Neuronal intranuclear inclusion disease (NIID) is a rare, progressive neurodegenerative disorder currently diagnosed through invasive biopsies or genetic testing with ethnic limitations. Existing biomarkers from cerebrospinal fluid or plasma are not fully noninvasive, and no urine-based biomarker has been identified. There is an urgent need for a noninvasive, definitive diagnostic tool to distinguish NIID from other neurodegenerative diseases and healthy individuals. We developed a homogeneous digital immunoassay using two-color quantum dot (QD)-labeled antibodies to quantify p62 in urinary cell nuclei, achieving a detection limit of 47 fM. The assay demonstrated high selectivity and a wide dynamic range across three orders of magnitude. Analysis of urine samples from 10 NIID patients, 4 healthy controls, and 13 patients with other neurodegenerative disorders (myasthenia gravis, cerebral infarction, and Parkinson's disease) revealed that p62 levels were significantly elevated only in NIID patients. Spike recovery tests confirmed measurement accuracy (91%-106%), and p62 levels showed no correlation with disease stage in this limited cohort. This study introduces the first noninvasive urinary biomarker for NIID using a novel homogeneous digital immunoassay. The significantly elevated p62 levels specifically in NIID patients highlight its potential as a reliable, noninvasive diagnostic tool, enabling distinction from other neurodegenerative conditions and facilitating earlierand more accessible diagnosis.

Objective To retrospectively analyze the clinical features of patients with neuromyelitis optica spectrum disorder(NMOSD)who have or do not have Sjögren syndrome(SS)and to explore the association between the two con-ditions.Methods Retrospective analysis was conducted on 78 NMOSD patients who were admitted to the Affiliated Hos-pital of Xuzhou Medical University from January 2018 to September 2023.The patients were divided into two groups:a comorbidity group(44 patients with SS)and a non-comorbidity group(34 patients without SS).Both groups were com-pared for initial symptoms,disease course patterns(unidirectional or multiphasic),the Expanded Disability Status Scale(EDSS)scores at enrollment,annual relapse rate,laboratory test results,and MRI lesion characteristics.Results There were no statistically significant differences between the two groups in terms of the proportion of initial symptoms of myelitis and optic neuritis,disease course patterns,EDSS scores at enrollment,gender distribution,or annual relapse rate(P>0.05).The use of cyclophosphamide in the comorbidity group was significantly higher than in the non-comor-bidity group(P=0.003).There were no significant differences in cerebrospinal fluid(CSF)parameters(white blood cell count,protein quantification,CSF IgA,IgM,and IgG levels),as well as serum complement C3 and C4 levels be-tween the two groups(P>0.05).However,the comorbidity group showed significantly higher levels of serum IgA,IgM,and IgG,compared with the non-comorbidity group(P<0.05).Conclusions NMOSD and SS represent immune comor-bidity rather than concurrent complications.The comorbidity group shows elevated serum immunoglobulin levels and a greater tendency to use immunosuppressive agents during the maintenance phase.This suggests that the two conditions may share a common mechanism,where excessive B-cell activation leads to the production of similar autoantibodies that trigger cross-immune reactions through molecular mimicry,resulting in autoimmune attacks on different target organs.

Autoantibody- and complement-mediated cytotoxicity can cause autoimmune astrocytopathy that leads to CNS inflammatory demyelination. Formyl peptide receptor 2 (FPR2/ALX) governs the activation and propagation of immune response. However, the precise role of FPR2/ALX in neuroinflammation and the effect of FPR2/ALX stimulation on autoimmune astrocytopathy are poorly understood. Using a mouse model of autoimmune astrocytopathy induced by AQP4-IgG- and complement-mediated cytotoxicity, we found that the stimulation of FPR2/ALX with the small-molecule agonist Quin-C1 led to reduced brain lesion volume, astrocyte loss and demyelination. This was accompanied by enhanced anti-inflammatory activity of microglia and reduced infiltration of lymphocytes in the brain. FPR2/ALX stimulation also led to increased phosphorylation of SYK and AKT in mice with autoimmune astrocytopathy. Notably, the benefits of FPR2/ALX stimulation were attenuated in mice with autoimmune astrocytopathy after microglial depletion using the CSF1R inhibitor PLX5622 or natural killer (NK) cell depletion using an anti-NK1.1 monoclonal antibody. Additionally, the protective effects of FPR2/ALX stimulation were diminished in mice with autoimmune astrocytopathy that received the SYK inhibitor R406. Collectively, our findings demonstrate that FPR2/ALX stimulation may represent a promising therapeutic strategy to attenuate detrimental neuroinflammation in autoimmune astrocytopathy by modulating microglia and NK cells.FPR2/ALX stimulation suppresses autoimmune astrocytopathy: Using a mouse model of autoimmune astrocytopathy, we demonstrated that FPR2/ALX stimulation with the small molecule Quin-C1 reduces the CNS infiltration of lymphocytes and augments the anti-inflammatory activity of microglia, leading to attenuated astrocyte pathology induced by AQP4-IgG and complement-mediated attacks. Mechanistically, the benefits of FPR2/ALX stimulation using Quin-C1 involve microglia, natural killer (NK) cells, and SYK-AKT signaling.

BackgroundThe role of histone deacetylase 6 (HDAC6) in neurodegenerative diseases, particularly Alzheimer's disease (AD), has attracted significant research interest. Peroxiredoxin 2 (Prx2), a key antioxidant enzyme and HDAC6 substrate, plays a neuroprotective role against oxidative stress-mediated apoptosis.ObjectiveThis study systematically investigates the neuroprotective mechanism of the HDAC6-Prx2 axis in both cellular and transgenic AD models.MethodsAn AD model was established by bilateral hippocampal microinjection of Aβ1-42 oligomers in mice. The assessments of mice or their brain samples were included behavioral tests, immunofluorescence, western blot, NADP+/NADPH ratio, and oxidative stress assays. HDAC6-mediated acetylation of Prx2 was confirmed via co-immunoprecipitation, and the specific site was identified.ResultsThe disruption of the HDAC6-Prx2 interaction can significantly alleviate the apoptosis of hippocampal neurons in AD mice and salvage learning/memory deficits. Inhibiting HDAC6 can increase the acetylation level of Prx2 K196, thereby enhancing its antioxidant activity. Acetylated Prx2 inhibits the excessive production of reactive oxygen species (ROS), which is mechanically linked to HDAC6-dependent neuronal apoptosis This pathway mechanistically links HDAC6 activity to oxidative stress-induced apoptosis. HDAC6-mediated deacetylation of Prx2 K196 was shown to exacerbate oxidative damage and cognitive decline.ConclusionsThe study identifies a novel pathway where HDAC6 inhibition elevates Prx2 K196 acetylation, breaking the vicious cycle of ROS and apoptosis. Dual targeting of HDAC6 activity and Prx2 acetylation status represents a promising therapeutic strategy for AD.

Background Current clinical decision tools for assessing the risk of symptomatic intracranial hemorrhage (sICH) in patients with vertebrobasilar artery occlusion (VBAO) who received endovascular treatment (EVT) have limited performance. This study develops and validates a clinical risk score to precisely estimate the risk of sICH in VBAO patients.Methods The derivation cohort recruited patients with VBAO who received EVT from the Posterior Circulation IschemIc Stroke Registry in China. Based on the posterior circulation-Alberta Stroke Program Early CT Score (pc-ASPECTS) evaluation method, the cohort was further divided into non-contrast CT (NCCT) and diffusion weighted imaging (DWI) cohorts to construct predictive models. sICH was diagnosed according to the Heidelberg Bleeding Classification within 48 hours of EVT. Clinical signature was constructed in the derivation cohort using machine learning and was validated in two additional cohorts from Asia and Europe.Results We enrolled 1843 patients who underwent EVT and had complete data. pc-ASPECTS of 1710 patients was evaluated on NCCT and 699 patients on DWI. In the NCCT cohort, 1364 individuals made up the training set, of whom 101 (7.4%) developed sICH. In the DWI cohort, the training set consisted of 560 individuals, with 44 (7.9%) experiencing sICH. Predictors of sICH were: glucose, pc-ASPECTS, time from estimated occlusion to groin puncture (EOT), poor collateral circulation, and modified Thrombolysis in Cerebral Infarction (mTICI) score. From these predictors, we derived the weighted poor collateral circulation-EOT-pc-ASPECTS-mTICI-glucose (PEACE) score. The PEACE score showed good discrimination in the training set (area under the curve (AUC)NCCT=0.85; AUCDWI=0.86), internal validation set (AUCNCCT=0.81; AUCDWI=0.82), and two additional external validation set (Asia: AUCNCCT=0.78, AUCDWI=0.80; Europe: AUCNCCT=0.74, AUCDWI=0.78).Conclusion The PEACE score reliably predicted the risk of sICH in VBAO patients who underwent EVT.

BackgroundNeuronal intranuclear inclusion disease (NIID) is a neurodegenerative disorder caused by GGC repeat expansions in NOTCH2NLC, leading to uN2CpolyG protein deposition. Although immune-mediated renal lesions have been described in NIID, the systemic immunoinflammatory profile associated with kidney injury and its relationship with genetic burden remain undefined. This study investigated peripheral immune alterations in NIID-related nephropathy and their correlation with repeat expansion size.MethodsThis multicenter retrospective study enrolled 150 genetically and pathologically confirmed NIID patients from nine tertiary hospitals (2019-2024). Using KDIGO criteria, patients were stratified into NIID with kidney injury (NIID-KD, n=100) and NIID with no kidney injury (NIID-ND, n=50) groups. Peripheral inflammatory markers were assessed in 110 patients, and 12 T-cell-related cytokines were measured in a subset of 35 patients. Multivariable analyses adjusting for disease duration were performed. GGC repeat numbers were quantified in 48 patients.ResultsAfter adjustment for disease duration, the NIID-KD group maintained significantly higher white blood cell counts, neutrophil counts, monocyte counts, and neutrophil-to-lymphocyte ratio compared to NIID-ND (all P < 0.05). Cytokine profiling revealed selectively elevated IL-6 levels in the NIID-KD group (P = 0.042), whereas IL-17 elevation did not persist after adjustment (P = 0.239). No significant difference in GGC repeat expansion size was observed between groups among genotyped patients.ConclusionNIID-associated kidney injury is characterized by a distinct immunoinflammatory signature with sustained neutrophilic and monocytic activation and IL-6 upregulation, suggesting involvement of innate immunity and IL-6-mediated inflammation in renal pathology. The absence of direct correlation between repeat expansion size and kidney involvement indicates that while genetic mutation confers disease susceptibility, acquired inflammatory mechanisms critically determine renal phenotype. These findings provide clinical evidence linking proteinopathy to innate immune activation in NIID.

BACKGROUND: Superficial siderosis of the central nervous system (SSCNS) is a rare neurodegenerative disorder resulting from chronic hemorrhage into the subarachnoid space. This study aims to summarize its clinical and paraclinical features to improve clinical recognition. METHODS: We retrospectively analyzed the medical records of 14 patients diagnosed with SSCNS at the Affiliated Hospital of Xuzhou Medical University and Xuanwu Hospital between August 2011 and April 2023. Data on clinical manifestations, cerebrospinal fluid (CSF), imaging findings, treatment, and prognosis were collected and summarized. RESULTS: Among 14 patients (6 males, 8 females; mean age 53.1 years), the most common clinical manifestations were hearing loss (14/14, 100%), ataxia (12/14, 85.7%), and pyramidal tract dysfunction (12/14, 85.7%). Brain MRI revealed characteristic superficial siderosis in all cases, with susceptibility-weighted imaging (SWI) demonstrating superior sensitivity. Spinal cord involvement was observed in 13 patients (92.9%). CSF pressure predominantly falling within the normal range, while lumbar CSF exhibited signs of hemorrhage or yellowing, elevated red blood cell counts, and varying degrees of increased protein content. Sensorineural hearing loss was confirmed in 7/8 tested patients (87.5%). Potential bleeding sources were identified in 12 patients (85.7%), including prior surgery, trauma, and vascular abnormalities. Treatment was primarily symptomatic, with most patients (12/14) showing minimal improvement in core symptoms during hospitalization. CONCLUSION: Superficial siderosis of the central nervous system is a progressive neurodegenerative disorder characterized by the clinical triad of hearing loss, ataxia, and pyramidal tract dysfunction. MRI, particularly T2-weighted imaging (T2WI) and SWI sequences demonstrating a characteristic peripheral low-signal band, provides high diagnostic sensitivity and represents the cornerstone of diagnosis. Early identification remains challenging yet critical, while management should focus on locating the underlying bleeding source and providing comprehensive supportive care. TRIAL REGISTRATION: Not applicable.

BACKGROUND:The aim of this study was to investigate the relationships between imaging indicators of obesity, as measured by computed tomography (CT), and clinical outcomes at 90 days and 1 year after emergent endovascular therapy (EVT). METHODS:Participants with emergent large vessel occlusion (ELVO) who underwent EVT were prospectively enrolled. During hospitalization, CT scans were performed to evaluate the visceral adipose tissue area (VATA) and skeletal muscle area (SMA) at the level of the third lumbar spine. Multivariate regression analysis was used to assess the correlation of obesity-related imaging measures with various outcomes: mortality, favorable functional outcomes (modified Rankin scale (mRS) score 0-2), and functional improvement (shift in mRS score) at 90 days and 1 year. RESULTS:A total of 306 ELVO patients were included in the study, with a median age of 64 years and a median baseline National Institutes of Health Stroke Scale (NIHSS) score of 18. After adjusting for potential confounders, the VATA-to-SMA ratio (VSR) was significantly associated with a favorable functional outcome (OR 0.30, 95% CI 0.13 to 0.70) at 90 days and a favorable functional outcome (OR 0.27, 95% CI 0.12 to 0.61) and functional improvement (OR 0.33, 95% CI 0.12 to 0.92) at the 1 year follow-up. CONCLUSION:Our study indicated that lower VSR levels are associated with favorable functional outcomes, along with functional improvement at 90 days and 1 year of follow-up.

BACKGROUND:Air pollution exposure (both individual and joint) is associated with dementia, but its relation to early-onset dementia (EOD) and late-onset dementia (LOD) remains inconclusive. Meanwhile, the modification by genetic predisposition and mediation by accelerated biological aging are also unclear. METHODS:A cohort of 285 774 dementia-free participants from the UK Biobank was analyzed. Exposure levels of four major air pollutants (PM2.5, PM10, NO2, and NOx), two air pollution scores (APS1 and APS2) were obtained, and their associations with all-cause dementia (ACD), EOD and LOD were assessed via Cox models. Genetic predisposition to dementia was evaluated and the mediation role of PhenoAge-Accel was investigated under the counterfactual framework. RESULTS:During a median follow-up of 13.4 years, 3 898 participants developed ACD, including 231 with EOD and 3 650 with LOD. Per IQR increase of PM2.5, PM10, NO2, NOx, APS1 and APS2 was associated with 6.5% (95%CIs) (2.3%-10.9%), 6.8% (2.2%-11.5%), 4.6% (0%-9.5%), 5.3% (0.7%-10.0%), 6.8% (2.7%-11.1%), or 6.7% (2.2%-11.4%) higher risk of incident ACD, exhibiting a stronger effect on EOD than LOD. Participants with the highest polygenic risk score and air pollution scores possessed the greatest risk of ACD, EOD, and LOD. PhenoAge-Accel moderately mediated the influence of air pollution exposure on ACD risk, especially among low genetic risk participants, with slightly lower mediation effects for EOD than LOD. Similar results were found when adopting KDMAge-Accel. CONCLUSIONS:Long-term joint exposure to air pollutants exhibited stronger associations with EOD than LOD, and accelerated biological aging serves as a partial mediator in this adverse connection.

BACKGROUND:The long-term benefits of endovascular thrombectomy (EVT) for basilar artery occlusion (BAO) in patients with low National Institutes of Health Stroke Scale scores upon admission remain unclear. This study aimed to compare the 1-year clinical follow-up outcomes of best medical management (BMM) alone versus BMM plus EVT. METHODS:Patients with BAO and admission National Institutes of Health Stroke Scale score of ≤10 at 65 stroke centers in China from December 2015 to June 2022 were retrospectively enrolled. The primary outcome was favorable functional outcome (a modified Rankin Scale score of 0-3 at 1 year). Early (door-to-puncture time ≤120 minutes) and late EVT (door-to-puncture time >120 minutes) classifications were defined as surrogates for comparing initial treatment with EVT versus late (potentially rescue) EVT after initially being treated with BMM only. Multivariable logistic regression and propensity score matching analyses were used to assess the association between treatment and outcomes. RESULTS:Among 1232 patients who had 1-year follow-up data, 856 (69.5%) were men, and the mean (SD) age was 65 (12) years. After adjustment for confounders, there were no significant differences between EVT and BMM in favorable functional outcome (odds ratio, 0.96 [95% CI, 0.71-1.29]; P=0.778). The cumulative 1-year mortality rate was 16.4% in the EVT group versus 13.7% in the BMM group (odds ratio, 1.23 [95% CI, 0.86-1.77]; P=0.262). Predefined subgroup analyses revealed that late EVT was inferior to early EVT (odds ratio, 0.47 [95% CI, 0.28-0.79]; P=0.005), while no significant difference was observed between BMM and early EVT in 1-year outcomes (odds ratio, 0.87 [95% CI, 0.63-1.21]; P=0.421). CONCLUSIONS:In this long-term follow-up study among patients with BAO admitted with a National Institutes of Health Stroke Scale score of ≤10, there were no significant differences in functional outcomes and mortality at 1 year between BMM plus EVT and BMM alone.

Exploring the causal relationship between focal brain lesions and post-stroke depression (PSD) can provide therapeutic insights. However, a gap exists between causal and therapeutic information. Exploring post-stroke brain repair processes post-stroke could bridge this gap. We defined a depression network using the normative connectome and investigated the predictive capacity of lesion-induced network damage on depressive symptoms in discovery cohort of 96 patients, at baseline and six months post-stroke. Stepwise functional connectivity (SFC) was used to examine topological changes in the depression network over time to identify patterns of network reorganization. The predictive value of reorganization information was evaluated for follow-up symptoms in discovery and validation cohort 1 (22 worsening PSD patients) as well as for treatment responsiveness in validation cohort 2 (23 antidepressant-treated patients). We evaluated the consistency of significant reorganization areas with neuromodulation targets. Spatial correlations of network reorganization patterns with gene expression and neurotransmitter maps were analyzed. The predictive power of network damage for symptoms diminished at follow-up compared to baseline (Delta adjusted R-2 = -0.070, p < 0.001). Reorganization information effectively predicted symptoms at follow-up in the discovery cohort (adjust R-2 = 0.217, 95 %CI: 0.010 to 0.431), as well as symptom exacerbation (r = 0.421, p = 0.033) and treatment responsiveness (r = 0.587, p = 0.012) in the validation cohorts. Regions undergoing significant reorganization overlapped with neuromodulatory targets known to be effective in treating depression. The reorganization of the depression network was associated with immune-inflammatory responses gene expressions and gamma-aminobutyric acid. Our findings may yield important insights into the repair mechanisms of PSD and provide a critical context for developing post-stroke treatment strategies.

This study aimed to elucidate the clinical and radiological profiles of Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS), targeting an enhanced comprehension and more efficient diagnosis of this rare disorder among medical professionals. We conducted a retrospective cohort study, encompassing a detailed analysis of clinical and imaging data from nine CLIPPERS patients diagnosed between 2016 and 2023 at Xuzhou Medical University Affiliated Hospital and Beijing Xuanwu Hospital. Our study included nine patients, comprising seven males and two females, with ages varying from 9 to 79 years.The clinical spectrum was broad, including lower limb weakness (5 cases), unsteady gait (6), lower limb numbness (2), visual impairments (4), dizziness and headaches (5), cognitive impairments (2), facial sensory abnormalities (2), language disturbances (4), nausea and vomiting (1), limb twitching (1), fever (1), and chest and abdominal discomfort (1).Brain MRI scans uniformly disclosed multifocal lesions with slightly prolonged T1 and pronounced T2 signal characteristics in the brainstem, notably in the pons, as well as in bilateral thalami, cerebellum, and basal ganglia. High signal intensity on FLAIR sequences and variable signal intensity on DWI sequences were observed, with post-contrast imaging exhibiting the pathognomonic punctate and curvilinear ‘pepper-like’ enhancement. Cervical spinal cord MRIs from two patients mirrored this enhancement pattern. Pathological examination via biopsy in two cases—one of brain tissue and one of spinal cord tissue—demonstrated perivascular infiltration of CD3 + T lymphocytes, accompanied by CD20+, CD5+, and CD68 + cell infiltrations. A favorable response to corticosteroid therapy was observed across all patients, with marked amelioration in clinical symptoms and radiological findings. Remarkably, one patient, diagnosed with classical Hodgkin’s lymphoma two years post-onset, showed no signs of recurrence on subsequent PET-CT scans following standard chemotherapy. The remaining patients were either on steroid maintenance therapy or received a combination of steroids and immunosuppressants, with symptomatic improvement noted in all. CLIPPERS syndrome is distinguished by its characteristic MRI features and demonstrates a robust response to corticosteroid therapy, leading to rapid clinical and radiological improvement. In scenarios with ambiguous diagnosis, pathological tissue biopsy offers essential confirmation.

Background The mechanism underlying necroptosis in pulmonary vessel endothelial cells (PVECs) resulting from long non-coding RNA (lncRNA)-induced alternative splicing (AS) of target genes in acute lung injury (ALI) remains unclear. Methods Lipopolysaccharide (LPS)-induced expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and lncRNAs was analyzed via RT-PCR in PVECs. Full-transcriptome sequencing was used to detect AS-related mRNAs. The interaction between lncRNA MALAT1 and target gene transmembrane BAX inhibitor motif-containing 6 (TMBIM6) was verified using a dual-luciferase reporter system. Necroptosis was measured as protein levels of phosphorylated receptor-interacting serine/threonine kinase 1 (RIPK1), RIPK3, and mixed-lineage kinase domain-like (MLKL) proteins, as well as flow cytometer measurement. Antisense of MALAT1, TMBIM6, TMBIM6-225 and RIPK1 inhibitor were transfected into a rat model of LPS-induced ALI. Hematoxylin and eosin (H&E) and immunohistochemical staining were performed to evaluate lung injury. Results LPS upregulated the expression of TNF-α, IL-1β, IL-6, p-RIPK1, p-RIPK3, p-MLKL, MALAT1, and TMBIM6-225 (an AS isoform of MALAT1-targeted gene TMBIM6) in PVECs. However, it downregulated the expression of TMBIM6. An antisense of MALAT1 inhibited TMBIM6-225 and downregulated p-MLKL. The pro-necroptotic effect of MALAT1 was verified in an LPS-induced MALAT1/shMALAT1-transfected ALI rat model in vivo. The necroptotic effect was reversed by treatment with necrostatin-1. Conclusions LPS-induced MALAT1 causes AS of TMBIM6, and the AS variant TMBIM6-225 aggravates ALI by promoting PVEC necroptosis via the p-RIPK1, p-RIPK3, and p-MLKL complex.

We employed a novel method for collecting oral mucosal epithelial cells, an anagar-paraffin double-embedding technique for cell fixation in cytopathological processing. OMEC biopsy demonstrated a high diagnostic efficacy for NIID: H&E staining revealed inclusions in 60% (12/20) of patients, TEM confirmed them in 40% (8/20) of cases and immunofluorescence detected p62-positive aggregates in 9/20 (45%) and uN2CpolyG in 8/20 (40%) of cases, respectively. OMEC biopsy is a simple, noninvasive technique for detecting intranuclear inclusions in NIID, avoiding the need for invasive surgical procedures such as skin or labial gland biopsies.

Although a single nucleotide polymorphism for N-acetyltransferase 10 (NAT10) has been identified in patients with early-onset stroke, the role of NAT10 in ischemic injury and the related underlying mechanisms remains elusive. Here, we provide evidence that NAT10, the only known RNA N4-acetylcytidine (ac4C) modification "writer", is increased in the damaged cortex of patients with acute ischemic stroke and the peri-infarct cortex of mice subjected to photothrombotic (PT) stroke. Pharmacological inhibition of NAT10 with remodelin on Days 3-7 post-stroke or astrocytic depletion of NAT10 via targeted virus attenuates ischemia-induced infarction and improves functional recovery in PT mice. Mechanistically, NAT10 enhances ac4C acetylation of the inflammatory cytokine tissue inhibitor of metalloproteinase 1 (Timp1) mRNA transcript, which increases TIMP1 expression and results in the accumulation of microtubule-associated protein 1 light chain 3 (LC3) and progression of astrocyte autophagy. These findings demonstrate that NAT10 regulates astrocyte autophagy by targeting Timp1 ac4C after stroke. This study highlights the critical role of ac4C in the regulation of astrocyte autophagy and proposes a promising strategy to improve post-stroke outcomes via NAT10 inhibition.

This study aims to examine clinical, laboratory, neuroimaging and perinatal differences between pregnant women with isolated PRES and those with concurrent HELLP syndrome, thus improving clinicians’ understanding of these conditions. A cross-sectional analysis was performed on 60 pregnant and postpartum women diagnosed with PRES at the Affiliated Hospital of Xuzhou Medical University, spanning from January 2014 to March 2024. These patients were divided into two groups based on laboratory findings: the isolated PRES group and the PRES-HELLP group. The study compared general clinical parameters (risk factors, neurological symptoms), laboratory tests, neuroimaging data (affected brain regions), and perinatal outcomes between the two groups. The study included 40 patients with isolated PRES and 20 patients with PREScombined with HELLP syndrome. Patients in the PRES-HELLP group exhibited lower platelet count, platelet-to-lymphocyte ratio (PLR), serum albumin (ALB), serum sodium ion (Na+), serum total calcium ion (Ca2+), and Apgar scores (both at 1 and 5 min), along with elevated CRP, liver enzymes, and urea levels compared to those in the PRES group (P < 0.05). Concurrent HELLP syndrome exacerbates maternal and fetal risks in pregnant women with PRES, emphasizing the significance of prompt recognition.

Neuronal intranuclear inclusion disease (NIID) is a rare neurodegenerative disease primarily diagnosed through diffusion-weighted imaging (DWI). However, the limitation of human visual interpretation and clinical experience can lead to inaccuracies in diagnosis. This research proposes a deep learning method based on cross self-supervision, alongside the construction of Co-ResNet50 and CO-ViT models for intelligent auxiliary diagnosis of NIID. This method uses self-supervised learning and effectively combines the characteristics of ResNet50 and ViT networks to improve the model’s feature extraction capabilities. The experiment preprocessed 249 DWI data and divided them into 204 training sets and 45 test sets. The results reveal that the CO-ResNet50 model has the best performance, with an accuracy of 95.49%, precision of 95.51%, recall of 95.44%, F1 score of 0.954 7, and AUC of 0.989 7. These findings underscore the model's potential to provide support for clinical NIID diagnosis.

Background:Treating refractory generalized myasthenia gravis is still a big challenge, so new treatments are needed. Several studies have shown the potential of chimeric antigen receptor (CAR) T cell therapy in the treatment of autoimmune diseases. However, no clinical trial of bispecific CAR T cells targeting refractory myasthenia gravis has been done. We developed autologous anti-B-cell maturation antigen (BCMA) and CD19 bispecific CAR T cells to evaluate the safety and efficacy in refractory myasthenia gravis. Methods:This single-arm, phase 1 trial (ChiCTR2200061267) was conducted at the Affiliated Hospital of Xuzhou Medical University in refractory generalized myasthenia gravis patients (Myasthenia Gravis Activities of Daily Living [MG-ADL] ≥6-point, and Quantitative Myasthenia Gravis scale [QMG] ≥8-point). Anti-BCMA/CD19 bispecific CAR T cells were administered at 1.0 × 106, 3.0 × 106, and 5.0 × 106 CAR T cells per kg. Primary endpoints assessed safety (dose-limiting toxicities, maximum tolerated dose, and adverse events); secondary endpoints assessed disease severity and other related indexes. Findings:Between May 3, 2023, and June 19, 2024, 18 patients were enrolled and received apheresis and a single CAR T cell infusion. Mean age was 41 years (SD 12) and 12 (67%) participants were female. The anti-BCMA/CD19 bispecific CAR T cells were generally safe, with no dose-limiting toxicities, no immune effector cell-associated neurotoxicity syndrome, and only grade 1 cytokine release syndrome (39% of patients). The most common grade 3 or worse adverse events within 28 days were hematological toxicities, including three leukopenia, three neutropenia, one anaemia, and one thrombocytopenia. All were transient and manageable. 17 participants completed follow-up. Clinical improvements by day 180 were -8.6 (95% CI -10.2 to -7.0) for MG-ADL score and -15.4 (-17.6 to -13.2) for QMG score. 14 participants (82%) achieved minimal manifestations, 15 (88%) stopped glucocorticoids, all stopped non-steroidal immunosuppressants, and eight (47%) had anti-acetylcholine receptor antibody negative seroconversion. Interpretation:Anti-BCMA/CD19 CAR T cells showed good safety and efficacy in refractory generalized myasthenia gravis. A large proportion of participants had a minimal manifestation status and discontinued glucocorticoids and non-steroidal immunosuppressants, and a certain proportion of anti-acetylcholine receptor antibodies turned negative. Funding:National Natural Science Foundation of China, Basic Research Program of Jiangsu, Young academic leaders of Jiangsu Qinglan Project, and Construction Project of High Level Hospital of Jiangsu Province.

Background: The gut-microbiome-brain axis (GMBA) implies the connection between inflammatory bowel disease (IBD) and Alzheimer's disease (AD). We aimed to comprehensively explore the relation between IBD (and its subtypes) and AD, early-onset AD (EOAD) and late-onset AD (LOAD) from a genetic pleiotropy perspective. Methods: Relying on summary statistics (N = 472,868 for AD, 185,204 for EOAD, 191,061 for LOAD, 59,957 for IBD, 45,975 for CD, and 40,266 for UC), we first performed Mendelian Randomization to examine the causal association between IBD and AD by leveraging vertical pleiotropy. Then, we estimated global and local genetic correlations, followed by cross-trait association analysis to identify SNPs and genes with horizontal pleiotropy. Particularly, we utilized multi-trait colocalization analysis to assess the role of microbes in the common genetic etiology underlying the two types of diseases. Finally, we conducted functional enrichment analysis for pleiotropic genes. Results: We discovered suggestively causal relations between IBD (and its subtypes) and EOAD (ORIBD = 1.06 [1.01-1.11], ORCD = 1.05 [1.01-1.10], ORUC = 1.08 [1.01-1.15]) as well as between UC and LOAD (OR = 1.04 [1.01-1.08]), and discovered 44 local regions showing suggestively significant genetic correlations between IBD (and its subtypes) and AD (and EODA and LOAD). We further detected substantial genetic overlap, as characterized by 182 AD-associated, 3 EOAD-associated and 51 LOAD-associated pleiotropic SNPs as well as 291 pleiotropic genes. Pleiotropic genes more likely enriched in the GMBA-relevant tissues such as brain, intestine and esophagus. Moreover, we identified three microorganisms related to these disease pairs, including the Catenibacterium, Clostridia, and Prevotella species. Conclusion: The suggestively causal associations and shared genetic basis between IBD and its subtypes with AD, EOAD and LOAD may commonly drive their co-occurrence, and gut microbes might partly explain the shared genetic etiology. Further studies are warranted to elaborate the possibly biological mechanisms underlying the two types of diseases.

Listeria monocytogenes meningoencephalitis (LMM) is a rare but severe central nervous system (CNS) infection. This study aimed to characterize the clinical manifestations, diagnostic findings, treatment responses, and prognostic factors associated with LMM. We retrospectively analyzed the clinical data of 13 patients diagnosed with LMM at Xuzhou Medical University Affiliated Hospital between 2018 and 2023. An additional five cases were identified through a literature search in the China National Knowledge Infrastructure (CNKI) and Wanfang databases from 2019 to 2022. Clinical features, cerebrospinal fluid (CSF) and blood test results, imaging findings, treatments, and outcomes were summarized. Among 18 patients (11 males, 7 females; mean age 51.6 ± 17.2 years), all had acute onset with fever (100