Abstract Background Multiple sclerosis (MS) is a debilitating neuroinflammatory disease. Experimental autoimmune encephalomyelitis (EAE) is a commonly used rodent model for MS. Forsythoside A (FA), a natural compound derived from Forsythia suspensa , exhibits anti-inflammatory and neuroprotective properties; however, its efficacy in EAE and its underlying mechanism remain unclear. Purpose To explore the therapeutic effect of FA on EAE and its mechanism. Methods EAE was induced in C57BL/6 mice treated with FA (20/60 mg/kg) from day 7. Clinical scores, histopathology (H&E, LFB, immunofluorescence), flow cytometry, and spinal cord RNA sequencing were analyzed. Network pharmacology, molecular docking, molecular dynamics (MD) simulations, and surface plasmon resonance (SPR) were employed to identify and validate the target of FA. In vitro studies using BV2 microglia with Tnfaip2 knockdown/overexpression confirmed the mechanism via qRT-PCR and Western blot. Results FA treatment dose-dependently alleviated clinical severity. While the 20 mg/kg dose showed a trend toward improvement without statistical significance, the 60 mg/kg dose significantly reduced CNS inflammation and demyelination. FA decreased peripheral Th1 cells in EAE mice. It suppressed microglial activation and pro-inflammatory markers (IL-1β, TNF-α, iNOS) expression. Transcriptomics and network analysis pinpointed TNF-α-induced protein 2 (Tnfaip2) in the TNF pathway. FA directly bound Tnfaip2 (K D = 28 µM), validated by docking, MD simulations, and SPR. In vitro, FA inhibited LPS-induced pro-inflammatory polarization and the Tnfaip2/NF-κB pathway in BV2 cells. Tnfaip2 overexpression abolished the anti-inflammatory effects of FA. Conclusion FA ameliorates EAE by suppressing pro-inflammatory microglial polarization via directly targeting Tnfaip2 and inhibiting the NF-κB pathway. This identifies the Tnfaip2/NF-κB axis as a potential therapeutic target for MS.

Bone marrow hematopoietic stem and progenitor cells (HSPCs) sense immune activation and instruct systemic immunity. However, the alterations of HSPCs in autoimmune diseases, which are driven by an active immune response, and their impact on disease activity and progression are not clear. Neuromyelitis optica spectrum disorder (NMOSD) is a B cell-mediated autoimmune neurological disease characterized by pathogenic autoantibodies against aquaporin-4 (AQP4-IgG). We observed aberrant bone marrow granulopoiesis in samples from individuals with NMOSD, which was accompanied by B cell clonal expansion. Aberrant granulopoiesis was mediated by hyperactivated JAK-STAT signaling, leading to an increase in ISG15+ neutrophils that produced B cell-activating factor (BAFF). These BAFF-producing neutrophils were sufficient to drive maturation of antibody-secreting cells and autoantibody production in vitro. Aberrant granulopoiesis was also observed in individuals with NMOSD receiving B cell depletion therapy who experienced relapse; in contrast, belimumab, a monoclonal antibody against BAFF, reduced autoantibody titers and number of relapses. Thus, targeting the bone marrow niche may present a treatment strategy for NMOSD and perhaps other B cell-mediated autoimmune diseases.

Acute exacerbations/worsening of generalized myasthenia gravis (gMG) require urgent intervention to prevent progression to life-threatening myasthenic crisis. This multicenter study evaluate the efficacy and safety of efgartigimod in gMG patients experiencing acute exacerbations/worsening to validate its potential as a rapid-acting therapeutic option. In this multicenter retrospective study (Jan 2024–Feb 2025), 61 gMG patients with acute exacerbations/worsening received weekly efgartigimod infusions for 4 weeks. Efficacy was assessed at baseline (W0) and weekly throughout the treatment cycle (W1–W7) using Myasthenia Gravis Foundation of America Post-Intervention Status (MGFA-PIS), Quantitative Myasthenia Gravis (QMG), and Myasthenia Gravis Activities of Daily Living (MG-ADL) scores, along with prednisone dosage reductions. Safety assessments were concurrently performed. Median age was 56 years (range: 39–68 years). Pulmonary infection (16/61, 26.2

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) is an autoimmune disorder affecting the central nervous system (CNS), characterized by the presence of autoantibodies against MOG (MOG-IgG) in serum or cerebrospinal fluid (CSF). While Epstein-Barr virus (EBV) is implicated in multiple sclerosis (MS), its role in MOGAD remains unclear. Here, we report five cases of newly diagnosed MOGAD manifesting as encephalitis, in whom concurrent EBV-related laboratory findings were detected. All patients tested positive for serum MOG-IgG by live cell-based assay (CBA). Regarding therapeutic response, three patients exhibited transient improvement in CSF parameters following initial antiviral therapy. However, clinical recovery was observed only after administration of corticosteroids (either high- or low-dose). In refractory cases, additional interventions with intravenous immunoglobulin (IVIG) or tocilizumab were applied. In conclusion, this case series suggests that EBV-associated immune activation may coexist with some MOGAD patients presenting as encephalitis, which requires validation in larger prospective and mechanistic studies in the future.

Objective Efgartigimod, a neonatal Fc receptor (FcRn) antagonist, has been shown to reduce pathogenic immunoglobulin G (IgG) autoantibodies, notably anti-acetylcholine receptor (AChR) antibodies, in myasthenia gravis (MG). While clinical trials have established its safety and efficacy, real-world evidence regarding its therapeutic effectiveness and steroid-sparing potential remains limited. This study aimed to evaluate the real-world efficacy and steroid-sparing benefits of efgartigimod in the clinical management of MG. Methods Forty-one patients with generalized myasthenia gravis (gMG) were enrolled in this prospective study. Participants received efgartigimod treatment and were followed for 26 weeks. Clinical outcomes, primarily Myasthenia Gravis Activities of Daily Living (MG-ADL) scores and corticosteroid dosages, were systematically evaluated. Statistical analyses were performed using R version 4.5.0. Results Patients were stratified into two cohorts based on treatment cycles: 22 received two cycles of efgartigimod, while 19 received a single cycle. Bulbar and respiratory symptoms improved within two weeks, whereas ocular and limb weakness required a more prolonged treatment duration to achieve clinical benefit. Myasthenia Gravis Activities of Daily Living (MG-ADL) scores demonstrated a significant decline, with a more rapid response observed in severe cases. By Week 26, the proportion of patients requiring more than 16mg/d of methylprednisolone decreased from 63.4% at baseline to 14.6%. The two-cycle cohort exhibited a lower mean cumulative methylprednisolone dose (4861.50mg vs. 5469.24mg). No treatment-related adverse effects were observed. Conclusion Efgartigimod demonstrated variable clinical responses across different muscle groups, with early improvements in bulbar and respiratory function alongside significant steroid-sparing advantages. Given that baseline MG-ADL scores serve as a reliable predictor of the time to achieve minimal symptom expression (MSE), and considering that repeated treatment cycles further augment therapeutic efficacy, efgartigimod represents a promising steroid-sparing immunomodulatory strategy for the management of MG.

OBJECTIVE:Neuromyelitis optica spectrum disorder (NMOSD) is a devastating neurological disease that lacks serological biomarkers that can accurately reflect disease activity. We established a live cell-based assay (LCBA) using serum with endogenous complement to quantify the overall cytotoxicity, offering a novel functional tool for monitoring disease activity. METHODS:111 samples from 65 AQP4-IgG+ NMOSD patients were enrolled in this prospective study for serological analysis of C1q, C5a, sC5b-9, CH50, and AQP4-IgG titers. A novel live cell-based complement-dependent cytotoxicity (NMO-LCBA-CDC) assay was developed using AQP4-transfected HEK293T cells exposed to test sera. Serum cytotoxicity was assessed by immunofluorescence and flow cytometry and quantified by calculating the cytotoxic index (CI). We also evaluated the cytotoxicity following intravenous methylprednisolone (IVMP) and subsequent rescue therapies. RESULTS:Serum C5a and sC5b-9 levels were significantly elevated during NMOSD acute attacks (p < 0.05). Following IVMP, the complement system including C5a, sC5b-9, CH50, and C1q decreased (p < 0.05), without change in AQP4-IgG titers. The CI was higher in the acute phase than in the remission phase (p = 0.0011). However, IVMP did not significantly reduce the CI during acute attacks. The NMO-LCBA-CDC assay demonstrated robust reproducibility in detecting serum cytotoxicity. Among IVMP non-responders receiving rescue therapy, both PE/IA and C5 inhibitors appeared to be associated with favorable CI reduction profiles. CONCLUSION:By integrating AQP4-IgG and endogenous complement activity, the NMO-LCBA-CDC assay provides a comprehensive assessment of serum cytotoxicity in NMOSD. It holds significant potential for monitoring disease activity and evaluating therapeutic effects in NMOSD.

Background:The necessity and optimal duration of post-thymectomy immunoregulatory medication (IM) in myasthenia gravis (MG) remain unclear. Objectives:This study aimed to evaluate whether IM is required after thymectomy in MG patients and to determine the appropriate duration of IM in patients without postoperative deterioration by comparing long-term clinical outcomes. Design:This triple-center, retrospective study included 1248 MG patients who underwent thymectomy. Among these patients, we compared outcomes between 483 patients without post-thymectomy IM and 765 patients receiving IM. Methods:Efficacy outcomes included post-thymectomy deterioration and minimal manifestation status (MMS) at 1 year. Safety outcomes, tumor growth, and serious complications were assessed between groups. Subgroup analyses were performed in mild cases (Myasthenia Gravis Foundation of America clinical classification (MGFA) ⩽2a at discharge), patients receiving IM for >1 year, and patients receiving IM for >2 years. Propensity score matching (PSM) was conducted for validation. Results:Relative to 438 MG patients underwent thymectomy with no-IM therapy, 756 thymectomized MG patients receiving concomitant IM showed significantly superior outcomes, including lower deterioration (hazard ratio (HR) = 0.44, adjusted p < 0.001), lower deteriorated MGFA class (adjusted coefficient = 0.94, p < 0.001), and higher odds of achieving MMS at 1 year (odds ratio = 2.06, adjusted p < 0.001). No significant differences were observed in tumor development (3 years: p = 0.78; 5 years: p = 0.27) or serious complications (p = 0.53). Similar trends were observed across subgroups. Among patients without postoperative deterioration, IM longer than 1 year reduced deterioration risk compared with ⩽1 year (HR = 0.67 (0.50-0.91), p = 0.01), whereas extending IM beyond 2 years offered no additional benefit (p = 0.137). PSM analysis confirmed these findings. Conclusion:Our real-world analysis of 1248 MG patients suggests that thymectomy alone is not sufficient to achieve satisfactory outcomes. Post-thymectomy IM is recommended for at least 1 year, while extending treatment beyond 2 years appears to offer no further advantage in patients without deterioration.

Purpose:Stroke remains a leading cause of death and disability worldwide, with carotid intima-media thickness (IMT) and carotid plaque being significant predictors of cerebrovascular diseases. Despite the established correlation between carotid IMT and stroke, the specific factors influencing IMT in populations with unstable plaques are not well understood. This study aimed to identify the influential factors affecting carotid IMT in individuals with asymptomatic (without prior cardiocerebrovascular events) unstable plaques and to explore sex-specific differences. Methods:Participants were recruited from 2713 patients who underwent carotid ultrasonography in Tianjin Jixian between 2019 and 2020. A total of 1070 individuals met the inclusion criteria, which required the presence of at least one unstable carotid plaque and no significant renal function abnormalities. Clinical and biochemical assessments were conducted, and carotid ultrasonography was performed to evaluate the IMT and plaque characteristics. Statistical analyses, including univariate and multiple linear regression analyses, were used to identify factors influencing IMT. Results:The study included 1070 patients with asymptomatic unstable plaques, comprising 616 males (57.6%) and 454 females (42.4%), with a mean age of 65.35 ± 7.75 years. Multivariate linear regression analysis confirmed that age (β = 0.247, P < 0.001), diabetes mellitus (β = 0.070, P = 0.046), and creatinine (β = 0.075, P = 0.036) were significant predictors of IMT in the overall population. In males, significant predictors included age (β = 0.209, P < 0.001), creatinine (β = 0.103, P = 0.010), and fasting plasma glucose (β = 0.086, P = 0.028). In females, significant predictors included age (β = 0.293, P < 0.001), diabetes mellitus (β = 0.113, P = 0.011), and smoking (β = 0.132, P = 0.003). These results emphasize the importance of considering sex-specific factors in the assessment and management of carotid atherosclerosis. Conclusion:These findings highlight the critical need for personalized approaches in reducing the risk of cerebrovascular diseases and improving patient outcomes. Among patients with asymptomatic unstable carotid plaques, male individuals need to focus more on renal function, while female requires more vigorous smoking cessation efforts.

BACKGROUND:Myasthenia gravis (MG) is an autoimmune disease predominantly driven by autoantibodies targeting acetylcholine receptor (AChR), resulting in muscle weakness. Efgartigimod, a neonatal Fc receptor (FcRn) blocker, reduces pathogenic immunoglobulin G in anti-AChR antibody-positive generalised MG (gMG). This study aimed to identify immune mechanisms underlying MG pathology and response to efgartigimod. METHODS:We constructed a single-cell atlas of peripheral immune cells from treatment-naïve and efgartigimod-treated patients with gMG. Comprehensive immunophenotyping was performed to compare the clonal diversity of B- and T-cell populations, alongside experimental validation to assess the activation of Th17-related pathways before and after FcRn blockade. RESULTS:B cells in patients with gMG exhibit heightened activation and differentiation, while T cells display distinct pro-inflammatory phenotypes. Enhanced intercellular signalling contributed to the pathogenicity associated with gMG. Efgartigimod mitigated upregulated antigen processing and presentation pathways in MG. Additionally, B-cell clonal diversity and IGHG1-bearing B-cell receptors increased. Transcriptional factor alterations were noted in suboptimal responders. Regulation of T-cell activity, particularly within Th17-related pathways, was associated with remission rates. CONCLUSIONS:These findings underscore immune heterogeneity and dynamics during efgartigimod treatment, providing mechanistic insights into therapeutic response in gMG. KEY POINTS:Aberrant B cells and pro-inflammatory T cells contribute critically to generalised myasthenia gravis (gMG) pathogenesis. Neonatal Fc receptor (FcRn) blockade induces immunoglobulin G (IgG) depletion feedback, reflected by increased class-switched BCRs. Th17 cell proliferation is attenuated following FcRn blockade. Antigen processing and presentation pathways are downregulated after FcRn blockade in gMG.

[This corrects the article DOI: 10.1016/j.lanwpc.2023.100846.].

Tocilizumab is effective in neuromyelitis optica spectrum disorder (NMOSD). It remains unclear when to initiate or discontinue tocilizumab treatment. We aimed to compare the efficacy of early versus escalation tocilizumab treatment in patients with NMOSD. A retrospective study of 41 patients with NMOSD who received regular tocilizumab administration was conducted. The early tocilizumab group comprised patients who started tocilizumab after their first attack, while the escalation group included patients who initially received empirical disease-modifying drugs (DMDs) and later escalated to tocilizumab after relapses. Tocilizumab was administered at 8 mg/kg with routine infusions at 4-week intervals. The primary outcome was improvement in the extended disability status scale (EDSS) score at months 3, 6, and 12 during the follow-ups. An additional secondary outcome was annualised relapse rate (ARR). The early tocilizumab treatment group showed reduced median EDSS scores at 3, 6 months, with no further reduction at 12 months. The escalation treatment group showed reduced EDSS score at 6 months, with no further reduction at 12 months. The Inter-group analysis showed the early tocilizumab treatment group had significantly lower EDSS scores at 3, 6, and 12 months compared to the escalation treatment group. The ARR was not different at 36 months. Additionally, no difference of ARR was observed in those who were transferred to low-dose rituximab. Early use of tocilizumab reduces the degree of disability compared to escalation treatment in NMOSD, with no much differences on relapse rate. Low-dose rituximab may be a feasible candidate switching from tocilizumab.

Tumefactive demyelination is a rare but clinically significant manifestation of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often posing diagnostic challenges due to its resemblance to neoplastic lesions. We report a case of a 45-year-old woman presenting with a 3-week history of limb weakness, slowed responsiveness, and aphasia. Neurological examination revealed confusion and sensory aphasia. Serum MOG antibody was positive at a titer of 1:320, while AQP4 and GFAP antibodies were negative. Cerebrospinal fluid (CSF) analysis showed a positive MOG antibody titer of 1:1. Brain MRI demonstrated a left frontal lobe mass with surrounding edema and patchy contrast enhancement. Brain biopsy revealed perivascular lymphocyte cuffing, focal myelin loss, and preserved axonal integrity, consistent with tumefactive demyelination. PET-CT revealed heterogeneous 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) uptake, with an L/WMET of 3.1 and L/WFDG of 2.6, supporting a possible demyelinating process. The patient was diagnosed with MOGAD and treated with intravenous methylprednisolone (IVMP), resulting in complete symptom remission and significant lesion reduction on follow-up MRI. Tocilizumab was initiated for relapse prevention, and serum MOG antibody titers decreased from 1:320 to 1:100 over nine months. This case highlights the importance of integrating clinical, radiological, and pathological findings to differentiate tumefactive demyelination from neoplastic lesions. Early diagnosis and treatment are crucial for favorable outcomes in MOGAD-associated tumefactive demyelination.

BackgroundSubcortical ischemic vascular dementia (SIVD) is a common subtype of vascular dementia. Currently, the bilateral common carotid artery stenosis (BCAS) mouse model is the most suitable SIVD rodent model. In this study, we investigated the functional and structural impairments in the hippocampus 1 month after BCAS.MethodsWe used behavioral tests, laser speckle flowmetry, long-term potentiation, histochemical staining, molecular experiments, and voxel-based morphometry to evaluate the hippocampal impairments.ResultsBehavioral studies revealed that BCAS mice exhibited worse performance. Laser speckle flowmetry detected an obvious decrease in cerebral blood flow. The synaptic plasticity of the perforant path-dentate gyrus pathway was inhibited. Decreased fractional anisotropy and increased mean diffusivity were detected in the hippocampus via diffusion tensor imaging data. A reduction in gray matter volume, which was most prominent in the hippocampus and its surrounding areas, was detected via voxel-based morphometry analysis. Impairments in cell morphology and myelin integrity were validated using histochemical staining and molecular biology techniques. In addition, the numbers of GFAP+ astrocytes and Iba1+ microglia increased in the hippocampus.ConclusionsOverall, our study demonstrates early functional and structural impairments in the hippocampus contributing to learning and memory deficits after 1 month of BCAS, indicating that the hippocampus is vulnerable to chronic cerebral ischemia.

Purpose:Carotid intima-media thickness (cIMT) is a widely recognized marker for assessing carotid atherosclerosis, which is a significant predictor of cardiovascular diseases such as ischemic stroke. The serum uric acid to high-density lipoprotein cholesterol ratio (UHR) has recently emerged as a potential combined marker for metabolic and inflammatory processes related to cardiovascular risk. This study aims to investigate the association between UHR and cIMT in a rural Chinese population, with a particular focus on differences across age and sex groups. Patients and methods:A cross-sectional study was conducted using data from the 2019 general physical examination of residents in Jizhou District, Tianjin, China. A total of 3,280 participants aged 45 years and older were included after excluding those with incomplete data or specific health conditions. Demographic and clinical data were collected through face-to-face interviews and physical examinations. Serum levels of uric acid (SUA) and high-density lipoprotein cholesterol (HDL-C) were measured, and UHR was calculated. Carotid intima-media thickness was assessed using ultrasound. Multivariate linear and logistic regression analyses were performed to evaluate the association between UHR and cIMT, adjusting for potential confounders. Subgroup analyses were conducted to explore variations in this association by age and sex. Receiver operating characteristic (ROC) analysis was used to compare the predictive value of UHR, SUA, and HDL-C for cIMT thickening. Results:The study population had a mean age of 64.10 ± 8.02 years, with 45.2% males and 54.8% females. The prevalence rates of hypertension, diabetes, smoking, and alcohol consumption were 77.2%, 19.7%, 41.4%, and 36.3%, respectively. Univariate analysis showed significant associations between UHR, age, hypertension, diabetes, smoking, alcohol consumption, systolic blood pressure (SBP), pulse pressure (PP) difference, glucose (GLU), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and cIMT. Multivariate analysis revealed that UHR was an independent risk factor for increased cIMT (β = 0.06, 95% CI [0.01-0.10], P = 0.017) and carotid intima-media thickening, particularly in older men. Subgroup analysis indicated that the association between UHR and cIMT was more pronounced in participants aged 60 years or older and in males. ROC analysis demonstrated that UHR had a higher predictive value for cIMT thickening in older men (AUC = 0.577, 95% CI [0.510-0.644], P < 0.05) compared to SUA or HDL-C alone. Conclusion:This study identifies UHR as a significant predictor of cIMT and carotid intima-media thickening, with a particularly strong association observed in older men. These findings suggest that UHR could serve as a valuable marker for early detection and intervention of carotid atherosclerosis.

We present a clinically instructive case of a 50-year-old woman with acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (MG) who subsequently developed glutamic acid decarboxylase 65 (GAD65) antibody-associated neurological disorders alongside a type B2 thymoma. This rare coexistence highlights the profound immune dysregulation induced by thymomas, wherein loss of self-tolerance emergence multiple concurrent autoimmune phenomena. The patient's favorable response to multimodal immunotherapy-including efgartigimod, high-dose corticosteroids, and rituximab-underscores the therapeutic imperative for early, targeted immunomodulation in such complex neuroimmunological syndromes. As no standardized treatment currently exists for MG with GAD65-IgG-associated neurological disorders, this case provides critical clinical insights into both the diagnostic and therapeutic approach for this complex disease.

ObjectiveWe investigated the risk factors associated with severe or critical Coronavirus disease 2019 (COVID-19) infection due to the Omicron variant in patients with myasthenia gravis (MG) and determined the potential effect of COVID-19 on myasthenic exacerbation during the Omicron pandemic.MethodsThis retrospective study included 287 patients with MG in Tianjin, China. Clinical data of the patients were collected using electronic questionnaires, databases, and clinical records.ResultsThe overall infection rate was 84.7%. Advanced age, comorbidities, generalized phenotype, and MG instability were drivers of COVID-19 severity, and post-COVID-19 myasthenic exacerbation. The concurrent use of a steroid-sparing agent did not affect COVID-19 susceptibility or severity. It did lower the risk of myasthenic exacerbation after COVID-19 infection. Patients with severe COVID-19 experienced myasthenic exacerbation earlier than patients with non-severe infection (p < 0.001). The severity of COVID-19 (Hazards Ratio = 3.04, 95% CI: 1.41–6.54, p = 0.004) and the clinical phenotype (Hazards Ratio = 3.29, 95% CI: 1.63–6.63, p < 0.001) emerged as independent risk factors for early MG exacerbation.ConclusionGenerally, patients with MG appear to be susceptible to the Omicron strains. Immunotherapy for MG did not increase COVID-19 susceptibility or severity. We do not advocate an immediate cessation of ongoing immunosuppressive treatments once a COVID-19 infection is diagnosed. Instead, a judicious evaluation of the risks and benefits, tailored to each individual, is recommended.

AimThe Triglyceride-Glucose (TyG) index, an indicator of insulin resistance, has been proposed as a predictor of cardiovascular diseases. However, its role in predicting stroke risk, particularly in low-income populations, is not well understood. This study aimed to investigate the predictive value of the TyG index for stroke incidence in a low-income Chinese population, with a focus on gender and age-specific differences.MethodsThis 10-year prospective cohort study included 3,534 participants aged ≥45 years from rural areas in northern China. Baseline data on demographic characteristics, lifestyle factors, and clinical measurements were collected. Participants were followed for stroke incidence, categorized into ischemic and hemorrhagic stroke. Multivariate logistic regression models were used to assess the association between the TyG index and stroke incidence, adjusting for potential confounders.ResultsDuring the follow-up period, 368 participants (10.4%) experienced a stroke, with 327 ischemic and 31 hemorrhagic strokes. TyG index was significantly associated with total and ischemic stroke incidence but not hemorrhagic stroke. After adjusting for confounding factors, for every one standard deviation increase in TyG index, the risk of stroke increased by 32% for overall stroke (RR: 1.32; 95% CI: 1.08-1.61; P=0.006) and 39% for ischemic stroke (RR: 1.39; 95% CI: 1.12-1.73; P=0.003). The risk of stroke in the highest TyG tertile levels (tertile 3) increased by 49% (RR: 1.49; 95% CI 1.11-1.99; P=0.007) for overall stroke, compared to those in the lowest tertile levels (tertile 1). For ischemic stroke, the risk of stroke increased by 53% (RR: 1.53; 95% CI 1.12-2.11; P=0.008) in the highest TyG tertile levels (tertile 3) compared to those in the lowest tertile levels (tertile 1).ConclusionThis 10-year prospective cohort study has established the TyG index as an independent predictor of both total and ischemic stroke incidence in a low-income Chinese population. The findings indicate that the TyG index is particularly effective in predicting stroke risk among women and older adults (≥60 years), but not for hemorrhagic stroke. These insights are crucial for improving clinical practice and stroke prevention strategies.

Background: Rituximab effectively targets B cells and reduces relapses in neuromyelitis optica spectrum disorder (NMOSD). But the ideal dosage and treatment intervals remain unanswered. We aimed to assess the efficacy and safety of low and ultralow-dose rituximab in NMOSD. Methods: We conducted a retrospective analysis of NMOSD patients treated with rituximab at two Chinese tertiary hospitals. Patients received either a low-dose regimen (500 mg reinfusion every 6 months) or an ultralowdose regimen: 100 to 300 mg rituximab based on CD19+B cells (100 mg for 1-1.5% of peripheral blood mononuclear cells, 200 mg for 1.5-5%, and 300 mg for over 5%). Results: We analyzed data from 136 patients (41 in the low-dose group, 95 in the ultralow-dose group) with median follow-up durations of 43 and 34.2 months, respectively. Both groups exhibited similar sex distribution, age at disease onset, annual relapse rate, and baseline disease duration. Survival analysis showed that ultralowdose rituximab was noninferior to low-dose rituximab in preventing relapses. Infusion reactions occurred in 20 of 173 (11.6%) low-dose treatments and 9 of 533 (1.7%) ultralow-dose treatments. B-cell re-emergence was observed in 137 of 236 (58.1%) monitors in the low-dose group and 367 of 1136 (32.3%) monitors in the ultralow-dose group. Conclusion: Ultralow dose rituximab was noninferior to low-dose rituximab in preventing NMOSD relapses. A randomized controlled trial is essential to validate these findings.