Predicting Study On Cerebral Infarction Risk After Minor Ischaemic Stroke

Objective:Minor Ischaemic Stroke(MIS)refers to the cerebral infarction with only Minor nerve function defects or lacunae.The MIS caused minor damage to the body and rarely attracted people's attention.However,the incidence of cerebral infarction after stroke is as high as 20%.However,the cause of recurrent cerebral infarction after MIS has not been reported yet.Early detection of a stroke with a high risk of stroke after MIS may effectively reduce the risk of stroke after MIS and reduce the national economic burden.This study used non-targeted metabolomics methods to screen for and identify potential biomarkers associated with the occurrence of MIS.The follow-up method was used to identify the patients who had recurrent cerebral infarction after MIS.Non-targeted metabolomics methods were used to screen and identify potential biomarkers associated with recurrent cerebral infarction after MIS.Finally,the targeted metabolomics method was used to validate the pre-screening of important metabolites in the rat experimental model body to determine the pathophysiological damage that potential biomarkers may have for cerebral infarction.The purpose of this study was to screen and identify potential biomarkers associated with the development of MIS and potential markers associated with recurrent cerebral infarction in MIS,and to establish a predictive model for recurrent stroke in MIS for predicting and intervention.The treatment of stroke provides new ideas,and at the same time provides advice for the clinical decision-making of the potential population of cerebral infarction after MIS.Method:In this study,follow-ups were conducted for patients with MIS,and population studies were first performed in combination with metabolomics methods.Rat brain experiments were also used to verify the findings of population studies.Population studies:(1)Select 400 hospitalized patients with neurological internal medicine in Taiyuan Central Hospital,and clinically diagnosed 400 patients with MIS and 210 healthy people examined at the Taiyuan Central Hospital Medical Center during the same period as the study subjects.Collect general demographic characteristics and fasting blood samples of the subjects,and perform non-targeted metabolomics,blood glucose,blood lipids,homocysteine,and high-sensitivity C-reactive protein assays on biological samples,and perform statistical analysis.Find metabolites and influencing factors associated with MIS.(2)After the MIS patients were admitted to hospital,they were followed up for 90 days to record whether the MIS patients had recurrent cerebral infarction,and the non-targeted patients with recurrent cerebral infarction after MIS and no recurrence of cerebral infarction after MIS.Metabolomics,blood glucose,blood lipids,homocysteine,and high-sensitivity C-reactive protein data were analyzed statistically to find the influencing factors of cerebral infarction after MIS.Experimental animal studies: Targeted metabolomics validation was performed in combination with animal experiments based on the population's findings.The level of trimethylamine oxide(TMAO)in experimental animals was varied by adding different levels of choline to the diet of experimental animals.The plasma TMAO was determined by liquid chromatography-mass spectrometry(LS/MS).And related metabolite levels,by comparing beam walking test,pathological changes of cerebral infarction and atherosclerosis in different TMAO levels,the correlation between TMAO and recurrent stroke in the MIS was judged.Results:1.To analysis of the related factors of MIS:(1)To analysis of general population demographic characteristics: There was a statistically significant difference in smoking,hypertension,and physical activity between the MIS group and the healthy control group(P<0.05).(2)To analysis of serum metabolites and MIS related factors: compared with healthy group,valine,lactate,alanine,glutamic acid,glutamine,pyruvate,TMAO,?-glucose and ?-glucose were increased,and lipid,N-acetylated glycoprotein,choline,and phosphatidylcholine were decreased.The contents of lactic acid,pyruvic acid and TMAO were statistically significant(P<0.001).(3)MIS risk model: hypertension(OR=4.033,95%CI(2.581~6.303),P<0.001),physical activity(OR=0.026,95%CI(0.006~0.113),P<0.001)smoking(OR=3.104,95%CI(1.783~5.402),P<0.001),elevated TMAO levels(OR=1.227,95%CI(1.106~1.483),P=0.034)were the influencing factors of the occurrence of MIS.2.Recurrence of cerebral infarction in MIS related factors analysis:(1)Comparison of clinical characteristics of the population: coronary heart disease,atrial fibrillation in the small stroke after recurrence of the group and no recurrence of the difference was statistically significant(P<0.05).(2)To analysis of related factors of serum metabolites and recurrence of cerebral infarction in MIS: TMAO,?-glucose,?-glucose,lactic acid,proline,glutamine,pyruvic acid,glutamic acid,isoleucine,The 12 strokes of succinate,citric acid,and alanine were higher in the MIS recurrence group than in the non-recurrence group,while the lipid,choline,and phosphatidyl glycoprotein levels were found in the MIS recurrence group.The content of lactic acid,succinic acid,pyruvic acid,and TMAO had a significant difference(P<0.05).(3)MIS recurrence risk model: atrial fibrillation [RR=4.597,95%CI(1.791~11.798),P=0.002],coronary heart disease [RR=2.279,95%CI(1.074~4.836),P=0.032 ],and elevated TMAO levels [RR=1.214,95%CI(1.006 to 1.465)P=0.043] were the influencing factors for recurrent stroke in MIS.3.The effect of TMAO on recurrent stroke in MIS:(1)The rats were divided into six groups include MIS group,normal diet group after MIS,low choline diet intervention group after MIS and MIS after high-dose choline diet group,sham operation group and control group,analysis of variance was performed after targeted metabolomic analysis.The results showed that: TMAO(F = 38.965,P <0.001).The difference was statistically significant,followed by a pairwise comparison of the MIS no recurrence group,MIS recurrence normal diet group,MIS recurrence low intervention group and MIS recurrence high intervention group,TMAO in each group.The difference was statistically significant(P<0.05)and gradually increased.(2)By observing the MIS group,MIS secondary to normal diet group,MIS secondary low choline diet intervention group,MIS secondary high-dose choline diet group,sham operation group and control group.The scores of balanced wood test in rats,pathological changes of cerebral infarction in rats and pathological changes of rat aorta were found.With the increase of TMAO and choline intervention in vivo,the corresponding neurological deficit scores,pathological changes of cerebral infarction and arteries were found.The severity of atherosclerosis has also gradually increased.By plotting the ROC curve,the area under the ROC curve(Az)of TMAO for neurological function,cerebral infarction size,and aortic pathology changes was 0.875,0.713,and 0.904,respectively,indicating TMAO's neurological deficit,cerebral infarction size,and aortic porridge.Hardening has a medium-high diagnostic value.This suggests that the TMAO levels of plasma may be a potential important predictor of recurrent recurret-stroke cerebral infarction.Conclusion:1.The increased levels of the three metabolites,lactic acid,pyruvate,and TMAO,may be related to the pathophysiological changes in the MIS population.High blood pressure,no physical activity,smoking,and increased TMAO content were the influencing factors for the occurrence of MIS.In particular,it was found that metabolite trimethylamine oxidation has a catalytic effect on the occurrence of MIS.2.The rate of cerebral infarction after a MIS was 16.25%,which was similar to the12%-20% recurrence rate reported in the literature.The serum metabolites of lactic acid,succinic acid,pyruvic acid,and trimethylamine oxide were increased in the body after cerebral infarction.The risk factors of atrial fibrillation,coronary heart disease,and increased trimethylamine oxide levels are commonly used as early predicting indicators for recurrent cerebral infarction after MIS.In particular,it was found that metabolite trimethylamine oxidation may promote cerebral infarction after MIS,combined with literature reports.It is most likely to be a biomarker of early-onset cerebral infarction after MIS.3.In animal experiments with MIS,it was found that the higher the dietary choline content,the higher the trimethylamine oxide content;and the higher the trimethylamine oxide level,which leads to increased neurological deficits,brain damage,and atherosclerosis.weight.The research group believes that trimethylamine oxide acts on the arterial intima by interfering with lipid metabolism and platelet hyperreactivity,resulting in atherosclerosis and cerebral infarction caused by proliferation of collagen fibers in the subendocardial intima.4.Trimethylamine oxide is highly diagnostic for neurological deficits,atherosclerosis,cerebral infarction size,and other important neuropathological changes in cerebral infarction.Therefore,the detection of TMAO levels in the human population may lead to early detection of cerebral infarction after stroke.The occurrence of potential population,the detection of TMAO for potential patients,provides an auxiliary judgment basis for recurrent cerebral infarction in MIS,and is of great significance in preventing the occurrence of cerebral infarction.