Bone marrow hematopoiesis drives multiple sclerosis progression.

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease of the central nervous system (CNS). Bone marrow hematopoietic stem and progenitor cells (HSPCs) rapidly sense immune activation, yet their potential interplay with autoreactive T cells in MS is unknown. Here, we report that bone marrow HSPCs are skewed toward myeloid lineage concomitant with the clonal expansion of T cells in MS patients. Lineage tracing in experimental autoimmune encephalomyelitis, a mouse model of MS, reveals remarkable bone marrow myelopoiesis with an augmented output of neutrophils and Ly6Chigh monocytes that invade the CNS. We found that myelin-reactive T cells preferentially migrate into the bone marrow compartment in a CXCR4-dependent manner. This aberrant bone marrow myelopoiesis involves the CCL5-CCR5 axis and augments CNS inflammation and demyelination. Our study suggests that targeting the bone marrow niche presents an avenue to treat MS and other autoimmune disorders.

Clinical outcome and peripheral immune profile of myasthenic crisis with omicron infections: A prospective cohort study.

The impact of Omicron infections on the clinical outcome and immune responses of myasthenia gravis (MG) remained largely unknown. From a prospective multicenter MG cohort (n = 189) with 197 myasthenic crisis (MC), we finally included 41 independent MG patients to classify into two groups: the Omicron Group (n = 13) and the Control Group (n = 28). In this matched cohort study, all-cause mortality was 7.69% (1/13) in Omicron Group and 14.29% (4/28) in Control Group. A higher proportion of elevated serum IL-6 was identified in the Omicron Group (88.89% vs 52.38%, P = 0.049). In addition, the proportions of CD3+CD8+T in lymphocytes and Tregs in CD3+CD4+ T cells were significantly elevated in the Omicron Group (both P = 0.0101). After treatment, the Omicron Group exhibited a marked improvement in MG-ADL score (P = 0.026) and MG-QoL-15 (P = 0.0357). MCs with Omicron infections were associated with elevated serum IL-6 and CD3+CD8+T response. These patients tended to present a better therapeutic response after fast-acting therapies and anti-IL-6 treatment.

Identification of ceRNA networks in type H and L vascular endothelial cells through integrated bioinformatics methods. / 通过整合的生物信息学方法鉴定H和Låž‹è¡€ç®¡å† çš®ç»†èƒžä¸­çš„ceRNA网络（英文）.

OBJECTIVES: Type H blood vessels are a subtype of bone-specific microvessels (CD31hiEmcnhi) that play an important regulatory role in the coupling of angiogenesis and osteogenesis. Despite reports on the distinct roles of type H and L vessels under physiological and pathological bone conditions, their genetic differences remain to be elucidated. This study aims to construct a competitive endogenous RNA (ceRNA) network of key gene for differencial expression (DE) in type H and L vascular endothelial cells (ECs) through integrated bioinformatic methods. METHODS: We downloaded relevant raw data from the ArrayExpress and the Gene Expression Omnibus (GEO) database and used the Limma R-Bioconductor package to screen for DE lncRNAs, DE miRNAs, and DE mRNAs between type H and L vascular ECs. A total ceRNA network was constructed based on their interactions, followed by refinement using protein-protein interaction (PPI) networks to select upregulated and downregulated key genes. Enrichment analysis was performed on these key genes. Random validation was conducted using flow cytometry and real-time RT-PCR. RESULTS: A total of 1 761 DE mRNAs, 187 DE lncRNAs, and 159 DE miRNAs were identified, and a comprehensive ceRNA network was constructed based on their interactions. Six upregulated (Itga5, Kdr, Tjp1, Pecam1, Cdh5, and Ptk2) and 2 downregulated (Csf1r and Il10) key genes were selected via PPI network to construct a subnetwork of ceRNAs related to these key genes. Upregulated key genes were mainly enriched in negative regulation of angiogenesis and vascular apoptosis. Results from flow cytometry and real-time RT-PCR were consistent with bioinformatics analysis. CONCLUSIONS: This study proposes a ceRNA network associated with upregulated and downregulated type H and L vascular ECs based on selected key genes, providing new insights into the regulatory mechanisms of type H and L vascular ECs in bone metabolism.

Landscape analysis of m6A modification regulators related biological functions and immune characteristics in myasthenia gravis.

BACKGROUND: N6-methyladenosine (m6A) modification has been recognized to play fundamental roles in the development of autoimmune diseases. However, the implication of m6A modification in myasthenia gravis (MG) remains largely unknown. Thus, we aimed to systematically explore the potential functions and related immune characteristics of m6A regulators in MG. METHODS: The GSE85452 dataset with MG and healthy samples was downloaded from Gene Expression Omnibus (GEO) database. m6A modification regulators were manually curated. The targets of m6A regulators were obtained from m6A2Target database. The differential expressed m6A regulators in GSE85452 dataset were identified by "limma" package and were validated by RT-PCR. Function enrichment analysis of dysregulated m6A regulators was performed using "clusterProfiler" package. Correlation analysis was applied for analyzing the relationships between m6A regulators and immune characteristics. Unsupervised clustering analysis was used to identify distinct m6A modification subtypes. The differences between subtypes were analyzed, including the expression level of all genes and the enrichment degree of immune characteristics. Weighted gene co-expression network analysis (WGCNA) was conducted to obtain modules associated with m6A modification subtypes. RESULTS: We found that CBLL1, RBM15 and YTHDF1 were upregulated in MG samples of GSE85452 dataset, and the results were verified by RT-PCR in blood samples from19 MG patients and 19 controls. The targeted genes common modified by CBLL1, RBM15, and YTHDF1 were mainly enriched in histone modification and Wnt signaling pathway. Correlation analysis showed that three dysregulated m6A regulators were closely associated with immune characteristics. Among them, RBM15 possessed the strongest correlation with immune characteristics, including CD56dim natural killer cell (r = 0.77, P = 0.0023), T follicular helper cell (r = - 0.86, P = 0.0002), Interferon Receptor (r = 0.78, P = 0.0017), and HLA-DOA (r = 0.64, P = 0.0200). Further two distinct m6A modification patterns mediated by three dysregulated m6A regulators was identified. Bioinformatics analysis found that there were 3029 differentially expressed genes and different immune characteristics between two m6A modification patterns. Finally, WGCNA analysis obtained a total of 12 modules and yellow module was the most positively correlated to subtype-2. CONCLUSION: Our findings suggested that m6A RNA modification had an important effect on immunity molecular mechanism of MG and provided a new perspective into understanding the pathogenesis of MG.

Causal association of the brain structure with the susceptibility, hospitalization, and severity of COVID-19: A large-scale genetic correlation study.

Brain structure is related to its ability to resist external pathogens. Furthermore, there are several abnormal anatomical brain events and central system symptoms associated with COVID-19. This study, which was conducted based on genetic variables, aimed to identify the causal association between brain structure and COVID-19 phenotypes. We performed a two-sample bidirectional Mendelian randomization analysis using genetic variables obtained from large genome-wide association studies as instruments to identify the potential causal effects of various brain imaging-derived phenotypes (BIDPs) traits on susceptibility, hospitalisation, and severity of COVID-19. We explored the genetic correlations of 1325 BIDPs with the susceptibility, hospitalisation, and severity of COVID-19 using Linkage Disequilibrium Score Regression. We observed a causal relationship between increased cortical thickness of the left inferior temporal area and an increased risk of increased COVID-19 infection (p = 4.29 × 10-4) and hospitalisation (p = 3.67 × 10-3). Moreover, the larger total surface area of the whole brain was negatively correlated with the risk of hospitalisation for COVID-19. Furthermore, there was a significant causal association between increased cerebrospinal fluid volume and decreased severity of COVID-19 (p = 3.74 × 10-3). In a conclusion, we provide new insights into the causal association between BIDPs and COVID-19 phenotypes, which may help elucidate the aetiology of COVID-19.

Association of immunosuppression treatment with generalization among patients with ocular myasthenia gravis: A propensity score analysis.

BACKGROUND: To analyze disease generalization in patients with ocular myasthenia gravis (OMG) treated with immunosuppression compared with patients without immunosuppression treatment. METHODS: In this retrospective cohort study, we analyzed data from patients with OMG at seven medical centers in China from January 1, 2015 to May 1, 2019 and compared disease generalization in patients (treated with immunosuppression vs. not treated) within 2 years of disease onset using raw and inverse probability of treatment weighting (IPTW) analyses. RESULTS: In the study population of 813 patients with OMG, 425 (52.3%) with immunosuppression had a mean (SD) onset age of 50.0 (15.1) years, and 188 (44.2%) were women. The remaining 388 (47.7%) patients were not immunosuppressed (mean age, 48.4 [15.0] years; 185 [47.7%] women). Disease generalization developed in 122 (31.4%) and 37 (8.7%) patients in the non-immunosuppression and immunosuppression groups, respectively. Relative to non-immunosuppression, immunosuppression was associated with a lower risk of generalization in a multivariable-adjusted Cox model (hazard ratio [HR] 0.27; 95% confidence interval [CI] 0.18-0.40; p < 0.001) and IPTW-weighted Cox model (HR 0.28; 95% CI 0.19-0.42; p < 0.001). In sensitivity analyses, longer duration of immunosuppression was associated with a lower risk of generalization (HR 0.90 for every 1-month increase; 95% CI 0.87-0.92; p < 0.001; IPTW-adjusted). Combination therapy with steroids and non-steroidal immunosuppressants showed superior efficacy in reducing the risk of generalization (HR 0.14; 95% CI 0.07-0.26; p < 0.001). CONCLUSION: Immunosuppression significantly reduced the 2-year risk of generalization in patients with OMG.

Nomogram for short-term outcome assessment in AChR subtype generalized myasthenia gravis.

BACKGROUND: An accurate prediction for prognosis can help in guiding the therapeutic options and optimizing the trial design for generalized myasthenia gravis (gMG). We aimed to develop and validate a predictive nomogram to assess the short-term outcome in patients with the anti-acetylcholine receptor (AChR) subtype gMG. METHODS: We retrospectively reviewed 165 patients with AChR subtype gMG who were immunotherapy naïve at the first visit from five tertiary centers in China. The short-term clinical outcome is defined as the achievement of minimal symptom expression (MSE) at 12 months. Of them, 120 gMG patients from Huashan Hospital were enrolled to form a derivation cohort (n = 96) and a temporal validation cohort (n = 24) for the nomogram. Then, this nomogram was externally validated using 45 immunotherapy naïve AChR subtype gMG from the other four hospitals. Multivariate logistic regression was used to screen independent factors and construct the nomogram. RESULTS: MSE was achieved in 70 (72.9%), 20 (83.3%), and 33 (73.3%) patients in the training, temporal validation, and external validation cohort, respectively. The duration ≤ 12 months (p = 0.021), ocular score ≤ 2 (p = 0.006), QMG score > 13 (p = 0.008), and gross motor score ≤ 9 (p = 0.006) were statistically associated with MSE in AChR subtype gMG. The nomogram has good performance in predicting MSE as the concordance indexes are 0.81 (95% CI, 0.72-0.90) in the development cohort, 0.944 (95% CI, 0.83-1.00) in the temporal validation cohort, and 0.773 (95% CI, 0.63-0.92) in the external validation cohort. CONCLUSION: The nomogram achieved an optimal prediction of MSE in AChR subtype gMG patients using the baseline clinical characters.

Rhizobium terrae sp. nov., Isolated from an Oil-Contaminated Soil in China.

A Gram-stain-negative, facultative aerobic, non-spore-forming, non-motile, non-flagellated, rod-shaped bacterium, designated strain NAU-18T was isolated from an oil-contaminated soil in China. Strain NAU-18T could grow at 10-42 °C (optimum, 30 °C), at pH 5.0-8.0 (optimum, 7.0) and in the presence of 0-2.0% (w/v) NaCl (optimum, 0.5% NaCl in R2A). The predominant fatty acids were C18:1ω7c (71.2%) and Summed feature 2 (5.1%), representing 76.3% of the total fatty acids. The major respiratory quinones were Q9 and Q10. The DNA G + C content of strain NAU-18T was 61.4 mol% based on its draft genome sequence. Genome annotation of strain NAU-18T predicted the presence of 6668 genes, of which 6588 are coding proteins and 80 are RNA genes. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain NAU-18T was a member of the genus Rhizobium and showed 96.93% (with 93.2% coverage) and 96.81% (with 100% coverage) identities with those of Neorhizobium alkalisoli CCBAU 01393T and Rhizobium oryzicola ZYY136T, respectively. In the phylogenetic analysis, strain NAU-18T and R. oryzicola ZYY136T are consistently placed in the same branch. Strain NAU-18T represents a novel species within the genus Rhizobium, for which the name Rhizobium terrae sp. nov. is proposed, with the type strain NAU-18T (=KCTC 62418T = CCTCC AB 2018075T).

The association between CD31hiEmcnhi endothelial cells and bone mineral density in Chinese women.

Osteoporosis is the most common bone disease in humans. During bone remodeling, specialized blood vessels influenced by the endothelial cells (CD31hiEmcnhi, also called type H cells) are formatted to supply nutrients. Reductions in vascular supply are associated with bone loss resulting in osteoporosis. Therefore, the objective of the present study was to explore the association between the CD31hiEmcnhi endothelial cells and bone mineral density (BMD). In this prospective study, 134 Chinese women were enrolled and examined. BMD was measured by DEXA method while the percentage of CD31hiEmcnhi endothelial cells in the intertrochanteric part was measured by flow cytometry. The percentage of CD31hiEmcnhi endothelial cells in postmenopausal subjects was significantly lower compared with premenopausal women (8.7 ± 4.0% vs 13.2 ± 5.6%, P < 0.01). Meanwhile, the CD31hiEmcnhi endothelial cell levels in osteopenia and osteoporosis were significantly lower compared with subjects with normal BMD (9.84 ± 4.2% in osteopenia and 7.11 ± 3.2% in osteoporosis vs 12.7 ± 5.6% in subjects with normal T score, P < 0.01). Multiple regression analyses showed that the CD31hiEmcnhi endothelial cells level was positively associated with femur neck and total hip BMD, but not with lumbar BMD. Our study suggests a significantly positive association between CD31hiEmcnhi endothelial cells and local BMD in Chinese women. The proportion of CD31hiEmcnhi endothelial cells is a marker of bone quality and represents a potential target for treatment of bone loss.

Huakuichenia soli gen. nov., sp. nov., a new member of the family Microbacteriaceae, isolated from contaminated soil.

A novel Gram-stain-positive, non-motile, rod-shaped bacterial strain designated LIP-1T was isolated from the contaminated soil of a pesticide factory in Xinyi, China, was investigated for its taxonomic allocation by a polyphasic approach. Cell growth occurred at 16-37 °C (optimum, 30 °C), in the presence of 0-2.0 % (w/v) NaCl (optimum, 0 %) and at pH 6.0-9.0 (optimum, pH 7.0). The major fatty acids of strain LIP-1T were anteiso-C15 : 0 (50.8 %), iso-C16 : 0 (17.6 %) and anteiso-C17 : 0 (17.4 %). The cell-wall peptidoglycan type was B2δ with 2,4-diaminobutyric acid as the diagnostic diamino acid. The major polar lipids were diphosphatidylglycerol and two unidentified glycolipids. The major menaquinones were MK-12 and MK-11. The genomic DNA G+C content was approximately 63.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain LIP-1T formed a distinct clade within the radiation of the family Microbacteriaceae and had the highest sequence similarity with Microbacterium ginsengisoli Gsoil 259T (96.01 %) followed by Cryobacterium arcticum SK1T (94.94 %). On the basis of the phylogenetic analyses and distinct phenotypic characteristics, a new genus, namely Huakuichenia gen. nov., is proposed, harbouring the novel species Huakuichenia soli gen. nov., sp. nov. with the type strain LIP-1T (=CCTCC AB 2015422T=KCTC 39698T).

Safety of SARS-CoV-2 vaccine in patients with autoimmune neurological conditions: A systematic review and meta-analysis.

Introduction: Risk of adverse effects and exacerbation in autoimmune neurological conditions (ANC)are frequently cited reasons for COVID-19 vaccine hesitancy. This study evaluates the ANC safety of COVID-19 vaccines in the real world. Methods: Electronic databases were searched to identify studies reporting the use of the COVID-19 vaccine in ANC. We selected studies that provided data on adverse effects and worsening conditions related to ANC after vaccination. The pooled incidence rates for various adverse effects, stratified for the disease category, dosage, and type of vaccine, were estimated. Results: Twenty-eight studies (31 vaccination cohorts) were included. The pooled incidence rate of general adverse events was 0.35 (95%CI, 0.27-0.43, I2 = 100 %). The pooled incidence rates of local injection reaction, fatigue, weakness, myalgia, fever, headache, and chills were 0.27 (0.18-0.36, I2 = 98 %), 0.16(0.11-0.21, I2 = 93 %), 0.15(0.00-0.31, I2 = 97 %), 0.13(0.08-0.19, I2 = 97 %), 0.11(0.07-0.15, I2 = 95 %), 0.11(0.07-0.16, I2 = 97 %), and 0.09 (0.03-0.16, I2 = 96 %), respectively. The pooled incidence rate of exacerbation adverse events was 0.05 (95%CI, 0.04-0.07, I2 = 84 %). Conclusion: According to available evidence, the administration of COVID-19 vaccines in individuals with autoimmune neurological disorders seems well-tolerated, with few reports of adverse events. Furthermore, exacerbation of autoimmune neurological conditions following vaccination appears to be infrequent.

Factors associated with the disease family burden of caregivers of myasthenia gravis patients in northwestern China: A cross-sectional study.

BACKGROUND: Patients with myasthenia gravis (MG) lose part of their working or living ability due to illness, and bring burden to caregivers. The purpose of this study was to explore the factors related to caregivers' disease family burden for MG patients in Northwest China. METHODS: The study utilized our Myasthenia Gravis database and distributed online questionnaires to both MG patients and their caregivers. The questionnaires included a general data collection form, the Patient Health Questionnaire-9 (PHQ-9) scale, and the Caregivers' Family Burden Scale of Disease (FBSD). Univariate analysis and multivariate linear regression analysis were run, with FBSD as the outcome variable for separate analyses. RESULTS: 178 MG patients were eligible for inclusion in the analysis, of whom 80 patients' caregivers had a positive family burden of MG. The daily activity burden of the family and the economic burden of the family were the heaviest among the six dimensions of the caregivers' family disease burdens. The factors independently associated with FBSD were depression symptom level, MG severity classification and family's monthly per capita income (p < 0.05). CONCLUSIONS: Depression symptom level, MG severity classification and family's monthly per capita income are independent factors related to the caregivers' disease family burden for MG patients.

Engineering an injectable gellan gum-based hydrogel with osteogenesis and angiogenesis for bone regeneration.

Injectable hydrogels are currently a topic of great interest in bone tissue engineering, which could fill irregular bone defects in a short time and avoid traditional major surgery. Herein, we developed an injectable gellan gum (GG)-based hydrogel for bone defect repair by blending nano-hydroxyapatite (nHA) and magnesium sulfate (MgSO4). In order to acquire an injectable GG-based hydrogel with superior osteogenesis, nHA were blended into GG solution with an optimized proportion. For the aim of endowing this hydrogel capable of angiogenesis, MgSO4 was also incorporated. Physicochemical evaluation revealed that GG-based hydrogel containing 5% nHA (w/v) and 2.5 mM MgSO4 (GG/5%nHA/MgSO4) had appropriate sol-gel transition time, showed a porosity-like structure, and could release magnesium ions for at least 14 days. Rheological studies showed that the GG/5%nHA/MgSO4 hydrogel had a stable structure and repeatable self-healing properties. In-vitro results determined that GG/5%nHA/MgSO4 hydrogel presented superior ability on stimulating bone marrow mesenchymal stem cells (BMSCs) to differentiate into osteogenic linage and human umbilical vein endothelial cells (HUVECs) to generate vascularization. In-vivo, GG/5%nHA/MgSO4 hydrogel was evaluated via a rat cranial defect model, as shown by better new bone formation and more neovascularization invasion. Therefore, the study demonstrated that the new injectable hydrogel, is a favorable bioactive GG-based hydrogel, and provides potential strategies for robust therapeutic interventions to improve the repair of bone defect.

Efficacy and safety of tocilizumab in patients with refractory generalized myasthenia gravis.

BACKGROUND: We aimed to compare the efficacy of tocilizumab with conventional immunotherapy in refractory patients with acetylcholine receptor antibody-positive (AChR-Ab+) generalized myasthenia gravis (gMG). METHODS: This single-center prospective cohort study was based on patients from an MG registry study in China and conducted from February 10, 2021 to March 31, 2022. Adult refractory patients with AChR-Ab+ gMG were assigned to tocilizumab or conventional immunotherapy groups. The primary efficacy outcome was the mean difference of MG activities of daily living (MG-ADL) change at weeks 4, 8, 12, 16, 20, 24 corresponding to that at the baseline between the two groups. A generalized estimating equation model was used for the primary outcome analysis. Safety was assessed based on adverse events. RESULTS: Of 34 eligible patients, 20 (mean [standard deviation] age, 53.8 [21.9] years; 12 [60.0%] female) received tocilizumab and 14 received conventional immunotherapy (45.8 [18.0] years; 8 [57.1%] female). The tocilizumab group had greater reduction in MG-ADL score at week 4 (adjusted mean difference, -3.4; 95% CI, -4.7 to -2.0; p < 0.001) than the conventional immunotherapy group, with significant differences sustained through week 24 (adjusted mean difference, -4.5; 95% CI, -6.4 to -2.6; p < 0.001). At week 24, the proportion of patients achieving higher levels of MG-ADL (up to 7-point reduction) and QMG (up to 11-point reduction) scores improvement was significantly greater with tocilizumab. Tocilizumab had acceptable safety profiles without severe or unexpected safety issues. CONCLUSION: Tocilizumab is safe and effective in improving the MG-ADL score and reducing prednisone dose in refractory AChR-Ab+ gMG, suggesting tocilizumab has the potential to be a valuable therapeutic option for such patients.

Serum Homer1 is a Novel Biomarker for Predicting the Clinical Outcomes of Acute Ischemic Stroke Patients.

Purpose: We aim to explore the relationship between Homer1 and the outcomes of AIS patients at 3 months. Patients and Methods: This prospective cohort study was conducted from May 2022 to March 2023. In this study, we investigated the association between serum Homer1 levels by enzyme-linked immunosorbent assay at admission and functional outcomes of patients at 3 months after AIS. Results: Overall, 89 AIS patients (48 good outcomes and 41 poor outcomes) and 83 healthy controls were included. The median serum Homer1 level of patients at admission with poor outcomes was significantly higher than that of patients with good outcomes (39.33 vs 33.15, P<0.001). Serum Homer1 levels at admission were positively correlated with the severity of AIS (r = 0.488, P<0.001). The optimal cutoff of serum Homer1 level as an indicator for an auxiliary diagnosis of 3 months functional outcomes was 35.07 pg/mL, with a sensitivity of 75.0% and a specificity of 92.7% (AUC 0.837; 95% CI [0.744-0.907]; P<0 0.001). The odds ratio of MRS > 2 predicted by the level of serum Homer1 after 3 months was 1.665 (1.306-2.122; P<0.001). Conclusion: Serum concentrations of Homer1 have a high predictive value for neurobehavioral outcomes after acute ischemic stroke. Higher serum Homer1 levels (>35.07 pg/mL) were positively associated with poor functional outcomes of patients 3 months post-stroke.

A predictive nomogram for short-term outcomes of myasthenia gravis patients treated with low-dose rituximab.

BACKGROUND: This study aims to establish and validate a predictive nomogram for the short-term clinical outcomes of myasthenia gravis (MG) patients treated with low-dose rituximab. METHODS: We retrospectively reviewed 108 patients who received rituximab of 600 mg every 6 months in Huashan Hospital and Tangdu Hospital. Of them, 76 patients from Huashan Hospital were included in the derivation cohort to develop the predictive nomogram, which was externally validated using 32 patients from Tangdu Hospital. The clinical response is defined as a ≥ 3 points decrease in QMG score within 6 months. Both clinical and genetic characteristics were included to screen predictors via multivariate logistic regression. Discrimination and calibration were measured by the area under the receiver operating characteristic curve (AUC-ROC) and Hosmer-Lemeshow test, respectively. RESULTS: Disease duration (OR = 0.987, p = 0.032), positive anti-muscle-specific tyrosine kinase antibodies (OR = 19.8, p = 0.007), and genotypes in FCGR2A rs1801274 (AG: OR = 0.131, p = 0.024;GG:OR = 0.037, p = 0.010) were independently associated with clinical response of post-rituximab patients. The nomogram identified MG patients with clinical response with an AUC-ROC (95% CI) of 0.875 (0.798-0.952) in the derivation cohort and 0.741(0.501-0.982) in the validation cohort. Hosmer-Lemeshow test showed a good calibration (derivation: Chi-square = 3.181, p = 0.923; validation: Chi-square = 8.098, p = 0.424). CONCLUSIONS: The nomogram achieved an optimal prediction of short-term outcomes in patients treated with low-dose rituximab.

Exploring the Roles of m6A-Modified circRNAs in Myasthenia Gravis Based on Multi-Omics Analysis.

Myasthenia gravis (MG) is an autoimmune disease mediated by autoantibodies. The important roles of circRNAs modified by m6A methylation have been reported in the pathogenesis of other autoimmune diseases, but remain unclear in MG. To address this point, we collected peripheral blood mononuclear cells from six MG patients and six healthy controls and performed m6A­circRNA epitranscriptomic microarray and RNA sequencing. Differentially m6A-modified circRNAs and differentially expressed genes (DEGs) were analyzed. A network was constructed containing 17 circRNAs, 30 miRNAs, and 34 DEGs. The GSE85452 dataset was downloaded. DEGs that were differentially expressed in the GSE85452 dataset were selected as seed genes. Finally, four candidate m6A-modified circRNAs (hsa_circ_0084735, hsa_circ_0018652, hsa_circ_0025731, and hsa_circ_0030997) were identified through a random walk with restart. We found that they had different degree correlations with different immune cells. The results of MeRIP-qPCR showed that the m6A methylated levels of hsa_circ_0084735 and hsa_circ_0025731 were downregulated in MG patients, while the other two circRNAs were not significantly different between MG and control group. For the first time, we explored the pathogenesis of MG at the epigenetic transcriptome level. Our results will open new perspectives for MG research and identify potential biomarkers and therapeutic targets for MG.

Environmental factors affecting the risk of generalization for ocular-onset myasthenia gravis: a nationwide cohort study.

BACKGROUND: The environmental effects on the prognosis of ocular myasthenia gravis (OMG) remain largely unexplored. AIM: To investigate the association between specific environmental factors and the generalization of OMG. DESIGN: The cohort study was conducted in China based on a nationwide multicenter database. METHODS: Adult patients with OMG at onset, who were followed up for at least 2 years until May 2022, were included. We collected data on demographic and clinical factors, as well as environmental factors, including latitude, socioeconomic status (per capita disposable income [PDI] at provincial level and education) and smoking. The study outcome was the time to the development of generalized myasthenia gravis (GMG). Cox models were employed to examine the association between environmental exposures and generalization. Restricted cubic spline was used to model the association of latitude with generalization risk. RESULTS: A total of 1396 participants were included. During a median follow-up of 5.15 (interquartile range [IQR] 3.37-9.03) years, 735 patients developed GMG within a median of 5.69 (IQR 1.10-15.66) years. Latitude of 20-50°N showed a U-shaped relation with generalization risk, with the lowest risk at around 30°N; both higher and lower latitudes were associated with the increased risk (P for non-linearity <0.001). Living in areas with lower PDI had 1.28-2.11 times higher risk of generalization. No significant association was observed with education or smoking. CONCLUSIONS: Latitude and provincial-level PDI were associated with the generalization of OMG in China. Further studies are warranted to validate our findings and investigate their potential applications in clinical practice and health policy.

Emerging trends and research foci of neuromyelitis optica spectrum disorder: a 20-year bibliometric analysis.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a demyelinating syndrome of the central nervous system. A tremendous amount of literature on NMOSD has been published. This study aimed to perform a bibliometric analysis of the publications on NMOSD and show its hotspots and development trends. Methods: We used the Web of Science Core Collection as a database and searched the literature published between 2002 and 2022. CiteSpace, VOSviewer, online bibliometric platform, and R-bibliometrix were used to conduct bibliometric analysis and network visualization, including the number of publications, citations, countries/regions, institutions, journals, authors, references, and keywords. Results: A total of 3,057 publications on NMOSD were published in 198 journals by 200 authors at 200 institutions from 93 countries/regions. The United States published the most literature and made great contributions to this field. The Mayo Clinic was the institution with the largest number of publications. The journal with the most publications was Multiple Sclerosis and Related Disorders, and the most co-cited journal was Neurology. The author with the most publications was Fujihara, K., while the most frequently co-cited author was Wingerchuk, DM. The current research hotspots may be focused on "efficacy," "multicenter," "interleukin-6 receptor blockade," "safety," "azathioprine," "tolerance," and "adult". Conclusion: This study was the first bibliometric analysis of publications on the NMOSD field, visualizing its bibliometric characteristics and gaining insight into the direction, hotspots, and development of global NMOSD research, which may provide helpful information for researchers. Future research hotspots might be conducting randomized controlled trials on targeted immunotherapy in the NMOSD field.

Causal relationships between CD25 on immune cells and hip osteoarthritis.

Objectives: Previous research has indicated a potential association between immune factors and osteoarthritis (OA), but the causal relationship between CD25 expression on immune cells and hip OA remains enigmatic. To shed light on this relationship, this study utilized the two-sample Mendelian Randomization (MR) method. Methods: Leveraging genome-wide association studies (GWAS) data from the UK Biobank and arcOGEN, the investigation encompasses a substantial European cohort comprising 15,704 hip OA cases and 378,169 controls. Genetic insights into CD25 stem from a subgroup of 3,757 individuals with European ancestry, encompassing 77 CD25-related traits. Several MR methods were applied, and robustness was assessed through heterogeneity and sensitivity analysis. Results: Among the 77 traits examined, 66 shared the same single nucleotide polymorphisms (SNPs) with hip OA. Of these, 7 CD25-related traits were found to be causally associated with hip OA (adjusted P><0.05), with F-statistics ranging from 33 to 122. These traits are specifically related to CD4+CD25+ T cells, exhibiting odds ratios (OR) and 95% confidence intervals (CI) less than 1. Notably, no causal link was discerned with the CD8+CD25+ T cell subset. Within absolute count (AC) and relative count (RC) trait types, a significant causal relationship was observed solely between CD4+CD25+ T cells and hip OA, without subtype localization. A more intricate examination of CD25 expression levels within the CD4+CD25+ T cell subset revealed a correlation with the CD39+ regulatory T (Treg) subset and hip OA, particularly within the CD39+ activated Treg subset. Furthermore, a notable causal relationship emerged between CD25 expression levels in the CD45RA- not Treg subset and hip OA. However, no significant causal link was established with any subsets of B cells. Conclusion: The genetic prediction suggests that CD25, particularly within the realm of CD4+CD25+ T cells, may exert a protective influence against the development of hip OA. These findings provide a novel therapeutic approach for the prevention and treatment of hip OA.