Macrophage-Derived GSDMD Plays an Essential Role in Atherosclerosis and Cross Talk Between Macrophages via the Mitochondria-STING-IRF3/NF-κB Axis.

BACKGROUND: Macrophages play a crucial role in atherosclerotic plaque formation, and the death of macrophages is a vital factor in determining the fate of atherosclerosis. GSDMD (gasdermin D)-mediated pyroptosis is a programmed cell death, characterized by membrane pore formation and inflammatory factor release. METHODS: ApoE-/- and Gsdmd-/- ApoE-/- mice, bone marrow transplantation, and AAV-F4/80-shGSDMD were used to examine the effect of macrophage-derived GSDMD on atherosclerosis. Single-cell RNA sequencing was used to investigate the changing profile of different cellular components and the cellular localization of GSDMD during atherosclerosis. RESULTS: First, we found that GSDMD is activated in human and mouse atherosclerotic plaques and Gsdmd-/- attenuates the atherosclerotic lesion area in high-fat diet-fed ApoE-/- mice. We performed single-cell RNA sequencing of ApoE-/- and Gsdmd-/- ApoE-/- mouse aortas and showed that GSDMD is principally expressed in atherosclerotic macrophages. Using bone marrow transplantation and AAV-F4/80-shGSDMD, we identified the potential role of macrophage-derived GSDMD in aortic pyroptosis and atherosclerotic injuries in vivo. Mechanistically, GSDMD contributes to mitochondrial perforation and mitochondrial DNA leakage and subsequently activates the STING (stimulator of interferon gene)-IRF3 (interferon regulatory factor 3)/NF-κB (nuclear factor kappa B) axis. Meanwhile, GSDMD regulates the STING pathway activation and macrophage migration via cytokine secretion. Inhibition of GSDMD with GSDMD-specific inhibitor GI-Y1 can effectively alleviate the progression of atherosclerosis. CONCLUSIONS: Our study has provided a novel macrophage-derived GSDMD mechanism in the promotion of atherosclerosis and demonstrated that GSDMD can be a potential therapeutic target for atherosclerosis.

Gratitude practice helps undergraduates who experienced an earthquake in China find meaning in life.

This study was conducted following a magnitude 6.8 earthquake that occurred in early September 2022, coinciding with the commencement of a positive psychology course for the affected students. A sample of 479 Chinese undergraduates was recruited for an intervention focused on weekly gratitude practice. Data were collected through an online questionnaire package at 3 time points: the first week of the course (Time 1), the fifth week (Time 2), and the ninth week (Time 3), assessing gratitude, learning engagement, and the meaning of life. Findings revealed that gratitude significantly predicted meaning in life through learning engagement over time. This highlights the significant mediating role of learning engagement in the context of earthquakes and provides insights for positive interventions aimed at facilitating personal growth among emerging adults in higher educational settings, particularly those who have experienced traumatic events such as earthquakes.

Exploring the link between brain topological resilience and cognitive performance in the context of aging and vascular risk factors: A cross-ethnicity population-based study.

Brain aging is typically associated with a significant decline in cognitive performance. Vascular risk factors (VRF) and subsequent atherosclerosis (AS) play a major role in this process. Brain resilience reflects the brain's ability to withstand external perturbations, but the relationship of brain resilience with cognition during the aging process remains unclear. Here, we investigated how brain topological resilience (BTR) is associated with cognitive performance in the face of aging and vascular risk factors. We used data from two cross-ethnicity community cohorts, PolyvasculaR Evaluation for Cognitive Impairment and Vascular Events (PRECISE, n = 2220) and Sydney Memory and Ageing Study (MAS, n = 246). We conducted an attack simulation on brain structural networks based on k-shell decomposition and node degree centrality. BTR was defined based on changes in the size of the largest subgroup of the network during the simulation process. Subsequently, we explored the negative correlations of BTR with age, VRF, and AS, and its positive correlation with cognitive performance. Furthermore, using structural equation modeling (SEM), we constructed path models to analyze the directional dependencies among these variables, demonstrating that aging, AS, and VRF affect cognition by disrupting BTR. Our results also indicated the specificity of this metric, independent of brain volume. Overall, these findings underscore the supportive role of BTR on cognition during aging and highlight its potential application as an imaging marker for objective assessment of brain cognitive performance.

Prevalence and Associated Factors of Atherosclerotic Plaque and Stenosis in Renal Arteries: A Community-Based Study.

The epidemiology of renal artery atherosclerosis in community populations is poorly documented. This study aimed to determine the prevalence of renal artery plaque (RAP) and atherosclerotic renal artery stenosis (ARAS), and the association of plaque and stenosis with vascular risk factors and kidney disease markers among community-dwelling adults. We conducted a cross-sectional analysis of the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study. RAP and ARAS were evaluated by thoracoabdominal computed tomography angiography. A total of 3045 adults aged 50-75 years were included. The prevalence of RAP and ARAS was 28.7% and 4.8%, respectively. The prevalence of RAP and ARAS was 41.3% and 7.7% in individuals aged ≥60 years, 42.9% and 8.7% in hypertensives, and 45.4% and 8.5% in individuals with chronic kidney disease. Older age, hypertension, higher total cholesterol level, and lower high-density lipoprotein cholesterol level were independently associated with RAP and ARAS. A higher urinary albumin-creatinine ratio was independently associated with RAP, whereas a reduced estimated glomerular filtration rate was independently associated with ARAS. In conclusion, there was a non-negligible prevalence of RAP and ARAS among the older, community population in China.

Disrupted pattern of rich-club organization in structural brain network from prediabetes to diabetes: A population-based study.

The network nature of the brain is gradually becoming a consensus in the neuroscience field. A set of highly connected regions in the brain network called "rich-club" are crucial high efficiency communication hubs in the brain. The abnormal rich-club organization can reflect underlying abnormal brain function and metabolism, which receives increasing attention. Diabetes is one of the risk factors for neurological diseases, and most individuals with prediabetes will develop overt diabetes within their lifetime. However, the gradual impact of hyperglycemia on brain structures, including rich-club organization, remains unclear. We hypothesized that the brain follows a special disrupted pattern of rich-club organization in prediabetes and diabetes. We used cross-sectional baseline data from the population-based PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study, which included 2218 participants with a mean age of 61.3 ± 6.6 years and 54.1% females comprising 1205 prediabetes, 504 diabetes, and 509 normal control subjects. The rich-club organization and network properties of the structural networks derived from diffusion tensor imaging data were investigated using a graph theory approach. Linear mixed models were used to assess associations between rich-club organization disruptions and the subjects' glucose status. Based on the graphical analysis methods, we observed the disrupted pattern of rich-club organization was from peripheral regions mainly located in frontal areas to rich-club regions mainly located in subcortical areas from prediabetes to diabetes. The rich-club organization disruptions were associated with elevated glucose levels. These findings provided more details of the process by which hyperglycemia affects the brain, contributing to a better understanding of the potential neurological consequences. Furthermore, the disrupted pattern observed in rich-club organization may serve as a potential neuroimaging marker for early detection and monitoring of neurological disorders in individuals with prediabetes or diabetes.

Blood Pressure Partially Mediated the Association of Insulin Resistance and Cerebral Small Vessel Disease: A Community-Based Study.

BACKGROUND: Insulin resistance as a significant vascular risk factor has been studied in relation to cerebral small vessel disease (SVD). Evidence suggests that insulin resistance might trigger high blood pressure (BP). Therefore, we aimed to investigate whether insulin resistance impacts SVD with a mediating effect of BP in nondiabetic subjects. METHODS AND RESULTS: PRECISE (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) study participants underwent brain and vascular imaging techniques and metabolomic risk factors measurements. Insulin resistance was evaluated by the insulin sensitivity index and the Homeostatic Model Assessment for Insulin Resistance based on the standard oral glucose tolerance test. On average, 2752 nondiabetic subjects (47.1% men) aged 60.9 years were included. The multivariable logistic regression model and linear regression model tested the association of insulin resistance with BP components (including systolic BP [SBP], diastolic BP (DBP), and pulse pressure [PP]) and SVD, and of BP components with SVD. In the mediation analysis, SBP, DBP, and PP were found to partially mediate the detrimental effect of insulin resistance (assessed by the insulin sensitivity index) on lacunes (mediation percentage: SBP, 31.15%; DBP, 34.21%; PP, 10.43%), white matter hyperintensity (mediation percentage: SBP, 37.34%; DBP, 44.15%; PP, 9.80%), and SVD total burden (mediation percentage: SBP, 42.07%; DBP, 49.29%; PP, 11.71%) (all P<0.05). The mediation analysis results were not significant when using the Homeostatic Model Assessment for Insulin Resistance to assess insulin resistance. CONCLUSIONS: Higher insulin resistance was associated with SVD in this community-dwelling population. The association of insulin resistance with lacunes, white matter hyperintensity, and SVD total burden was explained in part by BP. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03178448.

Macrophage-derived GSDMD promotes abdominal aortic aneurysm and aortic smooth muscle cells pyroptosis.

Macrophage is a vital factor in determining the fate of abdominal aortic aneurysm (AAA). The crosstalk between macrophage and other cells plays a crucial role in the development of aneurysm. Gasdermin D (GSDMD) is a vital executive protein of pyroptosis, which is a novel programmed cell death associated with inflammation. In this study, we identified aortic macrophage as the main expressing cell of GSDMD in AAA. Using Gsdmd-/-ApoE-/- mouse and AAV-F4/80-shGSDMD, we demonstrated the potential role of macrophage-derived GSDMD in AAA and aortic pyroptosis induced by Ang II in vivo. In vitro experiments showed that GSDMD promotes the pyroptosis of mouse primary peritoneal macrophages (MPMs), murine aortic vascular smooth muscle cells (MOVAS) and primary smooth muscle cells. Mechanistically, a mouse cytokine antibody array showed that Gsdmd-/- inhibited LPS + nigericin (LN)- induced secretion of multiple cytokines from MPMs. Furthermore, GSDMD is involved in the crosstalk between MPMs and MOVAS via cytokine secretion. This study provides a novel fundamental insight into macrophage-derived GSDMD in AAA and showed that GSDMD could be a promising therapeutic target for AAA.

Association of metabolic dysfunction-associated fatty liver disease with systemic atherosclerosis: a community-based cross-sectional study.

BACKGROUND: Data are limited on the association of metabolic dysfunction-associated fatty liver disease (MAFLD) with systemic atherosclerosis. This study aimed to examine the relationship between MAFLD and the extent of atherosclerotic plaques and stenosis, and presence of polyvascular disease (PolyVD). METHODS: In this cross-sectional study, MAFLD was diagnosed based on the presence of metabolic dysfunction (MD) and fatty liver disease (FLD). MAFLD was divided into three subtypes: MAFLD with diabetes mellitus (DM), MAFLD with overweight or obesity (OW), as well as MAFLD with lean/normal weight and at least two metabolic abnormalities. Atherosclerosis was evaluated, with vascular magnetic resonance imaging for intracranial and extracranial arteries, thoracoabdominal computed tomography angiography for coronary, subclavian, aorta, renal, iliofemoral arteries, and ankle-brachial index for peripheral arteries. The extent of plaques and stenosis was defined according to the number of these eight vascular sites affected. PolyVD was defined as the presence of stenosis in at least two vascular sites. RESULTS: This study included 3047 participants, with the mean age of 61.2 ± 6.7 years and 46.6% of male (n = 1420). After adjusting for potential confounders, MAFLD was associated with higher extent of plaques (cOR, 2.14, 95% CI 1.85-2.48) and stenosis (cOR, 1.47, 95% CI 1.26-1.71), and higher odds of presence of PolyVD (OR, 1.55, 95% CI 1.24-1.94) as compared with Non-MAFLD. In addition, DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD (All P < 0.05). However, lean-MAFLD was only associated with the extent of atherosclerotic plaques (cOR, 1.63, 95% CI 1.14-2.34). As one component of MAFLD, FLD per se was associated with the extent of plaques and stenosis in participants with MAFLD. Furthermore, FLD interacted with MD to increase the odds of presence of systemic atherosclerosis (P for interaction ≤ 0.055). CONCLUSIONS: MAFLD and its subtypes of DM-MAFLD and OW-MAFLD were associated with the extent of atherosclerotic plaques and stenosis, and presence of PolyVD. This study implicated that FLD might be a potential target of intervention for reducing the deleterious effects of MAFLD on systemic atherosclerosis.

Association between Life's Essential 8 and Cerebral Small Vessel Disease.

BACKGROUND: Given that associations of Life's Essential 8 (LE8) and cerebral small vessel disease (CSVD) or its imaging markers were unclear, we examined relationship between them. METHODS: The cross-sectional study included community residents from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events study. We calculated the total LE8 score, medical LE8 score and behavioural score, and categorised them into low (<60), moderate (60-79) or high (≥80) group. MRI markers included lacunes, white matter hyperintensities (WMH), enlarged perivascular spaces in basal ganglia (BG-EPVS) and cerebral microbleeds (CMB). In respect of, total CSVD score (0-4 points), WMH, lacunes or CMB were categorised as two grades, and BG-EPVS (N>10) was allocated one point. Based on modified total CSVD score (0-6 points), WMH or CMB was modified to three grades, and BG-EPVS (N>20) was allocated one point. RESULTS: Among 3061 participants in this study, 1424 (46.5%) were male. Higher LE8 score was associated with lower total CSVD score (moderate vs low: cOR 0.78, 95% CI 0.63 to 0.96; high vs low: cOR 0.44, 95% CI 0.33 to 0.59), and the medical score was inversely related to the total CSVD score. Furthermore, the medical score was inversely related to odds of WMH (p<0.05), modified WMH (p<0.05), lacunes (p<0.05) or BG-EPVS (p<0.05), and the behavioural score were inversely related to the odds of lacunes and BG-EPVS. CONCLUSIONS: Higher LE8 score which indicates better cardiovascular status was associated with lower burden of CSVD and its MRI markers. Longitudinal studies are needed to examine the causality.

Novel GSDMD inhibitor GI-Y1 protects heart against pyroptosis and ischemia/reperfusion injury by blocking pyroptotic pore formation.

Activation of gasdermin D (GSDMD) and its concomitant cardiomyocyte pyroptosis are critically involved in multiple cardiac pathological conditions. Pharmacological inhibition or gene knockout of GSDMD could protect cardiomyocyte from pyroptosis and dysfunction. Thus, seeking and developing highly potent GSDMD inhibitors probably provide an attractive strategy for treating diseases targeting GSDMD. Through structure-based virtual screening, pharmacological screening and subsequent pharmacological validations, we preliminarily identified GSDMD inhibitor Y1 (GI-Y1) as a selective GSDMD inhibitor with cardioprotective effects. Mechanistically, GI-Y1 binds to GSDMD and inhibits lipid- binding and pyroptotic pore formation of GSDMD-N by targeting the Arg7 residue. Importantly, we confirmed the cardioprotective effect of GI-Y1 on myocardial I/R injury and cardiac remodeling by targeting GSDMD. More extensively, GI-Y1 also inhibited the mitochondrial binding of GSDMD-N and its concomitant mitochondrial dysfunction. The findings of this study identified a new drug (GI-Y1) for the treatment of cardiac disorders by targeting GSDMD, and provide a new tool compound for pyroptosis research.

Prevalence and Risk Factors of Cerebral Small Vessel Disease from a Population-Based Cohort in China.

INTRODUCTION: Cerebral small vessel disease (CSVD) is a significant burden of morbidity and mortality among elderly people around the world. Epidemiological data with complete CSVD evaluations and a large sample size in the general population are still limited. METHODS: Community-dwelling residents in Lishui city in China from the cross-sectional survey of the Polyvascular Evaluation for Cognitive Impairment and Vascular Events (PRECISE) study were included in this study from 2017 to 2019. All participants underwent 3 Tesla brain magnetic resonance images to assess CSVD imaging markers. Demographic and risk factor data were collected. The general and age-specific prevalence of lacune, confluent white matter hyperintensity (WMH), moderate-severe enlarged perivascular spaces (EPVS), cerebral microbleed (CMB), and total CSVD score (an ordinal scale from 0 to 4, counting the presence of four imaging markers of CSVD) was evaluated. Associations between vascular risk factors and these markers were analyzed by multivariable logistic regression. RESULTS: A total of 3,063 participants were enrolled. The mean age was 61.2 years and 46.5% were men. The most prevalent CSVD marker was confluent WMH (16.7%), followed by CMB (10.2%), moderate-severe EPVS in the basal ganglia (BG-EPVS) (9.8%), and lacune (5.6%). 30.5% of the participants have at least one of the four markers (total CSVD score ≥1 points). The prevalence of CSVD markers increases as age increases. Age and hypertension were independent risk factors for four CSVD markers and the total CSVD score. CONCLUSIONS: In this Chinese cohort with community-based adults aged 50-75 years, our findings showed a prevalence of 30.5% for CSVD. The most prevalent CSVD marker was confluent WMH, followed by CMB, moderate-severe BG-EPVS, and lacune. The risk factors for CSVD must be strictly screened and controlled in adults living in the community.

Association of insulin resistance with intra- and extra-cranial atherosclerotic burden in the nondiabetic community population.

AIMS: Few population-based studies have investigated the association between insulin resistance and atherosclerotic burden in intra- and extra-cranial arteries. The purpose of this study is to explore the relationship between insulin resistance and intra- and extra-cranial atherosclerotic burden in community-based nondiabetic participants. METHODS: This is a cross-sectional analysis from a population-based prospective cohort-PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in China. The homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity indices (ISI0-120) were stratified by the quartiles, respectively. The atherosclerotic presence of plaques and burden was evaluated by high-resolution MRI. Binary or ordinal logistic regression was performed to assess the association between HOMA-IR or ISI0-120 and the presence and burden of atherosclerosis. RESULTS: Among the 2754 participants, the mean age was 60.9 ± 6.6 years, and 1296 (47.1%) were males. Compared with the lowest quartile of HOMR-IR, the highest quartile of HOMA-IR (indicating a higher level of insulin resistance) was associated with an increased presence of plaques (OR:1.54, 95% CI:1.14-2.08), and atherosclerotic burden (OR:1.53, 95%CI:1.14-2.07) in intracranial arteries. Meanwhile, we observed a similar relationship between HOMA-IR and the presence or burden in extracranial atherosclerosis. The first (indicating a higher level of insulin resistance) quartiles of ISI0-120 were associated with the intracranial plaques (Q1, OR:1.56, 95%CI:1.16-2.11) and atherosclerotic burden (Q1, OR:1.57, 95%CI:1.17-2.12), but not extracranial plaques or atherosclerotic burden, compared with the fourth quartile of ISI0-120. CONCLUSIONS: Insulin resistance was associated with an increased intra-and extra-cranial atherosclerotic burden in the nondiabetic elderly Chinese population.

Discordantly high Apo B with LDL-C or non-HDL-C in relation to presence and burden of cerebral atherosclerotic plaques.

BACKGROUND: Data are limited on associations between apolipoprotein B (Apo B) and cerebral atherosclerosis. OBJECTIVE: Our study aimed to estimate associations between discordant Apo B with low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (Non-HDL-C) and the odds of the presence and burden of intra-/extra-cranial atherosclerotic plaques. METHODS: This cross-sectional study was based on the baseline survey from the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study, a population-based prospective cohort study. Participants with complete baseline data but without taking lipid-lowering medication were included in this analysis. Discordant Apo B with LDL-C or Non-HDL-C were defined by residuals and cut-off values (LDL-C: 3.4 mmol/L, Non-HDL-C: 4.1 mmol/L). We used binary and ordinal logistic regression models to explore associations between discordant Apo B with LDL-C or Non-HDL-C and the presence and burden of intra-/extra-cranial atherosclerotic plaques. RESULTS: A total of 2,943 participants were enrolled in this study. Discordantly high Apo B with LDL-C was associated with an increased odds of the presence of intracranial atherosclerotic plaque [odds ratio (OR),1.28; 95%CI,1.01-1.61], intracranial atherosclerotic burden [common odds ratio (cOR), 1.31; 95%CI,1.04-1.64], the presence of extracranial atherosclerotic plaque (OR, 1.37; 95%CI,1.14-1.66), and extracranial atherosclerotic burden (cOR, 1.32; 95%CI,1.10-1.58) compared with the concordant group. Discordantly low Apo B with Non-HDL-C was associated with decreased odds of the presence and burden of intra-/extra-cranial atherosclerotic plaques. CONCLUSION: Discordantly high Apo B with LDL-C or Non-HDL-C were associated with an increased odds of the presence and burden of intra-/extra-cranial atherosclerotic plaques. This demonstrated that discordantly high Apo B might be important for early assessment of risk of cerebral atherosclerotic plaques in addition to LDL-C and Non-HDL-C.

Association of intracranial atherosclerosis with cerebral small vessel disease in a community-based population.

BACKGROUND AND PURPOSE: The purpose of this study was to explore the relationship between intracranial atherosclerosis and cerebral small vessel disease (CSVD). METHODS: Community-dwelling residents of Lishui, China in the PRECISE (Polyvascular Evaluation for Cognitive Impairment and Vascular Events) study were involved. Intracranial atherosclerosis was grouped by the severity of intracranial artery plaques with stenosis and burden. Four imaging markers including lacunes, white matter hyperintensity (WMH), cerebral microbleeds (CMBs), and perivascular spaces (PVS) as well as the CSVD burden scores were assessed. Logistic regression or ordinal logistic regression models with odds ratio (OR) or common OR (cOR) were used to estimate the relationship between intracranial atherosclerosis and CSVD markers and burdens. RESULTS: The mean age was 61.20 ± 6.68 years, and 1424 (46.52%) were men among 3061 participants included at baseline. Intracranial atherosclerotic burden was associated with the severity of the lacunes (OR = 4.18, 95% confidence interval [CI] = 1.83-9.58), modified WMH burden (cOR = 1.94, 95% CI = 1.01-3.71), presence of CMBs (OR = 2.28, 95% CI = 1.05-4.94), and CMB burden (OR = 2.23, 95% CI = 1.03-4.80). However, it was not associated with the WMH burden and PVS. Intracranial atherosclerotic burden was associated with CSVD burden (Wardlaw: cOR = 2.73, 95% CI = 1.48-5.05; Rothwell: cOR = 2.70, 95% CI = 1.47-4.95). The association between intracranial atherosclerosis and CSVD was obvious in participants with both anterior and posterior circulation artery stenosis. CONCLUSIONS: Based on a Chinese community population, there may be an association between intracranial atherosclerosis and CSVD, but its mechanism in relation to vascular risk factors still needs to be clarified.

Effect of routine inflammatory markers on clinical outcomes in acute basilar artery occlusion after endovascular thrombectomy: Results from ATTENTION registry.

BACKGROUND: To investigate the relationship between clinical routine inflammatory markers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), white blood cell count (WBC), neutrophils, lymphocytes, and platelets with clinical outcomes in acute basilar artery occlusion (BAO) patients receiving endovascular treatment (EVT). METHODS: We recruited 2134 acute BAO patients from 48 stroke centers across 22 Chinese provinces in the ATTENTION registry from 2017 to 2021. Blood samples were drawn at admission. An unfavorable functional outcome was defined using a modified Rankin Scale (mRS) of 4-6 at 90 days. Safety outcomes included mortality within 90 days and symptomatic intracerebral hemorrhage within 3 days. RESULTS: A total of 1044 patients were included in the final study. After adjusting for confounding factors, the upper quartiles of WBC and NLR were related to 90-day unfavorable functional outcome (mRS = 4-6) compared with those in the lowest quartile (WBC: quartile 4, odds ratio (OR) = 1.85, 95% confidence interval (CI) = 1.22-2.80; NLR: quartile 4, OR = 2.02, 95% CI = 1.34-3.06). The higher quartiles of WBC and NLR were also related to the increased risk of mortality at 90 days. Restricted cubic spline regression analysis showed an incremental trend between NLR and 90-day unfavorable functional outcome (Pnonlinearity = 0.055). In subgroup analysis, a significant interaction was found between NLR and bridging therapy for predicting unfavorable functional outcome (P = 0.006). CONCLUSION: Higher WBC and NLR on admission are significantly related to unfavorable functional outcome and mortality at 90 days in acute BAO patients receiving EVT. Significant interaction was found between increased NLR and bridging therapy on these outcome measures.

Association between Urine Albumin-to-creatinine Ratio and Intracranial Atherosclerotic Plaque in Chinese Adults - Results from the PRECISE Study.

AIMS: Intracranial plaque may cause stroke in the absence of luminal stenosis. Although urine albumin-to-creatinine ratio (ACR) has been proved an established risk factor for cardiovascular disease, stroke and carotid atherosclerosis, little is known on the relationship between urine ACR and intracranial plaque. METHODS: Subjects with history of stroke or coronary heart disease (CHD) were excluded in the PRECISE study. The intracranial plaque was assessed by vessel wall magnetic resonance imaging (MRI). Subjects were stratified according to ACR tertiles. Logistic regression and ordinal regression were performed to analyze the association between ACR and the presence of intracranial plaque or sum of the stenosis score for each artery. RESULTS: 2962 individuals were included with the mean age of 61.0±6.6 years. The median ACR was 11.7mg/g (interquartile range 7.0-22.0 mg/g), and the mean estimated glomerular filtration rate (eGFR) based on combination of creatinine and cystatin C was 88.5±14.8 ml/min·1.73m2. 495 (16.7%) participants had intracranial plaque. The highest ACR tertile with ACR ＞16.00mg/g was independently associated with the presence of intracranial plaque (OR 1.38, 95% CI: 1.05-1.82, p=0.02) and the odds of higher intracranial plaque burden (common OR 1.39, 95% CI: 1.05-1.83, p=0.02) after adjustment of confounding factors. No significant association was observed between eGFR and intracranial plaque presence or intracranial plaque burden. CONCLUSIONS: Among a low-risk community-dwelling population without prior stroke or CHD in China, ACR was independently associated with intracranial plaque presence and plaque burden measured by vessel wall MRI.

The evaluation and treatment of acute anterior circulation occlusion stroke with high clot burden: Progressive stratified aspiration thrombectomy vs. stent retriever thrombectomy.

OBJECTIVE: To evaluate the safety and effectiveness of the progressive stratified aspiration thrombectomy (PSAT) in treatment of patients with acute ischemic stroke and large vessel occlusion (AIS-LVO). METHODS: 117 AIS-LVO patients with high clot burden who underwent emergency endovascular treatment were included. All patients were divided into two groups according to surgical technique: PSAT group, stent retriever thrombectomy (SRT) group. The primary outcome was the 90-day mRS, the secondary outcomes included recanalization rate, the 24-h and 7-day NIHSS, the 7-day symptomatic intracranial hemorrhage (SICH) rate and 90-days mortality. RESULTS: 65 patients underwent PSAT, and 52 patients underwent SRT. The PSAT group performed better than SRT group regarding the successful recanalization rate (86.3 % vs. 71.2 %, P < 0.05) and time from puncture to recanalization (70 min [IQR, 58-87 min] vs. 87 min [IQR, 68-103 min], P < 0.05). The 7-day NIHSS score of the PSAT group was lower than that of the SRT group (12 [10-18] vs. 12 [8-25], P < 0.05). It was worth noting that at the 90-day follow-up, the favorable functional outcome (mRS 0-2) rate of PSAT group was higher (P < 0.05). There was no significant difference in terms of the 24-h NIHSS score after surgery (15 [10-18] vs. 15 [10-22], P > 0.05), SICH (23.1 % vs. 26.9 %, P > 0.05) and mortality rate between the two groups (13.4 % vs. 19.2 %, P > 0.05). CONCLUSIONS: It is safe and effective to treat high clot burden AIS-LVO patients with PSAT, which has a better reperfusion rate and prognostic outcome than SRT.

Survival benefit of postoperative radiotherapy for pediatric patients with primary intracranial atypical teratoid/rhabdoid tumors: Propensity score analysis and prediction model construction in a multi-registry based cohort.

BACKGROUND: The role of postoperative radiotherapy (PORT) in children with primary intracranial atypical teratoid/rhabdoid tumor (AT/RT) remains controversial, and real-world data with large sample size are still lacking. This study aims to estimate the survival benefit of PORT in pediatric patients with resected AT/RT. METHODS: Using Seer database, we collected 246 eligible intracranial AT/RT patients diagnosed between 2000 and 2016 for our analysis. Propensity score matching (PSM) analysis was employed to minimize selection bias for evaluation of the PORT efficacy. Multivariate Cox regression was conducted to determine the factors related to the outcome. Interaction tests were further performed between PORT and the prognostic variables. After identifying the significant prognostic factors, we further developed a novel prediction model to predict the life expectancy of these patients, as well as the potential benefit from PORT. RESULTS: We found that PORT was significantly related to the improved survival after adjusting for other prognosticators in both the entire and PSM-matched cohort. Significant interactions of PORT with age at diagnosis and tumor extension were also observed. On basis of the prognostic indictors identified by L1-penalized lasso Cox regression analysis, a novel nomogram model was successfully established and externally validated. CONCLUSION: Our study indicated that PORT was significantly associated with the improved survival in pediatric AT/RT patients, and the greater survival benefit from PORT could be achieved in patients <3 years old or with locoregional tumors. The novel prediction model was developed to provide help in clinical practice and in the design of related trials.

Adherence to a healthy lifestyle and brain structural imaging markers.

Previous research has linked specific modifiable lifestyle factors to age-related cognitive decline in adults. Little is known about the potential role of an overall healthy lifestyle in brain structure. We examined the association of adherence to a healthy lifestyle with a panel of brain structural markers among 2,413 participants in PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in China and 19,822 participants in UK Biobank (UKB). A healthy lifestyle score (0-5) was constructed based on five modifiable lifestyle factors: diet, physical activity, smoking, alcohol consumption, and body mass index. Validated multimodal neuroimaging markers were derived from brain magnetic resonance imaging. In the cross-sectional analysis of PRECISE, participants who adopted four or five low-risk lifestyle factors had larger total brain volume (TBV; ß = 0.12, 95% CI: - 0.02, 0.26; p-trend = 0.05) and gray matter volume (GMV; ß = 0.16, 95% CI: 0.01, 0.30; p-trend = 0.05), smaller white matter hyperintensity volume (WMHV; ß = - 0.35, 95% CI: - 0.50, - 0.20; p-trend < 0.001) and lower odds of lacune (Odds Ratio [OR] = 0.48, 95% CI: 0.22, 1.08; p-trend = 0.03), compared to those with zero or one low-risk factors. Meanwhile, in the prospective analysis in UKB (with a median of 7.7 years' follow-up), similar associations were observed between the number of low-risk lifestyle factors (4-5 vs. 0-1) and TBV (ß = 0.22, 95% CI: 0.16, 0.28; p-trend < 0.001), GMV (ß = 0.26, 95% CI: 0.21, 0.32; p-trend < 0.001), white matter volume (WMV; ß = 0.08, 95% CI: 0.01, 0.15; p-trend = 0.001), hippocampus volume (ß = 0.15, 95% CI: 0.08, 0.22; p-trend < 0.001), and WMHV burden (ß = - 0.23, 95% CI: - 0.29, - 0.17; p-trend < 0.001). Those with four or five low-risk lifestyle factors showed approximately 2.0-5.8 years of delay in aging of brain structure. Adherence to a healthier lifestyle was associated with a lower degree of neurodegeneration-related brain structural markers in middle-aged and older adults.

Associations of deep medullary veins with vascular risk factors, laboratory indicators, and cerebral small vessel disease: A population-based study.

OBJECTIVE: Deep medullary veins (DMVs) were not considered a typical marker of cerebral small vessel disease (CSVD) due to limited understanding of their involvement in pathology of CSVD. This study aimsto investigate potential vascular risk factors for DMVs and their associations with CSVD. METHODS: In total, 1909 community-dwelling participants were included in this analysis. Demographic, clinical, laboratory, and imaging data were collected. DMV scores (0-18) werecalculated as the sum of bilateral frontal, parietal, and occipital regional scores using a semiquantitative visual scale (0-3). The presence, total burden, and imaging markers of CSVD were assessed. Linear regression analyses were conducted to explore potential vascular factors for DMV scores. Binary and ordinal logistic regression analyses were performed to investigate the associations of DMV scores with CSVD and its markers. RESULTS: Mean age was 61.8 (SD 6.5) years, and 1027 (53.8%) of participants were men. The median DMV scores were14 (IQR 12-16). DMV scores wererelated to age, male sex, body mass index, diastolic blood pressure, hypercholesterolaemia, atrial fibrillation, current drinking, total cholesterol, triglycerides, low-density lipoprotein, hemoglobin A1c, leukocytes, lymphocytes, hemoglobin, and platelets (p < .05). DMV scores wereassociated with the presence and total burden of CSVD (Rothwell's scale), modified white matter hyperintensity burden, and enlarged perivascular spaces in centrum semiovale (p < .05). However, these associations between DMV scores and CSVD disappeared after adjusting for potential confounders. CONCLUSION: Several conventional vascular factors were associated with DMVs. The relationship between DMVs and CSVD was vulnerable, suggesting decreased visible and discontinuous DMVs may differ mechanistically from traditional markers of CSVD.