| Objective(s): The expression of high-mobility group box 1(HMGB1)and its downstream molecules,nuclear factor-kappa light chain enhancer p65(Nuclear factor-kappa B,NF-κB p65)and tumor necrosis factor-α(TNF-α),were measured in peripheral serum of patients with acute ischemic stroke(AIS)thrombolysis.This study was carried out to investigate the practicality and reliability of the expression levels of serum HMGB1,NF-κB p65 and TNF-α in assessing the changes in disease,severity and prognosis of patients with AIS thrombolysis.This study will provide reference for clinical diagnosis and treatment.Methods: 1.A total of 41 patients with AIS from the Department of Neurology of the Second Affiliated Hospital of Kunming Medical University from June 2022 to January 2023 with onset time <6 hours and choosing intravenous thrombolytic therapy were included in the thrombolysis group,and peripheral venous blood was drawn before thrombolysis,on day 3(day 3)and on day 7(day 7)of thrombolysis.The peripheral venous blood was collected on day 2 of admission.The expression levels of HMGB1,NF-κ B p65 and TNF-α in peripheral blood were measured by ELISA in all enrolled patients;2.In the thrombolysis group,alteplase was given within 4.5 h of onset,with the total amount of drug calculated at 0.9 mg/kg(maximum dose not exceeding 90 mg),of which 10% was pushed intravenously within the first 1 min and the remaining 90%was continued intravenously for 1 h.Urokinase was given between 4.5 and 6.0 h.Urokinase was dissolved in 100-200 ml of 0.9% sodium chloride solution with 1million to 1.5 million U.and continue intravenous infusion for 30 min;initiate antiplatelet or anticoagulation therapy if no bleeding is seen on review of cranial CT after 24 h;3.In the thrombolysis group,neurological deficits were scored before thrombolysis,at day 3 and day 7,and patients were divided into mild impairment group(NIHSS score ≤ 5),moderate impairment group(NIHSS score 6-15)according to the National Institute of health stroke scale(NIHSS)),27 in the mild injury group and 14 in the moderate injury group before and on day 3 of thrombolysis,increasing to 39 in the mild injury group and decreasing to 2 in the moderate group on day 7(no group comparison could be made);29 in the good prognosis group and 12 in the poor prognosis group according to the modified Rankin score(mRS)90 days after discharge from hospital;4.All data were statistically analysed using the statistical software SPSS 26.0and Graph Pad Prism9.Measures that satisfied the normal distribution were expressed by the independent samples t-test;measures that did not satisfy the normal distribution were expressed by(M,IQR).The correlation between serum HMGB1,NF-κB P65 and TNF-α and the severity and prognosis of neurological deficits in patients with AIS was analysed using the Spearman method;the ROC curve was plotted using NIHSS severity and poor functional outcome as test variables to analyse their predictive value of disease severity and poor prognosis in patients with intravenous thrombolysis in AIS,with P<0.05 as the difference being The difference was considered statistically significant at P<0.05.Results: 1.There were no statistically significant differences between the thrombolysis group and the control group in terms of gender,age,days in hospital,history of hypertension,history of diabetes,history of coronary artery disease,history of previous stroke,history of smoking,history of alcohol consumption,weight,BMI,carotid atherosclerosis,carotid plaque,urea,creatinine,lipid-related parameters and homocysteine(P> 0.05).2.Serum HMGB1 expression level before thrombolysis was not elevated in the thrombolysis group compared with the control group,and the difference was not statistically significant(P > 0.05);serum HMGB1 expression level on day 3 was elevated in the thrombolysis group compared with that before thrombolysis(P < 0.05),and serum HMGB1 expression level on day 7 was not elevated compared with that on day 3,and the difference was not statistically significant(P > 0.05).3.There was no statistically significant difference in serum NF-κ B p65 expression levels in the periphery of the thrombolysis group before thrombolysis compared with the control group,respectively(P > 0.05);there was no significant change in serum NF-κB p65 expression levels in the thrombolysis group on day 3compared with that before thrombolysis(P > 0.05),and no significant change in serum NF-κB p65 expression levels on day 7 compared with that on day 3,with no statistically significant difference(P > 0.05).4.There was no significant change in the expression level of serum TNF-αbefore thrombolysis in the thrombolysis group compared with the control group,and the difference was not statistically significant(P > 0.05);the expression level of peripheral serum TNF-α in the thrombolysis group increased on day 3 compared with that before thrombolysis(P < 0.05),and the expression level of serum TNF-αon day 7 compared with that on day 3(P < 0.05),showing a trend of gradual increase.5.Peripheral serum HMGB1,NF-κB p65 and TNF-α expression levels on day3 in the rt-PA thrombolysis group were not statistically significant when compared with the urokinase thrombolysis group,respectively(P> 0.05,P > 0.05,P > 0.05).6.The serum HMGB1 expression level on day 3 was significantly higher in the moderate injury group than in the mild injury group(P< 0.01);the serum TNF-αexpression level on day 3 was significantly higher in the moderate injury group than in the mild injury group,(P< 0.01).On day 7,the number of injuries increased to 39 in the mild injury group and decreased to 2 in the moderate injury group(no group comparison could be made).7.The serum HMGB1 expression levels before thrombolysis,day 3 and day 7 in the poor prognosis group at 7 and 90 days were not statistically different from those in the good prognosis group,respectively(P> 0.05,P> 0.05,P> 0.05);the serum TNF-α expression levels at day 3 in the poor prognosis group at 90 days were higher than those in the good prognosis group(P< 0.05),and the serum TNF-α levels before thrombolysis and at day 7 in the poor prognosis group were the differences between the poor prognosis group and the good prognosis group were not statistically significant(P>0.05,P>0.05).8.According to Sperman correlation analysis,serum HMGB1 levels on day 3 in the thrombolysis group were positively correlated with NIHSS scores on day 3(r=0.345,P<0.05);serum NF-κB p65 levels before,on day 3 and on day 7 in the thrombolysis group were not correlated with NIHSS scores(r=0.030,P>0.05,r=0.016,P >0.05,r=0.075,P>0.05);serum TNF-α levels on day 3 in the thrombolysis group were significantly and positively correlated with NIHSS score at day 3(r=0.52,P<0.01).9.There was a significant correlation between peripheral serum HMGB1 and serum TNF-α expression level before thrombolysis in the thrombolysis group(r=0.738,P<0.01);a significant correlation between peripheral serum HMGB1 and serum TNF-αconcentration on day 3(r=0.473,P<0.01);and a significant correlation between peripheral serum HMGB1 and TNF-α concentration on day 7(r= 0.594,P<0.01).10.Peripheral serum TNF-α expression levels on day 3 in the thrombolysis group were positively correlated with the 90-day mRS score(r=0.497,P<0.01).11.Using the severity of neurological deficits as the outcome,the ROC curve results showed that the AUC of serum HMGB1 level on day 3 in the thrombolysis group for predicting severity was 0.83,with a sensitivity of 92.30% and specificity of75.00%,and the area under the curve of serum TNF-α level on day 3 in the thrombolysis group for predicting severity was 0.78,with a sensitivity of 69.20% and specificity of The ROC curve results showed that the AUC of peripheral serum TNF-α level on day 3 in the thrombolysis group for 90-day adverse prognosis was 0.76,with a sensitivity of 66.70% and specificity of 86.80%,using adverse functional prognosis as the outcome.Conclusion(s): 1.The expression levels of HMGB1,NF-κB p65 and TNF-αin serum of AIS patients did not increase in the hyperacute stage.2.The expression of serum HMGB1 and TNF-α increased after treatment in patients with intravenous thrombolysis of AIS and was positively correlated with the severity of neurological deficits,suggesting that serum HMGB1 and TNF-α are involved in the inflammatory injury process in AIS;3.The level of serum HMGB1 on day 3 after intravenous thrombolysis of AIS has a higher predictive value for disease severity than serum TNF-α;the level of serum TNF-α on day 3 is positively correlated with mRS score and has a certain predictive value for its short-term adverse prognosis.Dynamic monitoring of changes in serum HMGB1 and TNF-αcan be used as a useful reference indicator to determine changes in disease after intravenous thrombolysis in AIS. |
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