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Objective To explore the pathogenic mechanism of myelin oligodendrocyte glycoprotein-IgG（MOG-IgG）associated disorders （MOGAD） and screen the treatment drugs by establishing the MOGAD in vitro demyelination model. Methods The patient-derived MOG-IgG was purified by using the affinity chromatography based on transfected cells. The MOGAD in vitro demyelination model was constructed by the interaction between MOG-IgG and complement based on rat organotypic cerebellar slice and neuron-oligodendrocyte co-culture model. The expression level of myelin basic protein （MBP） and its colocalization with neurofilament protein （NF） were used as indicators to evaluate the myelin formation and injury. The myelin repair effect of drugs that promote the remyelination for multiple sclerosis was evaluated in this demyelination model. Results Highly-specific MOG-IgG was purified by the affinity chromatography based on transfected cells. After the treatment of antibodies and complement, the expression level of MBP and the colocalization degree of MBP-NF were significantly decreased in the MOG-IgG group （P = 0.003, P < 0.001）. After drug treatment, the expression levels of MBP were significantly up-regulated in the clemastine and domperidone groups （P = 0.030, P = 0.001）, and the colocalization degree of MBP-NF was significantly increased in the clemastine and domperidone groups （both P < 0.001）. Conclusions Highly-specific patient-derived MOG-IgG obtained by this method directly mediates myelin damage with the participation of complement. Clemastine and domperidone can promote the remyelination in this MOGAD in vitro demyelination model.

Objective Autoantibodies against MDA5 (melanoma differentiation-associated protein 5) serve as a biomarker for DM (dermatomyositis) and indicate a risk factor for interstitial lung disease (ILD). MDA5 is a protein responsible for sensing RNA virus infection and activating signalling pathways against it. However, little is known about the antigen epitopes on MDA5 autoantibodies. We aimed to determine the interaction of the MDA5 autoantibody–antigen epitope. Methods Cell-based assays (CBAs), immunoprecipitation-immunoblot assays, and various immunoblotting techniques were used in the study. Results We demonstrated that DM patient autoantibodies recognize MDA5 epitopes in a native conformation–dependent manner. Furthermore, we identified the central helicase domain （3Hel） formed by Hel1, Hel2i, Hel2, and pincer as the major epitopes. As proof of principle, the purified 3Hel efficiently absorbed MDA5 autoantibodies from patient sera through immunoprecipitation-immunoblot assay. Conclusion Our study uncovered the nature of the antigen epitopes on MDA5 and can provide guidance for diagnosis and a targeted therapeutic approach development. [ABSTRACT FROM AUTHOR]

Objectives: To access the trends and focuses of publications on public health emergency preparedness in the timeframe 1997-2019. Methods: Publications related to public health emergency preparedness (PHEP) were retrieved from the Web of Science Core Collection database. Bibliometric analyses including output statistics, co-authorship analysis, citation analysis, co-citation analysis, and co-occurrence analysis were performed and mapped using VOSviewer. Results: A total of 1058 publications on PHEP were included in this study. There was an increasing trend of publication output and citations since 2002. A total of 4605 authors from 1587 institutes and 92 countries contributed to the publications, and the United States lead the field. Disaster Medicine and Public Health Preparedness was the most active and co-cited journal among 243 journals. The knowledge foundation mainly focused on the professionals' capacity, education, and conceptions of PHEP. Epidemics, natural disasters, terrorism, education, and communication were the principle topics; while "vulnerable populations," "disaster medicine," and "hurricane" were the recent hotspots in this field. Conclusions: Significant progresses had been achieved worldwide in the past 2 decades, however, improvement of research activity and international collaboration is still a need for most countries. [ABSTRACT FROM AUTHOR]

Background and objective: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease. Although genetic factors are involved in its pathogenesis, limited evidence is available in this area. The aim of the present study was to identify the major genetic factors contributing to NMOSD in Chinese patients with aquaporin 4 (AQP4)‐IgG seropositivity. Methods: Whole‐exome sequencing (WES) was performed on 228 Chinese NMOSD patients seropositive for AQP4‐IgG and 1400 healthy controls in Guangzhou, South China. Human leukocyte antigen (HLA) sequencing was also utilized. Genotype model and haplotype, gene burden, and enrichment analyses were conducted. Results: A significant region of the HLA composition is on chromosome 6, and great variation was observed in DQB1, DQA2 and DQA1. HLA sequencing confirmed that the most significant allele was HLA‐DQB1*05:02 (p < 0.01, odds ratio [OR] 3.73). The genotype model analysis revealed that HLA‐DQB1*05:02 was significantly associated with NMOSD in the additive effect model and dominant effect model (p < 0.05). The proportion of haplotype "HLA‐DQB1*05:02‐DRB1*15:01" was significantly greater in the NMOSD patients than the controls, at 8.42% and 1.23%, respectively (p < 0.001, OR 7.39). The gene burden analysis demonstrated that loss‐of‐function mutations in NOP16 were more common in the NMOSD patients (11.84%) than the controls (5.71%; p < 0.001, OR 2.22). The IgG1‐G390R variant was significantly more common in NMOSD, and the rate of the T allele was 0.605 in patients and 0.345 in the controls (p < 0.01, OR 2.92). The enrichment analysis indicated that most of the genetic factors were mainly correlated with nervous and immune processes. Conclusions: Human leukocyte antigen is highly correlated with NMOSD. NOP16 and IgG1‐G390R play important roles in disease susceptibility. [ABSTRACT FROM AUTHOR]

Brain magnetic resonance imaging (MRI) performed in 2022 showed abnormal signals in bilateral upper cerebellar hemisphere, cerebellar vermis, bilateral thalamus, and bilateral hippocampus (Fig. Increased Cerebellum 18F-DPA-714 Uptake in Anti-Glutamate Kainate Receptor Subunit 2 Autoimmune Encephalitis Anti-glutamate kainate receptor subunit 2 (Gluk2) autoimmune encephalitis (AE) is a novel and very rare neuroimmune disease that was first reported in 2021.[1] Eight patients with this rare form of AE have been reported globally.[1] Herein, we report a patient with anti-Gluk2 antibodies presenting as cerebellar dysfunctions and limbic encephalitis. [Extracted from the article]

Background: Fluorouracil (5-FU) is widely used to treat metastatic colorectal cancer (mCRC), but real-world safety data is limited. Our study aimed to evaluate 5-FU's safety profile in a large mCRC population using the FAERS database., Research Design and Methods: We conducted disproportionality analyses to identify adverse drug events associated with 5-FU use in mCRC patients from 2004 to 2023. Subgroup analyses, gender difference analyses, and logistic regression were also performed., Results: We identified 1,458 reports with 5-FU as the primary suspected drug, with males accounting for 48.8% of reports. Gastrointestinal disorders were the most common adverse event (864 cases), while pregnancy-related conditions showed the strongest signal intensity (ROR = 2.97). We found 19 preferred terms with positive signals, including ischemic hepatitis (ROR = 59.32), blood iron increased (ROR = 59.32), and stress cardiomyopathy (ROR = 51.94). Males were more susceptible to weight loss and skin toxicity. Most adverse events occurred within the first month of 5-FU administration., Conclusion: Our study provides a comprehensive analysis of 5-FU's safety profile in mCRC patients, helping healthcare professionals mitigate risks in clinical practice.

Background and Objective: Heavy metals, ubiquitous in the environment, pose a global public health concern. The correlation between these and diabetic kidney disease (DKD) remains unclear. Our objective was to explore the correlation between heavy metal exposures and the incidence of DKD., Methods: We analyzed data from the NHANES (2005-2020), using machine learning, and cross-sectional survey. Our study also involved a bidirectional two-sample Mendelian randomization (MR) analysis., Results: Machine learning reveals correlation coefficients of -0.5059 and - 0.6510 for urinary Ba and urinary Tl with DKD, respectively. Multifactorial logistic regression implicates urinary Ba, urinary Pb, blood Cd, and blood Pb as potential associates of DKD. When adjusted for all covariates, the odds ratios and 95% confidence intervals are 0.87 (0.78, 0.98) ( p  = 0.023), 0.70 (0.53, 0.92) ( p  = 0.012), 0.53 (0.34, 0.82) ( p  = 0.005), and 0.76 (0.64, 0.90) ( p  = 0.002) in order. Furthermore, multiplicative interactions between urinary Ba and urinary Sb, urinary Cd and urinary Co, urinary Cd and urinary Pb, and blood Cd and blood Hg might be present. Among the diabetic population, the OR of urinary Tl with DKD is a mere 0.10, with a 95%CI of (0.01, 0.74), urinary Co 0.73 (0.54, 0.98) in Model 3, and urinary Pb 0.72 (0.55, 0.95) in Model 2. Restricted Cubic Splines (RCS) indicate a linear linkage between blood Cd in the general population and urinary Co, urinary Pb, and urinary Tl with DKD among diabetics. An observable trend effect is present between urinary Pb and urinary Tl with DKD. MR analysis reveals odds ratios and 95% confidence intervals of 1.16 (1.03, 1.32) ( p  = 0.018) and 1.17 (1.00, 1.36) ( p  = 0.044) for blood Cd and blood Mn, respectively., Conclusion: In the general population, urinary Ba demonstrates a nonlinear inverse association with DKD, whereas in the diabetic population, urinary Tl displays a linear inverse relationship with DKD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Lin, Han, Lin, Yu, Zhang, Ma, Li and Peng.)

Background: Liver metastasis (LM) stands as a primary cause of mortality in metastatic colorectal cancer (mCRC), posing a significant impediment to long-term survival benefits from targeted therapy and immunotherapy. However, there is currently a lack of comprehensive investigation into how senescent and exhausted immune cells contribute to LM., Methods: We gathered single-cell sequencing data from primary colorectal cancer (pCRC) and their corresponding matched LM tissues from 16 mCRC patients. In this study, we identified senescent and exhausted immune cells, performed enrichment analysis, cell communication, cell trajectory, and cell-based in vitro experiments to validate the results of single-cell multi-omics. This process allowed us to construct a regulatory network explaining the occurrence of LM. Finally, we utilized weighted gene co-expression network analysis (WGCNA) and 12 machine learning algorithms to create prognostic risk model., Results: We identified senescent-like myeloid cells (SMCs) and exhausted T cells (TEXs) as the primary senescent and exhausted immune cells. Our findings indicate that SMCs and TEXs can potentially activate transcription factors downstream via ANGPTL4-SDC1/SDC4, this activation plays a role in regulating the epithelial-mesenchymal transition (EMT) program and facilitates the development of LM, the results of cell-based in vitro experiments have provided confirmation of this conclusion. We also developed and validated a prognostic risk model composed of 12 machine learning algorithms., Conclusion: This study elucidates the potential molecular mechanisms underlying the occurrence of LM from various angles through single-cell multi-omics analysis in CRC. It also constructs a network illustrating the role of senescent or exhausted immune cells in regulating EMT.

Background: We conducted this study to describe detailed the clinical characteristics, ancillary test results and treatment response of a group of Chinese patients with anti-IgLON5 disease., Methods: We recruited 13 patients with positive IgLON5 antibodies in serum and/or cerebrospinal fluid from nine tertiary referral centers. Patients were enrolled from February 2017 to July 2021. We retrospectively collected information on the presenting and main symptoms, treatment response and follow-up outcomes., Results: The median age of onset for symptoms was 60 (range: 33-73) years and six of the 13 patients were females. The predominant clinical presentations included sleep disturbance (eight patients) and cognitive impairment (seven patients), followed by movement disorders (six patients). Parainfectious cause seemed plausible. Notably, we identified the first case of possible Epstein-Barr virus (EBV)-related anti-IgLON5 disease. Coexisting neural autoantibodies were identified in two patients. Furthermore, two patients had other autoimmune diseases. The IgG subclass was determined in four patients, including two with dominant IgG4 subtype and two with dominant IgG1 subtype. Additionally, 10 patients were treated with immunotherapy and four patients exhibited improvement. Overall, six of 10 patients for whom follow-up results were assessable had favorable clinical outcomes (modified Rankin Scale score ≤2)., Conclusions: The clinical spectrum of anti-IgLON5 disease is variable. Our results highlight a boarder spectrum of anti-IgLON5 disease., (© 2021 European Academy of Neurology.)