Background: Spinal cord injury (SCI) causes neurological dysfunction with devastating consequences. SCI pathogenesis is accompanied by inflammasome activation and neuronal damage. But the spatial pattern and the time course of neuronal pyroptosis and apoptosis after SCI should be further elucidated. The microglial voltage-gated proton channel (Hv1) is implicated in reactive oxygen species (ROS)-induced neuronal damage following ischemic stroke. However, there is a lack of quantification on the neuronal pyroptosis and apoptosis associated with microglial Hv1 after SCI. Methods: We analyzed spatial and temporal characteristics of neuronal pyroptosis and apoptosis following SCI and investigated the effects of Hv1 deficiency on neuronal pyroptosis and the nod-like receptor 3 (NLRP3) inflammasome pathway by using a mouse model of SCI. We tested the effects of Hv1-deficient microglia on ROS production in vivo and examined the relationship between ROS and neuronal pyroptosis in vitro. Results: We observed that apoptosis was detected closer to the injury core than pyroptosis. The incidence of neuronal apoptosis peaked on day 1 after SCI and occurred before pyroptosis. Hv1 deficiency reduced neuronal apoptosis and NLRP3-inflammasome-mediated pyroptosis, improved axonal regeneration, and reduced motor deficits. SCI led to elevated ROS levels, whereas Hv1 deficiency downregulated microglial ROS generation. In vitro, ROS upregulated neuronal pyroptosis and activated the NLRP3 inflammasome pathway, both of which were reversed by addition of a ROS scavenger. Our results suggested that microglial Hv1 regulated neuronal apoptosis and NLRP3-induced neuronal pyroptosis after SCI by mediating ROS production. Conclusion: Following SCI, neuronal pyroptosis lasted longer and occurred farther away from the injury core compared with that of neuronal apoptosis. Microglial Hv1 deficiency downregulated microglial ROS generation and reduced apoptosis and NLRP3-induced neuronal pyroptosis. Our findings may provide novel insights into Hv1-associated mechanisms underlying neuronal damage after SCI.

White matter hyperintensities (WMH) are imaging manifestations frequently observed in various neurological disorders, yet the clinical application of WMH quantification is limited. In this study, we designed a series of dedicated WMH labeling protocols and proposed a convolutional neural network named 2D VB-Net for the segmentation of WMH and other coexisting intracranial lesions based on a large dataset of 1,045 subjects across various demographics and multiple scanners using 2D thick-slice protocols that are more commonly applied in clinical practice. Using our labeling pipeline, the Dice consistency of the WMH regions manually depicted by two observers was 0.878, which formed a solid basis for the development and evaluation of the automatic segmentation system. The proposed algorithm outperformed other state-of-the-art methods (uResNet, 3D V-Net and Visual Geometry Group network) in the segmentation of WMH and other coexisting intracranial lesions and was well validated on datasets with thick-slice magnetic resonance (MR) images and the 2017 medical image computing and computer assisted intervention WMH Segmentation Challenge dataset (with thin-slice MR images), all showing excellent effectiveness. Furthermore, our method can subclassify WMH to display the WMH distributions and is very lightweight. Additionally, in terms of correlation to visual rating scores, our algorithm showed excellent consistency with the manual delineations and was overall better than those from other competing methods. In conclusion, we developed an automatic WMH quantification framework for multiple application scenarios, exhibiting a promising future in clinical practice.

Background: Immediately after spinal trauma, immune cells, and proinflammatory cytokines infiltrate the spinal cord and disrupt the focal microenvironment, which impedes axon regeneration and functional recovery. Previous studies have reported that regulatory T cells (Tregs) enter the central nervous system and exert immunosuppressive effects on microglia during multiple sclerosis and stroke. However, whether and how Tregs interact with microglia and modulate injured microenvironments after spinal cord injury (SCI) remains unknown.Method: Regulatory T cells spatiotemporal characteristics were analyzed in a mouse contusion SCI model. Microglia activation status was evaluated by immunostaining and RNA sequencing. Cytokine production in injured spinal cord was examined using Luminex. The role of STAT3 in Treg–microglia crosstalk was investigated in a transwell system with isolated Tregs and primary microglia.Results: Regulatory T cells infiltration of the spinal cord peaked on day 7 after SCI. Treg depletion promoted microglia switch to a proinflammatory phenotype. Inflammation‐related genes, such as ApoD, as well as downstream cytokines IL‐6 and TNF‐α were upregulated in microglia in Treg‐depleted mice. STAT3 inhibition was involved in Treg–microglia crosstalk, and STAT3 chemical blockade improved function recovery in Treg‐depleted mice.Conclusion: Our results suggest that Tregs promote functional recovery after SCI by alleviating microglia inflammatory reaction via STAT3.

China has experienced rapid economic growth and reduced poverty, but the associated changes of BMI categories of the Chinese population in recent years are unclear. We collected data from two-round cross-sectional National Health Service Surveys (NHSSs) conducted in China in 2013 and 2018. All family members with BMI available from the households sampled in NHSSs were included. We analyzed the standardized prevalence and changes of obesity and overweight by year, age, sex, and urban-rural area, and further identified risk factors for obesity and overweight. 273,688 individuals were included in 2013 and 25,6304 included in 2018. The standardized prevalence of obesity and overweight in adults were 19.3% (95%CI 19.1–19.4%) in 2013 and 25.6% (95%CI 25.3–25.8%) in 2018, versus 19.4% (95%CI 19·1–19.8%) in children and adolescents in 2013 and 15.8% (95%CI 15.5–16.1%) in 2018. The standardized prevalence of obesity and overweight was 16.9% (95%CI 16.0–17.3%) in young adults aged 19–29 in 2018, 48.2% higher than that in 2013 (11.4% [95%CI 11.0–11.6%]). Although the obesity and overweight prevalence was higher in urban areas, the growth rate in rural areas was 1.8 times higher than that in urban areas. Low education levels, low-income quintiles, marital status, alcohol consumption and former-smoking status were associated with higher obesity and overweight prevalence in adults. The rapidly increasing prevalence in young adults may lead to the growing chronic disease burden in the future, to the detriment of recent economic gains of rural families. National Health Commission of the People's Republic of China.

Aim: Insulin resistance was reported to increase the risk of ischemic stroke, which can be assessed by the triglyceride glucose (TyG) index. However, it remains unclear whether the TyG index influences the platelet reactivity during the treatment of ischemic patients. Methods: Ischemic stroke patients receiving dual antiplatelet therapy (DAPT) within 48 h onset were consecutively included. The TyG index was calculated as ln (fasting triglyceride [mg/dL] × fasting glucose [mg/dL]/2). The top quartile of TyG index was defined as insulin resistance. The platelet reactivity was assessed by thromboelastography. The platelet inhibition rate induced by arachidonic acid (AA) or adenosine diphosphate (ADP) was used to confirm the high residual on-treatment platelet reactivity (HRPR) to aspirin or clopidogrel, respectively. The association between TyG index and platelet reactivity was assessed by Kruskal–Wallis test. The independent risk factors of HRPR were determined by multivariate logistic regression analysis. Results: A total of 1002 patients were included and divided into 4 groups by quartiles of the TyG index (< 2.02; 2.02–2.27; 2.27–2.52; ≥2.52). The findings demonstrated that the maximum intensity of the clot increased, but the AA-induced platelet inhibition rate decreased, depending on the TyG index quartiles. No significant difference was found in the ADP-induced platelet inhibition rate among groups. The prevalence of aspirin HRPR increased depending on the TyG index quartile. Unlike the non-insulin resistance group, the insulin resistance group was independently associated with aspirin HRPR (OR = 1.689, 95% CI 1.14 to 2.51, P = 0.009). Conclusions: In acute ischemic stroke patients taking DAPT, the elevation of the TyG index is associated with enhanced platelet reactivity and higher prevalence of aspirin HRPR. Insulin resistance assessed by the TyG index could be an independent risk factor for aspirin HRPR.

We applied an MRI technique diffusion tensor imaging along the perivascular space (DTI-ALPS) for assessing glymphatic system (GS) in a genome-wide association study (GWAS) and phenome-wide association study (PheWAS) of 40,486 European individuals. Exploratory analysis revealed 17 genetic loci significantly associating with the regional DTI-ALPS index. We found 58 genes, including SPPL2C and EFCAB5 , which prioritized in the DTI-ALPS index subtypes and associated with neurodegenerative diseases. PheWAS of 241 traits suggested that body mass index and blood pressure phenotypes closely related to GS function. Moreover, we detected disrupted GS function in 44 of 625 predefined disease conditions. Notably, Mendelian randomization and mediation analysis indicated that lower DTI-ALPS index was a risk factor for ischemic stroke (odds ratio = 1.56, P = 0.028) by partly mediating the risk factor of obesity. Results provide insights into the genetic architecture and mechanism for the DIT-ALPS index and highlight its great clinical value, especially in cerebral stroke.