysis 4 groups of viral pneumonia with the syndrome of obstruction of the lung by phlegm heat disorder model of metabolic in plasma, we found 420 metabolites had the consistent trend adjustments.That was to say Chinese medicine Syndrome do have typical and symbolical metabolites group beyond the kinds of viruses.