| BackgroundThe harm of cerebrovascular disease(CVD)to human health is in line with heart disease and cancer.In China,CVD has surpassed ischemic heart disease,becoming the " First killer " of death,and the first cause of adult disability.Age is one of the risk factors for stroke,and aging has become a major problem in China.At the end of 2017,the population survey of China Mainland showed that people over 65 years old accounted for about 15.831 million people,accounting for 11.4% of the total population,and this proportion will be gradually rising.Stroke includes hemorrhagic and ischemic,and ischemic stroke,which is cerebral infarction,accounts for 60-80%.Large hemisphere infarction is a more serious type of cerebral infarction,and its morbidity and mortality are higher.The incidence of cerebral infarction is high,However,with the limited methods for effective treatment,its high disability and mortality have a serious burden on society,families and individuals.The pathophysiological mechanism of cerebral infarction is very complex.In addition to the neuronal cell necrosis caused by the initial ischemia,reperfusion injury and blood-brain barrier destruction,the inflammatory response bring a series of damage.Inflammatory cells are activated after ischemic brain injury,and peripheral innate immune and adaptive immune cells enter the central nervous system from the disrupted blood-brain barrier during reperfusion.In recent years,the immunology of ischemic stroke has pointed out that immune-related molecules and immune-related cells can affect the development and prognosis of stroke.After the occurrence of stroke,immunosuppression and immune activation may occur at the same time.Immunosuppression may have neuroprotective effects,while the body is exposed to infection,and the inflammatory reaction can remove necrotic tissue after immune activation,thus excessive inflammatory reaction occurs.Tissue damage and aggravation of brain function defects,affect the prognosis of patients.After the stroke,a variety of immune cells participate in the body’s immune response,in which T lymphocytes play a vital role,even can reflect the body’s immune status.T lymphocytes are mainly divided into two subgroups,of which CD4+ represents helper T lymphocytes,while CD8+ represents inhibitory T lymphocytes,and the ratio of CD4+/CD8+ is an important indicator reflecting the immune function in patients.Current research indicates that stroke-related pneumonia is the leading cause of death with cerebral infarction patients.Patients with large-area cerebral infarction have a significantly higher incidence of infection due to disturbance of consciousness,paralysis,aspiration,dysphagia,and immunosuppression.Among them,immunosuppression seems to play a critical role in large-area cerebral infarction than in light stroke.Animal studies have shown that the total number of peripheral blood lymphocytes decreased after a large area of cerebral infarction,the body’s immunoglobulin decreased,and the inhibition of mononuclear macrophage activity,suggesting an immunosuppressive state after infarction.Clinical studies have also been published that T lymphocyte subsets changed after cerebral infarction at home and abroad.The infarction patients in the neurological intensive care unit have large area,more complications and worse prognosis.But there were no studies about the dynamic changes of T lymphocyte subsets in peripheral blood of patients with large hemisphere infarction and the prediction of prognosis of the ratio of CD4+/CD8+.Based on the above basics,this study selected patients with large hemisphere infarction in intensive care unit as the research object,and dynamically monitored the changes of peripheral blood T lymphocyte subsets,and analyzed the degree of neurological deficit,post-stroke lung infection,and clinical outcome.The correlation between the ratio of CD4+/CD8+ on the severity of the disease and clinical outcomes in patients with large hemisphere infarction,which provide a theoretical basis for stratified management of large hemisphere infarction,preventive anti-infective therapy,immune intervention therapy,and assessment of prognosis.Chapter 1 Dynamic changes of T lymphocyte subsets in peripheral blood of patients with large hemispheric infarction and its clinical charactersAim: To investigate the dynamic changes of peripheral blood T lymphocyte subsets,GCS score and post-infarction pulmonary infection at different time points after infarction in patients with large hemisphere infarction,and to analyze their correlation.Methods: 1.Study object selection:65 patients with large hemispheric infarction(LHI)who were diagnosed and treated in the neurological intensive care unit(NICU)of the First Affiliated Hospital of Zhengzhou University from March 2016 to March 2017 were enrolled as LHI group.The enrolled patients were diagnosed and treated according to the “Management Guide for Large Area Hemisphere Infarction” issued by the American Society of Neurological Intensive Diseases in 2015.60 patients who were randomly matched according to age and gender were enrolled in the control group.The control group was from the First Affiliated Hospital of Zhengzhou University..All experimental protocols in this study were approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University 2.Observed indicators: 1.In the LHI group,5 ml of antithrombotic vein was collected from the elbow vein at 24 h,72 h,and 7 days after the onset of the disease.The control group only collected blood 5ml when enrolled.As well as blood test routine,blood lipid analysis and so on.2.The basic information of the subjects were collected by a professional individual,including gender,age,past history,personal history etc.Patients in the LHI group underwent GCS score according to admission,and were divided into three groups according to the scores.The patients in the LHI group were assessed for CPIS scores on the 7th day of the onset of the disease,and the severe infection and mild infection groups were performed.Follow-up,a modified Rankin scale score of 30 days of onset;3.Statistical methods :All data analysis were used SPSS23.0 software package,P < 0.05 was statistically significant cut-off.Results: 1.Dynamic changes of T lymphocyte subsets The absolute counts of CD3 were lower in the LHI group than in the control group at 24 h,72h,and 7d.The difference was statistically significant and gradually increased with the infarction time.The degree of elevation at different time points was statistically significant.The CD3+,CD4+ and the ratio of CD4+/CD8+ were lower than those of the control group at 24 h,72h and 7d.The difference was statistically significant and gradually increased with time,but there was no significant difference in the degree of elevation at different time points.CD8+ was statistically significant at 24 h,72h and 7d compared with the control group,but there was no statistically significant difference at different time points.2.Correlation between severity of infarction and T lymphocyte subsets Patients with LHI were divided into Light group,moderate group and severe group according to GCS score: the comparison of the ratio of CD4+/CD8+ between the three groups was significant at 24 h,72h and 7d.The heavier the disease,the lower the ratio;The absolute counts of CD3 were also significantly different between the light and moderate groups at 24 h and 72 h.The difference between the light group and the moderate group,the light group and the severe group at 7d was statistically significant,while the moderate group and severe group were not statistically significant.The absolute counts of CD3 in light,moderate and severe group increased with time,and CD3+,CD4+,CD8+,the ratio of CD4+/CD8+ did not change significantly with time.3.Correlation analysis between clinical outcome of infarction and T lymphocyte subsets According to the 30-day MRS score,the prognosis group and the poor prognosis group were classified.At 24 h,the absolute counts of CD3,CD3+,CD4+,the ratio of CD4+/CD8+ were statistically different between the prognosis and poor prognosis groups,while CD8+ was not statistically different;the prognosis was good at 72 h and 7d There were significant differences in the absolute counts of CD3,CD4+,CD8+,the ratio of CD4+/CD8+ between the poor prognosis group,but there was no statistical difference in CD3+.4.Correlation between post-infarction pulmonary infection and T lymphocyte subsets Comparison of different infection levels: Comparison of pulmonary infection severity group: According to the CPIS score,the disease was assessed on 7 days and divided into light infection and severe infection group.The absolute counts of CD3,CD4+,and the ratio of CD4+/CD8+ in the severe pulmonary infection group were lower than those in the light pulmonary infection group at various time points,and the difference was significant.The CD8+ in the severe pulmonary infection group was lower than the lihgt pulmonary infection group at each time point,and the difference was significant.There was no significant difference in CD3+ between the two groups.Conclusions: 1.After cerebral infarction,the absolute counts of CD3,CD3+,CD4+,the ratio of CD4+/CD8+ decreased in peripheral blood,suggesting that the cellular immunity of the body is inhibited.2.The absolute counts of CD3 and the ratio of CD4+/CD8+ were positively correlated with GCS and MRS scores,which provided a basis for clinical evaluation of disease status and prognosis.Chapter 2 Correlation between the ratio of CD4+/CD8+ and clinical outcomes in patients with large hemispheric infarctionAim: To explore the relationship between the ratio of CD4+/CD8+ and the clinical outcomes of patients with large hemispheric infarctionMethods: 1.Study object selection: The patients with acute cerebral hemisphere infarction admitted to the Department of Neurological Intensive Care Unit of the First Affiliated Hospital of Zhengzhou University from 2016.03~2018.07 were enrolled.According to the 2015 American Society of Neurological Intensive Diseases,the large-area hemisphere infarction was issued.Management Guide,the LHI group was enrolled in 300 cases,and 300 physical examinations were randomly matched according to age and gender into the control group.All experimental protocols in this study were approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University.2.Materials and Methods: In the LHI group,5 ml of antithrombotic vein was collected from the elbow vein 24 h after the onset of the disease.The control group was enrolled with 5 ml of blood to detect T lymphocyte subsets and blood routine.The LHI group was sent for C-reactive protein,blood lipids,fasting blood glucose,uric acid,homocysteine,bilirubin and the like.A physician recorded the gender,age,past history,and personal history of the subjects.GCS score,TOAST classification,and 7-day CPIS score were performed in the LHI group.The LHI group underwent a 30-day MRS score.All data were analyzed using SPSS 23.0 software,and P < 0.05 was statistically significant.Results: 1.LHI group the ratio of CD4+/CD8+ 1.33±0.43 was significantly lower compared to the control group 1.94±0.29.The ratio of CD4+/CD8+ in the severe group was 1.14±0.49,the ratio of CD4+/CD8+ in the moderate group was 1.35±0.33,and the ratio of CD4+/CD8+ in the mild group was 1.62±0.31.There was a statistical difference between the three groups.2.Among the different infarction types,169 cases of atherosclerosis,the ratio of CD4+/CD8+ was 1.27±0.47,which was lower than other types of infarction,and the difference was statistically significant.3.According to the MRS score prognosis group,the ratio of CD4+/CD8+ was 1.22±0.436 in the poor prognosis group and the ratio of CD4+/CD8+ was 1.57±0.286 in the prognosis group.The difference between the two groups was statistically significant.4.Logistic regression analysis showed that the ratio of CD4+/CD8+,LDLC,CRP and GCS scores were independent risk factors for poor prognosis of large area infarction in the cerebral hemisphere.5.ROC curve results show that the ratio of CD4+/CD8+ predicts cerebral infarction,the AUC is 0.886,and the 95% CI is 0.836 to 0.936.The prediction ability is very good.The best cut-off point for predicting poor prognosis of large-area cerebral infarction was the cut-off value of 1.215 at the time of the Yoden index.The sensitivity was 0.753,the specificity was 0.929,and the youden index was 0.682.6.Comparison of the ratio of CD4+/CD8+ and MRS assessment of poor prognosis:The ratio of CD4+/CD8+ of 1.215 was used as the demarcation point,and patients were divided into different prognosis,<1.1215 for poor prognosis,>1.215 for good prognosis,called ratio method;MRS≥4 for poor prognosis,and MRS<4 for good prognosis.called MRS method;there is no statistical difference in the evaluation of prognosis between the two methods.7.The ratio of CD4+/CD8+ in the light pulmonary infection group after hemorrhage was 1.576±0.023,and the ratio of CD4+/CD8+ in the severe infection group was 1.137±0.034.The difference between the two groups was statistically significant.Conclusions: 1.The ratio of CD4+/CD8+ is negatively correlated with neurological dysfunction.The lower the ratio,the more severe the neurological dysfunction.2.The ratio of CD4+/CD8+ is an independent predictor of poor prognosis.The best cut-off point for poor prognosis is 1.215.The ability to assess poor prognosis with the ratio of CD4+/CD8+ <1.215 and the improved Rankin score scale MRS≥4 to assess poor prognosis.The ability is comparable and the difference is not statistically significant.3.The ratio of CD4+/CD8+ is negatively correlated with the degree of pulmonary infection.The lower the ratio,the more severe the pulmonary infection in the course of the disease. |
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