BackgroundAging is an important factor in the development of Alzheimer’s disease (AD). The senescent cells can be recognized and removed by NK cells. However, NK cell function is gradually inactivated with age. Therefore, this study used senescence as an entry point to investigate how NK cells affect AD.MethodsThe study validated the correlation between cognition and aging through a prospective cohort of the National Health and Nutrition Examination Survey database. A cellular trajectory analysis of the aging population was performed using single-cell nuclear transcriptome sequencing data from patients with AD and different ages. The genome-wide association study (GWAS) cohort of AD patients was used as the outcome event, and the expression quantitative trait locus was used as an instrumental variable. Causal associations between genes and AD were analyzed by bidirectional Mendelian randomization (MR) and co-localization. Finally, clinical cohorts were constructed to validate the expression of key genes.ResultsA correlation between cognition and aging was demonstrated using 2,171 older adults over 60 years of age. Gene regulation analysis revealed that most of the highly active transcription factors were concentrated in the NK cell subpopulation of AD. NK cell trajectories were constructed for different age populations. MR and co-localization analyses revealed that CHD6 may be one of the factors influencing AD.ConclusionWe explored different levels of AD and aging from population cohorts, single-cell data, and GWAS cohorts and found that there may be some correlations of NK cells between aging and AD. It also provides some basis for potential causation.

Intracerebral haemorrhage (ICH) is a catastrophic subtype of stroke with severe morbidity and mortality. However, little progress has been made in the subsequent secondary injury. Artesunate, a water-soluble semi-synthetic derivative of artemisinin, exhibits remarkable pharmacological effects on anti-neuroinflammation. However, the effects of artesunate on ICH remain unknown. In the present study, haemoglobin (Hb) treatment in BV2 cell and collagenase type IV intracerebroventricular injection in Sprague-Dawley rats were used to establish in vitro and in vivo ICH models, respectively. For in vivo, the neurological scores, haematoma volume, brain oedema, inflammatory factors and iron deposition were evaluated. Besides, lipopolysaccharide (LPS) was used in in vitro to polarize BV2 cell to M1 phenotype. Cell viability, cellular reactive oxygen species (ROS), Fe2+ concentration, and lipid peroxidation levels, ferroptosis-associated proteins and mRNA, morphological of mitochondria were measured in vitro. Additionally, the AMP-activated protein kinase (AMPK)/mammalian/mechanistic target of rapamycin (mTOR) pathway were measured by western blot and immunofluorescence staining. The present in vivo results indicated that artesunate significantly ameliorated neurological deficits, haematoma volume and brain oedema in ICH rats. Besides, artesunate suppressed the M1-microglia relative inflammatory factors and up-regulated iron deposition. For in vitro, artesunate significantly selectively decreased the viability of LPS-stimulated BV2 cell. Furthermore, ROS and lipid peroxidation levels were up-regulated. And the glutathione peroxidase 4 (GPX4) were silenced via the AMPK/mTORC1 axis. Our finding supports that artesunate ameliorates the ICH secondary injury both in vitro and in vivo by inducing ferroptosis in microglia and further inhibiting inflammation mainly through the AMPK/mTORC1/GPX4 pathway. This finding may provide a novel target for ICH treatment.

We analyzed the clinical characteristics and outcomes of patients with Streptococcus suis meningitis in Liuzhou, China, to improve diagnostic accuracy and lower the chances of misdiagnosis. The major clinical manifesta-tions, auxiliary examination results, treatment strategies, treatment efficacy, and follow-up results of 17 consecutively admitted patients with S. suis meningitis were evaluated. The most common clinical manifestations were fever (15/17), sensorineural hearing loss (13/17), headache (11/17), and altered mental status (8/17). In addition, 64.71% of the patients had residual symptoms of sensorineural hearing loss at discharge, and moderate disabilities occurred in 68.75% of the patients in the form of sensorineural deafness (11/17) and hemiparesis (1/17). The cerebrospinal fluid (CSF) of nine patients was used for metagenomic analysis with next-generation sequencing. The metagenomic analysis of CSF of four patients was positive, whereas blood and CSF cultures were negative. The average modified Rankin Scale (mRS) and Activities of Daily Living (ADL) scores improved significantly at the 6-month follow-up compared with those at admission (P < 0.05). There was no correlation between altered mRS and ADL scores and the CSF findings (P . 0.05). Early admin-istration of antibiotics can prevent sensorineural hearing loss. Early CSF metagenomic analysis may be superior to blood and CSF culture.

BackgroundThe purpose of this study was to explore the diagnostic value of convolutional neural networks (CNNs) in middle cerebral artery (MCA) stenosis by analyzing transcranial Doppler (TCD) images.MethodsOverall, 278 patients who underwent cerebral vascular TCD and cerebral angiography were enrolled and classified into stenosis and non-stenosis groups based on cerebral angiography findings. Manual measurements were performed on TCD images. The patients were divided into a training set and a test set, and the CNN architecture was used to classify TCD images. The diagnostic accuracies of manual measurements, CNNs, and TCD parameters for MCA stenosis were calculated and compared.ResultsOverall, 203 patients without stenosis and 75 patients with stenosis were evaluated. The sensitivity, specificity, and area under the curve (AUC) for manual measurements of MCA stenosis were 0.80, 0.83, and 0.81, respectively. After 24 iterations of the running model in the training set, the sensitivity, specificity, and AUC of the CNNs in the test set were 0.84, 0.86, and 0.80, respectively. The diagnostic value of CNNs differed minimally from that of manual measurements. Two parameters of TCD, peak systolic velocity and mean flow velocity, were higher in patients with stenosis than in those without stenosis; however, their diagnostic values were significantly lower than those of CNNs (P < 0.05).ConclusionsThe diagnostic value of CNNs for MCA stenosis based on TCD images paralleled that of manual measurements. CNNs could be used as an auxiliary diagnostic tool to improve the diagnosis of MCA stenosis.

BACKGROUNDThe incidence of cerebral hemorrhage has rapidly increased over time, and vascular dysfunction has a significant influence on the pathogenesis and outcome of these patients. This is also the case for vasospasm in cerebral hemorrhage, but there is no method to assess this. We conducted this study to find molecular biomarkers of vasospasm in cerebral hemorrhage patients.METHODSRaw data of GSE37924 was downloaded from the Gene Expression Omnibus (GEO) database, including 66 samples with cerebral vasospasm and 62 samples without cerebral vasospasm. Differentially expressed genes (DEGs) between samples with cerebral vasospasm and those without cerebral vasospasm were analyzed using the limma package in R software. To determine the functions of DEGs, we conducted functional enrichment analysis of DEGs through the clusterProfiler package in R. The protein-protein interaction (PPI) network of DEGs was constructed through STRING (https://string-db.org/) and generated via Cytoscape software. To understand the correlation between DEGs and immune-related genes, immune-related cerebral vasospasm genes were obtained via intersecting immune-related genes and cerebral vasospasm DEGs. We also compared the infiltration of 28 immune cells between cases with cerebral vasospasm and those without cerebral vasospasm. Finally, we constructed a model to perform the validation experiments.RESULTSOf the DEGs, there were 24 upregulated and 21 downregulated genes in the vasospasm samples compared to the no-vasospasm samples. Functional enrichment analysis showed that these genes play key roles in several biological processes and signaling pathways such as the bone morphogenetic protein (BMP) signaling pathway, cellular response to BMP stimulus, natural killer cell chemotaxis, negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway, MHC protein complex binding, and receptor ligand activity, among others. CCL4, HLA-DQA1, IGF2, NTS, and so on were the significant immune-related genes. Furthermore, the immune cell infiltration results showed that there were differences between patients with vasospasm and those without vasospasm. Finally, we found that CCL4 had significantly higher expression in patients with vasospasm than those without vasospasm.CONCLUSIONSCCL4 is an important regulator of vascular dysfunction in cerebral hemorrhage.

Background and objectives: The findings on the associations between potential genetic variants and risk of Guillain-Barre syndrome (GBS) are controversial. We conducted a meta-analysis for candidate genes to provide the evidences for the current understanding of the genetic association with GBS.Methods: We searched relevant studies without language restriction in PubMed, Embase and Cochrane library through May 2011. The strengths of the associations between genetic variants and GBS risk were estimated by odds ratios (ORs) with 95% confidence intervals (CIs). Random-effects models or fixed effects model was applied based on the heterogeneity test.Results: We identified 12 case-control studies involving 1,590 GBS cases and 2,154 controls for the analysis. Because of limited eligible data, our meta-analysis specifically focused on 6 genetic variants of 3 candidate genes, TNF-alpha, Fc gamma R and CD1. We found that TNF-alpha. 308 G/A polymorphism was significantly associated with the risk of GBS in the overall population (CC + GA vs. AA: OR = 0.32, 95%CI = 0.16-0.62; GG vs. AA: OR = 036, 95%CI = 0.19-0.68). Subgroup analysis further provided evidence of significant association between TNF-alpha 308 G/A and risk of the GBS in Asian population (GG + GA vs. AA: OR = 32, 95%CI = 0.11-0.93; GG vs. AA: OR = 0.32, 95%CI = 0.15-0.68). In addition, we did not observe significant associations between Fc gamma RIIA R/H, Fc gamma RIIIA F/V, Fc gamma RIIIB NA1/NA2, CD1A 1/2 and CD1E 1/2 polymorphisms and susceptibility for developing GBS.Conclusions: Our findings showed that TNF-alpha 308A allele might be a moderate risk factor for GBS. However, the results should be interpreted with caution due to the limited number of studies available. (C) 2011 Elsevier B.V. All rights reserved.

OBJECTIVE:To evaluate the diagnostic value of 64-slice spiral computed tomographic angiography (CTA) in vertebral artery stenosis through a meta-analysis of the relevant data.METHODS:A database search of Cochrane Library, PubMed, EBSCO, CBM-disc and CNKI was performed to identify the relevant English and Chinese language articles with such keywords as 64-slice computer tomography, angiography and vertebral artery stenosis. Quality evaluation, heterogeneity test and sensitivity and specificity to the qualified original data were conducted. Summary receiver operating characteristic (SROC) curve, the area under curve (AUC) and diagnostic odds ratio (DROC) were also calculated.RESULTS:A total of 4 studies were eligible for meta-analysis. Among them, 1 was graded as A and 3 were graded as B. No heterogeneity was found based upon a fixed effect model. For vertebral artery stenosis > or = 50%, the pooled weighted sensitivity, specificity, DROC and SROC AUC was 0.98 (0.94 -1.00), 0.93 (0.89 -0.96), 526.33 and 0.9899 respectively; while for vertebral artery stenosis > or = 50%, the parameters were 0.98 (0.91 - 1.00), 0.97 (0.94 -0.99), 838.40 and 0.9932 respectively.CONCLUSIONS:64-slice spiral CTA has such a high level of accuracy, sensitivity and specificity in the non-invasive diagnosis of vertebral artery stenosis.