BACKGROUND AND PURPOSE:Caveolin-1 (Cav-1) is reported to mediate blood-brain barrier integrity after ischaemic stroke. Our purpose was to assess the role of circulating Cav-1 levels in predicting symptomatic intracranial haemorrhage (sICH) amongst ischaemic stroke patients after endovascular thrombectomy (EVT). METHODS:Patients with large-vessel occlusive stroke after EVT from two stroke centres were prospectively included. Serum Cav-1 level was tested after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. RESULTS:Of 325 patients (mean age 68.6 years; 207 men) included, 47 (14.5%) were diagnosed with sICH. Compared with patients without sICH, those with sICH had a lower concentration of Cav-1. After adjusting for potential confounders, multivariate regression analysis demonstrated that the increased Cav-1 level was associated with a lower sICH risk (odds ratio 0.055; 95% confidence interval 0.005-0.669; p = 0.038). Similar results were obtained when Cav-1 levels were analysed as a categorical variable. Using a logistic regression model with restricted cubic splines, a linear and negative association of Cav-1 concentration was found with sICH risk (p = 0.001 for linearity). Furthermore, the performance of the conventional risk factors model in predicting sICH was substantially improved after addition of the Cav-1 levels (integrated discrimination index 2.7%, p = 0.002; net reclassification improvement 39.7%, p = 0.007). CONCLUSIONS:Our data demonstrate that decreased Cav-1 levels are related to sICH after EVT. Incorporation of Cav-1 into clinical decision-making may help to identify patients at a high risk of sICH and warrants further consideration.

Background and purpose: Atherogenic index of plasma (AIP) is a newly identified as marker of lipid metabolism and glucose metabolism, showing significant predictive value in individuals with cardiovascular disease. This study aimed to explore the correlation between AIP and early neurological deterioration (END) in ischemic stroke patients after mechanical thrombectomy (MT). Methods: Patients with anterior circulation large artery occlusive stroke who underwent MT were retrospectively enrolled from 2 stroke center in China. The AIP is a logarithmically transformed ratio of triglycerides to highdensity lipoprotein cholesterol. END was defined as an increase of >= 4 point in National Institutes of Health Stroke Scale within 24 hours after surgery. Multivariable regression analysis and restricted cubic spline was utilized to determine the association of AIP index with risk of END. Results: Of 601 patients (mean age, 70.2 +/- 12.1 years; 62.1 % of male) enrolled, 91 (15.1 %) experienced postoperative END. After adjustment for potential confounders, higher AIP levels were significantly associated with an increased risk of END after MT treatment (Per 1-standard deviation increase; odd ratio, 1.474; 95 % confidence interval, 1.162-1.869, P = 0.001). Similar results were confirmed when the AIP was analyzed as a categorical variable. Restricted cubic spline further demonstrated a linear relationship between AIP and risk of END (P = 0.001 for linearity). Conclusions: The present study found that a higher AIP index were associated with END in acute ischemic stroke patients following MT treatment for emergent large vessel occlusion.

Background: Time elapsed from stroke onset and baseline infarct volume is influential on endovascular thrombectomy (EVT) outcomes. Objectives: This study aimed to explore the utility of early infarct growth rate (EIGR) measured by apparent diffusion coefficient (ADC) in predicting symptomatic intracranial hemorrhage (sICH) of ischemic stroke patients after EVT. Methods: We retrospectively analyzed patients from the prospectively maintained stroke registry admitted between January 2019 and March 2023, presenting with large vessel occlusive stroke in the anterior circulation. EIGR was defined as ischemic core volume on magnetic resonance perfusion imaging (ADC ⩽620 × 10 −6 mm 2 /s) divided by the time from stroke onset to imaging. sICH was diagnosed according to the Heidelberg Bleeding Classification within 72 h after the procedure. Results: A total of 315 patients met the inclusion criteria. We observed sICH in 36 (11.4%) patients. After adjusting for the potential confounders, increased EIGR was confirmed to be independently associated with a higher risk of sICH (adjusted odds ratio, 1.033; 95% confidence interval (CI), 1.018–1.048; p = 0.001). Similar results were also confirmed when EIGR was analyzed as a categorical variable. Using a logistic regression model with restricted cubic splines, we found a linear correlation between EIGR and sICH risk ( p = 0.001 for linearity). Furthermore, adding EIGR to a model containing conventional risk factors significantly improved risk reclassification for sICH (category-free net reclassification index, 0.393; 95% CI, 0.227–0.560; p = 0.001; integrated discrimination improvement, 0.245; 95% CI, 0.146–0.343; p = 0.001). Conclusion: Increased EIGR may predict the sICH in ischemic stroke patients who receiving EVT.

Background and purposeThe baseline glucose-to-potassium ratio (GPR) is associated with poor outcomes in patients with acute brain injury and intracranial hemorrhage. However, the impact of serum GPR on clinical outcomes after endovascular thrombectomy (EVT) is unclear. This study aimed to evaluate the association between the GPR at admission and functional outcomes at 90 days after EVT.MethodsWe retrospectively reviewed our database for patients with acute ischemic stroke involving an anterior circulation large-vessel occlusion who received EVT between October 2019 and December 2021. The baseline serum GPR was measured after admission. The primary outcome was a 90-day poor outcome, which was defined as a modified Rankin scale score of 3–6.ResultsA total of 273 patients (mean age, 70.9 ± 11.9 years; 161 men) were finally included for analyses. During the 90-day follow-up, 151 patients (55.3%) experienced an unfavorable outcome. After adjusting for demographic characteristics and other potential confounders, the increased GPR was significantly associated with a higher risk of a 90-day poor outcome (odds ratio, 1.852; 95% confidence interval, 1.276–2.688, p = 0.001). Similar results were observed when the GPR was analyzed as a categorical variable. In addition, the restricted cubic spline observed a positive and linear association between the GPR and poor outcomes at 90 days (p = 0.329 for linearity; p = 0.001 for linearity).ConclusionOur study found that ischemic stroke patients with the higher GPR at admission were more likely to have an unfavorable prognosis at 3 months, suggesting that GPR may be a potential prognostic biomarker for ischemic stroke after EVT.

Background:Liver fibrosis has been reported to be associated with hematoma expansion and mortality in patients with intracerebral hemorrhage. This study aimed to detect the association between liver fibrosis and symptomatic intracranial hemorrhage (sICH) in ischemic stroke after mechanical thrombectomy (MT).Methods:We retrospectively included patients with large artery occlusion in the anterior circulation and treated with MT at a single stroke center. The fibrosis-4 index (FIB-4) was used to assess the severity of liver fibrosis. sICH was diagnosed according to the Heidelberg Bleeding Classification criteria. Multivariate logistic regression and restricted cubic spline analysis were conducted to examine the relationship between liver fibrosis and sICH.Results:Among the 578 patients (mean age, 70.1 years; 58.5% male) included in the study, 65 (11.2%) individuals were diagnosed with sICH. After adjusting for demographic characteristics and other potential confounders, a higher FIB-4 index was found to be independently associated with an increased risk of sICH (odds ratio: 1.306, 95% confidence interval: 1.127-1.512, P=0.001). Similar results were obtained when analyzing FIB-4 as a categorical variable.Conclusion:This study demonstrated that there is a significant association between FIB-4 and the risk of sICH in patients with acute ischemic stroke who underwent MT. Therefore, liver fibrosis could serve as a valuable parameter in monitoring the risk of sICH following MT.

Triggering receptor expressed on myeloid cells-like 2 (TREML2) is a newly identified susceptibility gene for Alzheimer’s disease (AD). It encodes a microglial inflammation-associated receptor. To date, the potential role of microglial TREML2 in neuroinflammation in the context of AD remains unclear. In this study, APP/PS1 mice were used to investigate the dynamic changes of TREML2 levels in brain during AD progression. In addition, lipopolysaccharide (LPS) stimulation of primary microglia as well as a lentivirus-mediated TREML2 overexpression and knockdown were employed to explore the role of TREML2 in neuroinflammation in the context of AD. Our results show that TREML2 levels gradually increased in the brains of APP/PS1 mice during disease progression. LPS stimulation of primary microglia led to the release of inflammatory cytokines including interleukin-1β, interleukin-6, and tumor necrosis factor-α in the culture medium. The LPS-induced microglial release of inflammatory cytokines was enhanced by TREML2 overexpression and was attenuated by TREML2 knockdown. LPS increased the levels of microglial M1-type polarization marker inducible nitric oxide synthase. This effect was enhanced by TREML2 overexpression and ameliorated by TREML2 knockdown. Furthermore, the levels of microglial M2-type polarization markers CD206 and ARG1 in the primary microglia were reduced by TREML2 overexpression and elevated by TREML2 knockdown. LPS stimulation increased the levels of NLRP3 in primary microglia. The LPS-induced increase in NLRP3 was further elevated by TREML2 overexpression and alleviated by TREML2 knockdown. In summary, this study provides the first evidence that TREML2 modulates inflammation by regulating microglial polarization and NLRP3 inflammasome activation. These findings reveal the mechanisms by which TREML2 regulates microglial inflammation and suggest that TREML2 inhibition may represent a novel therapeutic strategy for AD.

Background: Effects of YKL-40 on one-year clinical outcomes including poor clinical outcome, all-cause mortality, and stroke recurrence among acute ischemic stroke (AIS) patients remained elusive. The purpose of this study was to explore the association between serum YKL-40 at admission and one-year clinical outcomes in AIS patients.Methods: In this prospective cohort study, a total of 1002 participants out of 1361 AIS patients from two centers were included for current analysis. Serum YKL-40 concentrations were measured via enzyme-linked immunosorbent assay. Multivariable logistic or Cox regression were performed to explore the independent association of YKL-40 with one-year clinical outcomes, including poor outcome (modified Rankin Scale of 3-6), all-cause mortality, and recurrent stroke. C-statistic, net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the discriminatory and predictive power of YKL-40 when added to conventional model.Results: Compared with the first quartile of YKL-40, the adjusted odds ratios or hazard ratios with 95% confidence intervals of the fourth quartile were 3.032 (1.627-5.650) for poor outcome, 2.886 (1.320-6.308) for all-cause mortality and 1.694 (0.906-3.169) for recurrent stroke. The addition of serum YKL-40 to conventional model significantly improved reclassification for poor outcome (NRI 0.053, P = 0.031; IDI 0.018, P = 0.001) and all-cause mortality (NRI 0.162, P = 0.036).Conclusions: Elevated serum YKL-40 at admission might be independently associated with one-year poor outcome and all-cause mortality but not stroke recurrence among Chinese AIS patients.

Purpose:Neuron-specific enolase (NSE) is considered a biomarker for the severity of nervous system diseases. We sought to explore whether serum NSE concentration in ischemic stroke patients undergoing mechanical thrombectomy (MT) is related to 3-month functional outcome and symptomatic intracranial hemorrhage (sICH).Patients and Methods:We retrospectively collected the data of acute ischemic stroke patients with anterior circulation infarction receiving MT within 6 h in our stroke center. Favorable outcome and poor outcome at 3 months were defined as modified Rankin Scale (mRS) score 0-2 and 3-6, respectively. sICH was defined according to the Heidelberg bleeding classification. We used multivariate logistic regression model and receiver operating characteristic curves to investigate the correlation between NSE and clinical outcomes.Results:Among the 426 patients enrolled, 40 (9.4%) patients developed sICH. Three-month favorable outcome in 160 (37.6%) and poor outcome in 266 (62.4%) patients were observed. Serum NSE levels was significantly correlated with 3-month mRS score (R = 0.473, P < 0.001). A cutoff value of 15.29 and 23.12 ng/mL for serum NSE was detected in discriminating 3-month poor outcome (area under the curve, 0.724) and sICH (area under the curve, 0.716), respectively. Multivariate analysis showed that high serum NSE levels were independently associated with 3-month poor outcome (odds ratio [OR] 5.049, 95% confidence interval [CI] 2.933-8.689, P<0.001) and sICH (OR 5.111, 95% CI 2.210-11.820, P < 0.001).Conclusion:Our study demonstrated that high serum NSE levels after receiving MT were independently associated with 3-month poor outcome and sICH in acute ischemic stroke patients. Serum NSE levels could be a good predictor of clinical outcomes for patients receiving MT.

The impact of serum caveolin-1 (Cav-1) on clinical outcomes in patients after mechanical thrombectomy (MT) is unclear. We aimed to investigate the association between serum cav-1 levels and the 3-month functional outcome. We prospectively enrolled and analyzed patients with an anterior circulation large vessel occlusion who underwent MT. Serum cav-1 concentrations were tested after admission. The primary outcome was a 90-day modified Rankin Scale score of 3–6. Of the 237 recruited patients (mean age, 69.7 ± 12.1 years; 152 male), 131 (55.3

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-β and the concentrations of interleukin-1β, 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-β 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.

Introduction: Neutrophil extracellular traps play a role in the pathophysiology of stroke and are associated with severity and mortality. We aimed to investigate whether the citrullinated histone H3 (CitH3), a biomarker for neutrophil extracellular traps formation, is associated with the white matter lesion (WML) burden in ischemic stroke patients. Methods: Between September 2021 and April 2022, 322 patients were enrolled in this prospective observational cohort study. Serum CitH3 levels were measured after admission using an enzyme-linked immunosorbent assay. WMLs severity was graded according to the Fazekas scale and conceptually defined as mild (total Fazekas score 0–2) and severe (total Fazekas score 3–6). We used multivariable regression models to determine the relationship between CitH3 concentrations and the severity of WMLs burden. Results: One-hundred and forty-eight (46.0%) patients were diagnosed with severe WMLs burden after admission. Increased CitH3 levels (first quartile vs. fourth quartile of H3Cit, odds ratio, 3.311, 95% confidence interval, 1.336–8.027; p = 0.011) were independently associated with a greater WML burden in the fully adjusted multivariable model. Similar results were found when the H3Cit was analyzed as a continuous variable. Furthermore, the multiple-adjusted spline regression model showed a linear association between H3Cit levels and severe WMLs (P = 0.001 for linearity). Conclusions: In the present study, increased CitH3 levels were positively associated with extensive WMLs in ischemic stroke patients, indicating a role of neutrophil extracellular traps formation in the pathogenesis of WMLs.

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.

Background and Purpose: Little is known about the effect of soluble adhesion molecules on malignant brain edema (MBE) after endovascular thrombectomy (EVT). This study aimed to explore the association between serum concentrations of E-selectin and the risk of MBE in patients who received EVT. Methods: Patients with a large vessel occlusion stroke in the anterior circulation who underwent EVT were prospectively recruited. Serum soluble E-selectin concentrations were measured after admission for all patients. MBE was defined as a midline shift of ≥5 mm on follow-up imaging within 72 h after surgery. Multivariate logistic regression analyses were performed to determine the association between E-selectin levels and the risk of MBE. Results: Among the 261 included patients (mean age, 69.7 ± 12.3 years; 166 males), 59 (22.6%) developed MBE. Increasing circulating E-selectin levels were associated with an increased risk of MBE after multivariable adjustment (odds ratios [OR], highest vs. lowest quartile: 3.593; 95% confidence interval [CI], 1.178-10.956; p = 0.025). We further observed a significantly positive association between E-selectin and MBE (per 1-standard deviation increase; OR, 1.988; 95% CI, 1.379-2.866, p = 0.001) when the E-selectin levels were analyzed as a continuous variable. Furthermore, the restricted cubic spline demonstrated a linear correlation between serum E-selectin levels and the risk of MBE (p < 0.001 for linearity). Conclusions: In this prospective study, circulating levels of E-selectin were associated with an increased risk of MBE after EVT. Further mechanistic studies are warranted to elucidate the pathophysiology underlying this association.

Doxorubicin induces severe cardiotoxicity, accompanied by the high level of bilirubin in the blood. The conventional wisdom is that bilirubin is considered as a marker of liver damage. By contrast, here we aim to explore the potential protective effect of bilirubin on doxorubicin-induced cardiotoxicity, and investigate the mechanism for drug development. Doxorubicin was used to establish cardiotoxicity model in vitro and in vivo. The electrocardiogram (ECG), echocardiography and molecular biological methods were used to detect the effects of bilirubin on doxorubicin-induced cardiotoxicity. Consecutive intraperitoneal injection of bilirubin for 7 days significantly attenuated doxorubicin-induced arrhythmia, prolonged survival time and reduced the levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) and α-hydroxybutyrate dehydrogenase (α-HBDH) in mice. Bilirubin also markedly inhibited doxorubicin-induced phosphorylation of c-Jun N-terminal kinase (JNK) and connexin 43 (Cx43), and improved gap junction function in vitro and in vivo. In addition, bilirubin activated adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) and induced suppressor of cytokine signaling 3 (SOCS3) expression, which was abolished by Axl inhibition. Moreover, pretreatment with AMPK agonist or AMPK inhibitor could mimic or abolish the cardioprotective effect of bilirubin on H9C2 cells in vitro, respectively. Altogether, bilirubin upregulates gap junctions’ function to protect against doxorubicin-induced cardiotoxicity by activating AMPK-Axl-SOCS3 signaling axis. We enrich the physiological function of bilirubin, and provide theoretical support for drug development.

Background and purposeData on adhesion molecule levels in patients treated with mechanical thrombectomy (MT) are scarce. We aimed to evaluate the association among adhesion molecule levels, symptomatic intracranial hemorrhage (sICH), and clinical outcome and to determine whether the sICH influences the association of adhesion molecules with functional outcome.MethodsPatients with large artery occlusion in the anterior circulation and treated with MT were prospectively recruited. Adhesion molecules, such as soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin) were tested. An unfavorable outcome was defined as a 90-day modified Rankin Scale (mRS) score of 3–6. The sICH was diagnosed according to the Heidelberg Bleeding Classification within 72 h of endovascular treatment (EVT).ResultsOf the 310 enrolled patients (mean age, 68.5 years; 198 men), 46 (14.8%) experienced sICH and 173 (55.8%) experienced an unfavorable outcome at 90 days. After adjusting for potential confounders, patients with higher sVCAM-1 and sE-selectin levels had an increasing trend of sICH [4th quartile vs. 1st quartile for sVCAM-1; odds ratio (OR), 2.766, p = 0.085; sE-selectin; OR, 2.422, p = 0.086] and poor outcome (4th quartile vs. 1st quartile for sVCAM-1; OR, 2.614, p = 0.025; sE-selectin; OR, 2.325, p = 0.046). Furthermore, the sICH might partially mediate the worse functional outcome in patients with higher adhesion molecules levels (Sobel test, p < 0.001 for sVCAM-1 and p = 0.007 for sE-selectin).ConclusionsThere were significant relationships between levels of adhesion molecules and a 90-day poor outcome in patients with ischemic stroke treated with MT, which was partially mediated by sICH.

Abstract YKL-40 mediates vascular inflammation and plays a crucial role in the pathogenesis of acute ischemic stroke (AIS). Previous studies have identified YKL-40 as a potential diagnostic biomarker for AIS. However, in patients with AIS, the effects of YKL-40 on long-term clinical outcomes including poor clinical outcome, all-cause mortality, and stroke recurrence remained elusive.The purpose of this study was to explore the association between serum YKL-40 at admission and one-year clinical outcomes in AIS patients. In this prospective cohort study, a total of 1002 participants out of 1361 AIS patients from two centers were included for current analysis. Serum YKL-40 concentrations were measured via enzyme-linked immunosorbent assay. Multivariable logistic or Cox regression were performed to explore the independent association of YKL-40 with one-year clinical outcomes, including poor outcome (modified Rankin Scale of 3-6), all-cause mortality, and recurrent stroke. C-statistic, net reclassification index (NRI) and integrated discrimination improvement (IDI) were calculated to evaluate the discriminatoryand predictive power of YKL-40 when added to conventional model. Compared with the first quartile of YKL-40, the adjusted odds ratios or hazard ratios (95% CI) of the fourth quartile was 3.032 (1.627-5.650) for poor outcome, 2.886 (1.320-6.308) for all-cause mortality and 1.694 (0.906-3.169) for recurrent stroke. The addition of serum YKL-40 to conventional model significantly improved reclassification for poor outcome (NRI 0.053, P = 0.031; IDI 0.018, P = 0.001) and all-cause mortality (NRI 0.162, P = 0.036). In conclusion, elevated serum YKL-40 at baseline might be independently associated with one-year poor outcome and all-cause mortality but not stroke recurrence among Chinese AIS patients, suggesting that YKL-40 can potentially serve as a valuable prognosticbiomarker for AIS.

Objective: The objective of this study was to investigate the long-term effect of dual antiplatelet therapy (DAPT) using clopidogrel plus aspirin versus aspirin monotherapy after intravenous thrombolysis on functional outcomes in patients with minor stroke. Methods: Patients with acute ischemic stroke with a National Institutes of Health Stroke Scale score ≤ 5 who received either DAPT or aspirin monotherapy following recombinant tissue plasminogen activator intravenous thrombolysis were studied. Data recorded between January 2017 and December 2020 were retrospectively analyzed. The primary efficacy outcome was functional improvement at 1 year, measured by a 1-point decrease across modified Rankin Scale (mRS) scores. Secondary outcomes included complete rehabilitation (mRS = 0), an excellent outcome (mRS = 0–1), and a favorable outcome (mRS = 0–2) at 1 year, as well as the rates of stroke recurrence and all-cause mortality within 1 year. Results: A total of 238 patients were included, and follow-up data were available for 205 patients (86.1%). The distribution of 1-year outcomes on the mRS favored DAPT over aspirin monotherapy (adjusted common odds ratio (OR), 2.19; 95% confidence interval (CI), 1.12–4.28; p = 0.022). Patients who received DAPT, compared with those receiving aspirin alone, were more likely to achieve complete rehabilitation (adjusted OR, 2.44; 95% CI, 1.21–4.95; p = 0.013) at the 1-year follow-up. Additionally, the percentages of an excellent outcome and a favorable outcome did not differ, and the rates of stroke recurrence and all-cause mortality were comparable during the 1-year follow-up. Conclusions: Clopidogrel with aspirin following intravenous thrombolysis was associated with improved functional outcome at the 1-year follow-up for patients with minor stroke, and it did not increase the stroke recurrence rate and mortality.

Objective: This study aimed to investigate the association between high-mobility-group box 1 (HMGB1) and stroke-associated pneumonia (SAP) in acute ischemic stroke (AIS) patients. Methods: AIS patients were enrolled in two centers. The serum samples were collected within the first 24 h after admission, and HMGB1 levels were measured by enzyme-linked immunosorbent assay. Logistic regression models were used to calculate the odds ratio (OR) and 95% confidence interval (95% CI) of SAP for HMGB1 concentrations. Restricted cubic splines (RCS) were performed to explore the shapes of the association between HMGB1 concentrations and SAP. Results: From January 2022 to May 2022, a total of 420 AIS patients were enrolled. Ninety-six (22.9%) patients develop SAP. The levels of HMGB1 in the SAP group were higher than those in the non-SAP group (p < 0.001). Using the first quartile of HMGB1 group as a reference, patients in the fourth quartile of HMGB1 group had the highest likelihood of experiencing SAP in the unadjusted model (OR = 3.687; 95% CI: 1.851–7.344), age- and sex-adjusted model (OR = 3.511; 95% CI: 1.725–7.147), and multivariable-adjusted model (OR = 2.701; 95% CI: 1.045–6.981). HMGB1 was also independently associated with SAP as a continuous variable in the unadjusted model (OR = 1.132; 95% CI: 1.069–1.199), age- and sex-adjusted model (OR = 1.131; 95% CI: 1.066–1.200), and multivariable-adjusted model (OR = 1.096; 95% CI: 1.011–1.188). RCS showed a linear association between HMGB1 and SAP (p for linear trend = 0.008) Conclusions: HMGB1 might be able to act as a potential biomarker of SAP in AIS patients.

目的 探讨以脑梗死为首发表现的Trousseau's综合征患者的临床特点、诊疗及预后.方法 回溯南京医科大学附属南京医院(我院)2019年1月至2020年12月收治12例以脑梗死为首发表现的Trousseau's综合征患者的相关临床特点,详述1例以脑梗死为首发表现的典型Trousseau's综合征患者治疗过程,并复习相关文献进行讨论.结果 12例患者中有8例病理确诊为腺癌,D-二聚体平均值为(12.53±12.00)mg·L-1,梗死灶均累及多个血管供血区域,Trousseau's综合征评分均≥3分.典型病例为女性,71岁,因"左侧肢体乏力10 h"入院.入院后实验室检查:血小板降低,D-二聚体升高;头颅MRI示多灶性脑梗死;FDG-PET/CT示胰腺恶性肿瘤.诊断考虑以脑梗死为首发表现的Trousseau's综合征.予低分子肝素治疗后症状渐好转.结论 以脑梗死为首发表现的Trousseau's综合征治疗不同于常规脑梗死,预后极差.对于Trousseau's综合征评分≥3分者应考虑Trousseau's综合征相关脑梗死可能,以免延误原发病的诊治.

Background: Chronic cerebral hypoperfusion (CCH) is a contributing factor for neurodegenerative diseases. As a recently identified heptapeptide of the brain renin-angiotensin system, angiotensin-(1-7) has been revealed to activate its receptor MAS1 and thus ameliorated cognitive impairments in rats with CCH. Since hippocampal synaptic degeneration represents an important pathological basis of cognitive deficits, we hypothesize that activating MAS1-mediated signaling may alleviate CCH-induced synaptic degeneration in the hippocampus. Methods: In this study, we tested this hypothesis and uncovered the underlying mechanisms in a rat model of CCH induced by bilateral common carotid artery ligation surgery. At one week after the surgery, rats received a daily intraperitoneal vehicle injection or a non-peptidic MAS1 agonist AVE0991 for 8 weeks. During this procedure, Cerebral Blood Flow (CBF) was recorded. The levels of MAS1, amyloid-β (Aβ), neuroinflammatory cytokines, glial cell markers, and synaptophysin in the hippocampus were assessed at the end of the treatment period. Results : We showed that AVE0991 significantly alleviated hippocampal synaptic degeneration in rats with CCH. This protection might be achieved by facilitating CBF recovery, reducing hippocampal Aβ levels, and suppressing neuroinflammatory responses. Conclusions: These findings indicate that MAS1-mediated signaling may represent a novel therapeutic target for CCH-related neurodegenerative diseases.