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Dystonia Disease Metabonomics Diagnosis Exploration And Carotid Artery Adventitial Stripped Of Small Molecule Metabolites Differences Before And After Operation

Posted on:2014-05-04Degree:MasterType:Thesis
Country:ChinaCandidate:J M SunFull Text:PDF
GTID:2254330392966997Subject:Surgery
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BackgroundDystonia in1984international dystonia medical research funds is defined as a kind ofinvoluntary, sustained muscular contraction caused by abnormal distortion, repetitivemovements or postures of the syndrome. In recent years thanks to imaging, molecularbiology, genetics, genetic engineering, etc. The development of technology, enables us todystonia disease had a more profound understanding, but because of the complexity of thedisease itself, we can’t fundamentally complete interpretation of the disease. Referred to inthis study of dystonia except disease refers to the above similar to Parkinson’s disease,cerebral palsy, etc have definite etiological diagnosis, and systematic ways of diagnosisand treatment of agonist and antagonist muscle uncoordinated movement as the mainclinical manifestations of the disease.In recent years, with the progress of functional neurosurgery technology and mature,the disease diagnosis and treatment technology is obviously enhanced compared with the previous, but due to lack of awareness of the disease itself, the clinical manifestations ofdisease, make medical institutions have different standards to the diagnosis of this disease,easily cause misdiagnosis, missed diagnosis. Pure imaging (CT, MRI) inspection, andeven some single disease biomarkers can reflect from different angles, but also have theirlimitations, cannot complete provide powerful basis for disease diagnosis. This studyresonance metabolomics experiment an application based on mass spectrometrytechnology, combined with the model of principal component analysis (PCA), partialleast squares discriminant analysis (PLS-DA) and orthogonal partial least squaresdiscriminant analysis (OPLS-DA) research dystonia small molecule metabolites in serumin patients and healthy controls, in the form of a set of metabolites as dystonia smallmolecules metabolism disease markers, patients serum metabolomic diagnosis model isestablished. Hope to establish a noninvasive method in early diagnosis of dystonia.Surgery (outer membrane peeling common carotid artery, deep brain electricalstimulation implantation) as the current dystonia last treatment of disease, has been widelyused in the clinical work, but we can’t in vitreoretinal surgery is absolutely sure of thepatients with preoperative, or not to the effect of the intervention has a clear prediction.Make clinical doctors have to take some experimental results to predict the interventiontreatment, at the same time in order to reduce the economic burden of patients, such asDBS before surgical implants in vitro stimulation experiment stage). Still have a lot ofinconvenience, in this research the second part of the application of magnetic resonance(NMR) based on mass spectrometry metabonomics method, analyzed the CAA patientsbefore and after operation of small molecule metabolites in serum. Hope to reveal thelevel from metabolomic CAA improve dystonia, possible mechanisms.AimsApplication of nuclear magnetic resonance (1H-NMR), dystonia patients serummetabolomics technology research of small molecule metabolites (molecular weight lessthan1000) and normal differences in serum levels of small molecule metabolites, featuresin the screening of dystonia patients serum metabolites, and establish dystonia patientsserum metabolic profiles of diagnosis model, from the perspective of metabonomics study dystonia possible mechanisms of the disease, for early screening of dystonia, provides thebasis for clinic diagnosis. Due to carotid sympathetic nerve net outer membrane peelingtechnique (CAA) more to improve the clinical symptoms of dystonia reports, but theoperation mechanism is still not clear, so we on line7cases dystonia carotid stripped ofthe outer membrane and the clinical symptoms improved in patients with serum beforeand after comparison, hope from the perspective of metabonomics in the carotid arteryouter membrane peeling mechanism for further understanding.MethodsCollection in July2012-12month bayi rehabilitation center in sichuan province of18cases of patients with dystonia serum as experimental group, and collected7normalhealthy people (4cases were male, female3cases) as control group, serum using1h-nmrtechnology to detect the serum medium and small molecular metabolic spectrum, and thespectra of the integral data with principal component analysis (PCA) and partial leastsquares discriminant analysis (PLS-DA), to recognize the change of the serum metabolites.9cases of patients in experimental group accepted the CAA surgery including7cases ofpay off, we put as experiment2of7cases of experimental group were markedly improved,compared with preoperative serum, to observe the effects of small molecule metabolitesCAA for patients.Results1. Dystonia patients and healthy controls serum medium and small moleculemetabolites of1h-nmr macro map have obvious difference.2. PCA pattern recognition method failed to distinguish between the experimentalgroup and healthy control group;PLS-DA discriminant analysis method can clearlydistinguish between two groups.3. According to the difference between two groups of large chemical grade shouldrefer to the Human body small molecular Database Metabolome Database(http://www.hmdb.ca/), which find many kinds of small molecule metabolites may beaffected by the disease.4. The CAA surgery patients, before and after operation of small molecule metabolites1h-nmr macro map also have obvious difference, refer to the human bodysmall molecule databases to find various small molecule metabolites may affect theoperation effect.Conclusions1. The application of metabonomics technology, in the form of a set of metabolitesto tag dystonia is no clear biological markers of disease is feasible.2. Metabolome dystonia patients and health control group has significant difference,on the one hand of multidimensional model has diagnostic value, on the other hand toprovide us with the new clues to the mechanisms of disease research.3. The CAA can affect dystonia patients serum metabolites in the larger changes ofthe metabolites of biological information flow to do systematic and comprehensiveresearch is expected to shed light on the mechanisms of CAA treatment of dystoniadisease.
Keywords/Search Tags:dystonia, metabonomics, nuclear magnetic resonance, NMR, principalcomponent analysis, PCA, partial least squares, PLS, CAA
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