3-Month Prognostic Value of the Systemic Inflammatory Response Index Combined with Blood Glucose/ Potassium Ratio Score in Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis

3-Month Prognostic Value of the Systemic Inflammatory Response Index Combined with Blood Glucose/ Potassium Ratio Score in Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article 3-Month Prognostic Value of the Systemic Inflammatory Response Index Combined with Blood Glucose/ Potassium Ratio Score in Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis Zhijun Wen, Hanyu Cai, Nan Chen, Jie Ren, Jianhua Cheng, Yirui Huang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4950520/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective In recent years, an increasing number of studies have focused on the use of readily available inflammatory markers to predict the prognosis of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). The systemic inflammatory response index combined with blood glucose/potassium ratio (SIRI-GPR) score is a new combination index that can reflect the inflammatory and stress status. However, whether this index can predict the prognosis of patients with AIS underwent IVT has not been reported. The purpose of our study was to investigate the role of the SIRI-GPR(systemic inflammatory response index combined with blood glucose/potassium ratio) score in predicting the prognosis of patients with AIS(acute ischemic stroke) who underwent IVT at 3 months. Methods We analyzed 247 patients with AIS admitted to the emergency department of the neurology department of the First Affiliated Hospital of Wenzhou Medical University from July 2021 to July 2022. The primary outcome was a 3-month prognosis. Univariate analysis and multivariate logistic regression were used to analyze the possible influencing factors of 3-month poor prognosis in patients with AIS after IVT. Independent factors were included in the construction of the clinical prediction model. We assessed the nomogram models using ROC and calibration curves. Results A total of 119 patients with AIS were finally included in the cohort study. Multifactorial logistic regression analysis showed no significant association between SIRI or GPR and 3-month functional prognosis, however, the SIRI-GPR score was found to be an independent predictor of 3-month dysfunction, In addition, it was also investigated whether large artery occlusion (OR = 5.836, 95% CI 1.123 ~ 30.337, P = 0.036) and NIHSS score within 24h after IVT (OR = 1.371, 95% CI 1.167 ~ 1.612, P < 0.001) were the independent influences of poor prognosis at 3 months (P < 0.05). The nomogram prediction model we constructed showed that the SIRI-GPR score was a good predictor of 3-month prognosis for these patients. Conclusion The SIRI-GPR score can predict the 3-month prognosis in stroke patients treated with IVT. acute ischemic stroke(AIS) systemic inflammatory response index (SIRI) blood glucose/potassium ratio (GPR) intravenous thrombolysis(IVT) 3-month prognosis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Introduction Globally, stroke remains the second leading cause of death in humans and is one of the most common diseases in the world. According to relevant statistics, there are approximately 12.2 million new cases and 101 million prevalent cases in 2019, including 143 million cases of stroke disability and 65.5 million deaths from stroke. 1 Although public health policies and health care services are improving, the burden of stroke remains high, especially in some low-income countries, so there is still a need to explore effective primary prevention strategies as well as good prognostic measures to offset the possibility of a further increase in the absolute number of stroke cases in this large population. 2 Patients with acute ischemic stroke(AIS) require comprehensive treatment, including reperfusion therapy, complication management and rehabilitation treatment. 3 Among them, reperfusion therapy is the main treatment for AIS. 4 Reperfusion to salvage brain cells on the verge of necrosis in the ischemic semi-domain is an important way to delay or stop AIS. Reperfusion therapy includes intravenous thrombolysis(IVT) and mechanical thrombectomy, and rt-PA (recombinant tissue plasminogen activator) is the only approved and effective drug treatment in IVT. However, reperfusion injury caused by IVT can be characterized by hemorrhage and edema, such as symptomatic intracranial hemorrhage, which may counteract the benefits of reperfusion therapy and even lead to early neurological deterioration. Therefore, it is particularly important to find appropriate prognostic indicators for IVT. Inflammation and the immune response play an important role in secondary brain injury after stroke. 5 – 7 A large number of studies have shown that the neuroinflammatory response also plays an important role in the pathophysiology of ischemic stroke. 8 – 11 The systemic inflammation response index (SIRI) is a new comprehensive biomarker for inflammatory and tumor-related diseases that is calculated from the absolute numbers of neutrophils, monocytes and lymphocytes. The prognostic role of SIRI in stroke has been confirmed. 12 – 14 Stress response following stroke shows a prognostic value 15 , and hyperglycemia is a stress response in AIS. Potassium ions are the most abundant cations in human cells and play a vital role in physiological processes such as nerve conduction, heart beating, muscle contraction, and maintenance of normal kidney function. The blood glucose / blood potassium ratio (GPR) has been used to analyze circulatory diseases such as stroke and bleeding. It has been proved to be an early prognostic factor of central nervous system injury, including severe traumatic brain injury, 16 acute cerebral hemorrhage, 17 aneurysmal subarachnoid hemorrhage 18 and neuropsychiatric syndrome 19 after carbon monoxide poisoning. Matano et al found that there was a strong correlation between vasospasm and GPR in AIS. 20 Yuzhao Lu et al found that in patients with AIS, GPR was positively correlated with 30-day mortality, and there was a linear relationship between them, GPR at admission may be a promising indicator for short-term prognosis of patients with AIS. 21 Because the level of SIRI can reflect the level of systemic inflammatory response and immune response 10 , GPR reflects the stress state of the body, and according to the study of Xiangyu S et al in 2021, it is found that the body inflammatory response index combined with blood glucose/potassium ratio (SIRI-GPR) can be used to predict the poor prognosis of patients with aneurysmal subarachnoid hemorrhage, and the prognostic value of SIRI combined with GPR is higher than that of SIRI or GPR 22 . Therefore, we speculate that the SIRI-GPR may be of value in the 3-month prognosis of patients with AIS after IVT. the SIRI and GPR have not been simultaneously assessed as markers of the 3-month prognosis of patients with AIS after IVT. We combine SIRI with GPR as a new score to predict the prognosis of AIS patients treated with IVT for the first time. Since SIRI-GPR is used for the first time in IVT for AIS, the specific scores were not identified in the relevant literature and were extracted from the relevant lit-erature combined with the clinic. In this study, we aim to explore the predictive effect of the SIRI-GPR score on the poor prognosis of patients with AIS after IVT. 2. Materials and Methods 2.1. Research object and background This retrospective study was based on the database of patients with AIS treated by IVT collected by the Department of Neurology of the First Affiliated Hospital of Wenzhou Medical University from July 2021 to July 2022. There were 247 patients treated with IVT. The criteria for screening patients include: (1) over the age of 18; (2)Complete baseline clinical data; (3) All selected patients meet the diagnostic criteria for ischemic stroke according to the Chinese Guidelines for the diagnosis and treatment of AIS; (4) rt-PA infusion of 0.9mg/kg (maximum 90mg) in all selected patients within 4.5 hours of onset (10% dose as one injection, followed by 60 minutes of residual dose). (5) Venous blood samples were taken within 24 hours after IVT to measure neutrophil counts, monocyte counts, lymphocyte counts, blood glucose, serum potassium, etc. (6) The informed consent form has been signed by the patient or the patient's family. (7) complete the follow-up. The exclusion criteria included: (1) patients who underwent intravascular thrombectomy on the basis of IVT; (2) history of infection or confirmed infection, malignant tumor, rheumatism, hematological diseases or other diseases that significantly affected peripheral blood cells within 48 hours after admission; (3) patients with diabetes, (4) loss of follow-up. According to the exclusion criteria, 128 patients were excluded because of the reasons showing in the Fig. 1 . Finally, 119 patients were eligible for the study. The research program was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University and implemented in accordance with the Helsinki Declaration. 2.2. Laboratory parameters and clinical outcomes The laboratory data we collected included: (1) demographic characteristics (age and gender);(2) clinical characteristics (National Institutes of Health Stroke Score [NIHSS], BMI, blood pressure, history of smoking and alcohol use, presence or absence of large artery occlusion and presence or absence of eGFR ≤ 60); (3) medical history (presence of hypertension, dyslipidemia, previous stroke and atrial fibrillation). (4) Blood biochemistry values (monocyte, lymphocyte, neutrophil, and platelet counts, blood glucose, serum potassium, uric acid, creatinine, homocysteine, total cholesterol, triglycerides, HDL and LDL). Before the IVT and within 4.5 h of the AIS onset, the patients underwent emergency cranial CT/MRI neuroimaging. In addition, the severity of stroke was assessed using NIHSS scores within 24 hours after IVT treatment. Venous blood samples were taken from all patients within 24 hours after treatment to detect neutrophil, monocyte, lymphocyte and platelet counts, blood glucose, serum potassium and so on. The SIRI is defined as the ratio of neutrophil counts multiply monocyte counts to lymphocyte counts, and GPR is defined as the ratio of blood glucose to blood potassium, and the maximum Youden index (Youden index = sensitivity + specificity-1) is calculated from the receiver operating characteristic (ROC) curve to determine the optimal critical values of SIRI and GPR, thus SIRI and GPR are divided into a high group and a low group respectively. We graded the SIRI-GPR scores on a scale of 0 to 2: patients with low SIRI and low GPR had a score of 0; those with high SIRI and low GPR, or low SIRI and high GPR, had a score of 1; and those with high SIRI and high GPR had a score of 2. The functional prognosis of the patients was evaluated by modified Rankin score(mRS), and we categorized an mRS score between 0 and 2 as a favorable outcome and an mRS score between 3 and 6 as a poor outcome. 2.3. Statistical analysis The normal distribution of the data was tested using the Shapiro-Wilk normal test. F-test is used to test whether the variance between two data sets of normal distribution is equal. Continuous variables with normal distribution were expressed as mean ± standard deviation (mean ± SD) and compared by t-test, and continuous variables with non-normal distributions are expressed as median and interquartile range (M(P25, P75)) and compared using the Mann-Whitney U test. Classification variables are expressed as frequencies and percentages (n, %) and compared by chi-square test. Univariate analysis and multivariate logistic regression model were used to investigate the independent effect of SIRI-GPR score on clinical outcome (3-month prognosis after IVT), and adjusted the potential confounders. According to the independent risk factors obtained by multivariate Logistic regression of each outcome index, a nomogram was constructed to predict the clinical outcome (3-month prognosis after IVT) by R Studio software, and the Nomogram model was evaluated by ROC curve and correction curve. A p value < 0.05 was regarded as statistically significant. 3. Results 3.1. Patient characteristics The baseline condition of the 119 patients are shown in Table 2 , the most approximate index was calculated from the ROC curve of the original cohort study ( Figure 2 ). The cutoff values of SIRI and GPR in the 3-month prognosis after thrombolysis were 1.992 * 10 ^ 9 / L and 1.421 respectively ( Table 1 ). Among all IVT patients, according to the mRS score standard of follow-up at 3 months after onset, there were 74(62,2%) cases with favorable outcome (mRS ≤ 2 )and 45(37.8%) cases with poor outcome(mRS > 2 ). Table 1. The cutoff value of SIRI and GPR respectively. Area Under the Curve Variables AUC Cutoff value P value 95% CI of AUC GPR 0.692 1.421 <0.001 0.592-0.791 SIRI（*10^9/L） 0.763 1.992 <0.001 0.677-0.849 Abbreviations: AUC, Area under curve; Notes: P<0.05, The difference was statistically significant. 3.2. Comparison of baseline data of AIS patients grouped according to the outcome of 3 months after IVT The demographic, clinical and related laboratory data of the patients in general and the baseline grouped according to the prognosis are shown in Table 2 (at the end of the document text file ). We found that age, hypertension, previous stroke, large artery occlusion, NIHSS score within 24h after thrombolysis, blood glucose of 24 hours after thrombolysis, neutrophil counts (* 10 ^ 9), lymphocyte counts, SIRI (* 10 ^ 9 / L), GPR and SIRI-GPR score differed significantly between the two groups (p < 0.05), and we found the following distribution of SIRI-GPR scores in patients with poor prognosis at 3 months after thrombolysis: 6 (13.3%) patients had a post-thrombolysis SIRI-GPR score of 0, 17 (37.8%) had a SIRI-GPR score of 1, and 22 (48. 9%) had a SIRI-GPR score of 2. The difference in SIRI-GPR score between patients with good and poor prognosis at 3 months after thrombolysis was statistically significant (p < 0.001). Table 2. The baseline condition of the patients and the comparison of baseline data of AIS patients grouped according to prognostic outcome. Characteristics All patients（n=119） 3-month outcome Z /t /χ2 P value favorable outcome (mRS≤2) （n=74） Poor outcome (mRS>2) （n=45） Basic data age，M（P25，P75） 71.00（59.50,76.00） 66.00（55.00,73.00） 74.00（67.00,79.00） -3.548 <0.001 female，n（%） 33（27.7） 42（71.2） 39（63.9） 0.410 0.521 Risk factors hypertension，n（%） 76（63.9） 35（59.3） 48（78.7） 4.290 0.038 Hyperlipidemia， n（%） 23（19.3） 14（23.7） 10（16.4） 1.670 0.197 Atrial fibrillation ， n（%） 29（24.4） 11（18.6） 21（34.4） 1,78 0.182 Coronary heart disease，n（%） 6（5.0） 2（3.4） 5（8.2） 1.130 0.288 Previous stroke， n（%） 21（17.6） 5（8.5） 17（27.9） 6.290 0.012 History of smoking， n（%） 33（27.7） 18（30.5） 9（14.8） 0.041 0.840 History of alcohol consumption， n（%） 30（25.2） 14（23.7） 11（18.0） 0.520 0.471 Large artery occlusion，n（%） 20（16.8） 5（8.5） 16 （26.2） 14.140 <0.001 eGFR<=60, n（%） 10（8.4） 6（8.1） 4（8.9） <0.001 1.000 baseline data NIHSS score within 24h after thrombolysis， M（P25，P75） 3.00（2.00,8.50） 2.00（1.00,3.00） 10.00（5.00，14.00） -6.803 <0.001 Systolic blood pressure， M（P25，P75） 129.00（117.50,149.00） 128.00（117.00,145.00） 136.00（118.00,154.00） -1.455 0.146 Diastolic blood pressure， M（P25，P75） 76.00（67.00,85.00） 75.50（67.00,83.00） 76.00（67.00,89.00） -0.348 0.728 BMI，（x±s） 22.98±3.25 23.27±3.14 22.51±3.40 1.250 0.216 Blood biochemical index Blood glucose， M（P25，P75） 5.00（4.50,5.85） 4.95（4.40,5.40） 5.50（4.70,6.40） -2.751 0.006 Serum potassium， M（P25，P75） 3.72（3.53,3.93） 3.79（3.54,3.98） 3.67（3.53,3.87） -1.378 0.168 Homocysteine， M（P25，P75） 13.00（11.00,18.00） 13.00（11.00,17.00） 14.00（12.00,18.00） -1.050 0.294 Total cholesterol， （x±s） 4.64±0.89 4.65±0.91 4.62±0.87 0.200 0.842 Triglyceride， M（P25，P75） 1.13（0.88,1.59） 1.24（0.90,1.81） 1.07（0.83,1.33） -1.430 0.153 HDL ， M（P25，P75） 1.12（0.97,1.37） 1.13（0.95,1.31） 1.12（0.97,1.39） <0.001 1.000 LDL，（x±s） 2.96±0.80 3.02±0.85 2.86±0.71 1.080 0.285 Monocyte counts， M（P25，P75） 0.40（0.33,0.49） 0.39（0.33,0.48） 0.40（0.34,0.50） -0.853 0.394 Neutrophil counts（*10^9/L）， M（P25，P75） 5.46（3.98,7.01） 4.61（3.61,6.09） 6.51（4.98,8.40） -4.261 <0.001 Platelet counts（*10^9/L）， M（P25，P75） 194.00（168.00,237.50） 200.00（169.00,257.00） 186.00（155.00,208.00） -1.945 0.052 Lymphocyte counts (*10^9/L)， M（P25，P75） 1.34（0.93,1.66） 1.42（1.08,1.71） 1.02（0.76,1.42） -3.225 0.001 SIRI， M（P25，P75） 1.69（1.02,2.85） 1.28（0.88,1.99） 2.51（1.95,12.79） -4.800 <0.001 GPR， M（P25，P75） 1.37（1.19,1.64） 1.29（1.15，1.45） 1.46（1.33,1.89） -3.500 <0.001 Uric acid，（x±s） 331.16±96.44 336.53±95.40 322.33±98.57 0.780 0.439 Serum creatinine， M（P25，P75）） 73.00（65.00,88.00） 74.00（65.00,90.00） 72.00（64.00,82.00） -1.140 0.254 SIRI-GPR score， n（%） 0 point 1 point 2 points 48（40.3） 42（56.8） 6（13.3） 32.060 <0.001 42（35.3） 25（33.8） 17（37.8） 29（24.4） 7（9.5） 22（48.9） Abbreviations: BMI, body mass index；HDL, high density lipoprotein cholesterol；LDL, low density lipoprotein cholesterol； Notes: P＜0.05, The difference was statistically significant. 3.3. Analysis of correlation between SIRI-GPR score and 3-month functional prognosis of AIS patients receiving IVT Multivariate logistic regression analysis was performed with SIRI-GPR score and age, hypertension, previous stroke, presence or absence of large artery occlusion, NIHSS score within 24h after IVT, blood glucose, neutrophil counts, lymphocyte counts, SIRI(*10^9/L) and GPR ( Table 3 ). The results showed that the effect of presence or absence of large artery occlusion on the prognosis of acute stroke patients with IVT at 3 months after thrombolysis was statistically significant (OR=5.836,95%CI1.123~30.337,P=0.036), and the effect of NIHSS score within 24h after IVT on the prognosis of acute stroke patients with IVT was statistically significant (OR=1.371,95%CI1.167~1.612,P < 0.001). In the 3-month prognosis of IVT, the SIRI-GPR score (the adjusted OR value of 1 point was 4.877(95% CI 1.083~21.959,P= 0.039). The adjusted OR value of 2 points is 50.17(95%CI 3.151~798.809, p=0.0006) ) can independently predict the prognosis of AIS 3 months after IVT. The forest plot is drawn in R Studio software( Figure 3 ). Table 3 .Multivariate logistic regression analysis of 3-month functional prognosis in AIS patients with undergoing IVT Notes: P＜0.05, The difference was statistically significant. Based on the results of the SIRI-GPR score and multivariate logistic regression analysis after thrombolysis, a nomogram was established to predict the 3-month prognosis of patients with AIS after IVT. As shown in Figure 4 , the higher the total score, the higher the probability of poor prognosis at 3 months. The performance of the nomogram is verified internally and the ROC curve of the prediction model based on the SIRI-GPR score is constructed (Figure 5a ). The AUC index of the prediction model based on the SIRI-GPR score is 0.895 (95% CI 0.836-0.953). The calibration curve of internal verification ( Figure 5b ) shows that there is a good agreement between the predicted probability and the actual probability of 3 months of stroke patients with IVT. In addition, we examined the predictive Nomogram ROC curves without SIRI-GPR scores in the relative outcome metrics, as shown in supplementary Figure 6 . The AUC index of the predicted nomogram without SIRI-GPR scores (0.880 95% CI:0.817-0.943) was lower than that of the nomogram with SIRI-GPR scores included (0.895 95% CI: 0.838-0.953). 4. Discussion In this study, we found that the increase in SIRI-GPR score in patients with AIS after IVT was closely related to poor stroke outcome and was an independent predictor of prognosis at 3 months in patients with AIS who underwent intravenous thrombolysis at the first time. In addition, a nomogram model combining the SIRI-GPR score and other conventional risk factors was more favorable in its ability to discriminate the poor prognosis of IVT for AIS. The pathogenesis of AIS usually involves inflammation and immunity. The infiltration of inflammatory cells is the beginning of inflammatory response, and inflammation plays a key role in vascular injury. SIRI is a novel integrated immune-inflammatory index that relies on absolute values of peripheral blood neutrophil counts, monocyte counts, and lymphocyte counts. In the early stages of AIS, peripheral circulating neutrophils are first activated, resulting in the release of antimicrobial enzymes and chemicals. 23, 24 Some studies have also shown that the increase of neutrophil counts is related to the increase of infarct size, so the increase of neutrophil counts level may aggravate the blood-brain barrier injury by promoting the overexpression of matrix metalloproteinase-9. 25, 26 In addition, after AIS, monocytes are another important class of inflammatory cells, which can infiltrate the infarct site and aggravate brain damage. 27-29 In contrast to neutrophils and monocytes, some lymphocytes play a protective role during post-AIS inflammation and play a key role in controlling and alleviating local inflammation. 30 Compared to other blood cell ratios, such as neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR), SIRI symbolize different pathways related to inflammation and immunity in the body, and may provide a more comprehensive response to the body's inflammatory state. As such, the SIRI can accurately indicate adaptive immune responses and inflammatory responses, with the potential to serve as a reliable prognostic indicator. 31 Therefore, it is speculated that the level of SIRI may better reflect the severity of neuroinflammation in patients with AIS after IVT, which in turn reflects the severity of the patients' condition. The results of our study showed that there was a statistically significant difference in SIRI between the good prognosis group and the poor prognosis group. The SIRI of the poor prognosis group was significantly higher than that of the good prognosis group, which was also similar to the results of Min Chu et al. 13 In addition to inflammation and immune response in AIS its important role, the stress response also plays an important role. M.J. Brown and J. Brown first suggested a strong link between the renin-angiotensin-aldosterone system (RAAS) and stroke in 1986. 32 In the brain, the RAAS has an autocrine function that maintains cerebral dynamic homeostasis and blood flow regulation. Angiotensin II (Ang II) acts by stimulating angiotensin receptor subtype 1, leading to disruption of cerebral blood flow and tissue ischemia. 33 In the setting of an AIS, these effects of Ang II will further damage regions of the cerebral ischemic hemidiaphragm in areas where cells are still viable and will amplify the cerebral damage and loss of brain volume. 34-36 Subsequent studies have also found that stroke patients' neuronal damage may be associated with increased activity of angiotensin receptor subtype 1 in the brain-specific RAAS. 37, 38 Other possible mechanisms by which Ang II contributes to brain damage include induction of inflammation and production of reactive oxygen species, leading to brain damage and apoptosis. 39 In the context of acute disease, blood glucose may reflect the interaction of hormones involved in the stress response with concomitant insulin resistance, blood glucose is a major contributor to brain damage. Previous studies have confirmed that hyperglycemia may lead to increased oxidative stress, inflammatory responses, and endothelial dysfunction, resulting in brain tissue reperfusion injury. 40-44 It has also been found that IVT has a poorer prognosis in patients with AIS with electrolyte disturbances. 45, 46 Previously, Cheng et al. demonstrated that minor deviations of serum K + levels from the normal range may lead to severe muscle dysfunction, palpitations, arrhythmias, and deterioration of neurological function. 47-49 Multiple meta-analyses have reported that K + inhibits the formation of free radicals and prevents endothelial dysfunction. 50-52 In addition, blood potassium levels are mainly regulated by the ATP-Na + /K + pump on the cell surface regulation, there is an important relationship with glycemic changes. In the case of AIS stress, increased adrenergic hormones upregulate this pump, thereby decreasing K + levels. 53, 54 Stress-induced increases in insulin secretion and catecholamines due to intracellular K + uptake, and further hyperglycemia, will have clinical consequences. In addition, it has also been shown that lower blood potassium levels may be a marker of enhanced activity of the RAAS and may potentiate the adverse effects of other risk factors. 32, 55 The results of this study showed that there was a statistically significant difference in GPR between the good and poor prognosis groups, with the GPR in the poor prognosis group being significantly higher than that in the good prognosis group, and Yuzhao Lu et al. also previously found that GPR was positively correlated with 30-day mortality in patients with AIS, and that the two had a linear relationship. 21 Therefore, the GPR at the time of admission may be a promising predictor of short-term prognosis for patients with AIS. There are many clinical indicators related to the poor prognosis of patients with AIS after IVT for 3 months. It is now considered that the causes affecting the prognosis of IVT in stroke are diverse and complex and need to be evaluated comprehensively. In our study, Large artery occlusion, NIHSS score within 24h after thrombolysis and SIRI-GPR score after thrombolysis were found to be independently associated with poor prognosis at 3 months after IVT in AIS. Large artery occlusion is the cause of irreversibility, SIRI and GPR are both reversible causes, and are easy to obtain laboratory indicators. Among these indicators, the OR value of SIRI-GPR score is the highest, indicating that SIRI-GPR score plays the most important role in predicting the poor 3-month prognosis of AIS after IVT. Here, through the nomogram model to show the relationship between the independent risk factors of each outcome index, it is proved that SIRI-GPR score has a better correlation in predicting poor 3-month prognosis after IVT in AIS. Given that inflammatory and immune responses have been shown to play an important role in the prognosis of thrombolysis in AIS, and that the GPR can respond to the stress state of the organism, reflecting the activity of the RAAS, and that lymphoid organs are directly innervated by nerves, catecholamines are released from the nerve endings during stress in the organism, and stress hormones are regulated through adrenergic receptors and glucocorticoid receptors immune cell function 56 , and thus influence the immune response after thrombolysis in AIS. In our present study, GPR was used for the first time in a 3-month prognostic prediction study of IVT in AIS, and the results showed a statistically significant difference in GPR between the good prognosis and poor prognosis groups. The final results demonstrated that the SIRI-GPR score was a good predictor of 3-month prognosis in AIS after IVT, and thus, we hypothesized whether it is possible to intervene in the prognosis of IVT in AIS by decreasing the SIR-GPR score and thus provide timely intervention to enable the patients with AIS to have a good functional prognosis from IVT. There are several defects that need to be considered in depth. First of all, this study lacks a prospective design and does not further compare the dynamic changes of hematological inflammatory markers. Secondly, we did not collect the ASPECTS score and TOAST classification into our study. Thirdly, this study is a single-center study with relatively small sample size and short follow-up time, so there may be some bias and variation. Therefore, these factors may lead to our outcome SIRI and GPR have no independent predictive significance for 3-month functional prognosis. Finally, given that the samples are collected from only one city in China, the results may not be generalized. This also provides a research direction for the future: to collect dynamic blood biochemical data before and after IVT for accurate comparative study to see whether dynamic SIRI-GPR score has different effects on prognosis, and to study the specific effects of dynamic SIRI-GPR score on the prognosis of IVT in AIS, such as early prognosis (early neurological deterioration and bleeding transformation) and collect the ASPECTS score and TOAST classification into study. We also need further large-scale prospective studies and multicenter collaborative studies to verify our conclusions. 5. Conclusion In conclusion, in patients treated with IVT for AIS, the SIRI-GPR score can predict the 3-month prognosis in stroke patients treated with IVT, in another words, a higher SIRI-GPR score predicts a worse prognosis. Thus, monitoring SIRI-GPR scores in AIS patients treated with r-tPA may provide insight into therapeutic targets and warrants attention in future studies. Abbreviations IVT intravenous thrombolysis AIS acute ischemic stroke SIRI systemic inflammatory response index GPR blood glucose/potassium ratio rt-PA recombinant tissue plasminogen activator ROC receiver operating characteristic NIHSS National Institutes of Health Stroke Score mRS modified Rankin score Declarations Ethics approval and consent to participate This study was conducted by the ethical standards of the Human Research and Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University and abode by the Declaration of Helsinki's principles. Although we could not gain the patients' informed consent owing to the use of a retrospective research design, we were granted permission to gather data from our stroke registry. Consent for publication Not applicable Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding Work was supported by the Public Welfare Science and Technology Plan Project of Wenzhou City (Y20220819,Y2023849) Authors' contributions JC and YH: Funding acquisition, Project administration, Resources, Methodology, Validation, Formal analysis, Writing – review & editing and supervision. ZW: Visualization, Software, Writing - original draft, Conceptualization, Formal analysis, software and Investigation. HC, NC and JR: Data curation, Investigation. All authors read and approved the final manuscript. Acknowledgments We express our gratitude to all the patients in our study. ORCID Zhijun Wen’s ORCID record is https://orcid.org/0009-0009-7311-2074. References Global regional. national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021;20:795–820. Zhao Y, Hua X, Ren X, et al. Increasing burden of stroke in China: A systematic review and meta-analysis of prevalence, incidence, mortality, and case fatality. Int J Stroke. 2023;18:259–67. Herpich F, Rincon F. Management of Acute Ischemic Stroke. Crit Care Med. 2020;48:1654–63. Rabinstein AA. Treatment of Acute Ischemic Stroke. Continuum (Minneap Minn). 2017;23:62–81. Przykaza Ł. Understanding the Connection Between Common Stroke Comorbidities, Their Associated Inflammation, and the Course of the Cerebral Ischemia/Reperfusion Cascade. Front Immunol. 2021;12:782569. Vidale S, Consoli A, Arnaboldi M, Consoli D. Postischemic Inflammation in Acute Stroke. J Clin Neurol (Seoul Korea). 2017;13:1–9. Sun M-S, Jin H, Sun X, Huang S, Zhang F-L, Guo Z-N, Yang Y. Free Radical Damage in Ischemia-Reperfusion Injury: An Obstacle in Acute Ischemic Stroke after Revascularization Therapy. Oxidative Med Cell Longev. 2018;2018:3804979. Wang W, Wang Y, Qu C, et al. The RNA genome of hepatitis E virus robustly triggers an antiviral interferon response. Hepatology (Baltimore MD). 2018;67:2096–112. Kwon JH, Jang JW, Kim YW, et al. The usefulness of C-reactive protein and neutrophil-to-lymphocyte ratio for predicting the outcome in hospitalized patients with liver cirrhosis. BMC Gastroenterol. 2015;15:146. Yao Z, Zhang Y, Wu H. Regulation of C-reactive protein conformation in inflammation. Inflamm Res. 2019;68:815–23. Templeton AJ, McNamara MG, Šeruga B, et al. Prognostic role of neutrophil-to-lymphocyte ratio in solid tumors: a systematic review and meta-analysis. J Natl Cancer Inst. 2014;106:dju124. Zhou Y, Zhang Y, Cui M, Zhang Y, Shang X. Prognostic value of the systemic inflammation response index in patients with acute ischemic stroke. Brain Behav. 2022;12:e2619. Chu M, Luo Y, Wang D, Liu Y, Wang D, Wang Y, Zhao J. Systemic inflammation response index predicts 3-month outcome in patients with mild acute ischemic stroke receiving intravenous thrombolysis. Front Neurol. 2023;14:1095668. Chen YF, Qi S, Yu ZJ, Li JT, Qian TT, Zeng Y, Cao P. Systemic Inflammation Response Index Predicts Clinical Outcomes in Patients With Acute Ischemic Stroke (AIS) After the Treatment of Intravenous Thrombolysis. Neurologist. 2023;28:355–61. Feibel JH, Hardy PM, Campbell RG, Goldstein MN, Joynt RJ. Prognostic value of the stress response following stroke. JAMA. 1977;238:1374–6. Zhou J, Yang CS, Shen LJ, Lv QW, Xu QC. Usefulness of serum glucose and potassium ratio as a predictor for 30-day death among patients with severe traumatic brain injury. Clin Chim Acta. 2020;506:166–71. Wu XY, Zhuang YK, Cai Y, Dong XQ, Wang KY, Du Q, Yu WH. Serum glucose and potassium ratio as a predictive factor for prognosis of acute intracerebral hemorrhage. J Int Med Res. 2021;49:3000605211009689. Fujiki Y, Matano F, Mizunari T, et al. Serum glucose/potassium ratio as a clinical risk factor for aneurysmal subarachnoid hemorrhage. J Neurosurg. 2018;129:870–5. Demirtaş E, Korkmaz İ, Tekin YK, Demirtaş E, Çaltekin İ. Assessment of serum glucose/potassium ratio as a predictor for delayed neuropsychiatric syndrome of carbon monoxide poisoning. Hum Exp Toxicol. 2021;40:207–13. Matano F, Fujiki Y, Mizunari T, et al. Serum Glucose and Potassium Ratio as Risk Factors for Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage. J Stroke Cerebrovasc Dis. 2019;28:1951–7. Lu Y, Ma X, Zhou X, Wang Y. The association between serum glucose to potassium ratio on admission and short-term mortality in ischemic stroke patients. Sci Rep. 2022;12:8233. Xiangyu S, Huiping P. Predictive Effect of Systemic Inflammation Response Index Combined with Blood Glucose/Blood Potassium Ratio on Poor Prognosis of Patients with Aneurysmal Subarachnoid Hemorrhage. Chin Foreign Med Res 2021;19. Kolaczkowska E, Kubes P. Neutrophil recruitment and function in health and inflammation. Nat Rev Immunol. 2013;13:159–75. Jickling GC, Liu D, Ander BP, Stamova B, Zhan X, Sharp FR. Targeting neutrophils in ischemic stroke: translational insights from experimental studies. J Cereb Blood Flow Metab. 2015;35:888–901. Buck BH, Liebeskind DS, Saver JL, et al. Early neutrophilia is associated with volume of ischemic tissue in acute stroke. Stroke. 2008;39:355–60. Garau A, Bertini R, Colotta F, et al. Neuroprotection with the CXCL8 inhibitor repertaxin in transient brain ischemia. Cytokine. 2005;30:125–31. Jin R, Yang G, Li G. Inflammatory mechanisms in ischemic stroke: role of inflammatory cells. J Leukoc Biol. 2010;87:779–89. Kaito M, Araya S, Gondo Y, Fujita M, Minato N, Nakanishi M, Matsui M. Relevance of distinct monocyte subsets to clinical course of ischemic stroke patients. PLoS ONE. 2013;8:e69409. Ray MJ, Walters DL, Bett JN, Cameron J, Wood P, Aroney CN. Platelet-monocyte aggregates predict troponin rise after percutaneous coronary intervention and are inhibited by Abciximab. Int J Cardiol. 2005;101:249–55. Liesz A, Zhou W, Na SY, et al. Boosting regulatory T cells limits neuroinflammation in permanent cortical stroke. J Neurosci. 2013;33:17350–62. Li J, Yuan Y, Liao X, Yu Z, Li H, Zheng J. Prognostic Significance of Admission Systemic Inflammation Response Index in Patients With Spontaneous Intracerebral Hemorrhage: A Propensity Score Matching Analysis. Front Neurol. 2021;12:718032. Brown MJ, Brown J. Does angiotensin-II protect against strokes? Lancet. 1986;2:427–9. Chrysant SG. The role of angiotensin II receptors in stroke protection. Curr Hypertens Rep. 2012;14:202–8. Brdon J, Kaiser S, Hagemann F, Zhao Y, Culman J, Gohlke P. Comparison between early and delayed systemic treatment with candesartan of rats after ischaemic stroke. J Hypertens. 2007;25:187–96. Dai WJ, Funk A, Herdegen T, Unger T, Culman J. Blockade of central angiotensin AT(1) receptors improves neurological outcome and reduces expression of AP-1 transcription factors after focal brain ischemia in rats. Stroke. 1999;30:2391–8. discussion 2398–2399. Ginsberg MD. Adventures in the pathophysiology of brain ischemia: penumbra, gene expression, neuroprotection: the 2002 Thomas Willis Lecture. Stroke. 2003;34:214–223. Jiang F, Yang J, Zhang Y, et al. Angiotensin-converting enzyme 2 and angiotensin 1–7: novel therapeutic targets. Nat Rev Cardiol. 2014;11:413–26. Sumners C, Horiuchi M, Widdop RE, McCarthy C, Unger T, Steckelings UM. Protective arms of the renin-angiotensin-system in neurological disease. Clin Exp Pharmacol Physiol. 2013;40:580–8. Wilms H, Rosenstiel P, Unger T, Deuschl G, Lucius R. Neuroprotection with angiotensin receptor antagonists: a review of the evidence and potential mechanisms. Am J Cardiovasc Drugs. 2005;5:245–53. Amin EF, Rifaai RA, Abdel-Latif RG. Empagliflozin attenuates transient cerebral ischemia/reperfusion injury in hyperglycemic rats via repressing oxidative-inflammatory-apoptotic pathway. Fundam Clin Pharmacol. 2020;34:548–58. Fiorentino TV, Prioletta A, Zuo P, Folli F. Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases. Curr Pharm Des. 2013;19:5695–703. Luc K, Schramm-Luc A, Guzik TJ, Mikolajczyk TP. Oxidative stress and inflammatory markers in prediabetes and diabetes. J Physiol Pharmacol 2019;70. Meza CA, La Favor JD, Kim DH, Hickner RC. Endothelial Dysfunction: Is There a Hyperglycemia-Induced Imbalance of NOX and NOS? Int J Mol Sci 2019;20. Nie Q, Zhu L, Zhang L, Leng B, Wang H. Astragaloside IV protects against hyperglycemia-induced vascular endothelial dysfunction by inhibiting oxidative stress and Calpain-1 activation. Life Sci. 2019;232:116662. Wu F-F, Hung Y-C, Tsai YH, et al. The influence of dehydration on the prognosis of acute ischemic stroke for patients treated with tissue plasminogen activator. BMC Cardiovasc Disord. 2017;17:154. Su J, Fu X, Tian Y, et al. Additional predictive value of serum potassium to Thrombolysis In Myocardial Infarction risk score for early malignant ventricular arrhythmias in patients with acute myocardial infarction. Am J Emerg Med. 2012;30:1089–94. Rodan AR. Potassium: friend or foe? Pediatr Nephrol. 2017;32:1109–21. Gariballa SE, Robinson TG, Fotherby MD. Hypokalemia and potassium excretion in stroke patients. J Am Geriatr Soc. 1997;45:1454–8. Cheng CJ, Kuo E, Huang CL. Extracellular potassium homeostasis: insights from hypokalemic periodic paralysis. Semin Nephrol. 2013;33:237–47. Vinceti M, Filippini T, Crippa A, de Sesmaisons A, Wise LA, Orsini N. Meta-Analysis of Potassium Intake and the Risk of Stroke. J Am Heart Assoc 2016;5. Larsson SC, Orsini N, Wolk A. Dietary potassium intake and risk of stroke: a dose-response meta-analysis of prospective studies. Stroke. 2011;42:2746–50. McCabe RD, Bakarich MA, Srivastava K, Young DB. Potassium inhibits free radical formation. Hypertension. 1994;24:77–82. Melek FE, Baroncini LA, Repka JC, Nascimento CS, Précoma DB. Oxidative stress and inflammatory response increase during coronary artery bypass grafting with extracorporeal circulation. Rev Bras Cir Cardiovasc. 2012;27:61–5. Crimi G, Somaschini A, Cattaneo M, Angiolillo DJ, Piscione F, Palmerini T, De Servi S. Cigarette smoking reduces platelet reactivity independently of clopidogrel treatment in patients with non-ST elevation acute coronary syndromes. Platelets. 2018;29:309–11. Ganten D, Lang RE, Lehmann E, Unger T. Brain angiotensin: on the way to becoming a well-studied neuropeptide system. Biochem Pharmacol. 1984;33:3523–8. Schulze J, Vogelgesang A, Dressel A. Catecholamines, steroids and immune alterations in ischemic stroke and other acute diseases. Aging Dis. 2014;5:327–39. Additional Declarations No competing interests reported. Supplementary Files Highlight.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4950520","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":346411733,"identity":"1106deb6-7e64-4d56-952e-244f84e44e05","order_by":0,"name":"Zhijun Wen","email":"","orcid":"","institution":"The First Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Zhijun","middleName":"","lastName":"Wen","suffix":""},{"id":346411734,"identity":"2752253d-33e2-44e9-8922-e1ad0d1a2ecd","order_by":1,"name":"Hanyu Cai","email":"","orcid":"","institution":"The Second Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hanyu","middleName":"","lastName":"Cai","suffix":""},{"id":346411735,"identity":"967dc179-7d0e-4244-93aa-32b5988fc530","order_by":2,"name":"Nan Chen","email":"","orcid":"","institution":"The First Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Nan","middleName":"","lastName":"Chen","suffix":""},{"id":346411736,"identity":"7e2d7aea-b5ea-47fe-8f71-41ddfdd9af1d","order_by":3,"name":"Jie Ren","email":"","orcid":"","institution":"The First Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jie","middleName":"","lastName":"Ren","suffix":""},{"id":346411737,"identity":"fd7e6182-3874-495e-9053-821da07b8e07","order_by":4,"name":"Jianhua Cheng","email":"","orcid":"","institution":"The First Affiliated Hospital of Wenzhou Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jianhua","middleName":"","lastName":"Cheng","suffix":""},{"id":346411738,"identity":"81f695a9-dbfc-4ef6-a8af-66b3fc8729fe","order_by":5,"name":"Yirui Huang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAwElEQVRIiWNgGAWjYNACg/88jO2NjQ8/EK+lglmGuedws7EE8VrOMNuwz0hvE+AhRjG/2OnEB4xtbDy8Mx+2MUgw2MnpNhDQIjk7d7MBYxsPj+TsxLYHBQzJxmYHCGgxuJ27TYKxTYLHcHZiu4EEw4HEbURqMeCxv3kQqJFoLQxnEngYZzASqQXsF4aKAzyMPYnAQDYgwi/80rkbHzAYHLBnbD/+8OGHCjs5glpAgPkPwp1EKB8Fo2AUjIJRQBgAAM6dPyT6thEkAAAAAElFTkSuQmCC","orcid":"","institution":"Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine","correspondingAuthor":true,"prefix":"","firstName":"Yirui","middleName":"","lastName":"Huang","suffix":""}],"badges":[],"createdAt":"2024-08-21 09:43:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4950520/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4950520/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":66675108,"identity":"b5b75d5b-508d-4236-83d9-34affc5142a0","added_by":"auto","created_at":"2024-10-15 11:03:54","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1797251,"visible":true,"origin":"","legend":"\u003cp\u003eResearch flow chart.\u003c/p\u003e","description":"","filename":"figure1.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4950520/v1/b0b66049595ad643cdbfdeaa.jpg"},{"id":66675109,"identity":"ba39a62b-e5f3-4840-a741-71acb0b0e16b","added_by":"auto","created_at":"2024-10-15 11:03:54","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":640916,"visible":true,"origin":"","legend":"\u003cp\u003eThe ROC curve of SIRI and GPR respectively.\u003c/p\u003e","description":"","filename":"figure2.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4950520/v1/60795b13b6afb445753fd4b9.jpg"},{"id":66676051,"identity":"c55978d1-0c6b-40a1-a4c0-467775439246","added_by":"auto","created_at":"2024-10-15 11:11:54","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":878809,"visible":true,"origin":"","legend":"\u003cp\u003eThe forest plot of multivariate logistic regression analysis results.\u003c/p\u003e","description":"","filename":"figure3.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4950520/v1/bac4796c48b8b6e147315e0f.jpg"},{"id":66675113,"identity":"83c5424b-c735-4be4-8977-4fea5d366d36","added_by":"auto","created_at":"2024-10-15 11:03:54","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":581953,"visible":true,"origin":"","legend":"\u003cp\u003eClinical Predictive Nomograph model based on SIRI-GPR score for 3-month prognosis.\u003c/p\u003e","description":"","filename":"figure4.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4950520/v1/c2f9381553c84286a74a6171.jpg"},{"id":66675111,"identity":"887a580c-2baa-4a1e-b2a5-b4f61a3084b4","added_by":"auto","created_at":"2024-10-15 11:03:54","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":88322,"visible":true,"origin":"","legend":"\u003cp\u003ea.The ROC curve of the prediction model based on the SIRI-GPR score\u003c/p\u003e\n\u003cp\u003eb.The calibration curve of internal verification\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4950520/v1/2ea7a16769fbc7ba99c4f557.jpg"},{"id":66676052,"identity":"772f6969-d5e2-47bb-a100-e3ac938cd451","added_by":"auto","created_at":"2024-10-15 11:11:54","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":738407,"visible":true,"origin":"","legend":"\u003cp\u003eThe predictive Nomogram ROC curves (with SIRI-GPR score and without SIRI-GPR score)\u003c/p\u003e","description":"","filename":"figure6.tif.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4950520/v1/70edaea3d59598519de97b26.jpg"},{"id":66677298,"identity":"9905b52f-4fa5-409f-becb-acb9db8807c1","added_by":"auto","created_at":"2024-10-15 11:27:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5368667,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4950520/v1/2162e7e8-3cbf-4422-b0e8-2d902eb4cf3f.pdf"},{"id":66675114,"identity":"815db819-7deb-439d-b479-f251972c0fdf","added_by":"auto","created_at":"2024-10-15 11:03:55","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":16147,"visible":true,"origin":"","legend":"","description":"","filename":"Highlight.docx","url":"https://assets-eu.researchsquare.com/files/rs-4950520/v1/85d60943b015dceb3160969f.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"3-Month Prognostic Value of the Systemic Inflammatory Response Index Combined with Blood Glucose/ Potassium Ratio Score in Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eGlobally, stroke remains the second leading cause of death in humans and is one of the most common diseases in the world. According to relevant statistics, there are approximately 12.2\u0026nbsp;million new cases and 101\u0026nbsp;million prevalent cases in 2019, including 143\u0026nbsp;million cases of stroke disability and 65.5\u0026nbsp;million deaths from stroke.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003eAlthough public health policies and health care services are improving, the burden of stroke remains high, especially in some low-income countries, so there is still a need to explore effective primary prevention strategies as well as good prognostic measures to offset the possibility of a further increase in the absolute number of stroke cases in this large population.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003ePatients with acute ischemic stroke(AIS) require comprehensive treatment, including reperfusion therapy, complication management and rehabilitation treatment.\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003eAmong them, reperfusion therapy is the main treatment for AIS.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003eReperfusion to salvage brain cells on the verge of necrosis in the ischemic semi-domain is an important way to delay or stop AIS. Reperfusion therapy includes intravenous thrombolysis(IVT) and mechanical thrombectomy, and rt-PA (recombinant tissue plasminogen activator) is the only approved and effective drug treatment in IVT. However, reperfusion injury caused by IVT can be characterized by hemorrhage and edema, such as symptomatic intracranial hemorrhage, which may counteract the benefits of reperfusion therapy and even lead to early neurological deterioration. Therefore, it is particularly important to find appropriate prognostic indicators for IVT.\u003c/p\u003e \u003cp\u003eInflammation and the immune response play an important role in secondary brain injury after stroke.\u003csup\u003e\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e A large number of studies have shown that the neuroinflammatory response also plays an important role in the pathophysiology of ischemic stroke.\u003csup\u003e\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e The systemic inflammation response index (SIRI) is a new comprehensive biomarker for inflammatory and tumor-related diseases that is calculated from the absolute numbers of neutrophils, monocytes and lymphocytes. The prognostic role of SIRI in stroke has been confirmed.\u003csup\u003e\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eStress response following stroke shows a prognostic value\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e, and hyperglycemia is a stress response in AIS. Potassium ions are the most abundant cations in human cells and play a vital role in physiological processes such as nerve conduction, heart beating, muscle contraction, and maintenance of normal kidney function. The blood glucose / blood potassium ratio (GPR) has been used to analyze circulatory diseases such as stroke and bleeding. It has been proved to be an early prognostic factor of central nervous system injury, including severe traumatic brain injury,\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e acute cerebral hemorrhage,\u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e aneurysmal subarachnoid hemorrhage\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e and neuropsychiatric syndrome\u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e after carbon monoxide poisoning. Matano et al found that there was a strong correlation between vasospasm and GPR in AIS.\u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e Yuzhao Lu et al found that in patients with AIS, GPR was positively correlated with 30-day mortality, and there was a linear relationship between them, GPR at admission may be a promising indicator for short-term prognosis of patients with AIS.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eBecause the level of SIRI can reflect the level of systemic inflammatory response and immune response\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, GPR reflects the stress state of the body, and according to the study of Xiangyu S et al in 2021, it is found that the body inflammatory response index combined with blood glucose/potassium ratio (SIRI-GPR) can be used to predict the poor prognosis of patients with aneurysmal subarachnoid hemorrhage, and the prognostic value of SIRI combined with GPR is higher than that of SIRI or GPR\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. Therefore, we speculate that the SIRI-GPR may be of value in the 3-month prognosis of patients with AIS after IVT. the SIRI and GPR have not been simultaneously assessed as markers of the 3-month prognosis of patients with AIS after IVT. We combine SIRI with GPR as a new score to predict the prognosis of AIS patients treated with IVT for the first time. Since SIRI-GPR is used for the first time in IVT for AIS, the specific scores were not identified in the relevant literature and were extracted from the relevant lit-erature combined with the clinic. In this study, we aim to explore the predictive effect of the SIRI-GPR score on the poor prognosis of patients with AIS after IVT.\u003c/p\u003e"},{"header":"2. Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Research object and background\u003c/h2\u003e \u003cp\u003eThis retrospective study was based on the database of patients with AIS treated by IVT collected by the Department of Neurology of the First Affiliated Hospital of Wenzhou Medical University from July 2021 to July 2022. There were 247 patients treated with IVT. The criteria for screening patients include: (1) over the age of 18; (2)Complete baseline clinical data; (3) All selected patients meet the diagnostic criteria for ischemic stroke according to the Chinese Guidelines for the diagnosis and treatment of AIS; (4) rt-PA infusion of 0.9mg/kg (maximum 90mg) in all selected patients within 4.5 hours of onset (10% dose as one injection, followed by 60 minutes of residual dose). (5) Venous blood samples were taken within 24 hours after IVT to measure neutrophil counts, monocyte counts, lymphocyte counts, blood glucose, serum potassium, etc. (6) The informed consent form has been signed by the patient or the patient's family. (7) complete the follow-up. The exclusion criteria included: (1) patients who underwent intravascular thrombectomy on the basis of IVT; (2) history of infection or confirmed infection, malignant tumor, rheumatism, hematological diseases or other diseases that significantly affected peripheral blood cells within 48 hours after admission; (3) patients with diabetes, (4) loss of follow-up. According to the exclusion criteria, 128 patients were excluded because of the reasons showing in the Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Finally, 119 patients were eligible for the study. The research program was approved by the Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University and implemented in accordance with the Helsinki Declaration.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Laboratory parameters and clinical outcomes\u003c/h2\u003e \u003cp\u003eThe laboratory data we collected included: (1) demographic characteristics (age and gender);(2) clinical characteristics (National Institutes of Health Stroke Score [NIHSS], BMI, blood pressure, history of smoking and alcohol use, presence or absence of large artery occlusion and presence or absence of eGFR\u0026thinsp;\u0026le;\u0026thinsp;60); (3) medical history (presence of hypertension, dyslipidemia, previous stroke and atrial fibrillation). (4) Blood biochemistry values (monocyte, lymphocyte, neutrophil, and platelet counts, blood glucose, serum potassium, uric acid, creatinine, homocysteine, total cholesterol, triglycerides, HDL and LDL). Before the IVT and within 4.5 h of the AIS onset, the patients underwent emergency cranial CT/MRI neuroimaging. In addition, the severity of stroke was assessed using NIHSS scores within 24 hours after IVT treatment. Venous blood samples were taken from all patients within 24 hours after treatment to detect neutrophil, monocyte, lymphocyte and platelet counts, blood glucose, serum potassium and so on.\u003c/p\u003e \u003cp\u003eThe SIRI is defined as the ratio of neutrophil counts multiply monocyte counts to lymphocyte counts, and GPR is defined as the ratio of blood glucose to blood potassium, and the maximum Youden index (Youden index\u0026thinsp;=\u0026thinsp;sensitivity\u0026thinsp;+\u0026thinsp;specificity-1) is calculated from the receiver operating characteristic (ROC) curve to determine the optimal critical values of SIRI and GPR, thus SIRI and GPR are divided into a high group and a low group respectively. We graded the SIRI-GPR scores on a scale of 0 to 2: patients with low SIRI and low GPR had a score of 0; those with high SIRI and low GPR, or low SIRI and high GPR, had a score of 1; and those with high SIRI and high GPR had a score of 2. The functional prognosis of the patients was evaluated by modified Rankin score(mRS), and we categorized an mRS score between 0 and 2 as a favorable outcome and an mRS score between 3 and 6 as a poor outcome.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. Statistical analysis\u003c/h2\u003e \u003cp\u003eThe normal distribution of the data was tested using the Shapiro-Wilk normal test. F-test is used to test whether the variance between two data sets of normal distribution is equal. Continuous variables with normal distribution were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD) and compared by t-test, and continuous variables with non-normal distributions are expressed as median and interquartile range (M(P25, P75)) and compared using the Mann-Whitney U test. Classification variables are expressed as frequencies and percentages (n, %) and compared by chi-square test. Univariate analysis and multivariate logistic regression model were used to investigate the independent effect of SIRI-GPR score on clinical outcome (3-month prognosis after IVT), and adjusted the potential confounders. According to the independent risk factors obtained by multivariate Logistic regression of each outcome index, a nomogram was constructed to predict the clinical outcome (3-month prognosis after IVT) by R Studio software, and the Nomogram model was evaluated by ROC curve and correction curve. A p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was regarded as statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003ch2\u003e3.1.\u0026nbsp; \u0026nbsp;\u0026nbsp;Patient characteristics\u003c/h2\u003e\n\u003cp\u003eThe baseline condition of the 119 patients are shown in \u003cem\u003eTable 2\u003c/em\u003e, the most approximate index was calculated from the ROC curve of the original cohort study (\u003cem\u003eFigure 2\u003c/em\u003e). The cutoff values of SIRI and GPR in the 3-month prognosis after thrombolysis were 1.992 * 10 \u003csup\u003e^\u003c/sup\u003e 9 / L and 1.421 respectively (\u003cem\u003eTable 1\u003c/em\u003e). Among all IVT patients, according to the mRS score standard of follow-up at 3 months after onset, there were 74(62,2%) cases with favorable outcome (mRS \u0026le; 2 )and 45(37.8%) cases with poor outcome(mRS \u0026gt; 2 ).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u003c/strong\u003e The cutoff value of SIRI and GPR respectively.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"513\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"5\"\u003e\n \u003cp\u003eArea Under the Curve\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.43469785575049%\" valign=\"bottom\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.865497076023392%\" valign=\"bottom\"\u003e\n \u003cp\u003eAUC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2729044834308%\" valign=\"bottom\"\u003e\n \u003cp\u003eCutoff value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.814814814814815%\" valign=\"bottom\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.612085769980506%\" valign=\"bottom\"\u003e\n \u003cp\u003e95% CI of AUC\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.43469785575049%\" valign=\"top\"\u003e\n \u003cp\u003eGPR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.865497076023392%\" valign=\"top\"\u003e\n \u003cp\u003e0.692\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2729044834308%\" valign=\"top\"\u003e\n \u003cp\u003e1.421\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.814814814814815%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.612085769980506%\" valign=\"top\"\u003e\n \u003cp\u003e0.592-0.791\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"29.43469785575049%\" valign=\"top\"\u003e\n \u003cp\u003eSIRI（*10^9/L）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"12.865497076023392%\" valign=\"top\"\u003e\n \u003cp\u003e0.763\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.2729044834308%\" valign=\"top\"\u003e\n \u003cp\u003e1.992\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.814814814814815%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"22.612085769980506%\" valign=\"top\"\u003e\n \u003cp\u003e0.677-0.849\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u003c/strong\u003e AUC, Area under curve; \u003cstrong\u003eNotes:\u003c/strong\u003e P\u0026lt;0.05, The difference was statistically significant.\u0026nbsp;\u003c/p\u003e\n\u003ch2\u003e3.2. \u0026nbsp; \u0026nbsp;Comparison of baseline data of AIS patients grouped according to the outcome of 3 months after IVT\u003c/h2\u003e\n\u003cp\u003eThe demographic, clinical and related laboratory data of the patients in general and the baseline grouped according to the prognosis are shown in \u003cem\u003eTable 2\u003c/em\u003e(at the end of the document text file ). We found that age, hypertension, previous stroke, large artery occlusion, NIHSS score within 24h after thrombolysis, blood glucose of 24 hours after thrombolysis, neutrophil counts (* 10 ^ 9), \u0026nbsp;lymphocyte counts, SIRI (* 10 ^ 9 / L), GPR and SIRI-GPR score differed significantly between the two groups (p \u0026lt; 0.05), and we found the following distribution of SIRI-GPR scores in patients with poor prognosis at 3 months after thrombolysis: 6 (13.3%) patients had a post-thrombolysis SIRI-GPR score of 0, 17 (37.8%) had a SIRI-GPR score of 1, and 22 (48. 9%) had a SIRI-GPR score of 2. The difference in SIRI-GPR score between patients with good and poor prognosis at 3 months after thrombolysis was statistically significant (p \u0026lt; 0.001).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2.\u0026nbsp;\u003c/strong\u003eThe baseline condition of the patients and the comparison of baseline data of AIS patients grouped according to prognostic outcome.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"102%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eCharacteristics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eAll patients（n=119）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"41.23711340206186%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e3-month outcome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eZ /t /\u0026chi;2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003eP value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.5%\" valign=\"top\"\u003e\n \u003cp\u003efavorable outcome\u003c/p\u003e\n \u003cp\u003e(mRS\u0026le;2)\u003c/p\u003e\n \u003cp\u003e（n=74）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"52.5%\" valign=\"top\"\u003e\n \u003cp\u003ePoor outcome\u003c/p\u003e\n \u003cp\u003e(mRS\u0026gt;2)\u003c/p\u003e\n \u003cp\u003e（n=45）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eBasic data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eage，M（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e71.00（59.50,76.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e66.00（55.00,73.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e74.00（67.00,79.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-3.548\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003efemale，n（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e33（27.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e42（71.2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e39（63.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e0.410\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.521\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eRisk factors\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003ehypertension，n（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e76（63.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e35（59.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e48（78.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e4.290\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eHyperlipidemia，\u003c/p\u003e\n \u003cp\u003en（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e23（19.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e14（23.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e10（16.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e1.670\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.197\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eAtrial fibrillation\u0026nbsp;，\u003c/p\u003e\n \u003cp\u003en（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e29（24.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e11（18.6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e21（34.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e1,78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.182\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eCoronary heart disease，n（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e6（5.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e2（3.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e5（8.2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e1.130\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.288\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003ePrevious stroke，\u003c/p\u003e\n \u003cp\u003en（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e21（17.6）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e5（8.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e17（27.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e6.290\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eHistory of smoking，\u003c/p\u003e\n \u003cp\u003en（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e33（27.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e18（30.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e9（14.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e0.041\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.840\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eHistory of alcohol consumption，\u003c/p\u003e\n \u003cp\u003en（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e30（25.2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e14（23.7）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e11（18.0）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e0.520\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.471\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eLarge artery occlusion，n（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e20（16.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e5（8.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e16 \u0026nbsp;（26.2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e14.140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eeGFR\u0026lt;=60, n（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e10（8.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e6（8.1）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e4（8.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003ebaseline data\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eNIHSS score within 24h after thrombolysis，\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e3.00（2.00,8.50）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e2.00（1.00,3.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e10.00（5.00，14.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-6.803\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eSystolic blood pressure，\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e129.00（117.50,149.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e128.00（117.00,145.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e136.00（118.00,154.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-1.455\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.146\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eDiastolic blood pressure，\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e76.00（67.00,85.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e75.50（67.00,83.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e76.00（67.00,89.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-0.348\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.728\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eBMI，（x\u0026plusmn;s）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e22.98\u0026plusmn;3.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e23.27\u0026plusmn;3.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e22.51\u0026plusmn;3.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e1.250\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.216\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003eBlood biochemical index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eBlood glucose，\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e5.00（4.50,5.85）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e4.95（4.40,5.40）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e5.50（4.70,6.40）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-2.751\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eSerum potassium，\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e3.72（3.53,3.93）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e3.79（3.54,3.98）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e3.67（3.53,3.87）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-1.378\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.168\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eHomocysteine，\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e13.00（11.00,18.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e13.00（11.00,17.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e14.00（12.00,18.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-1.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.294\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eTotal cholesterol，\u003c/p\u003e\n \u003cp\u003e（x\u0026plusmn;s）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e4.64\u0026plusmn;0.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e4.65\u0026plusmn;0.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e4.62\u0026plusmn;0.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e0.200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.842\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eTriglyceride，\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e1.13（0.88,1.59）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e1.24（0.90,1.81）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e1.07（0.83,1.33）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-1.430\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.153\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eHDL\u0026nbsp;，\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e1.12（0.97,1.37）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e1.13（0.95,1.31）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e1.12（0.97,1.39）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eLDL，（x\u0026plusmn;s）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e2.96\u0026plusmn;0.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e3.02\u0026plusmn;0.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e2.86\u0026plusmn;0.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e1.080\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.285\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eMonocyte counts，\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e0.40（0.33,0.49）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e0.39（0.33,0.48）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e0.40（0.34,0.50）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-0.853\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.394\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eNeutrophil counts（*10^9/L），\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e5.46（3.98,7.01）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e4.61（3.61,6.09）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e6.51（4.98,8.40）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-4.261\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003ePlatelet counts（*10^9/L），\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e194.00（168.00,237.50）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e200.00（169.00,257.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e186.00（155.00,208.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-1.945\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.052\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eLymphocyte counts (*10^9/L)，\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e1.34（0.93,1.66）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e1.42（1.08,1.71）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e1.02（0.76,1.42）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-3.225\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eSIRI，\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e1.69（1.02,2.85）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e1.28（0.88,1.99）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e2.51（1.95,12.79）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-4.800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eGPR，\u003c/p\u003e\n \u003cp\u003eM（P25，P75）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e1.37（1.19,1.64）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e1.29（1.15，1.45）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e1.46（1.33,1.89）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-3.500\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eUric acid，（x\u0026plusmn;s）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e331.16\u0026plusmn;96.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e336.53\u0026plusmn;95.40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e322.33\u0026plusmn;98.57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e0.780\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.439\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eSerum creatinine，\u003c/p\u003e\n \u003cp\u003eM（P25，P75））\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e73.00（65.00,88.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e74.00（65.00,90.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e72.00（64.00,82.00）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e-1.140\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e0.254\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" valign=\"top\"\u003e\n \u003cp\u003eSIRI-GPR score，\u003c/p\u003e\n \u003cp\u003en（%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"23.711340206185568%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e0 point\u003c/p\u003e\n \u003cp\u003e1 point\u003c/p\u003e\n \u003cp\u003e2 points\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.556701030927837%\" valign=\"top\"\u003e\n \u003cp\u003e48（40.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.587628865979383%\" valign=\"top\"\u003e\n \u003cp\u003e42（56.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.649484536082475%\" valign=\"top\"\u003e\n \u003cp\u003e6（13.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"7.216494845360825%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e32.060\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.278350515463918%\" rowspan=\"3\" valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.03448275862069%\" valign=\"top\"\u003e\n \u003cp\u003e42（35.3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.758620689655174%\" valign=\"top\"\u003e\n \u003cp\u003e25（33.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.206896551724135%\" valign=\"top\"\u003e\n \u003cp\u003e17（37.8）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"31.03448275862069%\" valign=\"top\"\u003e\n \u003cp\u003e29（24.4）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"32.758620689655174%\" valign=\"top\"\u003e\n \u003cp\u003e7（9.5）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"36.206896551724135%\" valign=\"top\"\u003e\n \u003cp\u003e22（48.9）\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eAbbreviations:\u0026nbsp;\u003c/strong\u003eBMI, body mass index；HDL, high density lipoprotein cholesterol；LDL, low density lipoprotein cholesterol；\u003cstrong\u003eNotes:\u003c/strong\u003e P＜0.05, The difference was statistically significant.\u003c/p\u003e\n\u003ch2\u003e3.3. \u0026nbsp; \u0026nbsp;Analysis of correlation between SIRI-GPR score and 3-month functional prognosis of AIS patients receiving IVT\u003c/h2\u003e\n\u003cp\u003eMultivariate\u0026nbsp;logistic regression analysis was performed with SIRI-GPR score and age, hypertension, previous stroke, presence or absence of large artery occlusion, NIHSS score within 24h after IVT, blood glucose, neutrophil counts, lymphocyte counts, SIRI(*10^9/L) and GPR (\u003cem\u003eTable 3\u003c/em\u003e). The results showed that the effect of presence or absence of large artery occlusion on the prognosis of acute stroke patients with IVT at 3 months after thrombolysis was statistically significant (OR=5.836,95%CI1.123~30.337,P=0.036), and the effect of NIHSS score within 24h after IVT on the prognosis of acute stroke patients with IVT was statistically significant (OR=1.371,95%CI1.167~1.612,P \u0026lt; 0.001). In the 3-month prognosis of IVT, the SIRI-GPR score (the adjusted OR value of 1 point was 4.877(95% CI 1.083~21.959,P= 0.039). The adjusted OR value of 2 points is 50.17(95%CI 3.151~798.809, p=0.0006) ) can independently predict the prognosis of AIS 3 months after IVT. The forest plot is drawn in R Studio software(\u003cem\u003eFigure 3\u003c/em\u003e).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e.Multivariate logistic regression analysis of 3-month functional prognosis in AIS patients with undergoing IVT\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\" height=\"390\" width=\"598\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNotes:\u003c/strong\u003e P＜0.05, The difference was statistically significant.\u003c/p\u003e\n\u003cp\u003eBased on the results of the SIRI-GPR score and multivariate logistic regression analysis after thrombolysis, a nomogram was established to predict the 3-month prognosis of patients with AIS after IVT. As shown in \u003cem\u003eFigure 4\u003c/em\u003e, the higher the total score, the higher the probability of poor prognosis at 3 months. The performance of the nomogram is verified internally and the ROC curve of the prediction model based on the SIRI-GPR score is constructed \u003cem\u003e(Figure 5a\u003c/em\u003e). The AUC index of the prediction model based on the SIRI-GPR score is 0.895 (95% CI \u0026nbsp;0.836-0.953). The calibration curve of internal verification (\u003cem\u003eFigure 5b\u003c/em\u003e) shows that there is a good agreement between the predicted probability and the actual probability of 3 months of stroke patients with IVT.\u003c/p\u003e\n\u003cp\u003eIn\u0026nbsp;addition, we examined the predictive Nomogram ROC curves without SIRI-GPR scores in the relative outcome metrics, as shown in supplementary\u0026nbsp;\u003cem\u003eFigure 6\u003c/em\u003e. The AUC index of the predicted nomogram without SIRI-GPR scores (0.880 95% CI:0.817-0.943) was lower than that of the nomogram with SIRI-GPR scores included (0.895 95% CI: 0.838-0.953).\u003c/p\u003e"},{"header":"4.\tDiscussion ","content":"\u003cp\u003eIn this study, we found that the increase in SIRI-GPR score in patients with AIS after IVT was closely related to poor stroke outcome and was an independent predictor of prognosis at 3 months in patients with AIS who underwent intravenous thrombolysis at the first time.\u0026nbsp;In addition, a nomogram model combining the SIRI-GPR score and other conventional risk factors was more favorable in its ability to discriminate the poor prognosis of IVT for AIS.\u003c/p\u003e\n\u003cp\u003eThe pathogenesis of AIS usually involves inflammation and immunity.\u0026nbsp;The infiltration of inflammatory cells is the beginning of inflammatory response, and inflammation plays a key role in vascular injury. SIRI is a novel integrated immune-inflammatory index that relies on absolute values of peripheral blood neutrophil counts, monocyte counts, and lymphocyte counts.\u0026nbsp;In the early stages of AIS, peripheral circulating neutrophils are first activated, resulting in the release of antimicrobial enzymes and chemicals.\u003csup\u003e23, 24\u003c/sup\u003eSome studies have also shown that the increase of neutrophil counts is related to the increase of infarct size, so the increase of neutrophil counts level may aggravate the blood-brain barrier injury by promoting the overexpression of matrix metalloproteinase-9.\u003csup\u003e25, 26\u003c/sup\u003e In addition, after AIS, monocytes are another important class of inflammatory cells, which can infiltrate the infarct site and aggravate brain damage.\u003csup\u003e27-29\u003c/sup\u003eIn contrast to neutrophils and monocytes, some lymphocytes play a protective role during post-AIS inflammation and play a key role in controlling and alleviating local inflammation.\u003csup\u003e30\u003c/sup\u003e Compared to other blood cell ratios, such as neutrophil/lymphocyte ratio (NLR), lymphocyte/monocyte ratio (LMR), and platelet/lymphocyte ratio (PLR), SIRI symbolize different pathways related to inflammation and immunity in the body, and may provide a more comprehensive response to the body\u0026apos;s inflammatory state. As such, the SIRI can accurately indicate adaptive immune responses and inflammatory responses, with the potential to serve as a reliable prognostic indicator.\u0026nbsp;\u003csup\u003e31\u003c/sup\u003eTherefore, it is speculated that the level of SIRI may better reflect the severity of neuroinflammation in patients with AIS after IVT, which in turn reflects the severity of the patients\u0026apos; condition.\u0026nbsp;The results of our study showed that there was a statistically significant difference in SIRI between the good prognosis group and the poor prognosis group. The SIRI of the poor prognosis group was significantly higher than that of the good prognosis group, which was also similar to the results of Min Chu et al.\u0026nbsp;\u003csup\u003e13\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eIn addition to inflammation and immune response in AIS its important role, the stress response also plays an important role. M.J. Brown and J. Brown first suggested a strong link between the renin-angiotensin-aldosterone system (RAAS) and stroke in 1986.\u0026nbsp;\u003csup\u003e32\u003c/sup\u003e In the brain, the RAAS has an autocrine function that maintains cerebral dynamic homeostasis and blood flow regulation. Angiotensin II (Ang II) acts by stimulating angiotensin receptor subtype 1, leading to disruption of cerebral blood flow and tissue ischemia.\u0026nbsp;\u003csup\u003e33\u003c/sup\u003e In the setting of an AIS, these effects of Ang II will further damage regions of the cerebral ischemic hemidiaphragm in areas where cells are still viable and will amplify the cerebral damage and loss of brain volume.\u0026nbsp;\u003csup\u003e34-36\u003c/sup\u003e Subsequent studies have also found that stroke patients\u0026apos; neuronal damage may be associated with increased activity of angiotensin receptor subtype 1 in the brain-specific RAAS.\u0026nbsp;\u003csup\u003e37, 38\u003c/sup\u003e Other possible mechanisms by which Ang II contributes to brain damage include induction of inflammation and production of reactive oxygen species, leading to brain damage and apoptosis.\u0026nbsp;\u003csup\u003e39\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn the context of acute disease, blood glucose may reflect the interaction of hormones involved in the stress response with concomitant insulin resistance, blood glucose is a major contributor to brain damage. Previous studies have confirmed that hyperglycemia may lead to increased oxidative stress, inflammatory responses, and endothelial dysfunction, resulting in brain tissue reperfusion injury.\u0026nbsp;\u003csup\u003e40-44\u003c/sup\u003e It has also been found that IVT has a poorer prognosis in patients with AIS with electrolyte disturbances.\u0026nbsp;\u003csup\u003e45, 46\u003c/sup\u003e Previously, Cheng et al. demonstrated that minor deviations of serum K\u003csup\u003e+\u003c/sup\u003e levels from the normal range may lead to severe muscle dysfunction, palpitations, arrhythmias, and deterioration of neurological function.\u0026nbsp;\u003csup\u003e47-49\u003c/sup\u003e Multiple meta-analyses have reported that K\u003csup\u003e+\u003c/sup\u003e inhibits the formation of free radicals and prevents endothelial dysfunction.\u0026nbsp;\u003csup\u003e50-52\u003c/sup\u003e In addition, blood potassium levels are mainly regulated by the ATP-Na\u003csup\u003e+\u003c/sup\u003e/K\u003csup\u003e+\u003c/sup\u003e pump on the cell surface regulation, there is an important relationship with glycemic changes. In the case of AIS stress, increased adrenergic hormones upregulate this pump, thereby decreasing K\u003csup\u003e+\u003c/sup\u003e levels.\u0026nbsp;\u003csup\u003e53, 54\u003c/sup\u003e Stress-induced increases in insulin secretion and catecholamines due to intracellular K\u003csup\u003e+\u003c/sup\u003e uptake, and further hyperglycemia, will have clinical consequences. In addition, it has also been shown that lower blood potassium levels may be a marker of enhanced activity of the RAAS and may potentiate the adverse effects of other risk factors.\u003csup\u003e32, 55\u003c/sup\u003e The results of this study showed that there was a statistically significant difference in GPR between the good and poor prognosis groups, with the GPR in the poor prognosis group being significantly higher than that in the good prognosis group, and Yuzhao Lu et al. also previously found that GPR was positively correlated with 30-day mortality in patients with AIS, and that the two had a linear relationship. \u003csup\u003e21\u003c/sup\u003e Therefore, the GPR at the time of admission may be a promising predictor of short-term prognosis for patients with AIS.\u003c/p\u003e\n\u003cp\u003eThere are many clinical indicators related to the poor prognosis of patients with AIS after IVT for 3 months. It is now considered that the causes affecting the prognosis of IVT in stroke are diverse and complex and need to be evaluated comprehensively. In our study, Large artery occlusion, NIHSS score within 24h after thrombolysis and SIRI-GPR score after thrombolysis were found to be \u0026nbsp;independently associated with poor prognosis at 3 months after IVT in AIS. Large artery occlusion is the cause of irreversibility, SIRI and GPR are both reversible causes, and are easy to obtain laboratory indicators. Among these indicators, the OR value of SIRI-GPR score is the highest, indicating that SIRI-GPR score plays the most important role in predicting the poor 3-month prognosis of AIS after IVT. Here, through the nomogram model to show the relationship between the independent risk factors of each outcome index, it is proved that SIRI-GPR score has a better correlation in predicting poor 3-month prognosis after IVT in AIS.\u003c/p\u003e\n\u003cp\u003eGiven that inflammatory and immune responses have been shown to play an important role in the prognosis of thrombolysis in AIS, and that the GPR can respond to the stress state of the organism, reflecting the activity of the RAAS, and that lymphoid organs are directly innervated by nerves, catecholamines are released from the nerve endings during stress in the organism, and stress hormones are regulated through adrenergic receptors and glucocorticoid receptors immune cell function\u003csup\u003e56\u003c/sup\u003e, and thus influence the immune response after thrombolysis in AIS. In our present study, GPR was used for the first time in a 3-month prognostic prediction study of IVT in AIS, and the results showed a statistically significant difference in GPR between the good prognosis and poor prognosis groups. The final results demonstrated that the SIRI-GPR score was a good predictor of 3-month prognosis in AIS after IVT, and thus, we hypothesized whether it is possible to intervene in the prognosis of IVT in AIS by decreasing the SIR-GPR score and thus provide timely intervention to enable the patients with AIS to have a good functional prognosis from IVT.\u003c/p\u003e\n\u003cp\u003eThere are several defects that need to be considered in depth. First of all, this study lacks a prospective design and does not further compare the dynamic changes of hematological inflammatory markers. Secondly, we did not collect the ASPECTS score and TOAST classification into our study. Thirdly, this study is a single-center study with relatively small sample size and short follow-up time, so there may be some bias and variation. Therefore, these factors may lead to our outcome SIRI and GPR have no independent predictive significance for 3-month functional prognosis. Finally, given that the samples are collected from only one city in China, the results may not be generalized. This also provides a research direction for the future: to collect dynamic blood biochemical data before and after IVT for accurate comparative study to see whether dynamic SIRI-GPR score has different effects on prognosis, and to study the specific effects of dynamic SIRI-GPR score on the prognosis of IVT in AIS, such as early prognosis (early neurological deterioration and bleeding transformation) and collect the ASPECTS score and TOAST classification into study. We also need further large-scale prospective studies and multicenter collaborative studies to verify our conclusions.\u003c/p\u003e"},{"header":"5.\tConclusion","content":"\u003cp\u003eIn conclusion, in patients treated with IVT for AIS, the SIRI-GPR score can predict the 3-month prognosis in stroke patients treated with IVT, in another words, a higher SIRI-GPR score predicts a worse prognosis. Thus, monitoring SIRI-GPR scores in AIS patients treated with r-tPA may provide insight into therapeutic targets and warrants attention in future studies.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.80470162748644%\" valign=\"top\"\u003e\n \u003cp\u003eIVT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"64.19529837251356%\" valign=\"top\"\u003e\n \u003cp\u003eintravenous thrombolysis\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.80470162748644%\" valign=\"top\"\u003e\n \u003cp\u003eAIS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"64.19529837251356%\" valign=\"top\"\u003e\n \u003cp\u003eacute ischemic stroke\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.80470162748644%\" valign=\"top\"\u003e\n \u003cp\u003eSIRI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"64.19529837251356%\" valign=\"top\"\u003e\n \u003cp\u003esystemic inflammatory response index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.80470162748644%\" valign=\"top\"\u003e\n \u003cp\u003eGPR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"64.19529837251356%\" valign=\"top\"\u003e\n \u003cp\u003eblood glucose/potassium ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.80470162748644%\" valign=\"top\"\u003e\n \u003cp\u003ert-PA\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"64.19529837251356%\" valign=\"top\"\u003e\n \u003cp\u003erecombinant tissue plasminogen activator\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.80470162748644%\" valign=\"top\"\u003e\n \u003cp\u003eROC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"64.19529837251356%\" valign=\"top\"\u003e\n \u003cp\u003ereceiver operating characteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.80470162748644%\" valign=\"top\"\u003e\n \u003cp\u003eNIHSS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"64.19529837251356%\" valign=\"top\"\u003e\n \u003cp\u003eNational Institutes of Health Stroke Score\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"35.80470162748644%\" valign=\"top\"\u003e\n \u003cp\u003emRS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"64.19529837251356%\" valign=\"top\"\u003e\n \u003cp\u003emodified Rankin score\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis study was conducted by the ethical standards of the Human Research and Ethics Committee of the First Affiliated Hospital of Wenzhou Medical University and abode by the Declaration of Helsinki's principles. Although we could not gain the patients' informed consent owing to the use of a retrospective research design, we were granted permission to gather data from our stroke registry.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting interests\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eWork was supported by the Public Welfare Science and Technology Plan Project of Wenzhou City (Y20220819,Y2023849)\u003c/p\u003e\n\u003cp\u003eAuthors' contributions\u003c/p\u003e\n\u003cp\u003eJC and YH: Funding acquisition, Project administration, Resources, Methodology, Validation, Formal analysis, Writing – review \u0026amp; editing and supervision. ZW: Visualization, Software, Writing - original draft, Conceptualization, Formal analysis, software and Investigation. HC, NC and JR: Data curation, Investigation. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eWe express our gratitude to all the patients in our study.\u003c/p\u003e\n\u003cp\u003eORCID\u003c/p\u003e\n\u003cp\u003eZhijun Wen’s ORCID record is https://orcid.org/0009-0009-7311-2074.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGlobal regional. national burden of stroke and its risk factors, 1990\u0026ndash;2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol. 2021;20:795\u0026ndash;820.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao Y, Hua X, Ren X, et al. Increasing burden of stroke in China: A systematic review and meta-analysis of prevalence, incidence, mortality, and case fatality. 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Rev Bras Cir Cardiovasc. 2012;27:61\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCrimi G, Somaschini A, Cattaneo M, Angiolillo DJ, Piscione F, Palmerini T, De Servi S. Cigarette smoking reduces platelet reactivity independently of clopidogrel treatment in patients with non-ST elevation acute coronary syndromes. Platelets. 2018;29:309\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGanten D, Lang RE, Lehmann E, Unger T. Brain angiotensin: on the way to becoming a well-studied neuropeptide system. Biochem Pharmacol. 1984;33:3523\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchulze J, Vogelgesang A, Dressel A. Catecholamines, steroids and immune alterations in ischemic stroke and other acute diseases. Aging Dis. 2014;5:327\u0026ndash;39.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"acute ischemic stroke(AIS), systemic inflammatory response index (SIRI), blood glucose/potassium ratio (GPR), intravenous thrombolysis(IVT), 3-month prognosis","lastPublishedDoi":"10.21203/rs.3.rs-4950520/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4950520/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn recent years, an increasing number of studies have focused on the use of readily available inflammatory markers to predict the prognosis of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS). The systemic inflammatory response index combined with blood glucose/potassium ratio (SIRI-GPR) score is a new combination index that can reflect the inflammatory and stress status. However, whether this index can predict the prognosis of patients with AIS underwent IVT has not been reported. The purpose of our study was to investigate the role of the SIRI-GPR(systemic inflammatory response index combined with blood glucose/potassium ratio) score in predicting the prognosis of patients with AIS(acute ischemic stroke) who underwent IVT at 3 months.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe analyzed 247 patients with AIS admitted to the emergency department of the neurology department of the First Affiliated Hospital of Wenzhou Medical University from July 2021 to July 2022. The primary outcome was a 3-month prognosis. Univariate analysis and multivariate logistic regression were used to analyze the possible influencing factors of 3-month poor prognosis in patients with AIS after IVT. Independent factors were included in the construction of the clinical prediction model. We assessed the nomogram models using ROC and calibration curves.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA total of 119 patients with AIS were finally included in the cohort study. Multifactorial logistic regression analysis showed no significant association between SIRI or GPR and 3-month functional prognosis, however, the SIRI-GPR score was found to be an independent predictor of 3-month dysfunction, In addition, it was also investigated whether large artery occlusion (OR = 5.836, 95% CI 1.123 ~ 30.337, P = 0.036) and NIHSS score within 24h after IVT (OR = 1.371, 95% CI 1.167 ~ 1.612, P \u0026lt; 0.001) were the independent influences of poor prognosis at 3 months (P \u0026lt; 0.05). The nomogram prediction model we constructed showed that the SIRI-GPR score was a good predictor of 3-month prognosis for these patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe SIRI-GPR score can predict the 3-month prognosis in stroke patients treated with IVT.\u003c/p\u003e","manuscriptTitle":"3-Month Prognostic Value of the Systemic Inflammatory Response Index Combined with Blood Glucose/ Potassium Ratio Score in Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-15 11:03:49","doi":"10.21203/rs.3.rs-4950520/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1dc66618-932b-42a2-b348-251e7a18923d","owner":[],"postedDate":"October 15th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-10-15T11:03:52+00:00","versionOfRecord":[],"versionCreatedAt":"2024-10-15 11:03:49","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4950520","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4950520","identity":"rs-4950520","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}