Comparative Study Of Serum Metabolomics Of Acute Cholangitis And AOSC Based On HPLC/Q-TOF-MS

Objective:In this study,High performance liquid chromatography/Quadrupole time-of-flight mass spectrometer technique was used in patients with acute cholangitis?AC?.Metabolomics comparison was performed with serum samples from healthy control population,patients with acute obstructive suppurative cholangitis?AOSC?and patients with acute cholangitis.Exploring the metabolic characteristics of AC and AOSC and screening for differential metabolites,through the metabolic pathway analysis of differential metabolites,from the metabolic point of view to lay the foundation for studying the molecular mechanisms of different stages of the same disease such as AC and AOSC.Method : According to the inclusion and exclusion criteria,Serum specimens of AC?34 cases?,AOSC patients?14 cases?and healthy examination subjects?20 cases?Hepatobiliary Surgery and Emergency Surgery of Hunan Provincial People's Hospital from September 01,2018 to November 30,2018 were collected.High performance liquid chromatography/Quadrupole time-of-flight mass spectrometer?HPLC/Q-TOF-MS?was used for metabolomic analysis of serum from AC patients and healthy subjects,AOSC patients and healthy subjects.Pre-processing of peak extraction,noise reduction,and standardization using Metaboscape 4.0 software,Principal component analysis?PCA?and partial least squares discriminant analysis?PLS-DA?usingSimca-P14.1 software And Orthogonal partial least squared discriminant analysis?OPLS-DA?,screened according to scalar projection importance?VIP>1?and statistical difference?P<0.05?in the best model after identification.Metabolites were differentially analyzed and metabolic pathways were analyzed for differential metabolites identified using the MetaboAnalyst 4.0 database.Results:1.This experiment was based on HPLC/Q-TOF-MS for the first time to obtain the unique metabolic characteristics of acute cholangitis,and successfully constructed a recognition model for distinguishing between AC and healthy control populations and distinguishing between AC and AOSC.2.Through multivariate data analysis,there was a significant difference in serum metabolic profiles between the AC group and the healthy control group.There are 15 different metabolites screened and identified,9of which showed a downward trend,namely:Tetradecanedioic acid,Pyridoxamine,Lyso?PE₂2:6,PC₂2:6,PC₁8:2?,2-Pyrrolidinone,D-alpha-Aminobutyric acid,23S_-23,25-dihdroxy-24-oxovitamine D323-_beta-glucuronide,5-_3-Hydroxyphenyl_-gamma-valerolactone-3_-O-glucuronide.9 of which showed a downward trend,namely:N-lactoyl-Leucine,L-Glutamicacid,Indoxyl sulfate,Isoleucylproline,2-Furoylgly-cine,Linoleoyl ethanolamide.3.Through multivariate data analysis,it was found that there were significant differences in the metabolic profiles of AC and AOSC groups.There are 13 different metabolites screened and identified;8 of them showed a downward trend,namely:2-Furoylglycine,Indoxyl sulfate,N-lactoyl-Leucine,S-Adenosylhomocysteine,Isoleucylproline,etc;There are five metabolites that are on the rise,namely:Tetradecanedioic acid,Nicotinamide N-oxide,Methylmalonylcarnitine,Lyso?PE₂2:6,PC₂2:6,PC₁8:2,PC₂0:4?,L-Methionine.4.Compared with the AC group,AOSC mainly causes abnormal metabolic pathways such as unsaturated fatty acid metabolism,amino acid,sugar metabolism,and phospholipid metabolism.Conclusions:This study is the first to explore the changes in metabolism during the course of AC and AOSC.AC and AOSC mainly cause abnormal metabolic pathways such as unsaturated fatty acid metabolism,amino acid,sugar metabolism,and phospholipid metabolism.These findings lay the foundation for the later study of the molecular mechanisms at different stages of the same disease,such as AC and AOSC.