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IntroductionPatients with Metabolic Syndrome (MetS) are considered at high-risk for incident stroke. An indicator of visceral adiposity dysfunction, the Chinese Visceral Adiposity Index (CVAI) is used to evaluate the dysfunction of visceral fat. Given the impact of visceral adiposity dysfunction on elevating cardiovascular hazards, this study aimed to examine the association between CVAI and stroke risk in MetS patients.MethodBetween November 2017 and December 2018, a total of 18,974 individuals aged ≥40 underwent standardized in-person clinical interviews in Hunan Province, with 6,732 meeting the criteria for MetS. After the baseline survey was completed, subsequent surveys were conducted biennially. The study was split into two stages performed at baseline and after two years. During the former, receiver-operating characteristic curves were used to assess the accuracy of using baseline CVAI in diagnosing MetS. After two years, we examined the association between CVAI and incident stroke in MetS patients using logistic regression, subgroup analysis, and restricted cubic spline (RCS) analysis.ResultAs evidenced by a higher AUC (AUC:0.741), CVAI demonstrated superior diagnostic performance relative to body mass index (AUC:0.631) and waist circumference (AUC:0.627) in diagnosing MetS. After a 2-year follow-up, 72 MetS patients had a stroke event. There was a robust positive correlation between incident stroke and CVAI in patients with MetS. Each 1 SD increase in CVAI was associated with a 1.52-fold higher risk of stroke after adjustment for confounding factors (aOR=1.52, 95%CI: 1.18-1.95). The RCS demonstrated a reduced risk of stroke for MetS patients when the CVAI was below 110.91. However, no significant correlation was detected between CVAI and stroke in non-MetS patients.ConclusionOur findings recommend CVAI as a superior screening tool for detecting MetS and suggest that reducing CVAI can mitigate the risk of stroke in patients with MetS.

Background and purposeStress hyperglycemia ratio (SHR), which is used to assess stress hyperglycemia, is associated with the functional outcome of ischemic stroke (IS). IS can induce the inflammatory response. Neutrophil counts and neutrophil-to-lymphocyte ratio (NLR) as good and easily available inflammatory biomarkers, the relationship between neutrophil counts and NLR and SHR were poorly explored in IS. We aimed to systemically and comprehensively explore the correlation between various blood inflammation markers (mainly neutrophil counts and NLR) and SHR.MethodsData from 487 patients with acute IS(AIS) in Xiangya Hospital were retrospectively reviewed. High/low SHR groups according to the median of SHR (≤1.02 versus >1.02). Binary logistic regression analysis was used to evaluate the correlation between neutrophil counts and NLR and high SHR group. Subgroup analyses were performed in the TOAST classification and functional prognosis.ResultsThe neutrophil counts and NLR were all clearly associated with SHR levels in different logistic analysis models. In the subgroup analysis of TOAST classification, the higher neutrophil counts and NLR were the independent risk factors for high SHR patients with large-artery atherosclerosis (LAA) (neutrophil: adjusted OR:2.047, 95% CI: 1.355-3.093, P=0.001; NLR: adjusted OR:1.315, 95% CI: 1.129-1.530, P2.ConclusionsThis study found that the neutrophil counts and NLR are positively associated with SHR levels in AIS patients. In addition, the correlation between neutrophil counts and NLR and different SHR levels are diverse according to TOAST classification and functional prognosis.

Background and objectiveThe association between infection and acute ischemic stroke (AIS) with diabetes mellitus (DM) remains unknown. Therefore, this study aimed to explore the effect of infection on AIS with DM.Materials and methodsThe data of patients with AIS and DM were extracted from the Chinese Stroke Center Alliance (CSCA) database from August 2015 to July 2019. The association between infections [pneumonia or urinary tract infection (UTI)] and in-hospital mortality was analyzed. Logistic regression models were used to identify the risk factors for in-hospital mortality of patients with infection.ResultsIn total, 1,77,923 AIS patients with DM were included in the study. The infection rate during hospitalization was 10.5%, and the mortality rate of infected patients was 3.4%. Stroke-associated infection was an independent risk factor for an early poor functional outcome [odds ratio (OR) = 2.26, 95% confidence interval (CI): 1.97–2.34, P < 0.0001] and in-hospital mortality in AIS patients with DM. The in-hospital mortality after infection was associated with age (OR = 1.02, 95% CI: 1.01–1.03, P < 0.0001), male (OR = 1.39, 95% CI: 1.13–1.71, P = 0.0018), reperfusion therapy (OR = 2.00, 95% CI: 1.56–2.56, P < 0.0001), and fasting plasma glucose at admission (OR = 1.05, 95% CI: 1.03–1.08, P < 0.0001). In contrast, antiplatelet drug therapy (OR = 0.63, 95% CI: 0.50–0.78, P < 0.0001) and hospital stay (OR = 0.96, 95% CI: 0.94–0.97, P < 0.0001) were independent protecting factors against in-hospital mortality of patients with infection.ConclusionInfection is an independent risk factor of in-hospital mortality for patients with AIS and DM, and those patients require strengthening nursing management to prevent infection.

The nanocomposites formed by graphene oxide (GO) and carbazate-modified polyvinyl alcohol (PVA-N) were developed to investigate their multiple properties for wide applications. Their physicochemical characterizations confirmed that the in situ reduced GO (rGO) not only decreased the crystallization but also induced the porous structures inside the nanocomposites. Significantly, it revealed that the comprehensive performance of PVA-N2-2%GO consisted of PVA-N2 with the carbazate degree of substitution (DS) of 7% and the weight ratio (wt%) of 2% GO displayed 79% of tensile elongation and tensile strength of 5.96 N/mm2 (MPa) by tensile testing, glass transition temperature (Tg) of 60.8°C and decomposition temperature (Td) of 303.5°C by TGA and DSC, surface contact angle at 89.4 ± 2.1°, and electrical conductivity of 9.95 × 10−11 S/cm. The abovementioned comprehensive performance was enhanced with the increased amount of in situ rGO, contributed by the high DS of the carbazate group in PVA-N and high amount of GO. The rGO by in situ reduction was the main driving force for enhancing the multiple properties inside the nanocomposites.

Background: To discover novel metabolic biomarkers of ischemic stroke (IS), we carried out a two-stage metabolomic profiling of IS patients and healthy controls using untargeted and targeted metabolomic approaches.Methods: We applied untargeted liquid chromatography-mass spectrometry (LC-MS) to detect the plasma metabolomic profiles of 150 acute IS patients and 50 healthy controls. The candidate differential microbiota-derived metabolite phenylacetylglutamine (PAGln) was validated in 751 patients with IS and 200 healthy controls. We evaluated the associations between PAGln levels and the severity and functional outcomes of patients with IS. Clinical mild stroke was defined as the National Institutes of Health Stroke Scale (NIHSS) score 0–5, and moderate-severe stroke as NIHSS score >5. A favorable outcome at 3 months after IS was defined as the modified Rankin Scale (mRS) score 0–2, and unfavorable outcome as mRS score 3–6.Results: In untargeted metabolomic analysis, we detected 120 differential metabolites between patients with IS and healthy controls. Significantly altered metabolic pathways were purine metabolism, TCA cycle, steroid hormone biosynthesis, and pantothenate and CoA biosynthesis. Elevated plasma PAGln levels in IS patients, compared with healthy controls, were observed in untargeted LC-MS analysis and confirmed by targeted quantification (median 2.0 vs. 1.0 μmol/L; p < 0.001). Patients with moderate-severe stroke symptoms and unfavorable short-term outcomes also had higher levels of PAGln both in discovery and validation stage. After adjusting for potential confounders, high PAGln levels were independently associated with IS (OR = 3.183, 95% CI 1.671–6.066 for the middle tertile and OR = 9.362, 95% CI 3.797–23.083 for the highest tertile, compared with the lowest tertile) and the risk of unfavorable short-term outcomes (OR = 2.286, 95% CI 1.188–4.401 for the highest tertile).Conclusions: IS patients had higher plasma levels of PAGln than healthy controls. PAGln might be a potential biomarker for IS and unfavorable functional outcomes in patients with IS.

Background: Bilirubin plays a paradoxical role in the pathological mechanism of stroke. To date, few clinical studies have investigated the effect of serum bilirubin on symptomatic intracranial atherosclerotic stenosis (sICAS). This study aims to evaluate the connection between serum bilirubin and sICAS.Methods: From September 2015 to May 2020, 1,156 sICAS patients without hepatobiliary diseases admitted to our hospital were included. Patients were distributed into none-mild (0–49%), moderate (50–69%) and severe-occlusion sICAS groups (70–100%) by the degree of artery stenosis. Moderate and severe-occlusion sICAS patients were classified into three groups by the number of stenotic arteries (single-, two- and multiple-vessel stenosis). The relationship between serum bilirubin levels and sICAS was analyzed by logistic regression analysis.Results: In univariable analyses, sICAS patients with severe and multiple atherosclerotic stenoses had lower levels of total bilirubin (Tbil), direct bilirubin (Dbil), and indirect bilirubin (Ibil). In multinomial logistic regression analyses, when compared with the highest tertile of bilirubin, lower levels of Tbil, Dbil, and Ibil showed higher risks of severe-occlusion sICAS (95% CI: 2.018–6.075 in tertile 1 for Tbil; 2.380–7.410 in tertile 1 for Dbil; 1.758–5.641 in tertile 1 for Ibil). Moreover, the logistic regression analyses showed that lower levels of Tbil, Dbil, and Ibil were related to multiple (≥3) atherosclerotic stenoses (95% CI: 2.365–5.298 in tertile 1 and 2.312–5.208 in tertile 2 for Tbil; 1.743–3.835 in tertile 1 and 1.416–3.144 in tertile 2 for Dbil; 2.361–5.345 in tertile 1 and 1.604–3.545 in tertile 2 for Ibil) when compared with tertile 3.Conclusions: Our findings suggest that lower bilirubin levels may indicate severe and multiple intracranial atherosclerotic stenoses.

Background: The contribution of metabolic profile to the cerebral collateral circulation in acute ischemic stroke (AIS) has not been fully outlined. In this study, we conducted a metabolomic study to assess the relationship between the metabolic biomarkers and the collateral status of AIS.Methods: A two-stage study was conducted from September 2019 to June 2021 in our hospital. There were 96 subjects including 66 patients with AIS and 30 healthy controls in the discovery stage and 80 subjects including 53 patients with AIS and 27 healthy controls in the validation stage. Collateral circulation was assessed by the Tan score based on computed tomographic angiography (CTA). Liquid chromatography-tandem mass spectrometry was used to identify differential metabolic markers. Then, an ELISA was employed to detect the plasma levels of sphingosine-1-phosphate (S1P).Results:There were 114 differential metabolites between patients with AIS and control groups and 37 differential metabolites between good collateral circulation (GCC) and poor collateral circulation (PCC) groups. The pathway enrichment analysis revealed that arginine biosynthesis was the only statistically significant pathway between AIS and control groups and sphingolipid metabolism was the only statistically significant pathway between GCC and PCC groups. The differential metabolites sphinganine-1-phosphate (SA1P) and S1P belong to the sphingolipid metabolism. In the discovery stage, when the GCC group was compared with the PCC group, the receiver operating characteristic (ROC) analysis showed that plasma SA1P relative levels demonstrated an area under the curve (AUC) of 0.719 (95% CI: 0.582–0.834), and S1P levels demonstrated an AUC of 0.701 (95% CI: 0.567–0.819). In addition, both plasma SA1P and S1P relative levels showed significant negative correlations with the 90-day modified Rankin Scale (mRS) score. In the validation sample, higher plasma S1P levels were independent predictors of GCC (p = 0.014), and plasma S1P levels demonstrated an AUC of 0.738 (95% CI: 0.599–0.849) to differentiate patients with GCC from patients with PCC. In addition, plasma S1P levels also showed significant negative correlations with the 90-day mRS score.Conclusion: We first illustrated the association between plasma metabolic profiles and cerebral collateral circulation in patients with AIS. Plasma S1P levels might be a potential diagnostic biomarker for predicting collateral circulation status in patients with AIS.

Background: Neutrophil-to-lymphocyte ratio (NLR) is an indicator of poor prognosis in acute ischemic stroke (AIS), but associations between NLR with stroke severity and prognosis of intracranial atherosclerotic stenosis (ICAS)-related ischemic events have not been well-elucidated; therefore, we aimed to evaluate whether admission NLR levels correlate with the early stroke severity and short-term functional prognosis in patients with symptomatic intracranial atherosclerotic stenosis (sICAS).Methods: This retrospective study enrolled 899 consecutive patients with AIS attributed to ICAS at Xiangya Hospital stroke center between May 2016 and September 2020. The initial stroke severity was rated by the admission National Institutes of Health Stroke Scale (NIHSS) scores, and the short-term prognosis was evaluated using the 14-day modified Rankin Scale (mRS) scores after stroke onset. A severe stroke was defined as NIHSS >8; an unfavorable functional outcome was defined as mRS scores of 3–6. Admission NLR was determined based on circulating neutrophil and lymphocyte counts.Results: The median admission NLR of all patients was 2.80 [interquartile range (IQR), 2.00–4.00]. In univariate analysis, admission NLR was significantly elevated in patients with severe stroke and poor short-term prognosis. After multivariate adjustment, admission NLR levels were significantly correlated with severe stroke [odds ratio (OR), 1.132; 95% confidence interval (95% CI), 1.038–1.234; P = 0.005] and unfavorable short-term prognosis (OR, 1.102; 95% CI, 1.017–1.195; P = 0.018) in Model 1. In Model 2, the highest NLR tertile (≥3.533) remained an independent predictor of severe stroke (OR, 2.736; 95% CI, 1.590–4.708; P < 0.001) and unfavorable functional outcome (OR, 2.165; 95% CI, 1.416–3.311; P < 0.001) compared with the lowest NLR tertile (

Background: White matter hyperintensity (WMH) burden is associated with a higher risk of ischemic stroke. Phenylacetylglutamine (PAGln) is a gut microbiota-derived metabolite that may induce cardiovascular events by activating platelets and increasing the risk of thrombosis. The relationship between plasma PAGln and WMH burden in patients with ischemic stroke is unknown. This study was designed to investigate the association between plasma PAGln and WMH burden in patients with acute ischemic stroke.Methods: A total of 595 patients with acute ischemic stroke were enrolled in this study within 14 days of symptom onset. The burden of WMH was evaluated using the Fazekas scale based on the fluid-attenuated inversion recovery sequence. The severity of overall WMH was defined as none–mild WMH (total Fazekas score 0–2) or moderate–severe WMH (total Fazekas score 3–6). Based on the severity of periventricular WMH (P-WMH) and deep WMH (D-WMH), patients were categorized into either a none–mild (Fazekas score 0–1) group or a moderate–severe (Fazekas score 2–3) group. Plasma PAGln levels were quantified using liquid chromatography–mass spectrometry.Results: We found that patients with moderate–severe overall WMH showed higher plasma PAGln levels than patients with none–mild overall WMH, and similar results were found in the analyses according to P-WMH and D-WMH. The logistic regression analysis showed that the fourth PAGln quartile was independently associated with moderate–severe overall WMH (adjusted 95% CI 1.134–4.018) and P-WMH (adjusted 95% CI 1.174–4.226).Conclusion: These findings suggest that higher plasma PAGln levels are associated with moderate–severe overall WMH and P-WMH in patients with acute ischemic stroke.

Background: Adipokines have been proven to be associated with atherosclerotic diseases such as ischemic stroke and coronary heart disease. The role of novel adipokines in the development of symptomatic intracranial atherosclerotic stenosis (sICAS) and extracranial atherosclerotic stenosis (sECAS) has not yet been investigated. This study aimed to evaluate the plasma levels of novel adipokines in patients with sICAS and sECAS and their associations with the prognosis of sICAS groups.Methods: A total of 134 patients with acute ischemic stroke attribute to large-artery atherosclerosis (LAA) and 66 age- and sex-matched controls without atherosclerotic stenosis (NCAS) were included in this study. The LAA group was further sub-classified as sICAS (n = 102) and sECAS (n = 32) according to the location of atherosclerosis. Demographics, clinical parameters, angiographical features and plasma levels of novel adipokines (apelin, visfatin, omentin, RBP-4) were assayed and compared among groups.Results: LAA patients had significantly lower levels of omentin [39.92 (30.74–52.61) ng/ml vs. 54.42 (34.73–79.91) ng/ml, P < 0.001] and visfatin [11.32 (7.62–16.44) ng/ml vs. 13.01 (9.46–27.54) ng/ml, P < 0.001] than those in the NCAS group. Multiple logistic regression analysis identified that the lowest tertile of omentin was independently associated with LAA (OR, 3.423; 95% CI, 1.267–9.244, when referenced to the third tertile). Levels of omentin, visfatin and RBP-4 showed no significant difference between sICAS and sECAS groups. However, median concentrations of apelin were lower in sECAS [84.94 (46.88–130.41) ng/mL) than in sICAS [118.64 (93.22–145.08) ng/mL, P = 0.002] and NCAS [114.38 (80.56–162.93) ng/mL, P = 0.004]. Logistic regression analysis showed that the lowermost tertile of apelin was independently associated with sECAS (OR, 5.121; 95% CI, 1.597–16.426) when adjusted for risk factors. As for sICAS patients, spearman coefficient analysis showed no significant correlation between these four adipokines and the severity of sICAS or the number of vessels with intracranial stenoses. Patients with severe stroke had lower levels of apelin (P = 0.005), while the other three adipokines showed no such difference. During follow up, no difference was found between these four novel adipokines and short- and long-term outcome of sICAS.Conclusions: Lower levels of omentin are independent biomarkers of LAA while low apelin plasma levels seem to be risk factors of sECAS.