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Serum And Cerebrospinal Fluids Metabolomics Study On Tubercular Meningitis Patients

Posted on:2018-07-26Degree:MasterType:Thesis
Country:ChinaCandidate:Y M LiFull Text:PDF
GTID:2334330536986196Subject:Clinical Laboratory Science
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Objective:To explore the specific metabolites in patients with tuberculous meningitis in cerebrospinal fluid and serum,through analysis of the change of these metabolites in the number and nature of the patient’s body,and in the process of development of the disease metabolism mechanism for metabolic ion representative,early diagnosis of tuberculous meningitis in assisted clinical monitoring,to improve the prognosis of the patients.Methods:A total of 47 CSF samples were analyzed by ultra performance liquid chromatography coupled with mass spectrometry(UPLC-MS).The serum samples were collected from 107 patients.Samples from November 2014-December 2016 in Tianjin Haihe Hospital Department of the brain and cerebrospinal fluid specimens from patients with tuberculosis hospitalized a total of 47 cases,including 21 cases of TBM patients with non tuberculous meningitis in 26 cases,30 cases of other selected healthy subjects.A total of 102 patients were included in the study,including male and female,with a total of 45 cases,with a total of 21 patients(male,female,and mean age(48.01 +.12.35)),with a total of 12 patients,with a mean age of 9(+).The control group included 26 cases of non tuberculous meningitis group(N-TBM group),pulmonary tuberculosis group(group TB)and healthy control group(group N)of 30 cases.In N-TBM group,14 cases were male,12 were female,the average age(45.56 + 19.43)years old,including bacterial meningitis in 7 cases;15 cases of viral meningitis,4 cases of meningitis caused by other factors;TB group of 25 cases,male 15 cases,female 10 cases,average age(46.56 + 15.43)years;a total of 30 cases of healthy control group,male 16 cases,female 14 cases,average age(43.56 + 21.43)years old.Cerebrospinal fluid and serum samples were detected by UPLC-MS.The data obtained were Normalized into Mzmine2.0 software;principal component analysis to construct pattern recognition system data and then processed into SIMCA-P+12.0.1.0 software(PCA)and orthogonal partial least squares(OPLS-DA)for preliminary screening and selection of metabolites,variable importance in projection values of the model two classification of OPLS-DA(VIP)and VIP,metabolic markers screening of S;early metabolites after screening by using SPSS 21 independent samples nonparametric test,identification of specific metabolic markers;ROC curve,evaluate the characteristic metabolic marker for the diagnosis efficiency of diagnosis of tuberculous meningitis.Results:The OPLS-DA model was established based on the CSF and serum metabolite data.The accuracy of the model was 100%,which could be well divided into tuberculous meningitis group and non tuberculous meningitis group.The 23 characteristic ions were identified in the cerebrospinal fluid,and one of them was identified.The serum was characterized by the discovery of a total of 31 characteristic ions,and a total of 5 of them were identified.The characteristics of ions in the cerebrospinal fluid metabolism including Methyl(7Z,9Z,9’Z)-6’-apo-y-caroten-6’-oate,Dihydromaleimide beta-D-glucoside),sorbitan monooleate 、 Sorbitan oleate,Panaxydol linoleate.In the serum may feature metabolic markers including Octadecanamide and(LysoPC(18:0)20:4(5Z),phosphatidic acid,8Z,11 Z,14Z)e/2:0),5 metabolites is expected to become TB meningitis serum markers.Conclusion:Metabonomic study on UPLC-MS platform combined with orthogonal partial least squares discriminant analysis(OPLS-DA)model based on multivariate statistics analysis method,to select specific and tuberculous meningitis and has strong diagnostic efficacy analysis of metabolites,generation and development mechanism of these endogenous metabolites in the pathological process of tuberculous meningitis in the help the early clinical diagnosis and therapy.Can be used as a potential diagnostic marker for tuberculous meningitis in the field of clinical research.
Keywords/Search Tags:Tuberculous meningitis, UPLC, metabonomics, metabolite profiles, ROC, OPLS-DA
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