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Abstract Background Life’s Essential 8 (LE8), the recently updated construct for quantifying cardiovascular health, is related to the risks of cardiovascular events. The present study aimed to evaluate associations of LE8 score with the multi-territorial extent of atherosclerosis in a community-dwelling population. Methods Data were derived from the baseline cross-sectional survey of the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study in Lishui City. The LE8 included overall, medical and behavior LE8 scores, and were categorized as low (

Summary: Background: Endovascular therapy (EVT) was demonstrated effective in acute large vessel occlusion (LVO) with large infarction. Revealing subgroups of patients who would or would not benefit from EVT will further inform patient selection for EVT. Methods: This post-hoc analysis of the ANGEL-ASPECT trial, a randomised controlled trial of 456 adult patients with acute anterior-circulation LVO and large infarction, defined by ASPECTS 3–5 or infarct core volume 70–100 mL, enrolled from 46 centres across China, between October 2, 2020 and May 18, 2022. Patients were randomly assigned (1:1) to receiving EVT and medical management or medical management alone. One patient withdrew consent, 455 patients were included in this post-hoc analysis and categorised into 4 subgroups by lower or higher NIHSS (< or ≥16) and smaller or larger infarct core (< or ≥70 mL). Those with lower NIHSS & smaller core, and higher NIHSS & larger core were considered clinical-radiological matched subgroups; otherwise clinical-radiological mismatched subgroups. Primary outcome was 90-day modified Rankin Scale (mRS). ANGEL-ASPECT is registered with ClinicalTrials.gov, NCT04551664. Findings: Overall, 139 (30.5%) patients had lower NIHSS & smaller core, 106 (23.3%) higher NIHSS & larger core, 130 (28.6%) higher NIHSS & smaller core, and 80 (17.6%) lower NIHSS & larger core. There was significant ordinal shift in the 90-day mRS toward a better outcome with EVT in clinical-radiological matched subgroups: lower NIHSS & smaller core (generalised OR, 1.76; 95% CI, 1.18–2.62; p = 0.01) and higher NIHSS & larger core (1.64; 1.06–2.54; 0.01); but not in the two clinical-radiological mismatched subgroups. Interpretation: Our findings suggested that in patients with anterior-circulation LVO and large infarction, EVT was associated with improved 90-day functional outcomes in those with matched clinical and radiological severities, but not in those with mismatched clinical and radiological severities. Simultaneous consideration of stroke severity and infarct core volume may inform patient selection for EVT. Funding: Unrestricted grants from industry [Covidien Healthcare International Trading (Shanghai), Johnson & Johnson MedTech, Genesis MedTech (Shanghai), and Shanghai HeartCare Medical Technology].

Background Elevated white blood cell count, fibrinogen levels, and lower levels of albumin signify higher systemic inflammatory response, hypercoagulable state, and poorer nutritional status, respectively. However, a consistent conclusion could not be drawn on whether the association between inflammatory markers and cardiovascular disease was affected by the presence of chronic kidney disease (CKD). We aimed to explore the association between inflammation and adverse outcomes in patients with acute ischemic stroke (AIS), as well as whether this association differs due to the presence of CKD. Methods and Results This research was based on the Third China National Stroke Registry. The main adverse outcomes were poor functional outcome, stroke recurrence, and combined vascular event after 1 year. Inflammation was defined as the worst quartile of at least 2 of the aforementioned 3 markers. Finally, 8493 patients with AIS were enrolled in this study. The adjusted odds ratios/hazard ratios and 95% CIs of inflammation were 1.58 (1.34–1.86) for poor functional outcomes, 1.25 (1.06–1.47) for stroke recurrence, and 1.25 (1.06–1.46) for combined vascular event. The association between inflammation and adverse outcomes existed only in patients with AIS without CKD, although the interaction between CKD and inflammation was not statistically significant. (P for interaction >0.05). Conclusions Inflammation, which was defined as a combination of fibrinogen, white blood cell count, and albumin, was associated with all 1‐year adverse outcomes among patients with AIS. Routine assessment of these biomarkers could become a potential part of the clinical evaluation for patients with AIS, especially those without CKD, aiding clinicians in risk stratification and treatment decision‐making.

Abstract 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

BackgroundThe optimal control thresholds for systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with white matter hyperintensity (WMH) are still unclear.MethodA longitudinal retrospective study of patients with brain magnetic resonance imaging (MRI) scans with intervals of more than 3 years was conducted. Blood pressure records during hospitalization and from outpatient visits between baseline and the last MRI scan were collected. The outcome was the change in total WMH from baseline to the final visit.ResultsAmong the 965 patients with MRI scans, 457 patients with detailed longitudinal blood pressure records were ultimately included and classified into the WMH absent group (n = 121), mild WMH group (n = 126), and moderate to severe WMH group (n = 210). Both baseline and longitudinal mean SBP, DBP, and SBP SD were significantly associated with WMH severity (p

Abstract Infant emotional stimuli can preferentially engage adults’ attention and provide valuable information essential for successful interaction between adults and infants. Exploring the neural processes of recognizing infant stimuli promotes better understandings of the mother-infant attachment mechanisms. Here, combining task-functional magnetic resonance imaging (Task-fMRI) and resting-state fMRI (rs-fMRI), we investigated the effects of infants’ faces on the brain activity of adults. Two groups including 26 women and 25 men were recruited to participate in the current study. During the task-fMRI, subjects were exposed to images of infant emotional faces (including happy, neutral, and sad) randomly. We found that the brains of women and men reacted differently to infants’ faces, and these differential areas are in facial processing, attention, and empathetic networks. The rs-fMRI further showed that the connectivity of the default-mode network-related regions increased in women than in men. Additionally, brain activations in regions related to emotional networks were associated with the empathetic abilities of women. These differences in women might facilitate them to more effective and quick adjustments in behaviors and emotions during the nurturing infant period. The findings provide special implications and insights for understanding the neural processing of reacting to infant cues in adults.

Abstract Background Insulin resistance is an important cause of cardiovascular events and cerebral infarction development. We aimed to investigate the association of the triglyceride glucose (TyG) index with atherosclerotic burden and plaques in coronary, intra- and extracranial arteries in participants with non-diabetes, and compared the results with that of the homeostasis model assessment of insulin resistance (HOMA-IR). Methods Participants without diabetes in the PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study were included. We categorized participants by tertiles of the TyG index and the concordance/discordance of the TyG index and HOMA-IR. Discordance was defined as a TyG index equal to or greater than the median and HOMA-IR less than the median, or vice versa. The atherosclerosis plaques and burden in coronary, intra- and extracranial arteries were evaluated. The association of HOMA-IR and TyG index with the presence of atherosclerotic plaques and atherosclerotic burden was assessed by binary and ordinal logistic regression models, respectively. Results Among 2,719 included participants, the average age was 60.9 (± 6.6) years, and 53.0% were female. Both TyG index and HOMA-IR were associated with increased odds of coronary/intra- and extracranial atherosclerotic plaques and burden after adjustment for age, sex, currenting smoking and drinking (all P

Abstract Objective Contribution of individual and combined inflammatory markers in prognosis after stroke was still undefined. We aimed to investigate the association of systemic and local vascular inflammatory markers and recurrent stroke as well as impact on poor functional outcome. Methods In this pre-specified substudy of the Third China National Stroke Registry (CNSR-III), 10,472 consecutive acute ischemic stroke or TIA patients with available centralized-measured levels of Interleukin-6 (IL-6), high sensitive C-reactive protein (hsCRP), IL-1 receptor antagonist (IL-1Ra), lipoprotein-associated phospholipase A2 mass (Lp-PLA2) and activity (Lp-PLA2-A), and YKL-40 from 171 sites were enrolled. The primary outcomes consisted of stroke recurrence and poor functional outcome defined as modified Rankin Scale (mRS) score of 2–6 within 1 year. Results There were 1026 (9.8%) and 2395 (23.4%) patients with recurrent stroke and poor functional outcome within 1 year. The highest quartiles of IL-6 (adjusted HR, 1.36; 95% CI 1.13–1.64; P = 0.001), hsCRP (adjusted HR, 1.41; 95% CI 1.17–1.69; P = 0.0003) and YKL-40 (adjusted HR, 1.28; 95% CI 1.06–1.56; P = 0.01) were associated with increased risk of recurrent stroke; and the highest quartiles of IL-6 (adjusted OR 1.93; 95% CI 1.64–2.27; P

Abstract Background The plant-specific IQ67-domain (IQD) gene family plays an important role in plant development and stress responses. However, little is known about the IQD family in common wheat (Triticum aestivum L), an agriculturally important crop that provides more than 20% of the calories and protein consumed in the modern human diet. Results We identified 125 IQDs in the wheat genome and divided them into four subgroups by phylogenetic analysis. The IQDs belonging to the same subgroup had similar exon–intron structure and conserved motif composition. Polyploidization contributed significantly to the expansion of IQD genes in wheat. Characterization of the expression profile of these genes revealed that a few T. aestivum (Ta)IQDs showed high tissue-specificity. The stress-induced expression pattern also revealed a potential role of TaIQDs in environmental adaptation, as TaIQD-2A-2, TaIQD-3A-9 and TaIQD-1A-7 were significantly induced by cold, drought and heat stresses, and could be candidates for future functional characterization. In addition, IQD genes in the A, B and D subgenomes displayed an asymmetric evolutionary pattern, as evidenced by their different gain or loss of member genes, expression levels and nucleotide diversity. Conclusions This study elucidated the potential biological functions and evolutionary relationships of the IQD gene family in wheat and revealed the divergent fates of IQD genes during polyploidization.

Abstract Purpose Resting metabolic rate (RMR) could represent metabolic health status. This study aims to examine the association of the predicted RMR with 1‐year poor functional outcome and all‐cause mortality in patients with ischemic stroke as a proxy of metabolic profile. Methods A total of 15,166 patients with ischemic stroke or transient ischemic attack (TIA) from the Third China National Stroke Registry (CNSR‐III) were enrolled in this study. The Harris–Benedict equation based on sex, age, weight, and height was used to predict RMR. The primary endpoints were poor functional outcome defined as ≥3 modified Rankin Scale (mRS) score and all‐cause mortality within 1 year. The association between predicted RMR and prognosis was assessed by multivariable regression analysis. Besides that, subgroup analysis of age, sex, and body mass index (BMI) with predicted RMR was also performed. Results 12.85% (1657) individuals had poor functional outcome and 2.87% (380) died of whatever causes within 1 year. An inverse association was found between predicted RMR with poor functional outcome and all‐cause mortality. Compared to the lowest quartile, the highest quartile was significantly associated with lower risk of poor functional outcome (adjusted odds ratio [OR], 0.43 [95% confidence interval (CI) 0.33–0.56]) and all‐cause mortality (adjusted hazard ratio [HR], 0.44 [95% CI 0.28–0.71]). No significant interaction was between predicted RMR and specified subgroup. Conclusions Predicted RMR by the Harris–Benedict equation seems to be an independent protective predictor of poor functional outcome and all‐cause mortality after ischemic stroke as a metabolic proxy.

Abstract Cognitive function following acute ischemic stroke (AIS) is critical to prognosis and quality of life. Hypertension is a risk factor for stroke and is associated with post stroke cognitive impairment (PSCI). However, the optimal blood pressure parameters after AIS is unknown. This is a sub‐study of the Impairment of CognitiON and Sleep after acute ischemic stroke or transient ischemic attack in Chinese patients (ICONS) study conducted between August 2015 and March 2018. Cognition was assessed at two‐week (2w), three‐month (3 m), and twelve‐month (12 m) by Montreal Cognitive Assessment (MoCA). A total of 682 participants who met the inclusion criteria were enrolled. The primary outcome was cognitive changes after 3 and 12 months post stroke. Among 682 participants, the mean age was 59.35 ± 10.40 years and 72.29% were men. PSCI patients with high systolic blood pressure (SBP ≥140 mm Hg) at 3 m not only had worse cognition as evidenced by MoCA scores at 3 m but also predicted worse scores at 12 m. When participants were stratified into cognitively stable/improved (MoCA score ≥0, 2w vs. 12 m) and cognitively impaired (MoCA score ≤‐2, 2w vs. 12 m), those with high SBP were more likely to be cognitively impaired (OR 2.17, 95%CI 1.12–4.21, p

Abstract Chromosomal copy number variants (CNVs) are an important cause of congenital malformations and mental retardation. This study reported a large Chinese pedigree (4-generation, 76 members) with mental retardation caused by chromosome microduplication/microdeletion. There were 10 affected individuals with intellectual disability (ID), developmental delay (DD), and language delay phenotypes. SNP array analysis was performed in the proband and eight patients and found all of them had a microduplication of chromosome 4p16.3p15.2 and a microdeletion of chromosome 8p23.3p23.2. The high-resolution karyotyping analysis of the proband had unbalanced karyotype [46, XY, der(8)t(4;8)(p15.2;p23.1)mat], his mother had balanced karyotype [46, XX, t(4;8) (p15.2;p23.1)], whereas his father had normal karyotype [46,XY]. Fluorescence in situ hybridization (FISH) analysis further confirmed that the proband’s mother had a balanced translocation between the short arm terminal segment of chromosome 4 and the short arm end segment of chromosome 8, ish t(4;8)(8p + ,4q + ;4p + ,8q +). In conclusion, all the patients inherited chromosomes 8 with 4p16.3p15.2 duplication and 8p23.3p23.2 deletion from their parental balanced translocation, which might be the cause of the prevalence of intellectual disability. Meanwhile, 8p23.3p23.2 deletion, rather than 4p16.3p15.2 duplication might cause a more severe clinical syndrome.

Abstract Background and purpose Diabetes mellitus is a strong independent risk factor for stroke recurrence. However, the association between diabetes duration and the prognosis of stroke remains uncertain. We aimed to characterize whether an association exists between diabetes duration and stroke outcomes in patients with ischemic stroke or transient ischemic attack (TIA). Methods Between 2015 and 2018, 14,674 patients with ischemic stroke or TIA within 7 days and older than 18 years from the Third China National Stroke Registry (CNSR‐III) were included in this analysis. Diabetes duration at baseline was collected by face‐to‐face interviews and further categorized into groups of without diabetes, diabetes

ObjectivePrevious neuroimaging studies have shown abnormal brain-bladder control network in children with primary nocturnal enuresis (PNE). The hippocampus, which has long been considered to be an important nerve center for memory and emotion, has also been confirmed to be activating during micturition in several human imaging studies. However, few studies have explored hippocampus-related functional networks of PNE in children. In this study, the whole resting-state functional connectivity (RSFC) of hippocampus was investigated in children with PNE.MethodsFunctional magnetic resonance imaging data of 30 children with PNE and 29 matched healthy controls (HCs) were analyzed in our study. We used the seed-based RSFC method to evaluate the functional connectivity of hippocampal subregions defined according to the Human Brainnetome Atlas. Correlation analyses were also processed to investigate their relationship with disease duration time, bed-wetting frequency, and bladder volume.ResultsCompared with HCs, children with PNE showed abnormal RSFC of the left rostral hippocampus (rHipp) with right fusiform gyrus, right Rolandic operculum, left inferior parietal lobule, and right precentral gyrus, respectively. Moreover, decreased RSFC of the left caudal hippocampus (cHipp) with right fusiform gyrus and right supplementary motor area was discovered in the PNE group. There were no significant results in the right rHipp and cHipp seeds after multiple comparison corrections. In addition, disease duration time was negatively correlated with RSFC of the left rHipp with right Rolandic operculum (r = −0.386, p = 0.035, uncorrected) and the left cHipp with right fusiform gyrus (r = −0.483, p = 0.007, uncorrected) in the PNE group, respectively. In the Receiver Operating Characteristic (ROC) analysis, all the above results of RSFC achieved significant performance.ConclusionsTo our knowledge, this is the first attempt to examine the RSFC patterns of hippocampal subregions in children with PNE. These findings indicated that children with PNE have potential dysfunctions in the limbic network, sensorimotor network, default mode network, and frontoparietal network. These networks may become less efficient with disease duration time, inducing impairments in brain-bladder control, cognition, memory, and emotion. Further prospective research with dynamic observation of brain imaging, bladder function, cognition, memory, and emotion is warranted.

ObjectivePrimary nocturnal enuresis (PNE) is a common developmental condition in school-aged children. The objective is to better understand the pathophysiology of PNE by using insula-centered resting-state functional connectivity (rsFC).MethodsWe recruited 66 right-handed participants in our analysis, 33 with PNE and 33 healthy control (HC) children without enuresis matched for gender and age. Functional and structural MRI data were obtained from all the children. Seed-based rsFC was used to examine differences in insular functional connectivity between the PNE and HC groups. Correlation analyses were carried out to explore the relationship between abnormal insula-centered functional connectivity and clinical characteristics in the PNE group.ResultsCompared with HC children, the children with PNE demonstrated decreased left and right insular rsFC with the right medial superior frontal gyrus (SFG). In addition, the bilateral dorsal anterior insula (dAI) seeds also indicated the reduced rsFC with right medial SFG. Furthermore, the right posterior insula (PI) seed showed the weaker rsFC with the right medial SFG, while the left PI seed displayed the weaker rsFC with the right SFG. No statistically significant correlations were detected between aberrant insular rsFC and clinical variables (e.g., micturition desire awakening, bed-wetting frequency, and bladder volume) in results without global signal regression (GSR) in the PNE group. However, before and after setting age as a covariate, significant and positive correlations between bladder volume and the rsFC of the left dAI with right medial SFG and the rsFC of the right PI with right medial SFG were found in results with GSR in the PNE group.ConclusionTo the best of our knowledge, this study explored the rsFC patterns of the insula in children with PNE for the first time. These results uncovered the abnormal rsFC of the insula with the medial prefrontal cortex without and with GSR in the PNE group, suggesting that dysconnectivity of the salience network (SN)-default mode network (DMN) may involve in the underlying pathophysiology of children with PNE. However, the inconsistent associations between bladder volume and dysconnectivity of the SN-DMN in results without and with GSR need further studies.

BackgroundObservational studies indicated that cholesterol efflux capacity (CEC) of high-density lipoprotein (HDL) is inversely associated with cardiovascular events, independently of the HDL cholesterol concentration. The aim of the study is to examine the casual relevance of CEC for coronary artery disease (CAD) and myocardial infarction (MI), and compare it with that for ischemic stroke and its subtypes using a Mendelian randomization approach.MethodsWe performed a 2-sample Mendelian randomization to estimate the casual relationship of CEC with the risk of CAD, MI, and ischemic stroke. A CEC-related genetic variant (rs141622900) and other five genetic variants were used as the instrumental variables. Association of genetic variants with CAD were estimated in a GWAS involving 60,801 CAD cases and 123,504 controls. They were then compared with the associations of these variants with ischemic stroke and its subtypes (large vessel, small vessel, and cardioembolic) involving 40,585 ischemic stroke cases and 406,111 controls.ResultsUsing the SNP of rs141622900 as the instrument, a 1-SD increase in CEC was associated with 45% lower risk for CAD (odds ratio [OR] 0.55, 95% confidence interval [CI] 0.44–0.69, p < 0.001) and 33% lower risk for MI (odds ratio [OR] 0.67, 95% CI 0.52–0.87, p = 0.002). By contrast, the causal effect of CEC was much weaker for ischemic stroke (odds ratio [OR] 0.79, 95% CI 0.64–0.97, p = 0.02; p for heterogeneity = 0.03) and, in particular, for cardioembolic stroke (p for heterogeneity = 0.006) when compared with that for CAD. Results using five genetic variants as the instrument also indicated consistently weaker effects on ischemic stroke than on CAD.ConclusionGenetic predicted higher CEC may be associated with decreased risk of CAD. However, the casual association of CEC with ischemic stroke and specific subtypes would need to be validated in further Mendelian randomization studies.

Background The aim of this study was to investigate the association between hsCRP (high‐sensitivity C‐reactive protein) and prognosis over time after stroke onset. Methods and Results In this prespecified prospective substudy of the Third China National Stroke Registry, a total of 9438 patients with acute ischemic stroke or transient ischemic attack and measured hsCRP were included. Patients were categorized into 3 groups according to the sampling time after index onset (

Individual variability of cognitive factors in second language (L2) grammar learning has long been the focus in the field of L2 acquisition. Most explored the issue by focusing on one factor like cognitive control, working memory, statistical learning (SL), or attention. Few investigated the topic by taking all these factors into consideration. However, different factors might interact and collaboratively contribute to the learning process. Examining the issue by considering all the factors might yield different results and facilitate our understanding of the mechanism subserving L2 grammar learning. Therefore, this study explored whether and how these factors predicted L2 grammar learning. A total of 34 college students completed a set of cognitive measurements on these cognitive factors, after which they were trained with artificial grammar over 5 consecutive days. Using multiple regression analysis and machine learning algorithms, we found that in the initial phase, SL was the more significant predictor, whereas in the intermediate and the last phases, cognitive control served as the more significant predictor. In other words, in the initial phase of L2 grammar learning, SL might play an important role, whereas in the intermediate and proficient phase, the updating component of cognitive control might play a more significant role. The findings provided empirical evidence to the neurocognitive account of grammar learning, shedding light on the mechanism of L2 grammar learning.

Abstract Resting state functional magnetic resonance imaging studies of nocturnal enuresis have focused primarily on regional metrics in the blood oxygen level dependent (BOLD) signal ranging from 0.01 to 0.08 Hz. However, it remains unclear how local metrics show in sub-frequency band. 129 children with nocturnal enuresis (NE) and 37 healthy controls were included in this study. The patients were diagnosed by the pediatricians in Shanghai Children’s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, according to the criteria from International Children's Continence Society (ICCS). Questionnaires were used to evaluate the symptoms of enuresis and completed by the participants. In this study, fALFF, ReHo and PerAF were calculated within five different frequency bands: typical band (0.01–0.08 Hz), slow-5 (0.01–0.027 Hz), slow-4 (0.027–0.073 Hz), slow-3 (0.073–0.198 Hz), and slow-2 (0.198–0.25 Hz). In the typical band, ReHo increased in the left insula and the right thalamus, while fALFF decreased in the right insula in children with NE. Besides, PerAF was increased in the right middle temporal gyrus in these children. The results regarding ReHo, fALFF and PerAF in the typical band was similar to those in slow-5 band, respectively. A correlation was found between the PerAF value of the right middle temporal gyrus and scores of the urinary intention-related wakefulness. Results in other bands were either negative or in white matter. NE children might have abnormal intrinsic neural oscillations mainly on slow-5 bands.

Elevated levels of high-sensitivity C-reactive protein (hsCRP) were associated with an increased risk of recurrent stroke. However, it is still unknown whether the predictive value of hsCRP differed according to the severity of cerebrovascular disease. We used the cohort of the prospective multicenter cohort study of the Third China National Stroke Registry (CNSR-III), in which 10,765 consecutive patients with acute ischemic stroke or transient ischemic attack (TIA) had hsCRP levels measured. Patients were classified into minor stroke, or TIA, and non-minor stroke. The primary outcome was a new stroke within 1 year. Cox proportional hazards models were used to assess the association of hsCRP and its outcome. Elevated levels of hsCRP were associated with an increased risk of recurrent stroke in minor stroke or TIA patients, irrespective of using a National Institutes of Health Stroke Scale (NIHSS) score of ≤3 (the highest quartile vs. the lowest quartile: adjusted hazard ratio, 1.48; 95% CI, 1.12–1.97; p = 0.007) or ≤5 (the highest quartile vs. the lowest quartile: adjusted hazard ratio, 1.45; 95% CI, 1.15–1.84; p = 0.002) to define minor stroke. Such association was more apparent in the large-artery atherosclerosis subtype. However, for the patients with non-minor stroke, the association of hsCRP with recurrent stroke disappeared.

Purpose: Brain areas frequently implicated in language recovery after stroke comprise perilesional sites in the left hemisphere and homotopic regions in the right hemisphere. However, the neuronal mechanisms underlying language restoration are still largely unclear. Methods and materials: In the present study, we investigated the brain function in 15 patients with poststroke aphasia and 30 matched control subjects by combining the regional homogeneity (ReHo) and amplitudes of low-frequency fluctuation (ALFF) analysis methods based on resting-state fMRI. Results: Compared to the control subjects, the patients with aphasia exhibited increased ReHo and ALFF values in the ipsilateral perilesional areas and increased ReHo in the contralesional right middle frontal gyrus. Conclusions: The increased spontaneous brain activity in patients with poststroke aphasia during the recovery period, specifically in the ipsilateral perilesional regions and the homologous language regions of the right hemisphere, has potential implications for the treatment of patients with aphasia.

Positive valence bias refers to speakers responding faster to positive than negative information in L2 emotion words. Few researchers paid attention to the initial learning phase of L2 Chinese emotion idioms in which whether positive valence bias was acquired, based on the three-stage model of L2 vocabulary acquisition. Besides, whether the semantic information would modulate positive valence bias at the initial learning phase remained unclear. This study reports two experiments on speakers learning Chinese as a second language (CSL) to investigate positive valence bias in the initial learning phase of new Chinese emotion idioms and the modulation of semantic information on positive valence bias. Chinese as a second language speakers, who had acquired new Chinese emotion idioms and passed the test for learned Chinese idioms with a high accuracy rate before formal experiments, participated in Experiments 1 and 2. In Experiment 1, target materials were new Chinese idioms with positive and negative information. Positive valence bias at the initial learning phase of Chinese idioms was investigated with valence judgments. Experiment 2 used a semantic relatedness decision task further to explore the semantic effect on positive valence bias. The result in the first experiment showed that positive valence bias appeared in Chinese emotion idioms even at the initial learning phase of the acquisition. Meanwhile, semantic information of Chinese emotion idioms appeared to affect positive valence bias in the infant learning phase in Experiment 2. The findings revealed that semantic information would affect the performance of positive valence bias, suggesting that the semantic processing would automatically access the valence at the infant learning phase L2 Chinese emotion idioms. The research results provided evidence that positive valence bias would form in the infant learning phase of Chinese emotion idiom acquisition, based on the L2 vocabulary acquisition model.

Abstract Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) manifests principally as a suite of cognitive impairments, particularly in the executive domain. Executive functioning requires the dynamic coordination of neural activity over large-scale networks. It remains unclear whether changes in resting-state brain functional network connectivity and regional homogeneities (ReHos) underly the mechanisms of executive dysfunction evident in CADASIL patients. Methods In this study, 22 CADASIL patients and 44 matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). Independent component analysis (ICA) was used to measure functional brain network connectivity, and ReHos were calculated to evaluate local brain activities. We used seed-based functional connectivity (FC) analyses to determine whether dysfunctional areas (as defined by ReHos) exhibited abnormal FC with other brain areas. Relationships among the mean intra-network connectivity z-scores of dysfunctional areas within functional networks, and cognitive scores were evaluated using Pearson correlation analyses. Results Compared to the controls, CADASIL patients exhibited decreased intra-network connectivity within the bilateral lingual gyrus (LG) and the right cuneus (CU) (thus within the visual network [VIN)], and within the right precuneus (Pcu), inferior frontal gyrus (IFG), and precentral gyrus (thus within the frontal network [FRN]). Compared to the controls, patients also exhibited significantly lower ReHos in the right precuneus and cuneus (Pcu/CU), visual association cortex, calcarine gyri, posterior cingulate, limbic lobe, and weaker FC between the right Pcu/CU and the bilateral parahippocampal gyrus (PHG), and between the right Pcu/CU and the right postcentral gyrus. Notably, the mean connectivity z-scores of the bilateral LG and the right CU within the VIN were positively associated with compromised attention, calculation and delayed recall as revealed by tests of the various cognitive domains explored by the Mini-Mental State Examination. Conclusions The decreases in intra-network connectivity within the VIN and FRN and reduced local brain activity in the posterior parietal area suggest that patients with CADASIL may exhibit dysfunctional visuomotor behaviors (a hallmark of executive function), and that all visual information processing, visuomotor planning, and movement execution may be affected.

Background and Purpose: Although elevated serum lipoprotein (a) [Lp(a)] is considered to be a risk factor of ischemic stroke, the relationship between Lp(a) and cognitive impairment after stroke remains unclear. This study investigated the association between serum Lp(a) and cognitive function after acute ischemic stroke (AIS) or transient ischemic attack (TIA).Methods: The study included 1,017 patients diagnosed with AIS or TIA from the cognition subgroup of the Third China National Stroke Registry (CNSR3). Montreal Cognitive Assessment (MoCA) at 2 weeks or discharge, 3 months, and 1 year was evaluated. The primary outcome was cognitive impairment at 1 year, defined as MoCA ≤ 22. The secondary outcome was cognition improvement at 1 year compared with 2 weeks. The association between Lp(a) levels and cognitive function was analyzed.Results: Among the 1,017 patients included, 326 (32.1%) had cognitive impairment at 1 year. Patients with MoCA ≤ 22 at 1 year were older, received less education, and had higher baseline NIHSS, higher proportion of ischemic stroke history, large artery atherosclerosis (LAA) subtype, and multiple infarctions (P < 0.05 for all). Patients with highest Lp(a) quartile had slightly higher percentage of cognitive impairment at 1 year but without statistical difference. In subgroup analysis of LAA subtype, the patients with highest Lp(a) quartile had higher percentage of cognitive impairment at 1 year (adjusted OR:2.63; 95% CI: 1.05–6.61, P < 0.05). What is more, the patients with highest Lp(a) quartile in LAA subtype had lower percentage of cognition improvement at 1 year. However, similar results were not found in small artery occlusion (SAO) subtype.Conclusion: Higher Lp(a) level was associated with cognitive impairment and less improvement of cognition in patients after AIS or TIA with large-artery atherosclerosis subtype.

Abstract Spin‐torque memristors are proposed in 2009, and can provide fast, low‐power, and infinite memristive behavior for neuromorphic computing and large‐density non‐volatile memory. However, the strict requirements of combining high magnetoresistance, stable domain wall pinning and current‐induced switching in a single device pose difficulties in physical implementation. Here, a nanoscale spin‐torque memristor based on a perpendicular‐anisotropy magnetic tunnel junction with a CoFeB/W/CoFeB composite free layer structure is experimentally demonstrated. Its tunneling magnetoresistance is higher than 200%, and memristive behavior can be realized by spin‐transfer torque switching. Memristive states are retained by strong domain wall pinning effects in the free layer. Experiments and simulations suggest that nanoscale vertical chiral spin textures can form around clusters of W atoms under the combined effect of opposite Dzyaloshinskii–Moriya interactions and the Ruderman–Kittel–Kasuya–Yosida interaction between the two CoFeB free layers. Energy fluctuation caused by these textures may be the main reason for the strong pinning effect. With the experimentally demonstrated memristive behavior and spike‐timing‐dependent plasticity, a spiking neural network to perform handwritten pattern recognition in an unsupervised manner is simulated. Due to advantages such as long endurance and high speed, the spin‐torque memristors are competitive in the future applications for neuromorphic computing.

Background: Low heart rate variability (HRV) is known to be associated with increased all-cause, cardiovascular, and cerebrovascular mortality but its association with clinical outcomes in patients with transient ischemic attack (TIA) or minor stroke is unclear.Methods: We selected TIA and minor stroke patients from a prospective registration study. From each continuous electrocardiograph (ECG) record, each QRS complex was detected and normal-to-normal (N-N) intervals were determined. The standard deviation of all N-N intervals (SDNN) and the square root of the mean squared differences of successive N-N intervals (RMSSD) were calculated. Logistic regression analysis and Cox regression analysis were performed to assess the outcomes of patients at 90 days, and the odds and risk ratios (OR/HR) of each index quartile were compared.Results: Compared with SDNN patients in the lowest quartile, neurological disability was significantly reduced in other quartile groups at 90 days, with significant differences [OR of group Q2 was 0.659; 95% confidence interval (CI), 0.482–0.900; p = 0.0088; OR of group Q3 was 0.662; 95% CI, 0.478–0.916; p = 0.0127; OR of group Q4 was 0.441; 95% CI, 0.305–0.639; p

Abstract Currently double-interface magnetic tunnel junctions (MTJs) have been developed for enhancing the thermal stability barrier at the nanoscale technology node. Dzyaloshinskii–Moriya interaction (DMI) inevitably exists in such devices due to the use of the heavy-metal/ferromagnet structures. Previous studies have demonstrated the detrimental effect of DMI on the conventional single-interface spin-transfer torque (STT) MTJs. Here, in this work, we will prove that the detrimental effect of DMI could be almost eliminated in the double-interface STT-MTJ. This conclusion is attributed to the suppressing effect of Ruderman–Kittel–Kasuya–Yosida (RKKY) interaction on the DMI. Detailed mechanisms are analyzed based on the theoretical models and micromagnetic simulation results. Our work highlights the importance of appropriately controlling the DMI in the composite free layer of the double-interface STT-MTJ.

Abstract Background Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) mainly manifests with cognitive impairment. Cognitive deficits in patients with CADASIL are correlated with structural brain changes such as lacunar lesion burden, normalized brain volume, and anterior thalamic radiation lesions, but changes in resting-state functional brain activity in patients with CADASIL have not been reported. Methods This study used resting-state functional magnetic resonance imaging (fMRI) to measure the amplitude of low-frequency fluctuation (ALFF) in 22 patients with CADASIL and 44 healthy matched controls. A seed-based functional connectivity (FC) analysis was used to investigate whether the dysfunctional areas identified by ALFF analysis exhibited abnormal FC with other brain areas. Pearson’s correlation analysis was used to detect correlations between the ALFF z-score of abnormal brain areas and clinical scores in patients with CADASIL. Results Patients with CADASIL exhibited significantly lower ALFF values in the right precuneus and cuneus (Pcu/CU) and higher ALFF values in the bilateral superior frontal gyrus (SFG) and left cerebellar anterior and posterior lobes compared with controls. Patients with CADASIL showed weaker FC between the areas with abnormal ALFF (using peaks in the left and right SFG and the right Pcu/CU) and other brain areas. Importantly, the ALFF z-scores for the left and right SFG were negatively associated with cognitive performance, including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment scores (MoCA), respectively, whereas those of the right Pcu/CU were positively correlated with the MMSE score. Conclusions This preliminary study provides evidence for changes in ALFF of the right Pcu/CU, bilateral SFG and left cerebellar anterior and posterior lobes, and associations between ALFF values for abnormal brain areas and cognitive performance in patients with CADASIL. Therefore, spontaneous brain activity may be a novel imaging biomarker of cognitive impairment in this population.

Small sample learning ability is one of the most significant characteristics of the human brain. However, its mechanism is yet to be fully unveiled. In recent years, brain-inspired artificial intelligence has become a very hot research domain. Researchers explored brain-inspired technologies or architectures to construct neural networks that could achieve human-alike intelligence. In this work, we presented our effort at evaluation of the effect of dynamic behavior and topology co-learning of neurons and synapses on the small sample learning ability of spiking neural network. Results show that the dynamic behavior and topology co-learning mechanism of neurons and synapses presented in our work could significantly reduce the number of required samples, while maintaining a reasonable performance on the MNIST data-set, resulting in a very lightweight neural network structure.

Perpendicular magnetic tunnel junctions with large tunnel magnetoresistance and low junction resistance are promising for the magnetic random access memories. Here the authors achieve the spin-transfer-torque switching in perpendicular magnetic tunnel junctions with 249% tunnel magnetoresistance and low resistance-area product.

A low high-density lipoprotein cholesterol (HDL-C) level is an identified risk factor for cardiovascular diseases. However, results on the association between HDL-C levels and adverse outcomes in diabetic status still remain limited and controversial. Herein, we evaluated the association between HDL-C levels and adverse outcomes among acute ischemic stroke (AIS) patients with diabetes mellitus. The cohort comprised 3824 AIS patients with diabetes mellitus (62.7 ± 10.5 years; 34.2% women) from the Third China National Stroke Registry (n = 15,166). Patients were classified into five groups by quintiles of HDL-C. The outcomes included recurrent stroke and major adverse cardiovascular events (MACEs) within 1 year. The relationship between HDL-C levels and the risk of adverse outcomes was analyzed by Cox proportional hazards models. Patients in the lowest quintile of HDL-C had a higher risk of recurrent stroke (hazard ratio (HR) 1.59, 95% confidence interval (CI), 1.12–2.25) and MACEs (HR 1.53, 95% CI, 1.09–2.15) during 1-year follow-up compared with those in the highest quintile of HDL-C. There were linear associations between HDL-C levels and the risks of both recurrent stroke and MACEs. Low HDL-C levels were associated with higher risks of recurrent stroke and MACEs within 1 year in AIS patients with diabetes mellitus.

Abstract Background Migraine constitute a disorder characterized by recurrent headaches, and have a high prevalence, a high socio-economic burden and severe effects on quality of life. Our previous fMRI study demonstrated that some brain regions are functional alterations in migraineurs. As the function of the human brain is related to its structure, we further investigated white and gray matter structural alterations in migraineurs. Methods In current study, we used surface-based morphometry, voxel-based morphometry and diffusion tensor imaging analyses to detect structural alterations of the white matter and gray matter in 32 migraineurs without aura compared with 32 age- and gender-matched healthy controls. Results We found that migraineurs without aura exhibited significantly increased gray matter volume in the bilateral cerebellar culmen, increased cortical thickness in the lateral occipital-temporal cortex, decreased cortical thickness in the right insula, increased gyrification index in left postcentral gyrus, superior parietal lobule and right lateral occipital cortex, and decreased gyrification index in the left rostral middle frontal gyrus compared with controls. No significant change in white matter microstructure was found in DTI analyses. Conclusion The significantly altered gray matter brain regions were known to be associated with sensory discrimination of pain, multi-sensory integration and nociceptive information processing and were consistent with our previous fMRI study, and may be involved in the pathological mechanism of migraine without aura.

ObjectivePrimary monosymptomatic nocturnal enuresis (PMNE) refers to bed-wetting in children who have no other lower urinary tract symptoms and are never dry for more than 6 months. Our previous studies demonstrated that children with PMNE exhibited brain functional abnormalities compared with healthy controls; however, researches on the abnormalities in gray matter were limited. This study aimed to investigate brain structural changes in gray matter of children with PMNE using magnetic resonance imaging (MRI).MethodsGray matter volumes (GMVs) and gyrification indices (GIs) were calculated using voxel-based and surface-based morphometry analyses of structural MRI data acquired from 26 children with PMNE and 28 healthy children. To identify between-group differences in gray matter, two-sample t-tests were conducted on GMV and GI images separately.ResultsCompared with the controls, children with PMNE showed significantly increased GMVs in the supplementary motor area and medial prefrontal cortex regions (mean GMV in PMNE: 0.54 ± 0.07 l; mean GMV in controls: 0.50 ± 0.06 l) and reduced GIs in the right precuneus (mean GI in PMNE: 25.74° ± 2.34°; mean GI in controls: 27.97° ± 1.79°).ConclusionChildren with PMNE showed abnormal GMVs in frontal lobe and GIs in precuneus, and these changes might be involved in the pathological mechanism of PMNE.

BackgroundBotulinum toxin type A (BoNT-A) is generally considered safe and is widely used to treat a variety of clinical conditions involving muscle hyperactivity and for cosmetic purposes. However, the effects of BoNT-A poisoning (botulism) on brain function are poorly understood.Methodology/principal findingsHerein, we investigated brain functions in 9 patients who received illegal cosmetic injections of botulinum and 18 matched controls by combining the analysis methods of regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) based on resting-state fMRI. Compared with the controls, the patients with botulism exhibited significantly reduced ReHo values in the left posterior lobe of the cerebellum extending to the right anterior lobe of the cerebellum, as well as in the right anterior lobe of the cerebellum extending to the parahippocampal gyrus and right posterior lobe of the cerebellum. The patients with botulism also showed weakened ALFF values in the right anterior lobe of the cerebellum extending to the left anterior lobe of the cerebellum and right posterior lobe of the cerebellum, as well as in the right anterior lobe of the cerebellum.Conclusions/significanceThe results indicate that BoNT-A may modulate cerebral activation in specific areas, which may play roles in both the adverse effects of botulism and the mechanism underlying clinical treatment with BoNT-A.

Magnetic tunnel junction (MTJ), which arises from emerging spintronics, has the potential to become the basic component of novel memory, logic circuits, and other applications. Particularly since the first demonstration of current induced magnetization switching in MTJ, spin transfer torque magnetic random access memory (STT-MRAM) has sparked a huge interest thanks to its non-volatility, fast access speed, and infinite endurance. However, along with the advanced nodes scaling, MTJ with in-plane magnetic anisotropy suffers from modest thermal stability, high power consumption, and manufactural challenges. To address these concerns, focus of research has converted to the preferable perpendicular magnetic anisotropy (PMA) based MTJ, whereas a number of conditions still have to be met before its practical application. This paper overviews the principles of PMA and STT, where relevant issues are preliminarily discussed. Centering on the interfacial PMA in CoFeB/MgO system, we present the fundamentals and latest progress in the engineering, material, and structural points of view. The last part illustrates potential investigations and applications with regard to MTJ with interfacial PMA.

In recent years, Intelligent Transportation Systems (ITS) have developed a lot. More and more sensors and communication technologies (e.g., cloud computing) are being integrated into cars, which opens up a new design space for vehicular-based applications. In this paper, we present the Spatial Optimized Dynamic Path Planning algorithm. Our contributions are, firstly, to enhance the effective of loading mechanism for road maps by dividing the connected sub-net, and building a spatial index; and secondly, to enhance the effect of the dynamic path planning by optimizing the search direction. We use the real road network and real-time traffic flow data of Karamay city to simulate the effect of our algorithm. Experiments show that our Spatial Optimized Dynamic Path Planning algorithm can significantly reduce the time complexity, and is better suited for use as a real-time navigation system. The algorithm can achieve superior real-time performance and obtain the optimal solution in dynamic path planning.

Nocturnal enuresis (NE) is a common disorder in school-aged children. Previous studies have reported that children with NE exhibit structural, functional and neurochemical abnormalities in the brain, suggesting that children with NE may have cognitive problems. Additionally, children with NE have been shown to process emotions differently from control children. In fact, most cases of NE resolve with age. However, adults who had experienced NE during childhood may still have potential cognitive or emotion problems, and this possibility has not been thoroughly investigated.In this work, we used functional magnetic resonance imaging (fMRI) to evaluate brain functional changes in adults with a history of NE. Two groups, consisting of 21 adults with NE and 21 healthy controls, were scanned using fMRI. We did not observe a significant abnormality in activation during the Go/NoGo and Stroop tasks in adults with a history of NE compared with the control group. However, compared to healthy subjects, young adults with a history of NE mainly showed increased activation in the bilateral temporoparietal junctions, bilateral dorsolateral prefrontal cortex, and bilateral anterior cingulate cortex while looking at negative vs. neutral pictures.Our results demonstrate that adults with a history of childhood NE have no obvious deficit in response inhibition or cognitive control but showed abnormal neural responses to emotional stimuli.

MicroRNAs (miRNAs) are a class of endogenous small noncoding RNAs which regulate diverse molecular and biochemical processes at a post-transcriptional level in plants. As the ancestor of domesticated wheat, wild emmer wheat (Triticum turgidum ssp. dicoccoides) has great genetic potential for wheat improvement. However, little is known about miRNAs and their functions on salinity stress in wild emmer. To obtain more information on miRNAs in wild emmer, we systematically investigated and characterized the salinity-responsive miRNAs using deep sequencing technology. A total of 88 conserved and 124 novel miRNAs were identified, of which 50 were proven to be salinity-responsive miRNAs, with 32 significantly up-regulated and 18 down-regulated. miR172b and miR1120a, as well as mi393a, were the most significantly differently expressed. Targets of these miRNAs were computationally predicted, then Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that the targets of salinity-responsive miRNAs were enriched in transcription factors and stress-related proteins. Finally, we investigated the expression profiles of seven miRNAs ranging between salt-tolerant and sensitive genotypes, and found that they played critical roles in salinity tolerance in wild emmer. Our results systematically identified the salinity-responsive miRNAs in wild emmer, not only enriching the miRNA resource but also laying the foundation for further study on the biological functions and evolution of miRNAs in wild wheat and beyond.

RNA editing is an important way to convert cytidine (C) to uridine (U) at specific sites within RNA molecules at a post-transcriptional level in the chloroplasts of higher plants. Although it has been systematically studied in many plants, little is known about RNA editing in the wheat D genome donor Aegilops tauschii L. Here, we investigated the chloroplast RNA editing of Ae. tauschii and compared it with other wheat relatives to trace the evolution of wheat. Through bioinformatics prediction, a total of 34 C-to-U editing sites were identified, 17 of which were validated using RT-PCR product sequencing. Furthermore, 60 sites were found by the RNA-Seq read mapping approach, 24 of which agreed with the prediction and six were validated experimentally. The editing sites were biased toward tCn or nCa trinucleotides and 5′-pyrimidines, which were consistent with the flanking bases of editing sites of other seed plants. Furthermore, the editing events could result in the alteration of the secondary structures and topologies of the corresponding proteins, suggesting that RNA editing might impact the function of target genes. Finally, comparative analysis found some evolutionarily conserved editing sites in wheat and two species-specific sites were also obtained. This study is the first to report on RNA editing in Aegilops tauschii L, which not only sheds light on the evolution of wheat from the point of view of RNA editing, but also lays a foundation for further studies to identify the mechanisms of C-to-U alterations.

Magnetic tunnel junction nanopillar with interfacial perpendicular magnetic anisotropy (PMA-MTJ) becomes a promising candidate to build up spin transfer torque magnetic random access memory (STT-MRAM) for the next generation of non-volatile memory as it features low spin transfer switching current, fast speed, high scalability, and easy integration into conventional complementary metal oxide semiconductor (CMOS) circuits. However, this device suffers from a number of failure issues, such as large process variation and tunneling barrier breakdown. The large process variation is an intrinsic issue for PMA-MTJ as it is based on the interfacial effects between ultra-thin films with few layers of atoms; the tunneling barrier breakdown is due to the requirement of an ultra-thin tunneling barrier (e.g.,

Background This study aimed to investigate the relationship between overall obesity, central obesity and brain volumes, as well as to determine the extent to which cardiometabolic and inflammatory measures act as mediators in the association between body mass index (BMI), waist-hip ratio (WHR) and brain volumes.Methods In the context of counterfactual framework, mediation analysis was used to explore the potential mediation in which cardiometabolic and inflammatory measures may mediate the relationship between BMI, WHR, and brain volumes.Results Among 2413 community-dwelling participants, those with high BMI or WHR levels experienced an approximately brain ageing of 4 years. Especially, individuals with high WHR or BMI under the age of 65 exhibited white matter hyperintensity volume (WMHV) differences equivalent to around 5 years of ageing. Conversely, in the high-level WHR population over the age of 65, premature brain ageing in gray matter volume (GMV) exceeded 4.5 years. For GMV, more than 45% of the observed effect of WHR was mediated by glycaemic metabolism indicators. This proportion increases to 78.70% when blood pressure, triglyceride, leucocyte count, and neutrophil count are jointly considered with glycaemic metabolism indicators. Regarding WHR and BMI’s association with WMHV, cardiometabolic and inflammatory indicators, along with high-density lipoprotein cholesterol, mediated 35.50% and 20.20% of the respective effects.Conclusions Overall obesity and central obesity were associated with lower GMV and higher WMHV, a process that is partially mediated by the presence of cardiometabolic and inflammatory measures.

Objectives Endovascular therapy (EVT) now penetrates the once obscure realm of large infarct core volume acute ischaemic stroke (LICV-AIS). This research aimed to investigate the potential correlation between different anaesthetic approaches and post-EVT outcomes in LICV-AIS patients.Methods Between October 2020 and May 2022, the China ANGEL-Alberta Stroke Programme Early CT Score (ASPECT) trial studied patients with LICV-AIS, randomly assigning them to the best medical management (BMM) or BMM with EVT. This post hoc subgroup analysis categorised subjects receiving BMM with EVT into general anaesthesia (GA) and non-GA groups based on anaesthesia type. We applied multivariable logistic regression to evaluate the relationship between anaesthesia during EVT and patient functional outcomes, as measured by the modified Rankin scale (mRS), in addition to the occurrence of complications. Further adjustment for selection bias was achieved through propensity score matching (PSM).Results In total, 230 patients with LICV-AIS were enrolled (GA 84 vs Non-GA 146). No significant difference was observed between the two groups in terms of the proportion of patients who achieved an mRS score of 0–2 at 90 days (27.4% for the GA group vs 31.5% for the non-GA group, p=0.51). However, the GA group had significantly longer median surgical times (142 min vs 122 min, p=0.03). Furthermore, GA was associated with an increased risk of postoperative pneumonia (adjusted OR 2.03, 95% CI 1.04 to 3.98). The results of PSM analysis agreed with the results of the multivariate regression analysis. No significant difference in intracranial haemorrhage incidence or mortality rate was observed between the groups.Conclusion This post hoc analysis of subgroups of the ANGEL-ASPECT trial suggested that there may be no significant association between the choice of anaesthesia and neurological outcomes in LICV-AIS patients. However, compared with non-GA, GA prolongs the duration of EVT and is associated with a greater postoperative pneumonia risk.Trial registration number NCT04551664.

Background The benefit–risk profile of tenecteplase in the elderly patients with acute ischaemic stroke (AIS) is uncertain. We sought to investigate the efficacy and safety of 0.25 mg/kg tenecteplase compared with alteplase for AIS patients aged ≥80 years.Methods We performed a post hoc analysis of the Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-2 Trial, a randomised, phase 3, non-inferiority clinical trial. Disabling AIS patients aged ≥80 years who initiated intravenous thrombolytics within 4.5 hours of symptom onset were enrolled from June 2021 to May 2022 across 53 centres in China and were randomly allocated to receive 0.25 mg/kg tenecteplase or 0.9 mg/kg alteplase. The primary efficacy outcome was the proportion of participants with a modified Rankin Scale (mRS) score of 0–1 at 90 days. Symptomatic intracranial haemorrhage (sICH) within 36 hours was the safety outcome.Results Of 137 participants, mRS 0–1 at 90 days occurred in 37 (49.3%) of 75 in the tenecteplase group vs 20 (33.9%) of 59 in the alteplase group (risk ratio (RR) 1.47, 95% CI 0.96 to 2.23). sICH within 36 hours was observed in 3 (4.0%) of 76 in the tenecteplase group and two (3.3%) of 61 in the alteplase group (RR 1.30, 95% CI 0.20 to 8.41).Conclusions The risk–benefit profile of tenecteplase thrombolysis was preserved in the elderly patients, which lends further support to intravenous 0.25 mg/kg tenecteplase as an alternative to alteplase in these patients.

Background and purpose The benefits of thrombolytic therapy before endovascular thrombectomy in cases of acute ischaemic stroke, with a large infarction volume, remain unclear. This analysis aims to evaluate the effectiveness and safety of bridging therapy and endovascular therapy among patients with large cerebral infarctions.Methods In this post-hoc analysis of the multicentre prospective study of ANGEL-ASPECT (Acute Anterior Circulation Large Vessel Occlusive Patients with a Large Infarct Core), participants were divided into two groups: an endovascular therapy group and a bridging therapy group. The primary outcome was the modified Rankin Scale (mRS) score at 90 days. The primary safety outcome was symptomatic intracranial haemorrhage. Ordinal logistic regression was performed to compare the primary endpoint between the two groups. Subgroup analyses were conducted to further explore potential risk factors associated with the outcomes.Results 122 patients were included, of whom 77 (63%) underwent endovascular therapy and 45 (37%) underwent bridging therapy. The median scores on mRS at 90 days of the bridging therapy group and the endovascular therapy group were 3 (2–5) and 4 (2–6), with no significant differences (common OR 1.36; 95% CI 0.71 to 2.61). Symptomatic intracranial haemorrhage was reported in three patients who were in the endovascular and bridging therapy groups (relative risk (RR) 1.71; 95% CI 0.36 to 8.12). The mortality between two groups did not differ (RR 0.75; 95% CI 0.37 to 1.54).Conclusions Our study indicated that endovascular therapy alone might be a viable option for patients with large cerebral infarctions, displaying no noticeable disparity in outcomes compared with bridging therapy.

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 (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

Background and purpose Multiple factors play important roles in the occurrence and prognosis of stroke. However, the roles of monogenic variants in all-cause ischaemic stroke have not been systematically investigated. We aim to identify underdiagnosed monogenic stroke in an adult ischaemic stroke/transient ischaemic attack (TIA) cohort (the Third China National Stroke Registry, CNSR-III).Methods Targeted next-generation sequencing for 181 genes associated with stroke was conducted on DNA samples from 10 428 patients recruited through CNSR-III. The genetic and clinical data from electronic health records (EHRs) were reviewed for completion of the diagnostic process. We assessed the percentages of individuals with pathogenic or likely pathogenic (P/LP) variants, and the diagnostic yield of pathogenic variants in known monogenic disease genes with associated phenotypes.Results In total, 1953 individuals harboured at least one P/LP variant out of 10 428 patients. Then, 792 (7.6%) individuals (comprising 759 individuals harbouring one P/LP variant in one gene, 29 individuals harbouring two or more P/LP variants in different genes and 4 individuals with two P/LP variants in ABCC6) were predicted to be at risk for one or more monogenic diseases based on the inheritance pattern. Finally, 230 of 792 individuals manifested a clinical phenotype in the EHR data to support the diagnosis of stroke with a monogenic cause. The most diagnosed Mendelian cause of stroke in the cohort was cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. There were no relationships between age or family history and the incidence of first symptomatic monogenic stroke in patients.Conclusion The rate of monogenic cause of stroke was 2.2% after reviewing the clinical phenotype. Possible reasons that Mendelian causes of stroke may be missed in adult patients who had an ischaemic stroke/TIA include a late onset of stroke symptoms, combination with common vascular risks and the absence of a prominent family history.

Introduction It remains unclear whether enlarged perivascular spaces (EPVS) predict poor clinical outcomes in patients with acute ischaemic stroke (AIS) or transient ischaemic attack (TIA).Method Data were obtained from the Third China National Stroke Registry study. We estimated EPVS in basal ganglia (BG) and centrum semiovale (CSO) using a semiquantified scale (Grade from 0 to 4). Using Cox and logistic regression analyses, the associations of EPVS with 3-month and 1-year adverse outcomes (including recurrent stroke, ischaemic stroke, haemorrhagic stroke, combined vascular event, disability and mortality) were explored. Sensitivity analyses of any association of cerebral small vessel disease at baseline and development of a small arterial occlusion (SAO) were conducted.Result Among 12 603 patients with AIS/TIA, median age was 61.7±11.6 years, and 68.2% were men. After adjusting for all potential confounders, frequent-to-severe BG-EPVS was associated with a decreased risk of recurrent ischaemic stroke (HR 0.71, 95% CI 0.55 to 0.92, p=0.01) but an increased risk of haemorrhagic stroke (HR 1.99, 95% CI 1.11 to 3.58, p=0.02) at 1 year after AIS/TIA, compared with none-to-mild BG-EPVS. Patients with frequent-to-severe CSO-EPVS had a decreased risk of disability (OR 0.76, 95% CI 0.62 to 0.92, p=0.004) and all-cause death (HR 0.55, 95% CI 0.31 to 0.98, p=0.04) within 3-month but not 1-year follow-ups, compared with those with none-to-mild BG-EPVS. Sensitivity analyses showed that both BG-EPVS (HR 0.43, 95% CI 0.21 to 0.87, p=0.02) and CSO-EPVS (HR 0.58, 95% CI 0.35 to 0.95, p=0.03) were associated with a decreased risk of subsequent ischaemic stroke in patients with SAO during 1-year follow-up.Conclusion BG-EPVS increased the risk of haemorrhagic stroke in patients already with AIS/TIA within 1 year. Therefore, caution is recommended when selecting antithrombotic agents for secondary stroke prevention in patients with AIS/TIA and more severe BG-EPVS.

Background Although stroke management, primary and secondary preventions have been improved in China last decades, the trends and predictors of major vascular events after ischaemic stroke or transient ischaemic attack (TIA) at national scale are less known.Methods Data were obtained from the three phases of China National Stroke Registry (CNSR), including CNSR-Ⅰ (years 2007–2008), CNSR-Ⅱ (years 2012–2013) and CNSR-III (years 2015–2018). For comparison, patients who were diagnosed as ischaemic stroke or TIA were included. Kaplan-Meier estimates of myocardial infarction (MI) or vascular death were calculated at 1 year. Independent predictors were further assessed with a Cox proportional hazards regression.Results From 2007 to 2018, a total of 50 284 patients with ischaemic stroke or TIA were enrolled in this study. A declining trend was found in 1-year MI or vascular death (p for trend 6 were associated with both an increased risk of MI or vascular death and recurrent stroke. While early antiplatelet therapy and lipid-lowering agents at discharge predicted a reduced risk.Conclusion A declining trend and current low incidence of MI or vascular death, rather than recurrent stroke, after ischaemic stroke or TIA were observed in China. Traditional factors were found as independent predictors. These findings suggested there is still much room to improve for stroke management.