Oxidative phosphorylation regulates B cell effector cytokines and promotes inflammation in multiple sclerosis.

Dysregulated B cell cytokine production contributes to pathogenesis of immune-mediated diseases including multiple sclerosis (MS); however, the underlying mechanisms are poorly understood. In this study we investigated how cytokine secretion by pro-inflammatory (GM-CSF-expressing) and anti-inflammatory (IL-10-expressing) B cells is regulated. Pro-inflammatory human B cells required increased oxidative phosphorylation (OXPHOS) compared with anti-inflammatory B cells. OXPHOS reciprocally modulated pro- and anti-inflammatory B cell cytokines through regulation of adenosine triphosphate (ATP) signaling. Partial inhibition of OXPHOS or ATP-signaling including with BTK inhibition resulted in an anti-inflammatory B cell cytokine shift, reversed the B cell cytokine imbalance in patients with MS, and ameliorated neuroinflammation in a myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalitis mouse model. Our study identifies how pro- and anti-inflammatory cytokines are metabolically regulated in B cells and identifies ATP and its metabolites as a "fourth signal" that shapes B cell responses and is a potential target for restoring the B cell cytokine balance in autoimmune diseases.

Somatostatin-SSTR3-GSK3 modulates human T-cell responses by inhibiting OXPHOS.

Introduction: Somatostatin (SST) is a peptide hormone primarily synthesized in the digestive and nervous systems. While its impact on the endocrine system is well-established, accumulating evidence suggests a crucial role for SST and its analogues in modulating immune responses. Despite this, the precise mechanism through which SST regulates T cells has remained largely unknown. Methods: To elucidate the impact of SST on human T cells, we conducted a series of experiments involving cell culture assays, molecular analyses, and metabolic profiling. Human T cells were treated with SST, and various parameters including proliferation, cytokine production, and metabolic activities were assessed. Additionally, we employed pharmacological inhibitors and genetic manipulations to dissect the signaling pathways mediating SST's effects on T cells. Results: We showed that SST diminishes T-cell proliferation by influencing IL-2 production and T-cell mitochondrial respiration, while having no discernible impact on TCR-induced glycolysis. Our findings also identified that the regulatory influence of SST on T-cell responses and metabolism is contingent on its receptor, SSTR3. Moreover, we demonstrated that SST governs T-cell responses and metabolism by acting through the T-cell metabolic checkpoint GSK3. Discussion: Our study provides novel insights into the immunoregulatory function of SST in human T cells, highlighting the complex interplay between hormonal signaling and immune regulation. Understanding the molecular mechanisms underlying SST's effects on T cells may offer therapeutic opportunities for manipulating immune responses in various pathological conditions.

Nomogram incorporating Epstein-Barr virus DNA and a novel immune-nutritional marker for survival prediction in nasopharyngeal carcinoma.

BACKGROUND: Since Immune response, nutritional status and Epstein-Barr Virus (EBV) DNA status have been confirmed to be relevant to the prognosis of patients with nasopharyngeal carcinoma (NPC), we believe that the combination of these factors is of great value for improving the predictive ability. LA (lymphocytes × albumin), a novel indicator, had not been studied yet in NPC. We combined it with EBV DNA and used nomograms to increase the accuracy of prognosis. METHODS: A total of 688 NPC patients were retrospectively reviewed and further divided into training and validation cohort randomly. Kaplan-Meier analyses were used to to distinguish the different survival outcomes. Multivariate Cox analyses were used to identify the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). Calibration curves, concordance indexes (C-indexes) and decision curve analyses (DCA) were used to evaluate the nomograms' predictive value. RESULTS: Patients with low LA and positive EBV DNA correlated with poorer 5-year PFS and OS (all P < 0.005). In multivariate Cox analyses, LA and EBV DNA were both confirmed to be independent prognostic factors for PFS and OS (all P < 0.05). Prognostic nomograms incorporating LA and EBV DNA achieved ideal C-indexes of 0.69 (95% CI: 0.65-0.73) and 0.77 (95% CI: 0.71-0.82) in the prediction of PFS and OS. Otherwise, the calibration curves and DCA curves also revealed that our nomograms had pleasant predictive power. CONCLUSIONS: LA is a novel and powerful biomarker for predicting clinical outcomes in NPC. Our nomograms based on LA and EBV DNA can predict individual prognosis more accurately and effectively.

Impact of sex on treatment-related adverse effects and prognosis in nasopharyngeal carcinoma.

BACKGROUND: In nasopharyngeal cancer (NPC), women have a lower incidence and mortality rate than men. Whether sex influences the prognosis of NPC patients remains debatable. We retrospectively examined the influence of sex on treatment-related side effects and prognosis in NPC. METHODS: Clinical data of 1,462 patients with NPC treated at the Southern Hospital of Southern Medical University from January 2004 to December 2015 were retrospectively examined. Statistical analysis was performed to assess differences in overall survival (OS), distant metastasis-free survival (DMFS), local recurrence-free survival(LRFS), and progression-free survival(PFS), as well as treatment-related adverse effects, including myelosuppression, gastrointestinal responses, and radiation pharyngitis and dermatitis, between men and women. RESULTS: Women had better 5-year OS (81.5% vs. 87.1%, P = 0.032) and DMFS (76.2% vs. 83.9%, P = 0.004) than men. Analysis by age showed that the prognoses of premenopausal and menopausal women were better than those of men, whereas prognoses of postmenopausal women and men were not significantly different. Additionally, women had a better prognosis when stratified by treatment regimen. Furthermore, chemotherapy-related adverse effects were more severe in women than in men; however, the incidences of radiation laryngitis and dermatitis were not significantly different between the sexes. Logistic regression analysis revealed that the female sex was an independent risk factor for severe myelosuppression and gastrointestinal reactions. CONCLUSIONS: Chemotherapy-related side effects are more severe but the overall prognosis is better in women with NPC than in men with NPC. Patients may benefit from a personalized treatment approach for NPC. TRIAL REGISTRATION: This study was approved by the Medical Ethics Committee of Nanfang Hospital of the Southern Medical University (NFEC-201,710-K3).

Cerebrospinal fluid biomarkers of neuroinflammation and postoperative neurocognitive disorders in patients undergoing orthopaedic surgery: protocol for a systematic review and meta-analysis.

INTRODUCTION: Postoperative neurocognitive disorders (PNDs) are characterised by gradual cognitive decline or change occurring after anaesthesia and surgery, and they are common in patients undergoing orthopaedic surgery. The onset of PNDs has been associated with dementia or other types of neurocognitive disorders in later life. Moreover, cerebrospinal fluid (CSF) biomarkers of neuroinflammation, including amyloid beta-40 peptide, amyloid beta-42 peptide, total tau protein, phosphorylated tau protein and neurofilament light chain, have been reported to be crucial in several high-quality clinical studies on PNDs. However, the role of these biomarkers in the onset of PNDs remains controversial. Therefore, this study aims to determine the association between CSF biomarkers of neuroinflammation and the onset of PNDs in patients undergoing orthopaedic surgery, which will provide novel insights for investigating PNDs and other types of dementia. METHODS AND ANALYSIS: This systematic review and meta-analysis will be conducted in accordance with the Preferred Reporting Items for Systematic Reviewd and Meta-Analyses 2020 statement. Moreover, we will search MEDLINE (via OVID), EMBASE and the Cochrane Library without any language and date restrictions. Observational studies will be included. Two reviewers will independently perform the entire procedure, and disagreements will be settled by discussion between them and consultation with a third reviewer. Standardised electronic forms will be generated to extract data. The risk of bias in the individual studies will be evaluated using the Newcastle-Ottawa scale. All statistical analyses will be performed using the RevMan software or the Stata software. ETHICS AND DISSEMINATION: This study will include peer-reviewed published articles; thus, no ethical issues will be involved. Further, the final manuscript will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42022380180.

Systemic immune-inflammation index during treatment predicts prognosis and guides clinical treatment in patients with nasopharyngeal carcinoma.

PURPOSE: Systemic immune-inflammation index (SII) has been demonstrated to be closely associated with the poor prognosis of nasopharyngeal carcinoma (NPC). However, the role of SII during treatment of NPC has not been reported. This study aimed to determine the prognostic value of SII during treatment for NPC patients. METHODS: A total of 759 patients diagnosed with NPC were included in this retrospective study (393 in training cohort and 366 in validation cohort). The correlation between variables was analyzed by the chi-squared test, the Fisher's exact test or the likelihood test. Kaplan-Meier method and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The independent prognostic factors were determined by multivariate analysis of Cox proportional hazards regression model. The uncontrolled risk was analyzed by Logistic regression. Receiver operating characteristic (ROC) curves were used to assess prognostic value. RESULTS: The optimal cut-off point for the SII during treatment was 937.32. High SII during treatment group had higher uncontrolled risk than low SII during treatment group (p = 0.008). In multivariate Cox proportional hazard models analysis, SII during treatment was an independent prognostic factor for 5-year PFS (p < 0.001) and 5-year OS (p < 0.001). All results were found in the training cohort and confirmed in the validation cohort. CONCLUSIONS: The SII during treatment is a promising indicator of predicting the survival in NPC patients, especially the risk of uncontrolled occurrence. By monitoring the SII during treatment, it is possible to better evaluate the treatment effect and formulate personalized treatment.

Effects of writers, erasers and readers within miRNA-related m6A modification in cancers.

BACKGROUND: As one of the most abundant post-transcriptional mRNA modifications, N6-methyladenosine (m6A) has attracted extensive attention from scientists. Emerging evidence indicates that m6A modification plays a significant role in cancer-related signalling pathways. Existing research demonstrates that m6A modifications were also identified in miRNAs and contribute to cancer-related signalling pathways. METHODS: A literature retrieval has been performed to collect m6A-miRNA-related original articles published in recent years. Later, a systematic analysis has been conducted to abstract and classify the relationships between m6A modification and miRNAs, and their contributions to tumorigenesis and cancer development. RESULTS: Accumulating literature provides important insights into multiple relationships between m6A modifications and miRNAs. Mechanically, m6A writer and eraser alter pri-miRNAs m6A levels, and m6A readers could dually modulate pri-miRNAs processing and pri-miRNAs degradation. It is also been demonstrated that miRNAs impair m6A regulators' translation to influence m6A medication function in return. Aberrant expressions of m6A regulators and miRNAs could dysregulate proliferative, apoptosis, cell adhesion-related, and malignant transformation signalling pathways, and contribute to tumour occurrence and development. CONCLUSION: This review summarizes the interrelationship between m6A modification and miRNAs; highlights the combined effects of each type of m6A regulator and miRNAs in cancers. These findings enhance our understanding of m6A-miRNAs' multiple interactions and significant modulatory role in tumorigenesis and progression.

Combination of smoking and Epstein-Barr virus DNA is a predictor of poor prognosis for nasopharyngeal carcinoma: a long-term follow-up retrospective study.

BACKGROUND: This retrospective study was performed to determine the prognostic potential of smoking and its combination with pre-treatment plasma Epstein-Barr virus (EBV) DNA levels in patients with nasopharyngeal carcinoma (NPC). METHODS: Medical records of 1080 non-metastatic NPC patients who received intensity-modulated radiotherapy were reviewed. Male patients were categorized as never and ever smokers, and the smoking amount, duration, and cumulative consumption were used to evaluate dose-dependent effects. Survival outcomes were assessed using Kaplan-Meier survival analysis and the multivariate Cox regression analysis. Propensity score matching (PSM) was constructed. RESULTS: The 5-year overall survival (OS) was worse for ever smokers than never smokers, and significantly decreased with the increase of smoking amount, duration, and cumulative consumption. Compared with never smokers, the multivariate-adjusted hazard ratio (HR) of death was higher in ever smokers (HR = 1.361, P = 0.049), those smoked ≥20 cigarettes/day (HR = 1.473, P = 0.017), those smoked for ≥30 years (HR = 1.523, P = 0.023), and those cumulative smoked for ≥30 pack-years (HR = 1.649, P = 0.005). The poor prognostic effects of smoking was also confirmed in the PSM analysis. The combination of cumulative smoking consumption and pre-treatment EBV DNA levels was proven to be an independent poor prognostic factor for male NPC, and the risk of death, progression, and distant metastases gradually increased with both factors (P < 0.001). CONCLUSIONS: Combination of smoking and pre-treatment EBV DNA levels as a predictor of poor prognosis could further improve the risk stratification and prognostication for NPC.

Altered functional connectivity and topology structures in default mode network induced by inflammatory exposure in aged rat: A resting-state functional magnetic resonance imaging study.

Inflammatory stress in anesthesia management and surgical process has been reported to induce long-term cognitive dysfunction in vulnerable aged brain, while few studies focused on the network mechanism. The default mode network (DMN) plays a significant role in spontaneous cognitive function. Changes in topology structure and functional connectivity (FC) of DMN in vulnerable aged brain following inflammatory stress-induced long-term cognitive dysfunction are rarely studied. Eighty-eight aged male rats received intraperitoneal injection of lipopolysaccharide (LPS) as treatment or equal amount of normal saline (NS) as control. Morris Water Maze (MWM) was performed to assess short- (<7 days) and long-term (>30 days) learning and spatial working memory. Enzyme-linked immunosorbent assay (ELISA) was used to measure systemic and hippocampus inflammatory cytokines. Real-time polymerase chain reaction (RT-PCR) was used to measure the changes in gene level. Resting-state functional magnetic resonance imaging (rs-fMRI) was used to exam brain function prior to MWM on days 3, 7, and 31 after LPS exposure. Graph theory analysis was used to analyze FC and topology structures in aged rat DMN. Aged rats treated with LPS showed short- and long-term impairment in learning and spatial working memory in MWM test. Graph theory analysis showed temporary DMN intrinsic connectivity increased on day 3 followed with subsequent DMN intrinsic connectivity significantly altered on day 7 and day 31 in LPS-exposed rats as compared with controls. Short- and long-term alterations were observed in FC, while alterations in topology structures were only observed on day 3. Rats with inflammatory stress exposure may cause short- and long-term alterations in intrinsic connectivity in aged rat's DMN while the changes in topology structures only lasted for 3 days. Inflammatory stress has prolonged effects on FC, but not topology structures in venerable aged brain.

Association between hyperuricemia and metabolic syndrome: A cross-sectional study in Tibetan adults on the Tibetan plateau.

Purpose: This study aimed to assess the relationship of serum uric acid with metabolic syndrome and its components in Tibetan adults on the Tibetan plateau. Methods: A total of 307 participants were enrolled in this study and biochemical parameters including serum uric acid, fasting plasma glucose, white blood cell, lymphocyte count, mononuclear cells, alanine aminotransferase, aspartate aminotransferase, creatinine, and lipid profile were analyzed using standard methods. The IDF criteria were applied to define metabolic syndrome. The association of serum uric acid with metabolic syndrome and its components was evaluated by multivariable logistic regression models. Results: The overall prevalence of metabolic syndrome was 17.3% (53/307) with 19.6% (31/158) in females and 14.8% (22/149) in male participants. The prevalence of hyperuricemia was 40.7% (125/307) with significant differences between the male (53.7%,80/149) and female (28.5%,45/158) groups. In regression analysis, we observed that the risk of MetS was higher in participants in the hyperuricemia group (adjusted OR, 4.01; 95% CI, 2.02~7.99) compared with those in the normouricemia group. After adjusting for all confounding factors, a 9% higher risk of MetS could be shown in participants with SUA increased per 10umol/L (adjusted OR, 1.09; 95% CI, 1.04~1.14). These relationships were not affected by sex or age (p >0.05). After adjusting for the confounding factors, hyperuricemia is positively associated with abdominal obesity (adjusted OR, 2.53; 95% CI, 1.41~4.53), elevated blood pressure (adjusted OR, 2.61; 95% CI, 1.37~4.97), and elevated triglycerides(adjusted OR, 2.47; 95% CI, 1.09~5.57). Conclusions: In our study, hyperuricemia is significantly associated with the prevalence of metabolic syndrome and part of its components, and these relationships are not affected by sex or age. Given the high prevalence of MetS and hyperuricemia among Tibetan adults, more studies are required to explore the role of SUA in the pathogenesis of MetS.

The association between altitude and serum folate levels in Tibetan adults on the Tibetan plateau.

This study investigated the relationship between residence altitude and serum folate levels in healthy Tibetans living on the Tibetan Plateau. Participants were selected from those who underwent physical examinations at our health center between November 2019 and February 2020. Demographic characteristics and medical histories were collected, and fasting blood was tested for serum folate and other hematological indicators. The relationship between altitude and serum folate levels was analyzed using a multivariable linear regression model. Serum folate levels were associated with altitude (ß = - 0.44; 95% confidence interval [CI] - 0.71; - 0.16), hemoglobin (ß = - 0.01; 95% CI - 0.03; - 0.00), red blood cells (ß = - 0.72; 95% CI - 1.18; - 0.27), hematocrit (ß = - 0.07; 95% CI - 0.12; - 0.02), high-density lipoprotein cholesterol (ß = 2.67; 95% CI 1.35; 3.98), and sex (ß = 0.68; 95% CI 0.12; 1.23). Multivariate linear regression analysis revealed that altitude was negatively associated with serum folate levels. After adjusting for confounding factors, serum folate levels decreased by 0.33 ng/mL per each 500-m increase in altitude (ß = - 0.33; 95% CI - 0.6; - 0.05; P = 0.022). Altitude was negatively associated with serum folate levels in Tibetan adults. The relationship between altitude and folate levels should be further explored in populations of different races and disease states. Further large-scale prospective studies should illustrate the causality of this relationship.

Prognostic value of systemic inflammation response index in nasopharyngeal carcinoma with negative Epstein-Barr virus DNA.

BACKGROUND: Inflammatory parameters and Epstein-Barr virus (EBV) DNA status have been confirmed to be associated with prognosis in nasopharyngeal carcinoma (NPC) patients. However, there are few in-depth studies on the prognosis of NPC patients with negative EBV DNA. Our study aimed to look for inflammatory biomarkers that can identify disease progression in NPC patients with negative EBV DNA. METHODS: A total of 795 NPC patients were recruited, and ultimately 325 NPC patients with negative EBV DNA were included in this study (170 in training cohort and 155 in validation cohort). Kaplan-Meier method and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The multivariate analysis of Cox proportional hazards regression model was used to determine the independent prognostic factors. Receiver operating characteristic (ROC) curves were used to assess prognostic value. The logistic regression was used to evaluate the relationship between EBV DNA status and inflammatory parameters. The correlation between clinical characteristics was analyzed by the chi-squared test or the Fisher's exact test. RESULTS: The optimal cutoff point for the SIRI was 1.12. The EBV DNA-negative NPC patients with high SIRI level had worse PFS and OS (all p < 0.001). In multivariate Cox proportional hazard models analysis, SIRI was an independent prognostic factor for PFS and OS (all p < 0.05), and had higher prognostic value than other indicators. Above results were found in the training cohort and confirmed in the validation cohort. In addition, EBV DNA status was not associated with any inflammatory parameters. CONCLUSIONS: The SIRI can provide more accurate risk stratification and better prognostic prediction for NPC patients with negative EBV DNA.

Brain changes correlate with neuropathic pain in patients with neuromyelitis optica spectrum disorders.

BACKGROUND: Neuropathic pain (NP) is a highly disturbing sensory experience in patients with neuromyelitis optica spectrum disorders (NMOSD). However, the brain changes in NMOSD patients with NP have rarely been studied. OBJECTIVE: The aim of the cross-sectional and follow-up longitudinal study was to investigate the brain changes in NMOSD patients with NP. METHODS: In the cross-sectional study, comparisons were performed between groups with NP (W-NP) and without NP (Wo-NP), and age, sex and years of education were adjusted. We compared the voxel-wise whole-brain gray matter (GM) volume, cortical thickness (CT), cortical surface area (CSA) and local gyrification index (LGI). Probabilistic tractography started from regions with significant between-group differences in GM volume, CT, CSA and LGI. We also compared fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) of the white matter (WM) skeleton using Tract-Based Spatial Statistics (TBSS). In the longitudinal study, the patients were followed for 2.0±0.0 years and underwent the same imaging scanning as the cross-sectional study. Changes of the CT, CSA, LGI and WM were obtained. RESULTS: Patients in the W-NP group were older than those in the Wo-NP group and showed significantly reduced LGI of the left temporal lobe and adjacent regions(regions of interest, ROIs), which participated in neuropathic pain processing, possibly by emotion and attention control. Probabilistic tractography started from ROIs, and the generated WM tracts showed decreased MD and RD in the W-NP group compared to the Wo-NP group. Using TBSS, both MD and RD decreased in extensive WM skeleton in the right hemisphere of the patients in the W-NP group. Additionally, in the follow-up longitudinal study, compared with patients in the Wo-NP group, patients in the W-NP group showed lower mean reduction rates of LGI of ROIs, and less increase of FA and more increases of MD, AD and RD in the extensive WM skeleton. CONCLUSIONS: These findings support the hypothesis that brain changes might correlate with NP in NMOSD patients and predict the changes related to NP over time.

Stable Intracerebral Transplantation of Neural Stem Cells for the Treatment of Paralysis Due to Ischemic Stroke.

NSI-566 is a stable, primary adherent neural stem cell line derived from a single human fetal spinal cord and expanded epigenetically with no genetic modification. This cell line is being tested in clinical trials in the U.S. for treatment of amyotrophic lateral sclerosis and spinal cord injury. In a single-site, phase I study, we evaluated the feasibility and safety of NSI-566 transplantation for the treatment of hemiparesis due to chronic motor stroke and determined the maximum tolerated dose for future trials. Three cohorts (n = 3 per cohort) were transplanted with one-time intracerebral injections of 1.2 × 107 , 2.4 × 107 , or 7.2 × 107 cells. Immunosuppression therapy with tacrolimus was maintained for 28 days. All subjects had sustained chronic motor strokes, verified by magnetic resonance imaging (MRI), initiated between 5 and 24 months prior to surgery with modified Rankin Scores [MRSs] of 2, 3, or 4 and Fugl-Meyer Motor Scores of 55 or less. At the 12-month visit, the mean Fugl-Meyer Motor Score (FMMS, total score of 100) for the nine participants showed 16 points of improvement (p = .0078), the mean MRS showed 0.8 points of improvement (p = .031), and the mean National Institutes of Health Stroke Scale showed 3.1 points of improvement (p = .020). For six participants who were followed up for 24 months, these mean changes remained stable. The treatment was well tolerated at all doses. Longitudinal MRI studies showed evidence indicating cavity-filling by new neural tissue formation in all nine patients. Although this was a small, one-arm study of feasibility, the results are encouraging to warrant further studies. Stem Cells Translational Medicine 2019;8:999-1007.

Should we pay attention to recombinant norovirus strain GII.P7/GII.6?

BACKGROUND: Recombinant norovirus strain GII.P7/GII.6 has been circulating in Asia and around the world for at least 20 years, but has been responsible for relatively few outbreaks. METHODS: We used statistical analyses, real-time reverse transcription - PCR, and genome sequence analyses to investigate an outbreak of gastroenteritis, identifying the pathogen, the risk factors associated with the outbreak, and the molecular features of GII.P7/GII.6 strains. RESULTS: An outbreak of gastroenteritis was reported at a school involving 12 students and lasting 6 days, from September 13 to September 18, 2017. Epidemiological studies suggested that norovirus was transmitted from person to person and not via contaminated food or drinking water in this outbreak. Using a sequence analysis of the junction region between open reading frames 1 and 2, the pathogen was identified as a recombinant norovirus (strain GII.P7/GII.6). The full-length genome of the outbreak strain shared 86%-97% identity with those of other GII.P7/GII.6 strains. Phylogenetic trees were constructed from partial open reading frame 1 (ORF1) and ORF2 sequences from the outbreak strain and GII.P7/GII.6 norovirus sequences available in GenBank. On the ORF1 tree, the partial sequences of ORF1 were grouped into cluster A (with GII.6), cluster B (with GII.7), and a separate cluster (C), based on the GII.6 and GII.7 reference strains. The ORF2 tree showed all GII.P7/GII.6 strains formed a cluster together with GII.6 strains. Amino-acid substitutions and insertions/deletions were common in the capsid protein, especially in it's P2 and P1 domains. The outbreak was controlled within several days using appropriate measures. CONCLUSIONS: Because it may play a prominent role in future outbreaks, recombinant norovirus strain GII.P7/GII.6 should be monitored with routine surveillance.

Association of GTF2IRD1-GTF2I polymorphisms with neuromyelitis optica spectrum disorders in Han Chinese patients.

Variants at the GTF2I repeat domain containing 1 (GTF2IRD1)-GTF2I locus are associated with primary Sjögren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that this susceptibility locus is shared by multiple autoimmune diseases. However, until now there were no studies of the correlation between GTF2IRD1-GTF2I polymorphisms and neuromyelitis optica spectrum disorders (NMOSD). This case control study assessed this association by recruiting 305 participants with neuromyelitis optica spectrum disorders and 487 healthy controls at the Department of Neurology, from September 2014 to April 2017. Peripheral blood was collected, DNA extracteds and the genetic association between GTF2IRD1-GTF2I polymorphisms and neuromyelitis optica spectrum disorders in the Chinese Han population was analyzed by genotyping. We found that the T allele of rs117026326 was associated with an increased risk of neuromyelitis optica spectrum disorders (odds ratio (OR) = 1.364, 95% confidence interval (CI) 1.019-1.828; P = 0.037). This association persisted after stratification analysis for aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) positivity (OR = 1.397, 95% CI 1.021-1.912; P = 0.036) and stratification according to coexisting autoimmune diseases (OR = 1.446, 95% CI 1.072-1.952; P = 0.015). Furthermore, the CC genotype of rs73366469 was frequent in AQP4-IgG-seropositive patients (OR = 3.15, 95% CI 1.183-8.393, P = 0.022). In conclusion, the T allele of rs117026326 was associated with susceptibility to neuromyelitis optica spectrum disorders, and the CC genotype of rs73366469 conferred susceptibility to AQP4-IgG-seropositivity in Han Chinese patients. The protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China (approval number: 2016-31) on March 2, 2016.

Increased expression of the membrane-bound CD40 ligand on peripheral CD4+ T cells in the acute phase of AQP4-IgG-seropositive neuromyelitis optica spectrum disorders.

Currently, no data are available regarding the expression levels of CD40L on CD4+ T cells in patients with neuromyelitis optica spectrum disorders (NMOSD). The percentage of circulating CD40L+CD4+ T cells was measured by flow cytometry in 23 NMOSD patients and 10 healthy controls. The ratio of CD40L+CD4+ to CD4+ T cells in patients at acute phase (18.28 ±â€¯15.56%) was significantly higher than that in healthy controls (7.23 ±â€¯5.94%, P = .032) and was positively correlated with disease severity (r = 0.532, P = .041). Thus, our results suggest an important role of this molecule in acute attacks of NMOSD.

Pain during the acute phase of Guillain-Barré syndrome.

In this study, we tried to describe the characteristics of pain and explore the association between the incidence of pain and abnormal laboratory test results in patients during the acute phase of Guillain-Barré syndrome (GBS).This retrospective cohort study enrolled 252 patients with GBS who were in the acute phase of the disease. We collected data regarding the location and type of pain, the onset time, clinical variables and laboratory tests, including the levels of uric acid (UA), albumin, cerebrospinal fluid protein (CSFP), cerebrospinal fluid glucose (CSFG), fasting glucose upon admission, and blood creatinine. The pain descriptors were compared to the severity of disease and laboratory examination results.Around 34.5% of the patients reported pain during the acute phase of GBS. Pain was negatively correlated with the disease severity during the acute phase. In total, 29 of the 87 (33.3%) patients reported pain during the 2 weeks preceding the onset of weakness. The concentration of CSFP was positively associated with the incidence of pain, while the concentrations of UA and albumin were not correlated with the incidence of pain.We found that 33.3% of the GBS patients experienced pain within 2 weeks of onset, and the pain was positively associated with CSFP concentration but was not correlated with disease severity.

Associations between tumor necrosis factor-α gene polymorphisms and the risk of Guillain-Barré syndrome and its subtypes: A systematic review and meta-analysis.

This meta-analysis aimed to assess the relationship between tumor necrosis factor-α (TNF-α) polymorphisms and Guillain-Barré syndrome (GBS) or its subtypes of acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor-sensory axonal neuropathy (AMSAN). A total of six studies with 1013 cases and 1029 controls were included. Our pooled data indicated that TNF-α 308G/A polymorphism was significantly associated with GBS, AMAN, and AMSAN but not with AIDP; TNF-α 857C/T polymorphism was significantly associated with AMAN but not with GBS or AIDP. Besides, no association was found between TNF-α 238G/A and 863C/A polymorphisms and GBS or its subtypes.

Association of TNFSF4 Polymorphisms with Neuromyelitis Optica Spectrum Disorders in a Chinese Population.

The tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene encodes a vital co-stimulatory molecule of the immune system and has been identified as a susceptibility locus for systemic lupus erythematosus, systemic sclerosis, and primary Sjögren's syndrome. However, the association of TNFSF4 polymorphisms with neuromyelitis optica spectrum disorders (NMOSD), an inflammatory, demyelinating autoimmune disease of the central nervous system, has not yet been investigated. To evaluate whether TNFSF4 polymorphisms contribute to risk of NMOSD, four single-nucleotide polymorphisms (SNPs) (rs1234315, rs2205960, rs704840, and rs844648) were selected and genotyped in a cohort of 312 patients with NMOSD and 487 healthy controls. Our study showed that rs844648 was associated with an increased risk of NMOSD, according to the allelic model (OR = 1.30, 95% CI 1.06-1.59, P = 0.011, Pcorr = 0.044). Significant associations of rs844648 (OR = 1.67, 95% CI 1.17-2.38, P = 0.005, Pcorr = 0.02) and rs704840 (OR = 1.75, 95% CI 1.17-2.63, P = 0.007, Pcorr = 0.027) with NMOSD occurrence were also observed under the recessive model. Moreover, linkage disequilibrium analysis revealed two blocks within TNFSF4; in one block, the haplotype Ars844648Grs704840 significantly increased the risk of NMOSD, whereas Grs844648Trs704840 reduced the risk. This study demonstrates an association between TNFSF4 polymorphisms and susceptibility for the development of NMOSD in the Chinese population.