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Importance Stroke is the leading cause of death in China. However, recent data about the up-to-date stroke burden in China are limited. Objective To investigate the urban-rural disparity of stroke burden in the Chinese adult population, including prevalence, incidence, and mortality rate, and disparities between urban and rural populations. Design, Setting, and Participants This cross-sectional study was based on a nationally representative survey that included 676 394 participants aged 40 years and older. It was conducted from July 2020 to December 2020 in 31 provinces in mainland China. Main Outcomes and Measures Primary outcome was self-reported stroke verified by trained neurologists during a face-to-face interviews using a standardized protocol. Stroke incidence were assessed by defining first-ever strokes that occurred during 1 year preceding the survey. Strokes causing death that occurred during the 1 year preceding the survey were considered as death cases. Results The study included 676 394 Chinese adults (395 122 [58.4%] females; mean [SD] age, 59.7 [11.0] years). In 2020, the weighted prevalence, incidence, and mortality rates of stroke in China were 2.6% (95% CI, 2.6%-2.6%), 505.2 (95% CI, 488.5-522.0) per 100 000 person-years, and 343.4 (95% CI, 329.6-357.2) per 100 000 person-years, respectively. It was estimated that among the Chinese population aged 40 years and older in 2020, there were 3.4 (95% CI, 3.3-3.6) million incident cases of stroke, 17.8 (95% CI, 17.5-18.0) million prevalent cases of stroke, and 2.3 (95% CI, 2.2-2.4) million deaths from stroke. Ischemic stroke constituted 15.5 (95% CI, 15.2-15.6) million (86.8%) of all incident strokes in 2020, while intracerebral hemorrhage constituted 2.1 (95% CI, 2.1-2.1) million (11.9%) and subarachnoid hemorrhage constituted 0.2 (95% CI, 0.2-0.2) million (1.3%). The prevalence of stroke was higher in urban than in rural areas (2.7% [95% CI, 2.6%-2.7%] vs 2.5% [95% CI, 2.5%-2.6%];P = .02), but the incidence rate (485.5 [95% CI, 462.8-508.3] vs 520.8 [95% CI, 496.3-545.2] per 100 000 person-years;P < .001) and mortality rate (309.9 [95% CI, 291.7-328.1] vs 369.7 [95% CI, 349.1-390.3] per 100 000 person-years;P < .001) were lower in urban areas than in rural areas. In 2020, the leading risk factor for stroke was hypertension (OR, 3.20 [95% CI, 3.09-3.32]). Conclusions and Relevance In a large, nationally representative sample of adults aged 40 years or older, the estimated prevalence, incidence, and mortality rate of stroke in China in 2020 were 2.6%, 505.2 per 100 000 person-years, and 343.4 per 100 000 person-years, respectively, indicating the need for an improved stroke prevention strategy in the general Chinese population.

Understanding tumor metabolism holds the promise of new insights into cancer biology, diagnosis and treatment. To assess human cancer metabolism, here we report a method to collect intra-operative samples of blood from an artery directly upstream and a vein directly downstream of a brain tumor, as well as samples from dorsal pedal veins of the same patients. After performing targeted metabolomic analysis, we characterize the metabolites consumed and produced by gliomas in vivo by comparing the arterial supply and venous drainage. N-acetylornithine, D-glucose, putrescine, and L-acetylcarnitine are consumed in relatively large amounts by gliomas. Conversely, L-glutamine, agmatine, and uridine 5-monophosphate are produced in relatively large amounts by gliomas. Further we verify that D-2-hydroxyglutarate (D-2HG) is high in venous plasma from patients with isocitrate dehydrogenases1 ( IDH1 ) mutations. Through these paired comparisons, we can exclude the interpatient variation that is present in plasma samples usually taken from the cubital vein. Cellular metabolism is altered in many cancer types and the advent of metabolomics has allowed us to understand more about how this is dysregulated. Here, the authors report a method named CARVE to analyse the arterial supply and venous drainage of glioma patients during surgery and identify the metabolites that may be consumed and produced by the cancer.

Prediction of memory performance (remembered or forgotten) has various potential applications not only for knowledge learning but also for disease diagnosis. Recently, subsequent memory effects (SMEs)-the statistical differences in electroencephalography (EEG) signals before or during learning between subsequently remembered and forgotten events-have been found. This finding indicates that EEG signals convey the information relevant to memory performance. In this paper, based on SMEs we propose a computational approach to predict memory performance of an event from EEG signals. We devise a convolutional neural network for EEG, called ConvEEGNN, to predict subsequently remembered and forgotten events from EEG recorded during memory process. With the ConvEEGNN, prediction of memory performance can be achieved by integrating two main stages: feature extraction and classification. To verify the proposed approach, we employ an auditory memory task to collect EEG signals from scalp electrodes. For ConvEEGNN, the average prediction accuracy was 72.07% by using EEG data from pre-stimulus and during-stimulus periods, outperforming other approaches. It was observed that signals from pre-stimulus period and those from during-stimulus period had comparable contributions to memory performance. Furthermore, the connection weights of ConvEEGNN network can reveal prominent channels, which are consistent with the distribution of SME studied previously.

Numerous observational studies have shown that depressive symptoms are common in individuals with mild cognitive impairment (MCI) who have a higher rate of progress to dementia. However, it is still uncertain whether there are any differences between MCI patients with and without depression symptom in their brain function activities. Here we have identified the brain function activity differences in two groups of MCI patients (with depression or without depression) using the resting state MRI (rsfMRI) measurements. 76 right-handed MCI subjects have been recruited in this study, including 27 MCI patients with depression symptom (MCID), 49 MCI patients without depression symptom (MCIND). Analyses based on 7 rsfMRI measurements, including four static measurements (ALFF, fALFF, PerAF, and ReHo) and three dynamic measurements (dALFF, dfALFF, and dReHo) have been used to explore the temporal variability of intrinsic brain activity. No significant differences in ALFF and dALFF between the two group were found. In the MCID group, fALFF decreased in temporal gyrus, frontal gyrus, inferior occipital gyrus, middle frontal gyrus and cerebellum, but increased in cuneus, calcarine, lingual; while PerAF increased in left parahippocampus. The differences of ReHo in the two groups was only found in cerebellum. Compared to MCIND group, dfALFF in MCID decreased in cuneus, occipital gyrus and calcarine, while dReHo in MCID increased in bilateral temporal gyrus, frontal gyrus, superior parietal gyrus, inferior parietal gyrus and precuneus. Our results may provide a better understanding in the relationship between the depressive symptoms and memory deficits.

Objective We analyzed the outcomes of patients suffering acute ischemic stroke (AIS) with large vessel occlusion (LVO) soon after pulmonary lobectomy. Methods We retrospectively reviewed the clinical records of patients who underwent pulmonary lobectomy to treat primary lung cancer. We retrieved clinical characteristics and the incidence of AIS with LVO. The clinical courses of patients who experienced AIS were reviewed. Results In 10 (0.3%) of 3406 patients, AIS with LVO developed soon (within 3 days) after pulmonary lobectomy. The lung resection site was on the left in eight patients (80%). All patients underwent thrombectomy and achieved complete recanalization (Thrombolysis in Cerebral Infarction [TICI] 3). The average time between symptom onset and recanalization was 165.5 min. Nine (90%) patients exhibited favorable outcomes (modified Rankin scale [mRS] score ≤ 2) at the 3-month follow-up. Conclusion Endovascular therapy effectively treats AIS with LVO that develops after lung surgery, and direct aspiration is a promising strategy. A large, multicenter study is warranted to further confirm these findings.

Background Asymptomatic internal carotid artery occlusion (aICAO) disrupts cerebral blood flow and can impair brain function. While previous research has primarily focused on abnormal functional connectivity between brain networks or regions in aICAO patients, less is known about specific regional brain activity alterations. This study investigated changes in local brain activity and their associations with cognitive function in patients with aICAO. Methods A total of 26 unilateral patients with aICAO without MRI lesions and 25 matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging and neuropsychological assessment. Local brain activity in patients with aICAO was investigated using percentage amplitude of fluctuation (PerAF) and degree centrality (DC). The association between the abnormal regional brain activity in patients with aICAO and cognitive function was also explored. Results Compared with HCs, patients with aICAO showed decreased PerAF in the ipsilateral (occlusion side, right) superior temporal gyrus (temporal pole), ipsilateral inferior frontal gyrus (triangular part). In addition, decreased DC was detected in the ipsilateral cuneus of patients with aICAO, while increased DC was observed in the contralateral (opposite to occlusion side, left) precuneus and contralateral inferior frontal gyrus (triangular part) among patients with aICAO. Furthermore, the DC value of contralateral precuneus in aICAO group was negatively correlated with Montreal Cognitive Assessment (MoCA) ( r = -0.612, p  = 0.002), Forward Digit Span Test (FDST) ( r = -0.677, p  = 0.001), and Backward Digit Span Test (BDST) ( r = -0.531, p  = 0.011) scores. Conclusions Our findings revealed abnormal local spontaneous brain activity within brain regions associated with cognitive functions in patients with unilateral aICAO. Notably, some of these abnormalities correlated with their cognitive impairments. This study contributes to the understanding of potential neural mechanisms underlying cognitive dysfunction in unilateral aICAO patients.

Background The disruption of the blood–brain barrier (BBB) plays a critical event in the pathogenesis of ischemia stroke. TGR5 is recognized as a potential target for the treatment for neurologic disorders. Methods This study investigated the roles of TGR5 activation in attenuating BBB damage and underlying mechanisms after middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were subjected to model of MCAO and TGR5 agonist, INT777, was administered intranasally. Small interfering RNA (siRNA) for TGR5 and BRCA1 were administered through intracerebroventricular injection 48 h before MCAO. Infarct volumes, brain water content, BBB permeability, neurological scores, Western blot, immunofluorescence staining and co- immunoprecipitation were evaluated. Results Endogenous TGR5 and BRCA1 were upregulated in the injured hemisphere after MCAO and TGR5 expressed in endothelial cells. Treatment with INT777 alleviated brain water content and BBB permeability, reduced infarction volume and improved neurological scores at 24 h and 72 h after ischemia. INT777 administration increased BRCA1 and Sirt1 expression, as well as upregulated expressions of tight junction proteins. Ischemic damage induced interaction of TGR5 with BRCA1. TGR5 siRNA and BRCA1 siRNA significantly inhibited expressions of BRCA1 and Sirt1, aggravated BBB permeability and exacerbated stroke outcomes after MCAO. The protective effects of INT777 at 24 h after MCAO were also abolished by TGR5 siRNA or BRCA1 siRNA. Conclusions Our findings demonstrate that activating TGR5 could reduce BBB breakdown and improve neurological functions through BRCA1/Sirt1 signaling pathway after MCAO. TGR5 may serve as a potential new candidate to relieve brain injury after MCAO.

Background Nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 (NLRP3) plays an important role in mediating inflammatory responses during ischemic stroke. Bile acid receptor Takeda-G-protein-receptor-5 (TGR5) has been identified as an important component in regulating brain inflammatory responses. In this study, we investigated the mechanism of TGR5 in alleviating neuroinflammation after middle cerebral artery occlusion (MCAO). Methods Sprague-Dawley rats were subjected to MCAO and TGR5 agonist INT777 was administered intranasally 1 h after MCAO. Small interfering RNAs (siRNA) targeting TGR5 and Pellino3 were administered through intracerebroventricular injection 48 h before MCAO. Infarct volumes and neurologic scores were evaluated, and ELISA, flow cytometry, immunofluorescence staining, immunoblotting, and co-immunoprecipitation were used for the evaluations. Results Endogenous TGR5 and Pellino3 levels increased after MCAO. TGR5 activation by INT777 significantly decreased pro-inflammatory cytokine, cleaved caspase-8, and NLRP3 levels, thereby reducing brain infarctions; both short- and long-term neurobehavioral assessments showed improvements. Ischemic damage induced the interaction of TGR5 with Pellino3. Knockdown of either TGR5 or Pellino3 increased the accumulation of cleaved caspase-8 and NLRP3, aggravated cerebral impairments, and abolished the anti-inflammatory effects of INT777 after MCAO. Conclusions TGR5 activation attenuated brain injury by inhibiting neuroinflammation after MCAO, which could be mediated by Pellino3 inhibition of caspase-8/NLRP3.

In neuroinflammation, distinguishing microglia from macrophages and identifying microglial-specific biomarkers in peripheral blood pose significant challenges. This study comprehensively profiled the extracellular vesicles (EVs) of microglia and macrophages, respectively, revealing co-expressed EVs with UCHL1 and CX3CR1 as EVs derived specifically from microglia in human blood. After extensive validation, using optimized nano flow cytometry, we evaluated plasma CX3CR1 + /UCHL1 + EVs across clinical cohorts [multiple sclerosis (MS), HTLV-1 associated myelopathy (HAM), Alzheimer’s disease (AD), and Parkinson’s disease (PD)], along with established neurodegenerative markers (NMDAR2A and NFL). The findings discovered a notable rise in CX3CR1 + /UCHL1 + EVs in MS, particularly heightened in HAM, in contrast to controls. Conversely, AD and PD exhibited unaltered or diminished levels of microglial EVs. An integrated model of CX3CR1 + /UCHL1 + , NMDAR2A + , and NFL + EVs demonstrated promising diagnostic potential for distinguishing MS from controls and HAM. As to the disease duration, CX3CR1 + /UCHL1 + EVs increased in the initial five years of MS, stabilizing thereafter, whereas NMDAR2A + and NFL + EVs remained stable initially but increased significantly in the subsequent five years, suggesting their correlation with disease duration. This study uncovers unique blood microglial EVs with potential as biomarkers for MS diagnosis, differentiation from HAM, and correlation with disease duration.

Abstract While converging evidence suggests linguistic roles of white matter tracts, detailed associations between white matter alterations of dual pathways and language abilities remain unknown in aphasic patients. We aimed to verify language functions of dual-pathway tracts from specific domains and investigate the influence of moderators. PubMed, Web of Science, Embase, and CENTRAL were searched for studies published between January 1, 1985 and March 17, 2019. A meta-analysis of 46 studies including 1353 aphasic patients was performed by pooling correlation coefficients between linguistic domains and diffusion metrics of dual-pathway tracts. Among these tracts, the fractional anisotropy (FA) value of the left inferior fronto-occipital fasciculus predominated across most linguistic aspects, showing the strongest correlations with global severity, comprehension, naming and reading ability. The left uncinate fasciculus and inferior longitudinal fasciculus also showed significant FA − comprehension correlations. For syntactic processing, FA values of the left superior longitudinal fasciculus and arcuate fasciculus showed significant positive correlations. Meta-regression revealed no influence of etiology on FA − language correlations, while sex had a moderating effect on the FA − comprehension correlation of the arcuate fasciculus, and age influenced the FA − naming correlation in the superior longitudinal fasciculus. In conclusion, multifunctional characteristics of tracts were revealed in aphasic patients, including broad linguistic associations of the inferior fronto-occipital fasciculus, and repetition and syntactic involvement of the arcuate fasciculus. Language associations of the inferior longitudinal fasciculus and uncinate fasciculus were clarified regarding comprehension subdomains. The insignificant moderating effect of the etiology indicates damage of dual pathways is the common neural mechanism, while sex and age influence the correlation with comprehension and naming ability, respectively, in specific tracts.