The up-regulation of SYNCRIP promotes the proliferation and tumorigenesis via DNMT3A/p16 in colorectal cancer.

Heterogeneous nuclear ribonucleoproteins (hnRNPs), a group of proteins that control gene expression, have been implicated in many post-transcriptional processes. SYNCRIP (also known as hnRNP Q), a subtype of hnRNPs, has been reported to be involved in mRNA splicing and translation. In addition, the deregulation of SYNCRIP was found in colorectal cancer (CRC). However, the role of SYNCRIP in regulating CRC growth remains largely unknown. Here, we found that SYNCRIP was highly expressed in colorectal cancer by analyzing TCGA and GEPIA database. Furthermore, we confirmed the expression of SYNCRIP expression in CRC tumor and CRC cell lines. Functionally, SYNCRIP depletion using shRNA in CRC cell lines (SW480 and HCT 116) resulted in increased caspase3/7 activity and decreased cell proliferation, as well as migration. Meanwhile, overexpression of SYNCRIP showed opposite results. Mechanistically, SYNCRIP regulated the expression of DNA methyltransferases (DNMT) 3A, but not DNMT1 or DNMT3B, which affected the expression of tumor suppressor, p16. More importantly, our in vivo experiments showed that SYNCRIP depletion significantly inhibited colorectal tumor growth. Taken all together, our results suggest SYNCRIP as a potent therapeutic target in colorectal cancer.

Single-cell RNA sequencing illuminates the ontogeny, conservation and diversification of cartilaginous and bony fish lymphocytes.

Elucidating cellular architecture and cell-type evolution across species is central to understanding immune system function and susceptibility to disease. Adaptive immunity is a shared trait of the common ancestor of cartilaginous and bony fishes. However, evolutionary features of lymphocytes in these two jawed vertebrates remain unclear. Here, we present a single-cell RNA sequencing atlas of immune cells from cartilaginous (white-spotted bamboo shark) and bony (zebrafish and Chinese tongue sole) fishes. Cross-species comparisons show that the same cell types across different species exhibit similar transcriptional profiles. In the bamboo shark, we identify a phagocytic B cell population expressing several pattern recognition receptors, as well as a T cell sub-cluster co-expressing both T and B cell markers. In contrast to a division by function in the bony fishes, we show close linkage and poor functional specialization among lymphocytes in the cartilaginous fish. Our cross-species single-cell comparison presents a resource for uncovering the origin and evolution of the gnathostome immune system.

Single-sample gene set enrichment analysis reveals the clinical implications of immune-related genes in ovarian cancer.

Purpose: Ovarian cancer (OC) is a common gynecological malignancy with poor prognosis and substantial tumor heterogeneity. Due to the complex tumor immune microenvironment (TIME) among ovarian cancer, only a few patients have an immune response to immunotherapy. To investigate the differences in immune function and identify potential biomarkers in OC, we established a prognostic risk scoring model (PRSM) with differential expression of immune-related genes (IRGs) to identify critical prognostic IRG signatures. Methods: Single-sample gene set enrichment analysis (ssGSEA) was used to investigate the infiltration of various immune cells in 372 OC patients. Then, COX regression analysis and Lasso regression analysis were used to screen IRGs and construct PRSM. Next, the immunotherapy sensitivity of different risk groups regarding the immune checkpoint expression and tumor mutation burden was evaluated. Finally, a nomogram was created to guide the clinical evaluation of the patient prognosis. Results: In this study, 320 immune-related genes (IRGs) were identified, 13 of which were selectively incorporated into a Prognostic Risk Scoring Model (PRSM). This model revealed that the patients in the high-risk group were characterized as having poorer prognosis, lower expression of immune checkpoints, and decreased tumor mutation load levels compared with those in the low-risk group. The nomogram based on the risk score can distinguish the risk subtypes and individual prognosis of patients with OC. Additionally, M1 macrophages may be the critical target for immunotherapy in OC patients. Conclusion: With the in-depth analysis of the immune microenvironment of OC, the PRSM was constructed to predict the OC patient prognosis and identify the subgroup of the patients benefiting from immunotherapy.

Cytomegalovirus and Epstein-Barr virus infections in patients with neuromyelitis optica spectrum disorder.

OBJECTIVES: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections in patients with Neuromyelitis optica spectrum disorder (NMOSD) remain unclear. The objective of this study was to investigate CMV and EBV infections in patients with NMOSD. METHODS: Serum immunoglobin (Ig) G antibodies against CMV and EBV were measured in patients with NMOSD and healthy controls (HCs), including anti-CMV, anti-EBV nuclear antigen-1 (EBNA-1), anti-EBV virus capsid antigen (VCA), and anti-EBV early antigen (EA) IgGs. The immune status ratio (ISR) was used to evaluate the serum anti-CMV and anti-EBV IgG levels and ISR ≧1.10 was defined as seropositivity. RESULTS: In total, 238 serum samples were collected from 94 patients with NMOSD and 144 HCs, and no significant difference of sex and age between NMOSD and HCs. Comparing to the HCs, patients with NMOSD exhibited significantly higher serum anti-CMV IgG level. In contrast, the serum anti-EBNA1 IgG level was significantly lower in patients with NMOSD than in HCs. The serum anti-VCA and anti-EA IgG levels did not differ between the two groups, but the anti-EA seropositivity was significantly higher in NMOSD group than that in HC group. We did not find associations between serum anti-CMV or anti-EBV IgG levels and NMOSD disease stage, immunotherapy, or disability score. CONCLUSIONS: Our findings indicated that increased CMV infection and EBV recent infection, as well as reduced EBV latency infection were associated with the risk of NMOSD. Prospective cohort studies are needed to verify our findings and clarify the correlation between CMV and EBV infections and clinical characteristics of NMOSD.

Integrating genetic and proteomic data to elucidate the association between immune system and blood-brain barrier dysfunction with multiple sclerosis risk and severity.

BACKGROUND: Immune system dysfunction and blood-brain barrier (BBB) impairment are implicated in multiple sclerosis (MS) risk and severity. However, the causal relationships and potential therapeutic targets remain unclear. METHODS: Leveraging the MRC IEU OpenGWAS data infrastructure, we extracted 1254 peripheral immune systems and 792 BBB biomarkers as genetic instruments for exposure. MS risk data from the International Multiple Sclerosis Genetics Consortium (IMSGC) (47,429 MS cases, 68,374 controls) served as one outcome, replicated in FinnGen (1048 cases, 217,141 controls) and the UK Biobank (1679 cases, 461,254 controls). Genetic associations with MS severity derived from IMSGC and MultipleMS Consortium GWAS data (12,584 cases). Two-sample, bidirectional, and protein drug-target MR analyses were conducted, along with interaction analysis of identified proteins and druggability assessment. RESULTS: Causal relationships between 45 immunological markers, 15 BBB markers, and MS risk were strongly supported. In peripheral immunity, the causal associations with MS are predominantly concentrated in CD4+ T cells and CD8+ T cells. Notably, anti-Epstein-Barr virus nuclear antigen (EBNA) IgG levels exhibited the most significant causal effect on MS risk (OR = 225.62, P = 5.63E-208), replicated in the MS severity (OR = 1.11, P = 0.04). Weak causal evidence was found between 62 immunological markers, 35 BBB markers, and MS severity. Reverse MR analysis suggested potential causal effects of MS risk on 8 markers. Drug-targeted MR analysis indicated potential therapeutic benefits in reducing MS risk for CD40 (OR = 0.71, P = 7.24E-13, PPH4 = 97.6 %), AHSG (OR = 0.88, P = 2.91E-05, PPH4 = 94.4 %), and FCRL3 (Sun BB et al.: OR = 0.83, P = 8.93E-09, PPH4 = 94.2 %, Suhre K et al.: OR = 0.88, P = 5.20E-08, PPH4 = 99.2 %). CONCLUSIONS: This study provides evidence supporting the causal effects of immune system and BBB dysfunction on MS risk and severity. It emphasizes the significant role of anti-EBNA IgG levels, CD4+ T cells, and CD8+ T cells in MS, and delineates the potential therapeutic benefits of targeting three proteins associated with MS risk: CD40, AHSG, and FCRL3.

Causal effects of gut microbiota on multiple sclerosis: A two-sample Mendelian randomization study.

BACKGROUND: Gut microbiota alterations in multiple sclerosis (MS) patients have been reported in observational studies, but whether these associations are causal is unclear. OBJECTIVE: We performed a Mendelian randomization study (MR) to assess the causal effects of gut microbiota on MS. METHODS: Independent genetic variants associated with 211 gut microbiota phenotypes were selected as instrumental variables from the largest genome-wide association studies (GWAS) previously published by the MiBioGen study. GWAS data for MS were obtained from the International Multiple Sclerosis Genetics Consortium (IMSGC) for primary analysis and the FinnGen consortium for replication and collaborative analysis. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. RESULTS: After inverse-variance-weighted and sensitivity analysis filtering, seven gut microbiota with potential causal effects on MS were identified from the IMSGC. Only five metabolites remained significant associations with MS when combined with the FinnGen consortium, including genus Anaerofilum id.2053 (odds ratio [OR] = 1.141, 95% confidence interval [CI]: 1.021-1.276, p = .021), Ruminococcus2 id.11374 (OR = 1.190, 95% CI: 1.007-1.406, p = .042), Ruminococcaceae UCG003 id.11361 (OR = 0.822, 95% CI: 0.688-0.982, p = .031), Ruminiclostridium5 id.11355 (OR = 0.724, 95% CI: 0.585-0.895, p = .003), Anaerotruncus id.2054 (OR = 0.772, 95% CI: 0.634-0.940, p = .010). CONCLUSION: Our MR analysis reveals a potential causal relationship between gut microbiota and MS, offering promising avenues for advancing mechanistic understanding and clinical investigation of microbiota-mediated MS.

Correlation between severe attacks and serum aquaporin-4 antibody titer in neuromyelitis optica spectrum disorder.

Aquaporin 4-immunoglobulin G (AQP4-IgG) specifically targets aquaporin 4 in approximately 80% of Neuromyelitis Optica Spectrum Disorder (NMOSD) cases. NMOSD is presently categorized as anti-AQP4-antibody (Ab) positive or negative based on AQP4-Ab presence. The association between antibody titers and patient prognosis remains unclear. Therefore, the present study explores the correlation between severe attacks and serum AQP4 Ab titers in patients with neuromyelitis optica spectrum disorder. Data were gathered retrospectively from 546 patients with NMOSD between September 1, 2009, and December 1, 2021. Patients were categorized based on their AQP4-Ab titers: AQP4 titer ≥ 1:320 were classified as the high-titer group, AQP4 (+ +), and AQP4 titer of ≤ 1:100 were classified as the low-titer group, AQP4 ( +). Clinical characteristics and prognoses between the two groups were compared. Patients with AQP4 ( +) exhibited few severe optic neuritis (SON) attacks (false discovery rate [FDR] corrected p < 0.001), a reduced percentage experiencing SON attacks, and a lower incidence of visual disability than patients with AQP4 (+ +). Patients with AQP4 (+ +) and AQP4 ( +) NMOSD exhibited significant difference in annual recurrence rate (ARR) (FDR-corrected p < 0.001). The lower AQP4 Ab titer group demonstrated reduced susceptibility to severe relapse with conventional immunosuppressive agents and rituximab (RTX) than the higher titer group. No significant differences in sex, age at onset, coexisting connective tissue diseases, motor disability, or mortality rates were observed between the two groups. Higher AQP4 Ab titers correlated with increased disease severity and visual disability in patients with NMOSD.

Analyzing the tourism efficiency and its influencing factors of China's coastal provinces.

Tourism efficiency has become an important role in promoting tourism competitiveness and driving sustainable development. It is particularly important to identify and agnalyze the factors and mechanisms that affect efficiency. This paper firstly evaluates the tourism efficiency of 11 coastal provinces regions in China from 2010 to 2020 by using the DEA-BBC model that includes undesirable outputs. After that, it investigates the internal driving mechanism of the efficiency change through the Malmquist index and its decomposition. Finally, it analyzes the external influencing elements of tourist efficiency by the Tobit model. The results show that: (1) Although the average value of the tourism efficiency was changed from 0.727 to 0.707, it does not achieve the target. Its trend shows fluctuating from 2010-2020, which indicates that the tourism efficiency of most provincial regions is not optimal. The main factor that restricts tourism efficiency is scale efficiency. (2) By analyzing the dynamic trend, it is found that the average increase of technical efficiency is 14.0%, the average increase of technical change is 9.5%, and the average increase of MI index is 25.4%. It indicates that the overall tourism efficiency of 11 coastal provinces region in China is on the rise. (3) The spatial difference of tourism efficiency is significant, but there is no obvious spatial correlation. (4) The influencing factors of tourism efficiency are consumer demand, industrial structure, labor force and urbanization.

Best acupuncture method for mammary gland hyperplasia: Evaluation of randomized controlled trials and Bayesian network meta-analysis.

Objective: To evaluate the effectiveness of different acupuncture treatments for mammary gland hyperplasia (MGH) using a network meta-analysis. Methods: Several databases were searched without language restrictions from 2000 to February 2023, including PubMed, Embase, Web of Science, Cochrane Library, China Science and Technology Journal Database, China Biology Medicine Database, Wanfang Database, China National Knowledge Infrastructure Database, and other professional websites and gray literature. Inclusion criteria were adult women diagnosed with MGH; intervention measures included acupuncture and related therapies; the control group was treated with simple drugs; and the research type was a randomized controlled trial (RCT). The primary outcomes were treatment effectiveness and estradiol and progesterone levels. Secondary outcomes were breast lump size and visual analog scale (VAS) score of breast pain. Exclusion criteria were studies unrelated to MGH, incorrect study populations, control measures or interventions, incomplete data, non-RCTs, case reports, and animal experiments. Cochrane tools were used to assess the risk of bias. The R software (x64 version 4.2.1), Review Manager 5.3 software and STATA 16.0 software were used for data analysis. Results: Following a rigorous screening process, data extraction, and quality assessment, 48 eligible RCTs encompassing 4,500 patients with MGH and 16 interventions were included. The results indicated that acupuncture, alone or in combination with traditional Chinese or Western medicine, had better therapeutic effects than conventional therapy. In terms of effectiveness, warm needle acupuncture was the best choice (94.6%). Bloodletting pricking was the most effective method (85.7%) for lowering progesterone levels. Bloodletting pricking was the most effective method (98.3%) for lowering estradiol levels. Manual acupuncture combined with traditional Chinese medicine was the most effective (74.5%) treatment to improve the size of the breast lump. Warm needle acupuncture was the most effective (69.8%) in improving the VAS score. Conclusion: Acupuncture therapy was more effective in treating MGH than drug therapy alone, and warm needle acupuncture and bloodletting pricking were the two best options. However, larger sample sizes and high-quality RCTs are required.

Clinical features and prognosis of Tibetan patients with neuromyelitis optica spectrum disorder are different from those of Han Chinese patients.

We compared the prognosis of Tibetan and Han Chinese patients with neuromyelitis optica spectrum disorder (NMOSD). The Expanded Disability Status Scale (EDSS) score at each attack, response to immunosuppressive therapy, risk of first relapse, severe attack, visual disability, motor disability, and total risk of disability were compared between Tibetan and Han Chinese patients. Tibetan patients showed higher EDSS during acute attacks. Annualized relapse rate did not differ between groups. Risk of severe attack, visual disability, and total risk of disability were higher in Tibetan patients. Tibetan patients with NMOSD have a higher risk of poor prognosis than Han Chinese patients.

Causal relationship between multiple sclerosis and cortical structure: a Mendelian randomization study.

BACKGROUND: Observational studies have suggested an association between multiple sclerosis (MS) and cortical structure, but the results have been inconsistent. OBJECTIVE: We used two-sample Mendelian randomization (MR) to assess the causal relationship between MS and cortical structure. METHODS: MS data as the exposure trait, including 14,498 cases and 24,091 controls, were obtained from the International Multiple Sclerosis Genetics Consortium. Genome-wide association study (GWAS) data for cortical surface area (SAw/nw) and thickness (THw/nw) in 51,665 individuals of European ancestry were obtained from the ENIGMA Consortium. The inverse-variance weighted (IVW) method was used as the primary analysis for MR. Sensitivity analyses were conducted to evaluate heterogeneity and pleiotropy. Enrichment analysis was performed on MR analyses filtered by sensitivity analysis. RESULTS: After IVW and sensitivity analysis filtering, only six surviving MR results provided suggestive evidence supporting a causal relationship between MS and cortical structure, including lingual SAw (p = .0342, beta (se) = 5.7127 (2.6969)), parahippocampal SAw (p = .0224, beta (se) = 1.5577 (0.6822)), rostral middle frontal SAw (p = .0154, beta (se) = - 9.0301 (3.7281)), cuneus THw (p = .0418, beta (se) = - 0.0020 (0.0010)), lateral orbitofrontal THw (p = .0281, beta (se) = 0.0025 (0.0010)), and lateral orbitofrontal THnw (p = .0417, beta (se) = 0.0029 (0.0014)). Enrichment analysis suggested that leukocyte cell-related pathways, JAK-STAT signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and prolactin signaling pathway may be involved in the effect of MS on cortical morphology. CONCLUSION: Our results provide evidence supporting a causal relationship between MS and cortical structure. Enrichment analysis suggests that the pathways mediating brain morphology abnormalities in MS patients are mainly related to immune and inflammation-driven pathways.

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.

Dietary fiber intake and cognitive impairment in older patients with chronic kidney disease in the United States: A cross-sectional study.

BACKGROUND: High-fiber diet has been associated with better cognitive performance. However, the association between dietary fiber intake and cognition in older patients with chronic kidney disease (CKD) remains unknown. Hence, this study aimed to investigate the effect of dietary fiber intake on cognition in older patients with CKD. METHODS: This study included participants aged ≥60 years who provided data on social demography, cognitive tests (Consortium to Establish a Registry for Alzheimer's disease Word Learning [CERAD-WL], CERAD Delayed Recall [CERAD-DR], Animal Fluency Test [AFT], and Digit Symbol Substitution Test [DSST]), diet, and other potential cognition-related variables from the National Health and Nutrition Examination Survey 2011-2014. Fully-adjusted multivariate logistic regression subgroup models were performed, and multiple linear regression analyses were employed to examine the association between dietary fiber intake and cognition in patients with CKD. RESULTS: A total of 2461 older adults were included, with 32% who suffered from CKD. Participants with CKD scored lower in CERAD-WL, CERAD-DR, AFT, and DSST. Patients with CKD consuming low dietary fiber (≤25 g/day) had a higher risk of CERAD-WL and DSST impairments. High dietary fiber intake eliminated the differences in CERAD-WL and DSST impairments between the CKD and non-CKD participants. However, no associations were observed between CKD and CERAD-DR and AFT impairments regardless of dietary fiber intake. A positive linear relationship between dietary fiber intake and AFT score was observed in older patients with CKD. CONCLUSION: High dietary fiber intake may benefit cognitive function in older patients with CKD. High-fiber diet management strategies could potentially mitigate cognitive impairment in this group of patients.

Association between COVID-19 and myasthenia gravis (MG): A genetic correlation and Mendelian randomization study.

BACKGROUND: Observational studies have suggested an association between coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG). Here, we aimed to estimate the genetic correlation and causal relationship between COVID-19 susceptibility, hospitalization, severity, and MG phenotypes using linkage disequilibrium score regression (LDSC) and Mendelian randomization (MR) approach. METHODS: Summary statistics of COVID-19 susceptibility, hospitalization, and severity were used as instrumental variables for exposure traits. Large-scale genome-wide association study (GWAS) data for MG were used as outcome traits. The inverse variance weighted approach was used for the main MR analysis, complemented by MR-Egger, weighted median, simple mode, and weighted mode methods. Sensitivity analysis was implemented using Cochran's Q test, MR-PRESSO method, and MR-Egger intercept test. RESULTS: LDSC analysis did not reveal any genetic correlation among COVID-19 susceptibility, hospitalization, severity, and MG phenotypes, including MG, early-onset MG, and late-onset MG (p > .05). Our MR analysis did not provide evidence supporting a causal effect of COVID-19 susceptibility, hospitalization, or severity on MG phenotypes (p > .05). Extensive sensitivity analysis strengthened the robustness and consistency of the MR estimates. CONCLUSION: Our study did not find evidence of a genetic correlation or causal relationship among COVID-19 susceptibility, hospitalization, severity, and MG. Future studies with more GWAS data are needed to evaluate the association between COVID-19 phenotypes and MG and its subgroups.

COVID-19 and the risk of neuromyelitis optica spectrum disorder: a Mendelian randomization study.

Background: An increasing number of studies have elucidated a close nexus between COVID-19 phenotypes and neuromyelitis optica spectrum disorder (NMOSD), yet the causality between them remains enigmatic. Methods: In this study, we conducted a Mendelian randomization (MR) analysis employing summary data sourced from genome-wide association studies (GWAS) pertaining to COVID-19 susceptibility, hospitalization, severity, and NMOSD. The primary MR analysis employed the Inverse variance weighted (IVW) approach, which was supplemented by MR-Egger, weighted median, simple mode, and weighted mode methods. We implemented various sensitivity analyses including Cochran's Q test, MR-PRESSO method, MR-Egger intercept, leave-one-out analysis, and funnel plot. Results: The MR results demonstrated a nominal association between COVID-19 susceptibility and the risk of AQP4+ NMOSD, as evidenced by the IVW method (OR = 4.958; 95% CI: 1.322-18.585; P = 0.018). Conversely, no causal association was observed between COVID-19 susceptibility, hospitalization, or severity and the increased risk of NMOSD, AQP4-NMOSD, or AQP4+ NMOSD. The comprehensive sensitivity analyses further bolstered the robustness and consistency of the MR estimates. Conclusion: Our findings provide compelling evidence for a causal effect of COVID-19 phenotype on AQP4+ NMOSD, shedding new light on the understanding of the comorbidity between COVID-19 and NMOSD.

Initial BMI effects on clinical presentation and prognosis in neuromyelitis optica spectrum disorder.

OBJECTIVE: To investigate the correlation among body mass index at onset, clinical features, and prognosis in patients with neuromyelitis optica spectrum disorder. METHOD: This retrospective cohort studied patients with neuromyelitis optica spectrum disorder from January 2015 to January 2022, grouping them by body mass index at onset. Demographics and clinical records were reviewed. Anderson-Gill, Kaplan-Meier, and Cox models evaluated the body mass index's effect on relapse risk and long-term outcomes. RESULTS: Of 246 patients with 799 neuromyelitis optica spectrum disorder attacks study, 36 patients had low, 133 had normal, 77 had high body mass index, with a mean onset age of 40 ± 13 years, and the population was 88% female. The medium follow-up time was 49 months; AQP4-IgG was found in 193 (78%) patients. Onset and relapse of area postrema syndrome were less frequent in patients with a normal body mass index. The annual relapse rate after immunosuppressive therapy was significantly lower in patients with a low body mass index. In the multivariable analysis, statistical correlation still existed between body mass index at onset and risk of relapse (HR = 1.03, 95% CI: 1.03-1.03, P < 0.001), risk of severe attack (HR = 0.92, 95% CI: 0.86-0.98, P = 0.013), risk of visual disability (HR = 0.9, 95% CI: 0.81-1, P = 0.047), and overall risk of disability (HR = 0.89, 95% CI: 0.82-0.98, P = 0.015) after adjusting various variables. INTERPRETATION: Lower body mass index at onset was associated with less frequent relapse but poor prognosis.

Case Report: Long segmental lesions of the spinal cord caused by exposure to xylene.

Xylene has the potential to cause nervous system disturbances since it is a lipophilic substance with high affinity for lipid-rich tissue, such as the brain. Involvement in the spinal cord, especially long segmental spinal cord lesions that permeate almost the entire cervical and thoracic spinal cord, is extremely rare. We report two cases of occupational exposure to excessive xylene, both of which presented with severe and rapidly progressive numbness and weakness in the limbs that, more importantly, led to poor outcomes: one died and the other was left severely disabled. In both, spinal magnetic resonance imaging showed long segmental lesions in the cervicothoracic spinal cord. These findings may provide some insights into the effects of xylene as an isolated agent on the spinal cord injury.

Immune Repertoire Profiling Reveals Its Clinical Application Potential and Triggers for Neuromyelitis Optica Spectrum Disorders.

BACKGROUND AND OBJECTIVES: Neuromyelitis optica spectrum disorders (NMOSD) is widely recognized as a CNS demyelinating disease associated with AQP4-IgG (T cell-dependent antibody), and its trigger is still unclear. In addition, although the treatment of NMOSD currently can rely on traditional immunosuppressive and modulating agents, effective methods to predict the efficacy of these therapeutics are lacking. METHODS: In this study, high-throughput T-cell receptor (TCR) sequencing was performed on peripheral blood from 151 pretreatment patients with AQP4-IgG+ NMOSD and 151 healthy individuals. We compared the TCR repertoire of those with NMOSD with that of healthy individuals and identified TCR clones that were significantly enriched in NMOSD. In addition, we treated 28 patients with AQP4-IgG+ NMOSD with immunosuppressants and followed up for 6 months to compare changes in NMOSD-specific TCRs (NMOSD-TCRs) before and after treatment. Moreover, we analyzed transcriptome and single-cell B-cell receptor (BCR) data from public databases and performed T-cell activation experiments using antigenic epitopes of cytomegalovirus (CMV) to further explore the triggers of AQP4-IgG+ NMOSD. RESULTS: Compared with healthy controls, patients with AQP4-IgG+ NMOSD had significantly reduced diversity and shorter CDR3 length of TCRß repertoire. Furthermore, we identified 597 NMOSD-TCRs with a high sequence similarity that have the potential to be used in the diagnosis and prognosis of NMOSD. The characterization of NMOSD-TCRs and pathology-associated clonotype annotation indicated that the occurrence of AQP4-IgG+ NMOSD may be associated with CMV infection, which was further corroborated by transcriptome and single-cell BCR analysis results from public databases and T-cell activation experiments. DISCUSSION: Our findings suggest that the occurrence of AQP4-IgG+ NMOSD may be associated with CMV infection. In conclusion, our study provides new clues to uncover the causative factors of AQP4-IgG+ NMOSD and provides a theoretical foundation for treating and monitoring the disease.

Visual disability in neuromyelitis optica spectrum disorders: prognostic prediction models.

Background and objectives: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system characterized by simultaneous or consecutive episodes of acute optic neuritis and transverse myelitis. Attacks of NMOSD can result in the accrual of severe visual disability over time. This study aimed to develop and validate prognostic models for visual disability risk within 1, 3, and 5 years. Methods: Medical records of NMOSD patients were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) regression algorithm and univariate and multivariate Cox regression analyses were performed to select predictors of visual disability. Two models predicting the probability of visual disability in 1, 3, and 5 years were developed based on different selections and displayed as nomograms. Risk scores were calculated for every patient, and a cut-off point was obtained to recognize patients at high risk. Results: In total, 161 (25.2%) patients developed visual disabilities during the follow-up period. Four visual disability-related factors were selected using LASSO regression: optic neuritis (ON) onset, higher annual relapse rate (ARR) before maintenance therapy, no maintenance immune suppression therapy (IST), and initial severe attack. Three additional predictors were determined using multivariate Cox regression: male sex, age at first onset, and positive AQP4-IgG serology. Discrimination and calibration were satisfied, with concordance indexes (C-index) close to 0.9 in both models. Decision curve analysis showed good clinical usefulness in both models, and Kaplan-Meier curves showed satisfactory discrimination between patients with high risk and low risk by the cut-off points. Conclusion: This study reported predictors of visual disability and generated nomograms. High-risk patients need more active treatment and management to avoid unfavorable outcomes.