Facilitation of Fenton-Like Reaction of Copper-Nitrogen-Doped Carbon-Based Nanocatalysts by Enhancing Hydroxyl Adsorption on Single-Atom Cu-NxC4- x Sites.

Copper-nitrogen-doped carbon-based nanocatalysts (Cu-NCs), containing atomically dispersed Cu-NxC4- x sites, are efficient in boosting the Fenton-like reaction. However, the mechanisms of the Fenton-like reaction, including the pH effect on the products and the effect of the coordination environment on catalytic activity, remain controversial, restricting the development of Cu-NCs. Cu-NCs are experimentally synthesized with Cu-N4 sites and prove that the Fenton-like reaction generates mainly hydroxyl radicals (·OH) in the acidic but ·OH and superoxide radicals (·O2 -) in the neutral. The density functional theory (DFT) calculations reveal that the catalytic activity of Cu-NCs in the Fenton-like reaction is associated with the adsorption strength of ·OH at the Cu site. Further investigation of the effect of the coordination environment of Cu-NCs indicates that the Cu-N2C2 site, which can enhance the ·OH adsorption strength, is an ideal catalyst site for the Fenton-like reaction. These results open the way to facilitating the catalytic activity of Cu-NCs in the Fenton-like reaction.

Endothelial Dysfunction and Parenchymal Hematoma in Ischemic Stroke Patients after Endovascular Thrombectomy.

INTRODUCTION: Endothelial dysfunction (ED) may result in parenchymal injury and therefore worsen the outcomes of ischemic stroke. This study aimed to determine whether ED could predict parenchymal hematoma (PH) in ischemic stroke patients treated with endovascular thrombectomy (EVT). METHODS: Patients with large artery occlusion in the anterior circulation and treated with EVT were prospectively enrolled from 2 stroke centers. Serum soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-selectin, and von Willebrand factor (vWF) were tested and summed to a standardized score to reflect the levels of ED. PH was diagnosed according to the Heidelberg Bleeding Classification. RESULTS: Of the 325 enrolled patients (mean age, 68.6 years; 207 men), 41 (12.6%) developed PH. Patients with PH had higher concentrations of soluble E-selectin, vWF, and ED sum score. After adjusting for demographic characteristics, National Institutes of Health Stroke Scale score, pretreatment Alberta stroke program early computed tomography score, and other potential confounders, the increased ED burden was associated with PH (odds ratio, 1.432; 95% confidence interval, 1.031-1.988; p = 0.032). Similar significant results were found in the sensitivity analysis. The multiple-adjusted spline regression model showed a linear association between the total ED score and PH (p = 0.001 for linearity). Adding the ED score to the conventional model significantly improved the risk prediction of PH (net reclassification improvement = 25.2%, p = 0.001; integrated discrimination index = 2.9%; p = 0.001). CONCLUSIONS: This study demonstrated that ED might be related to PH. Introducing the ED score could increase the reliability of the PH risk model for stroke patients treated with EVT.

Unraveling the Structure Transition and Peroxidase Mimic Activity of Copper Sites over Atomically Dispersed Copper-Doped Carbonized Polymer Dots.

The lack of systematic structural resolution makes it difficult to build specific transition-metal-atom-doped carbonized polymer dots (TMA-doped CPDs). Herein, the structure-activity relationship between Cu atoms and CPDs was evaluated by studying the peroxidase-like properties of Glu-Cu-CPDs prepared by using copper glutamate (Glu) with a Cu-N2 O2 initial structure. The results showed that the Cu atoms bound to Glu-Cu-CPDs in the form of Cu-N2 C2 , indicating that Cu-O bonds changed into Cu-C bonds under hydrothermal conditions. This phenomenon was also observed in other copper-doped CPDs. Moreover, the carboxyl and amino groups content decreased after copper-atom doping. Theoretical calculations revealed a dual-site catalytic mechanism for catalyzing H2 O2 . The detection of intracellular H2 O2 suggested their application prospects. Our study provides an in-depth understanding of the formation and catalytic mechanism of TMA-doped-CPDs, allowing for the generation specific TMA-doped-CPDs.

SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression.

BACKGROUND: Abnormal expression of long noncoding RNAs (lncRNAs) has been reported in the acute stage of acute ischemic stroke (AIS). This study aimed to explore differential lncRNA expression in the subpopulations of peripheral blood mononuclear cells (PBMCs) from AIS patients and further evaluate its underlying mechanisms in stroke-induced immunosuppression. METHODS: We reanalyzed lncRNA microarray data and investigated abnormally expressed lncRNAs in the subpopulations of PBMCs by magnetic cell sorting and real-time quantitative PCR. The potential mechanism of small nucleolar RNA host gene 15 (SNHG15) was explored through in vitro and in vivo approaches. RESULTS: The stroke-induced SNHG15 acted as a checkpoint to inhibit peripheral inflammatory responses. Functional studies showed that SNHG15 promoted M2 macrophage polarization. Mechanistically, SNHG15 expression was dysregulated through the Janus kinase (JAK)-signal transducer and activator of transcription 6 (STAT6) signaling pathway. SNHG15, localized in the cytoplasm, interfered with K63-linked ubiquitination of tumor necrosis factor receptor-associated factor 2 and thereby repressed the activation of mitogen-activated protein kinase and nuclear factor kappa-B signaling pathways and prevented the production of proinflammatory cytokines. Administration of an adenovirus targeting SNHG15 improved stroke-induced immunosuppression in mice. CONCLUSIONS: This study identified SNHG15 as a negative regulator of inflammation in stroke-induced immunosuppression, suggesting it as a novel biomarker and therapeutic target in stroke-associated infection. Trial registration ClinicalTrials.gov NCT04175691. Registered November 25, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04175691 .

Cumulative experience improves the procedures of mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomy has been widely performed for large vessel occlusion stroke. The present study aimed to determine whether cumulative experience could improve thrombectomy outcomes. METHODS: In this retrospective single-center analysis, patients who underwent mechanical thrombectomy with the Solitaire stent in 3 years from 25 April 2015 were enrolled in the current study. Patients' characteristics, durations of admission and treatment, recanalization rates, clinical outcomes, and hemorrhage transformation rates were compared among the 3 years. Logistic analysis was used to analyze the independent correlation of the years and procedural outcomes. RESULTS: A total of 222 patients underwent mechanical thrombectomy in the 3 years: 50 in the first year, 68 in the second year, and 104 in the third year. Door-to-puncture time (P < 0.001) and puncture-to-recanalization time (P = 0.033) decreased significantly among the 3 years, while successful recanalization rates increased (P = 0.001). Logistic regression analysis showed an independent increase in the successful recanalization rates in the second year and third year (P = 0.020, P = 0.001) as compared to that in the first year. CONCLUSIONS: Cumulative experience might improve the procedures of mechanical thrombectomy. The current findings suggested a potential benefit for centralization in the treatment of large vessel occlusion stroke.

Theoretical Study on the Aggregation and Adsorption Behaviors of Anticancer Drug Molecules on Graphene/Graphene Oxide Surface.

Graphene and its derivatives are frequently used in cancer therapy, and there has been widespread interest in improving the therapeutic efficiency of targeted drugs. In this paper, the geometrical structure and electronic effects of anastrozole(Anas), camptothecin(CPT), gefitinib (Gefi), and resveratrol (Res) on graphene and graphene oxide(GO) were investigated by density functional theory (DFT) calculations and molecular dynamics (MD) simulation. Meanwhile, we explored and compared the adsorption process between graphene/GO and four drug molecules, as well as the adsorption sites between carriers and payloads. In addition, we calculated the interaction forces between four drug molecules and graphene. We believe that this work will contribute to deepening the understanding of the loading behaviors of anticancer drugs onto nanomaterials and their interaction.

The association of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, and lymphocyte to monocyte ratio with post-thrombolysis early neurological outcomes in patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: To investigate the association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) with post-thrombolysis early neurological outcomes including early neurological improvement (ENI) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS). METHODS: AIS patients undergoing intravenous thrombolysis were enrolled from April 2016 to September 2019. Blood cell counts were sampled before thrombolysis. Post-thrombolysis END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase of ≥ 4 within 24 h after thrombolysis. Post-thrombolysis ENI was defined as NIHSS score decrease of ≥ 4 or complete recovery within 24 h. Multinomial logistic regression analysis was performed to explore the relationship of NLR, PLR, and LMR to post-thrombolysis END and ENI. We also used receiver operating characteristic curve analysis to assess the discriminative ability of three ratios in predicting END and ENI. RESULTS: Among 1060 recruited patients, a total of 193 (18.2%) were diagnosed with END and 398 (37.5%) were diagnosed with ENI. Multinomial logistic model indicated that NLR (odds ratio [OR], 1.385; 95% confidence interval [CI] 1.238-1.551, P = 0.001), PLR (OR, 1.013; 95% CI 1.009-1.016, P = 0.001), and LMR (OR, 0.680; 95% CI 0.560-0.825, P = 0.001) were independent factors for post-thrombolysis END. Moreover, NLR (OR, 0.713; 95% CI 0.643-0.791, P = 0.001) served as an independent factor for post-thrombolysis ENI. Area under curve (AUC) of NLR, PLR, and LMR to discriminate END were 0.763, 0.703, and 0.551, respectively. AUC of NLR, PLR, and LMR to discriminate ENI were 0.695, 0.530, and 0.547, respectively. CONCLUSIONS: NLR, PLR, and LMR were associated with post-thrombolysis END. NLR and PLR may predict post-thrombolysis END. NLR was related to post-thrombolysis ENI.

Admission blood cell counts are predictive of stroke-associated infection in acute ischemic stroke patients treated with endovascular therapy.

Stroke-associated infection (SAI) is a major medical complication in acute ischemic stroke patients (AIS) treated with endovascular therapy (EVT). Three hundred thirty-three consecutive patients with AIS caused by a large vessel occlusion in the anterior circulation who received EVT (142 (42.6%) of them were given IV tPA as bridging therapy) and 337 AIS patients who received IV tPA only (non-EVT) were enrolled in the study and evaluated to determine the association of inflammatory factors on admission with SAI. Among the 333 AIS patients undergoing EVT, SAI occurred in 219 (65.8%) patients. Patients with SAI had higher baseline National Institutes of Health Stroke Scale (NIHSS) total scores, white blood cell (WBC) and neutrophil counts, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) than those without SAI (P < 0.05). The multivariable logistic regression analyses showed that older age in addition to higher diastolic blood pressure (DBP), NIHSS score, fasting blood glucose, WBC and neutrophil counts, NLR, and PLR were significantly associated with SAI (P < 0.05). However, these associations were not revealed in 337 non-EVT AIS patients. Furthermore, based on the inflammatory markers, we developed a nomogram that provided the opportunity for more accurate predictions (compared with conventional factors) and appeared a better prognostic tool for SAI according to the decision curve analysis. In summary, if proven externally valid, our nomogram that included WBC count, NLR, and PLR may be a useful tool for SAI prediction in clinical practice.

Symptomatic Intracranial Hemorrhage After Mechanical Thrombectomy in Chinese Ischemic Stroke Patients: The ASIAN Score.

BACKGROUND AND PURPOSE: Symptomatic intracranial hemorrhage (sICH), potentially associated with poor prognosis, is a major complication of endovascular thrombectomy (EVT) for ischemic stroke patients. We aimed to develop and validate a risk model for predicting sICH after EVT in Chinese patients due to large-artery occlusions in the anterior circulation. METHODS: The derivation cohort recruited patients with EVT from the Endovascular Treatment for Acute Anterior Circulation Ischemic Stroke Registry in China. sICH was diagnosed according to the Heidelberg Bleeding Classification within 24 hours of EVT. Stepwise logistic regression was performed to derive the predictive model. The discrimination and calibration of the risk model were assessed using the C index and the calibration plot. An additional cohort of 503 patients from 2 stroke centers was prospectively enrolled to validate the new model. RESULTS: We enrolled 629 patients who underwent EVT as the derivation cohort, among whom 87 developed sICH (13.8%). In the multivariate adjustment, Alberta Stroke Program Early CT Score (odds ratio [OR], 0.85; P=0.005), baseline glucose (OR, 1.13; P=0.001), poor collateral circulation (OR, 3.06; P=0.001), passes with retriever (OR, 1.52; P=0.001), and onset-to-groin puncture time (OR, 1.79; P=0.024) were independent factors of sICH and were incorporated as the Alberta Stroke Program Early CT Score, Baseline Glucose, Poor Collateral Circulation, Passes With Retriever, and Onset-to-Groin Puncture Time (ASIAN) score. The ASIAN score demonstrated good discrimination in the derivation cohort (C index, 0.771 [95% CI, 0.716-0.826]), as well as the validation cohort (C index, 0.758 [95% CI, 0.691-0.825]). CONCLUSIONS: The ASIAN score reliably predicts the risk of sICH in Chinese ischemic stroke patients treated by EVT.

Intravenous thrombolysis for ischemic stroke with hyperdense middle cerebral artery sign: A meta-analysis.

Hyperdense middle cerebral artery sign (HMCAS) on admitting to neuroimaging is reported to have prognostic value for poor outcomes after thrombolysis, while evidence from studies comprising a sufficiently large sample size is limited. To detect prognostic predictors after thrombolysis could help improve therapeutic clinical strategies for acute ischemic stroke. We included prospective and retrospective studies of stroke patients that were treated with intravenous thrombolysis, in which functional outcomes (ie, a modified Rankin scale [mRS]) and systematic intracranial hemorrhage (sICH) were assessed in relation to HMCAS during pretreatment head CT. Random-effects models were used to calculate pooled risk ratios (RR) of poor outcomes and sICH for HMCAS patients as compared to patients without HMCAS. Eleven studies permitted identification of 11 818 patients. The risk of poor outcome at 3 months in the HMCAS-positive group was 1.56-fold the negative group (RR, 1.56; 95% CI 1.50-1.62; P < .001). The sICH risk when comparing both groups was found to be non-significant. Sensitivity analysis regarding studies performing thrombolysis within 3 hours also exhibited significant differences in their functional outcomes (RR, 1.56, 95% CI 1.49-1.62; P < .001) in patients with HMCAS as compared to non-HMCAS patients, although this was true for sICH risk. The presence of HMCAS on pretreatment CT predicts a poor outcome at 3 months after intravenous thrombolysis, while its relationship with the incidence of sICH was found to have no statistic value. Our study implies that more aggressive treatment should be considered for HMCAS patients.

Association between obstructive sleep apnea and risk of post-stroke depression: A hospital-based study in ischemic stroke patients.

BACKGROUND AND AIMS: Obstructive sleep apnea (OAS) is a common contributor as well as a frequent co-morbid condition in ischemic stroke. This study aimed to detect the correlation between OSA severity and post-stroke depression (PSD) in ischemic stroke patients. METHODS: From Mar 2017 to Dec 2018, 265 patients with symptom onset less than 14 days were consecutively recruited. All patients underwent polysomnography examination for diagnosis of OSA during hospitalization. PSD was identified using the Chinese version of the Structured Clinical Interview for DSM-IV at admission and 3-month. Logistic regression analyses were performed to assess the association between OSA severity and PSD. RESULTS: Among the 265 patients, the distribution of patients in terms of the OSA severity was as follows: 48 (18.1%) had no OSA, 85 (32.1%) had mild OSA, 54 (20.4%) had moderate OSA, and 78 (29.4%) had severe OSA. Patients diagnosed as PSD at admission and 3-month were 63 (23.8%) and 86 (32.5%), respectively. Univariate analysis showed that reduced OSA severity was correlated with PSD at 3-month (P = 0.003), but not at admission (P = 0.373). In multivariable analysis, after adjustment for covariates, severe OSA (compared with the patients without OSA; odds ratio, 4.04; 95% confidence interval, 1.38-9.62; P = 0.036) was significantly associated with increasing risk of 3-month PSD. Furthermore, multiple-adjusted spline regression model further confirmed a dose-response relationship between apnea-hypopnea index and 3-month PSD (P for linearity < 0.001). CONCLUSIONS: Our data showed that OSA severity was positively associated with 3-month PSD in ischemic stroke patients.

The association between high-sensitivity C-reactive protein at admission and progressive motor deficits in patients with penetrating artery infarctions.

BACKGROUND: A fraction of patients with penetrating artery infarction (PAI) experience progressive motor deficit deterioration (PMD). We sought to investigate the role of high-sensitivity C-reactive protein (hs-CRP) at admission in predicting PMD. METHODS: From January 2015 to September 2018, consecutive patients with PAI from three centers were prospectively enrolled in this study. PMD was defined as worsening of motor function score by ≥1 point on the National Institutes of Health Stroke Scale during the first 5 days after admission. Multivariable logistic regression analyses were performed to explore the relationship between hs-CRP and PMD in patients with PAI. We also performed receiver operating characteristic curve analysis and constructed a nomogram to assess the overall discriminative ability of hs-CRP in predicting PMD. RESULTS: We ultimately included 544 patients (mean age, 65.4 ± 11.8 years). A total of 85 (15.6%) patients were identified to have PMD. Multivariate logistic regression analysis showed that hs-CRP was independently associated with PMD (P = 0.001). The optimal cutoff value for hs-CRP as a predictor for PMD was 3.48 mg/L, with a sensitivity of 73.64% and a specificity of 82.35% (area under curve, 0.792). Moreover, the nomogram we constructed indicated that higher level of hs-CRP was an indicator of PMD (c-index = 0.780, P < 0.001). CONCLUSIONS: Our study suggested that hs-CRP might be a useful biomarker for predicting the risk of PMD in patients with PAI.

Leukoaraiosis is associated with poor outcomes after successful recanalization for large vessel occlusion stroke.

BACKGROUND: Leukoaraiosis (LA) is related to the dysfunction of the microcirculation and results in the impairment of the perfusion state. We investigated the association of LA and poor outcomes after successful recanalization by thrombectomy. METHODS: We retrospectively analyzed 97 patients with anterior large-artery occlusion who underwent thrombectomy and had successful recanalization (modified Treatment in Cerebral Ischemia Scale score 2b or 3). All patients underwent magnetic resonance imaging (MRI). LA was evaluated using fluid-attenuated inversion recovery MRI and graded using the Fazekas scale. Poor functional outcome at day 90 and symptomatic intracerebral hemorrhage (sICH) were compared between patients with absent to mild LA and moderate to severe LA. Logistic regression analyses were performed to determine the association of LA severity and outcomes. RESULTS: Moderate and severe LA occurred in 28.9% and 26.8% patients respectively. A higher proportion of poor outcomes were observed in patients with moderate to severe LA compared to patients with absent to mild LA (77.8% vs. 39.5%, p < 0.001). Logistic regression analyses showed patients with moderate to severe LA had 3.77 times (95%CI 1.21-11.76, p = 0.022) higher risk of having poor outcomes compared to patients with absent to mild LA. CONCLUSIONS: LA severity may be associated with poor outcomes after successful recanalization for ischemic stroke with anterior large vessel occlusion.

Soluble TREM1 concentrations are increased and positively correlated with total tau levels in the plasma of patients with Alzheimer's disease.

BACKGROUND/AIMS: Recently, we showed that triggering receptor expressed on myeloid cells 1 (TREM1) was involved in the pathogenesis of Alzheimer's disease (AD) since it modulated microglial phagocytic functions and thus affected amyloid-ß clearance in the brain. Interestingly, a soluble form of TREM1 (sTREM1) can be detected in the plasma of human. To date, whether sTREM1 concentrations were altered in the plasma under AD context remained unclear. METHODS: In this study, we compared the plasma concentrations of sTREM1 between 110 AD patients and 128 age- and gender-matched controls. Meanwhile, the relationship of sTREM1 concentrations with total tau levels in the plasma of AD patients was also assessed. RESULTS: We revealed that the concentrations of sTREM1 were significantly increased in AD patients. Meanwhile, the sTREM1 concentrations were gradually increased during disease progression. More importantly, we showed that the sTREM1 concentrations were positively correlated with the levels of total tau in the plasma of AD patients (r = 0.61, P < 0.001). The subsequent subgroup analysis indicated that this correlation was more pronounced in patients with severe dementia (Mini-Mental State Exam score < 10, r = 0.81, P < 0.01). CONCLUSION: These findings indicate a potential association between sTREM1 and tau pathology, and further confirm an involvement of this immune receptor in AD pathogenesis.

Circulating lipocalin-2 as a novel biomarker for early neurological deterioration and unfavorable prognosis after acute ischemic stroke.

INTRODUCTION: Lipocalin-2 (LCN2) is an acute-phase protein that could mediate neuroinflammation after brain injury. We aimed to evaluate if LCN2 level was associated with early neurological deterioration (END) in acute ischemic stroke patients, thus hindering clinical recovery. METHODS: We conducted a prospective study of acute ischemic stroke patients between June 2021 and February 2022. Serum LCN2 concentration was measured after admission using an enzyme-linked immunosorbent assay. Outcomes included END and 90-day poor functional outcome (modified Rankin Scale 3-6). The National Institutes of Health Stroke Scale increment ≥4 points within 72 h after admission was defined as END. RESULTS: A total of 253 acute ischemic stroke patients (mean age, 65.2 ± 13.4 years; 64.0% male) were recruited. In the multivariate adjustment, increased serum LCN2 levels (per 1-SD increase of LCN2) were associated with a higher risk of END (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.20-2.25; p = .002) and 90-day poor outcome (OR, 1.73; 95% CI, 1.22-2.45; p = .002). Restricted cubic splines found a linear relationship between LCN2 level and 90-day unfavorable outcome (END, p = .001 for linearity; 90-day poor outcome, p = .013 for linearity). Subgroup analysis further confirmed the significant association of LCN2 with clinical outcomes. CONCLUSIONS: This study demonstrated that higher circulating LCN2 level was associated with an increased risk of early clinical worsening and 90-day unfavorable outcomes in ischemic stroke patients.

Lamotrigine protects against cognitive deficits, synapse and nerve cell damage, and hallmark neuropathologies in a mouse model of Alzheimer's disease.

Lamotrigine (LTG) is a widely used drug for the treatment of epilepsy. Emerging clinical evidence suggests that LTG may improve cognitive function in patients with Alzheimer's disease. However, the underlying molecular mechanisms remain unclear. In this study, amyloid precursor protein/presenilin 1 (APP/PS1) double transgenic mice were used as a model of Alzheimer's disease. Five-month-old APP/PS1 mice were intragastrically administered 30 mg/kg LTG or vehicle once per day for 3 successive months. The cognitive functions of animals were assessed using Morris water maze. Hyperphosphorylated tau and markers of synapse and glial cells were detected by western blot assay. The cell damage in the brain was investigated using hematoxylin and eosin staining. The levels of amyloid-ß and the concentrations of interleukin-1ß, interleukin-6 and tumor necrosis factor-α in the brain were measured using enzyme-linked immunosorbent assay. Differentially expressed genes in the brain after LTG treatment were analyzed by high-throughput RNA sequencing and real-time polymerase chain reaction. We found that LTG substantially improved spatial cognitive deficits of APP/PS1 mice; alleviated damage to synapses and nerve cells in the brain; and reduced amyloid-ß levels, tau protein hyperphosphorylation, and inflammatory responses. High-throughput RNA sequencing revealed that the beneficial effects of LTG on Alzheimer's disease-related neuropathologies may have been mediated by the regulation of Ptgds, Cd74, Map3k1, Fosb, and Spp1 expression in the brain. These findings revealed potential molecular mechanisms by which LTG treatment improved Alzheimer's disease. Furthermore, these data indicate that LTG may be a promising therapeutic drug for Alzheimer's disease.

A Novel Metabolic Score for Insulin Resistance and Symptomatic Intracranial Hemorrhage in Ischemic Stroke Patients After Endovascular Thrombectomy.

Background and Purpose: Insulin resistance plays a pivotal role in the pathophysiology of ischemic stroke. This study aimed to determine the relationship between the novel metabolic score for insulin resistance (METS-IR) and symptomatic intracranial hemorrhage (sICH) after endovascular thrombectomy (EVT) in stroke patients. Methods: We retrospectively included patients with large artery occlusion in the anterior circulation and treated by EVT from 2 stroke centers (Nanjing First Hospital from September 2019 to April 2022, and Jinling Hospital from September 2019 to July 2021). The METS-IR was used as an alternative marker of insulin resistance and calculated using laboratory data after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. Results: Of the 410 enrolled patients (mean age, 69.8 ± 11.7 years; 60.7% men), 50 (12.2%) were diagnosed as sICH. After adjusting for demographic characteristics, poor collateral status, and other potential confounders, higher METS-IR was revealed to be independently associated with sICH (odds ratio, 1.076; 95% confidence interval, 1.034-1.120; P = 0.001). Similar significant results were obtained when defining METS-IR as a categorical variable. The restricted cubic spline uncovered a linear relationship between METS-IR and sICH (P < 0.001 for linearity). Furthermore, adding METS-IR to the conventional model significantly improved the risk prediction for sICH (net reclassification improvement = 15.8%, P = 0.035; integrated discrimination index = 2.6%; P = 0.017). Conclusion: This study demonstrated a significant association between METS-IR score and sICH in ischemic stroke patients treated with EVT. It could help monitor and manage sICH in patients after EVT.