Association of plasma sphingosine-1-phosphate levels with disease severity and prognosis after intracerebral hemorrhage.

Purpose: Sphingosine-1-phosphate (S1P) is a signaling lipid involved in many biological processes, including inflammatory and immune regulatory responses. The study aimed to determine whether admission S1P levels are associated with disease severity and prognosis after spontaneous intracerebral hemorrhage (ICH). Methods: Data of 134 patients with spontaneous ICH and 120 healthy controls were obtained from Biological Resource Sample Database of Intracerebral Hemorrhage at the First Affiliated Hospital of Zhengzhou University. Plasma S1P levels were measured. Regression analyses were used to analyze the association between S1P levels and admission and 90-day modified Rankin scale (mRS) scores. Receiver operating characteristic (ROC) curves assessed the predictive value of S1P levels for ICH severity and prognosis. Results: Patients with ICH exhibited elevated plasma S1P levels compared to the control group (median 286.95 vs. 239.80 ng/mL, p < 0.001). When divided patients into mild-to-moderate and severe groups according to their mRS scores both at admission and discharge, S1P levels were significantly elevated in the severe group compared to the mild-to-moderate group (admission 259.30 vs. 300.54, p < 0.001; 90-day 275.24 vs. 303.25, p < 0.001). The patients were divided into three groups with different concentration gradients, which showed significant statistical differences in admission mRS scores (3 vs. 4 vs. 5, p < 0.001), 90-day mRS scores (2.5 vs. 3 vs. 4, p < 0.001), consciousness disorders (45.5% vs. 68.2% vs. 69.6%, p = 0.033), ICU admission (29.5% vs. 59.1% vs. 89.1%, p < 0.001), surgery (15.9% vs. 47.7% vs. 82.6%, p < 0.001), intraventricular hemorrhages (27.3% vs. 61.4% vs. 65.2%, p < 0.001) and pulmonary infection (25% vs. 47.7% vs. 84.8%, p < 0.001). Multivariate analysis displayed that S1P level was an independent risk factor for disease severity (OR = 1.037, 95% CI = 1.020-1.054, p < 0.001) and prognosis (OR = 1.018, 95% CI = 1.006-1.030, p = 0.003). ROC curves revealed a predictive value of S1P levels with an area under the curve of 0.7952 (95% CI = 0.7144-0.8759, p < 0.001) for disease severity and 0.7105 (95% CI = 0.6227-0.7983, p < 0.001) for prognosis. Conclusion: Higher admission S1P is associated with worse initial disease severity and 90-day functional outcomes in intracerebral hemorrhage.

Fibrinogen-to-albumin ratio percentage: An independent predictor of disease severity and prognosis in anti-N-methyl-D-aspartate receptor encephalitis.

Purpose: This retrospective study aimed to investigate the relationship between fibrinogen-to-albumin ratio percentage (FARP) and disease severity and prognosis in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. Methods: Medical records and clinical characteristics from 181 patients with anti-NMDAR encephalitis were included. The modified Rankin Scale (mRS) was used to analyze disease severity and prognosis at admission and discharge, and correlations between FARP, disease severity, and prognosis were analyzed. Receiver operating characteristic (ROC) curves were used to evaluate the efficiency of FARP in assessing disease severity and prognosis. Results: Compared to the control group, patients with anti-NMDAR encephalitis had higher fibrinogen (Fib) levels (P < 0.001), neutrophil counts (P < 0.001), and FARP levels (P < 0.001) but had lower albumin levels (P = 0.003). The enrolled patients were divided into mild-to-moderate and severe groups according to their mRS scores both at admission and discharge. FARP levels were significantly elevated in the severe group compared to the mild-to-moderate group among patients with anti-NMDAR encephalitis both at admission and discharge (admission 6.0 vs. 7.40, P < 0.001; discharge 6.43 vs. 8.18, P<0.001). Indeed, the mRS scores at admission (56 vs. 26%, P < 0.001) and discharge (26 vs. 11%, P = 0.006) in the high FARP group were significantly higher than those in the low FARP group. Furthermore, FARP was positively correlated with the mRS scores at admission (r = 0.383, P < 0.001) and discharge (r =0.312, P < 0.001). In the multivariate analysis, FARP was significantly associated with disease severity (odds ratio [OR] = 1.416, 95% confidence interval [CI] = 1.117-1.795, P = 0.004) and prognosis (OR = 1.252, 95% CI = 1.010-1.552, P = 0.040). FARP-based ROC curves predicted disease severity, with a sensitivity of 0.756, a specificity of 0.626, and an area under the ROC curve of 0.722 (95% CI = 0.648-0.796, P < 0.001*). The ROC curve predicted the disease prognosis with a sensitivity of 0.703, a specificity of 0.667, and an area under the ROC curve of 0.723 (95% CI = 0.629-0.817, P < 0.001*). Conclusion: Our results indicate that FARP is a novel predictive marker for disease severity and prognosis of anti-NMDAR encephalitis.

Elevated plasma D-dimer levels in patients with anti-N-methyl-D-aspartate receptor encephalitis.

Purpose: We aimed to explore the difference in coagulation function between healthy individuals and patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis and its relationship with disease severity. Methods: We retrospectively compared coagulation function in 161 patients with first-attack anti-NMDAR encephalitis and 178 healthy individuals. The association between D-dimer levels and disease severity was analyzed using binary logistic regression. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of D-dimer levels for the severity of anti-NMDAR encephalitis. Results: Compared to control individuals, patients with anti-NMDAR encephalitis had higher D-dimer levels (median 0.14 vs. 0.05 mg/L, p < 0.001), blood white blood cell (WBC) count (median 8.54 vs. 5.95 × 109/L, p < 0.001), and neutrophil count (median 6.14 vs. 3.1 × 109/L, p < 0.001). D-dimers (median 0.22 vs. 0.10 mg/L, p < 0.001), blood WBC count (median 9.70 vs. 7.70 × 109/L, p < 0.001), neutrophil count (median 7.50 vs. 4.80 × 109/L, p < 0.001), and C-reactive protein (median 2.61 vs. 1.50 mg/l, p = 0.017) were higher; however, eosinophils (median 0.02 vs. 0.06 × 109/L, p < 0.001), and blood calcium (median 2.26 vs. 2.31 mmol/L, p = 0.003) were lower in patients with severe forms of anti-NMDAR encephalitis than in those with mild to moderate forms, and were associated with initial modified Rankin Scale scores. Multivariate analysis showed that D-dimer levels were significantly associated with severity [odds ratio =2.631, 95% confidence interval (CI) = 1.018-6.802, p = 0.046]. The ROC curve was used to analyze the predictive value of D-dimer levels for disease severity. The area under the curve was 0.716 (95% CI = 0.64-0.80, p < 0.001), and the best cut-off value was D-dimer = 0.147 mg/L (sensitivity 0.651; specificity, 0.705). Conclusion: Serum D-dimer and neutrophil levels were independent predictors of disease severity in patients with first-attack anti-NMDAR encephalitis.

Comparative analysis of clinical and imaging data of first-attack neuromyelitis optica spectrum disorders with and without connective tissue disease.

Background: The coexistence of neuromyelitis optica spectrum disorder (NMOSD) and connective tissue disease (CTD) is well recognized. The purpose of this study was to investigate and compare the characteristics of first attack NMOSD with and without CTD. Methods: A total of 113 Patients with NMOSD were included and were divided into two groups based on the presence of co-occurring CTD. Their demographic, clinical, laboratory, and image characteristics were obtained through inpatient medical records and follow-ups. Kaplan-Meier survival analysis was used to analyze the effect of CTD in NMOSD patients at the time of first recurrence. The risk factors that could predict complications of NMOSD with CTD was analyzed by binary logistic regression. The ability of homocysteine (Hcy) to predict the coexistence of NMOSD and CTD was analyzed and evaluated by the receiver operating characteristic curve. Results: The demographic data, clinical features, cerebrospinal fluid analysis, and MRI findings, except relapse events (including relapse rate, number of recurrences, and time of first recurrence), were similar between the two groups. The serum lymphocyte-to-monocyte ratio and albumin levels were lower (P < 0.05), while serum erythrocyte sedimentation rate and Hcy levels were higher in patients with NMOSD with CTD than in those without CTD (P < 0.001). Kaplan-Meier survival analysis showed that the time of first recurrence in NMOSD patients complicated with CTD was earlier than that of without CTD (log rank test P = 0.035). Logistic regression revealed that serum Hcy levels (OR 1.296, 95% CI, 1.050-1.601, P = 0.016) were independently associated with the occurrence of NMOSD with CTD. The receiver operating characteristic curve area was 0.738 (95% CI, 0.616-0.859; P < 0.001) for Hcy levels. Considering the Hcy concentration of 14.07 µmol/L as the cutoff value, the sensitivity and specificity of predicting the coexistence of first-attack NMOSD and CTD were 56 and 89.8%, respectively. Conclusions: When the first-attack NMOSD patients are complicated with CTD, they have a higher recurrence rate, more recurrences, earlier first recurrence, higher serum Hcy levels, and enhanced systemic inflammatory reactions. Furthermore, Hcy levels may help to screen for CTD in patients with first-attack NMOSD.

The altered functional connectivity density related to cognitive impairment in alcoholics.

Alcohol use disorder (AUD) is one of the most common substance use disorders contributing to both behavioral and cognitive impairments in patients with AUD. Recent neuroimaging studies point out that AUD is a typical disorder featured by altered functional connectivity. However, the details about how voxel-wise functional coordination remain unknown. Here, we adopted a newly proposed method named functional connectivity density (FCD) to depict altered voxel-wise functional coordination in AUD. The novel functional imaging technique, FCD, provides a comprehensive analytical method for brain's "scale-free" networks. We applied resting-state functional MRI (rs-fMRI) toward subjects to obtain their FCD, including global FCD (gFCD), local FCD (lFCD), and long-range FCD (lrFCD). Sixty-one patients with AUD and 29 healthy controls (HC) were recruited, and patients with AUD were further divided into alcohol-related cognitive impairment group (ARCI, n = 11) and non-cognitive impairment group (AUD-NCI, n = 50). All subjects were asked to stay stationary during the scan in order to calculate the resting-state gFCD, lFCD, and lrFCD values, and further investigate the abnormal connectivity alterations among AUD-NCI, ARCI, and HC. Compared to HC, both AUD groups exhibited significantly altered gFCD in the left inferior occipital lobe, left calcarine, altered lFCD in right lingual, and altered lrFCD in ventromedial frontal gyrus (VMPFC). It is notable that gFCD of the ARCI group was found to be significantly deviated from AUD-NCI and HC in left medial frontal gyrus, which changes probably contributed by the impairment in cognition. In addition, no significant differences in gFCD were found between ARCI and HC in left parahippocampal, while ARCI and HC were profoundly deviated from AUD-NCI, possibly reflecting a compensation of cognition impairment. Further analysis showed that within patients with AUD, gFCD values in left medial frontal gyrus are negatively correlated with MMSE scores, while lFCD values in left inferior occipital lobe are positively related to ADS scores. In conclusion, patients with AUD exhibited significantly altered functional connectivity patterns mainly in several left hemisphere brain regions, while patients with AUD with or without cognitive impairment also demonstrated intergroup FCD differences which correlated with symptom severity, and patients with AUD cognitive impairment would suffer less severe alcohol dependence. This difference in symptom severity probably served as a compensation for cognitive impairment, suggesting a difference in pathological pathways. These findings assisted future AUD studies by providing insight into possible pathological mechanisms.

An ischemia-homing bioengineered nano-scavenger for specifically alleviating multiple pathogeneses in ischemic stroke.

BACKGROUND: Ischemic stroke is one of the most serious global public health problems. However, the performance of current therapeutic regimens is limited due to their poor target specificity, narrow therapeutic time window, and compromised therapeutic effect. To overcome these barriers, we designed an ischemia-homing bioengineered nano-scavenger by camouflaging a catalase (CAT)-loaded self-assembled tannic acid (TA) nanoparticle with a M2-type microglia membrane (TPC@M2 NPs) for ischemic stroke treatment. RESULTS: The TPC@M2 NPs can on-demand release TA molecules to chelate excessive Fe2+, while acid-responsively liberating CAT to synergistically scavenge multiple ROS (·OH, ·O2-, and H2O2). Besides, the M2 microglia membrane not only can be served as bioinspired therapeutic agents to repolarize M1 microglia into M2 phenotype but also endows the nano-scavenger with ischemia-homing and BBB-crossing capabilities. CONCLUSIONS: The nano-scavenger for specific clearance of multiple pathogenic elements to alleviate inflammation and protect neurons holds great promise for combating ischemic stroke and other inflammation-related diseases.

Altered Global Signal Topography in Alcohol Use Disorders.

The most common symptom of patients with alcohol use disorders (AUD) is cognitive impairment that negatively affects abstinence. Presently, there is a lack of indicators for early diagnosis of alcohol-related cognitive impairment (ARCI). We aimed to assess the cognitive deficits in AUD patients with the help of a specific imaging marker for ARCI. Data-driven dynamic and static global signal topography (GST) methods were applied to explore the cross-talks between local and global neuronal activities in the AUD brain. Twenty-six ARCI, 54 AUD without cognitive impairment (AUD-NCI), and gender/age-matched 40 healthy control (HC) subjects were recruited for this study. We found that there was no significant difference with respect to voxel-based morphometry (VBM) and static GST between AUD-NCI and ARCI groups. And in dynamic GST measurements, the AUD-NCI patients had the highest coefficient of variation (CV) at the right insula, followed by ARCI and the HC subjects. In precuneus, the order was reversed. There was no significant correlation between the dynamic GST and behavioral scores or alcohol consumption. These results suggested that dynamic GST might have potential implications in understanding AUD pathogenesis and disease management.

Inhibition of microRNA-29b suppresses oxidative stress and reduces apoptosis in ischemic stroke.

MicroRNAs (miRNAs) regulate protein expression by antagonizing the translation of mRNAs and are effective regulators of normal nervous system development, function, and disease. MicroRNA-29b (miR-29b) plays a broad and critical role in brain homeostasis. In this study, we tested the function of miR-29b in animal and cell models by inhibiting miR-29b expression. Mouse models of middle cerebral artery occlusion were established using the modified Zea-Longa suture method. Prior to modeling, 50 nmol/kg miR-29b antagomir was injected via the tail vein. MiR-29b expression was found to be abnormally increased in ischemic brain tissue. The inhibition of miR-29b expression decreased the neurological function score and reduced the cerebral infarction volume and cell apoptosis. In addition, the inhibition of miR-29b significantly decreased the malondialdehyde level, increased superoxide dismutase activity, and Bcl-2 expression, and inhibited Bax and Caspase3 expression. PC12 cells were treated with glutamate for 12 hours to establish in vitro cell models of ischemic stroke and then treated with the miR-29 antagomir for 48 hours. The results revealed that miR-29b inhibition in PC12 cells increased Bcl-2 expression and inhibited cell apoptosis and oxidative damage. These findings suggest that the inhibition of miR-29b inhibits oxidative stress and cell apoptosis in ischemic stroke, producing therapeutic effects in ischemic stroke. This study was approved by the Laboratory Animal Care and Use Committee of the First Affiliated Hospital of Zhengzhou University (approval No. 201709276S) on September 27, 2017.

Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis.

Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for spinal cord injury, but immunological rejection and possible tumor formation limit its application. The therapeutic effects of MSCs mainly depend on their release of soluble paracrine factors. Exosomes are essential for the secretion of these paracrine effectors. Bone marrow mesenchymal stem cell-derived exosomes (BMSC-EXOs) can be substituted for BMSCs in cell transplantation. However, the underlying mechanisms remain unclear. In this study, a rat model of T10 spinal cord injury was established using the impact method. Then, 30 minutes and 1 day after spinal cord injury, the rats were administered 200 µL exosomes via the tail vein (200 µg/mL; approximately 1 × 106 BMSCs). Treatment with BMSC-EXOs greatly reduced neuronal cell death, improved myelin arrangement and reduced myelin loss, increased pericyte/endothelial cell coverage on the vascular wall, decreased blood-spinal cord barrier leakage, reduced caspase 1 expression, inhibited interleukin-1ß release, and accelerated locomotor functional recovery in rats with spinal cord injury. In the cell culture experiment, pericytes were treated with interferon-γ and tumor necrosis factor-α. Then, Lipofectamine 3000 was used to deliver lipopolysaccharide into the cells, and the cells were co-incubated with adenosine triphosphate to simulate injury in vitro. Pre-treatment with BMSC-EXOs for 8 hours greatly reduced pericyte pyroptosis and increased pericyte survival rate. These findings suggest that BMSC-EXOs may protect pericytes by inhibiting pyroptosis and by improving blood-spinal cord barrier integrity, thereby promoting the survival of neurons and the extension of nerve fibers, and ultimately improving motor function in rats with spinal cord injury. All protocols were conducted with the approval of the Animal Ethics Committee of Zhengzhou University on March 16, 2019.

Comparative analysis of clinical and imaging data between patients with myelin oligodendrocyte glycoprotein antibody disease and patients with aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder.

BACKGROUND: We aimed to compare the clinical data, laboratory findings, and imaging characteristics of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and aquaporin 4 antibody (AQP4)-positive neuromyelitis optica spectrum disorder (NMOSD), as detailed comparative analyses of laboratory data for both diseases are rare. METHODS: Our retrospective study compared the clinical data, laboratory findings, and imaging characteristics of 118 AQP4-positive patients with first-episode NMOSD and 25 patients with first-episode MOGAD. Logistic regression was used to determine the factors that differentiated MOGAD and AQP4-positive NMOSD. RESULTS: There were significant differences in age, symptoms, recurrence rate, laboratory indicators, and imaging examinations between patients with MOGAD and patients with AQP4-positive NMOSD. Patients with MOGAD were younger and had higher levels of uric acid than those with AQP4-positive NMOSD. The proportion of cortical gray matter/juxtacortical white matter lesions was significantly higher in the MOGAD group than in the NMOSD group. Logistic regression revealed that young age [odds ratio (OR) = 0.947, 95% confidence interval (CI) = 0.905-0.99], high uric acid level (OR = 1.016, 95% CI = 1.006-1.027), and cortical gray matter/juxtacortical white matter involvement (OR = 3.889, 95% CI = 1.048-14.442) were significantly related to MOGAD. CONCLUSION: The multivariate analysis of the present study demonstrated that age, uric acid level, and the presence of lesions in the cortical gray matter/juxtacortical white matter can aid in distinguishing patients with AQP4-positive NMOSD from those with MOGAD. These factors may also aid in determining which patients should be tested for antibodies.

Association of neutrophil-to-lymphocyte ratio (NLR) with the prognosis of first attack neuromyelitis optica spectrum disorder (NMOSD): a retrospective cohort study.

BACKGROUND: To investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and prognosis after the first attack of optic neuromyelitis optica spectrum disorder (NMOSD). METHODS: In this retrospective study, we included the medical records of 324 patients with first episode NMOSD and collected data on clinical parameters. Follow-up extended disability status scale (EDSS) score and relapse rate were analyzed using logistic regression models to determine the independent effect of NLR on outcomes; receiver operating characteristic (ROC) curves were applied to analyze the predictive value of NLR for the prognosis of NMOSD. Interaction and stratification analyses were used to explore the association between NLR and prognosis of patients with NMOSD, and Kaplan-Meier analysis was used to investigate the relationship between NLR and outcome. The association between NLR level with relapse rate and poor recovery was assessed by a Cox regression analysis. RESULTS: Patients in the high-NLR group had significantly higher EDSS scores and relapse rates at follow-up (both, P < 0.001) than did those in the low-NLR group. Univariate analysis showed revealed that NLR was significantly associated with relapse (odds ratio [OR] = 1.28, 95% confidence interval [CI]: 1.16-1.41, P < 0.001) and poor recovery (OR = 1.32, 95% CI: 1.20-1.46, P < 0.001), and these associations remained significant, even after multifactorial analysis (OR = 1.33, 95% CI: 1.11-1.59, P = 0.002; OR = 1.23, 95% CI: 1.06-1.43, P = 0.007, respectively). Stratified analysis showed that sex, platelet-to-lymphocyte ratio (PLR) level, and lymphocyte-to-monocyte technical ratio (LMR) level were strongly associated with relapse owing to elevated NLR; Kaplan-Meier survival curve analysis showed that the median time to relapse was significantly lower in the high-NLR group than in the low-NLR group (P < 0.001). A multivariate analysis showed a significant relationship between NLR level with relapse (HR = 1.07, 95%CI: 1.03-1.10, P = 0.001) and poor recovery (HR = 1.08, 95%CI: 1.04-1.11, P = 0.001). CONCLUSIONS: NLR may be used as a prognostic indicator for first onset NMOSD, and a high NLR may be significantly associated with high relapse rates and poor recovery.

Analysis of Predictive Risk Factors in Aquaporin-4-IgG Positive Highly Active Neuromyelitis Optica Spectrum Disorders.

Neuromyelitis optica spectrum disorders (NMOSDs) are inflammatory diseases with a high risk of recurrence and progressive disability, and it is crucial to find sensitive and reliable biomarkers for prognosis and the early prediction of relapse. Highly active NMOSD is defined as two or more clinical relapses within a 12-month period. In this study, we analyzed independent risk factors among patients with aquaporin-4 (AQP4)-IgG positive highly active NMOSD. In this retrospective study, we analyzed the data of 94 AQP4-IgG positive patients with highly active NMOSD and 105 AQP4-IgG positive controls with non-highly active NMOSD. In order to rule out possible effects of previous treatments (such as glucocorticoids, immunoglobulin, and immunosuppressants), we focused on the first-attack NMOSD patients admitted to our hospital. Clinical data, including the age of onset, gender, comorbidities, and serum analysis and cerebrospinal fluid (CSF) analysis results, were collected, after which logistic regression models were used to determine the associations between the clinical factors and relapse outcomes. The prevalence of connective tissue disease and the proportion of antinuclear antibody (ANA)-positivity were higher in the highly active NMOSD group than in the control group. The leukocyte counts, homocysteine (Hcy) levels, CSF leukocyte counts, protein concentrations, IgG indexes, and 24h IgG synthesis rates were also higher in the highly active NMOSD group. The results of multivariate analysis indicated that connective tissue disease comorbidity (OR = 5.953, 95% CI: 1.221-29.034, P = 0.027), Hcy levels (OR = 1.063, 95% CI: 1.003-1.126, P = 0.04), and 24h IgG synthesis rate (OR = 1.038, 95% CI: 1.003-1.075, P = 0.034) may be independent risk factors for AQP4-IgG positive highly active NMOSD relapse after adjusting for various variables. Comorbidity of connective tissue disease, Hcy levels, and 24h IgG synthesis rate may be independent risk factors for AQP4-IgG positive highly active NMOSD.

Clinical Characteristics and Risk Factors of Cerebral Hemorrhage in Patients with Occult Malignant Tumors.

PROPOSE: To investigate the clinical characteristics and potential risk factors of the first onset of cerebral hemorrhage in patients with occult malignant tumors. PATIENTS AND METHODS: In this retrospective study, 23 patients with occult malignant tumors with the first onset of cerebral hemorrhage were enrolled in the tumor group, and 92 patients without occult tumors in the same period were enrolled in the control group. There were no statistical differences in age and sex between both groups by propensity score matching. Collected clinical data included age, sex, smoking history, drinking history, hypertension history, diabetes history, past medical history, routine blood tests, neutrophil-to-lymphocyte ratio (NLR), liver and kidney function, fasting blood glucose level, coagulation function, tumor markers, imaging examinations, National Institute of Health stroke scale (NIHSS) score on admission, modified Rankin Scale (mRS) score 90 days after intracerebral hemorrhage and final mRS score. RESULTS: Compared with the control group, the tumor group had fewer patients with hypertension (52.2% vs 81.5%, P<0.05), and the NLR was significantly decreased in the tumor group (2.74 vs 5.46, P<0.05). The tumor group had a greater number of patients with the bleeding sites located in the lobar regions (43.5% vs.19.6%, P<0.05) and a higher coagulation dysfunction (52.2% vs 29.3%, P<0.05) than the control group. Multivariate logistic regression analysis revealed that no history of hypertension (OR: 3.141, 95% CI: 1.107-8.916), lobar cerebral hemorrhage (OR: 3.465 95% CI:1.172-10.243), and coagulation dysfunction (OR: 3.176, 95% CI: 1.131-8.913) were independent predictors of occult tumors, and the receiver operating characteristic (ROC) curve showed that the area under the curve of the three-index combined diagnosis was 0.748, C-statistic analysis also showed the same result. CONCLUSION: No history of hypertension, lobar cerebral hemorrhage, and coagulation dysfunction may be predictors of the risk of occult malignancies in patients with cerebral hemorrhage.

Serum Homocysteine Level Is a Predictor of Relapse and Prognosis in Patients With First-Attack Neuromyelitis Optica Spectrum Disorders.

Background: Many patients with neuromyelitis optica spectrum disorders (NMOSD) experience the adverse consequences of relapse and disability aggravation. Thus, it is necessary to identify sensitive and reliable biomarkers for early prognosis. This study investigated whether serum homocysteine (Hcy) level was associated with the risk of relapse or poor prognosis in first-attack NMOSD patients. Methods: We enrolled 161 first-attack NMOSD patients in this retrospective study. We reviewed their medical records and evaluated their initial Expanded Disability Status Scale (EDSS). Clinical outcomes were measured by the final EDSS and the relapse rate. The association between Hcy levels and EDSS score at last follow-up was analyzed by binary logistic regression. The association between Hcy levels and relapse rate was assessed by Cox regression analysis. Receiver operating characteristic (ROC) curve analysis was used to predict the target value of Hcy reduction. Results: Compared with the high Hcy group, the final EDSS score in the low Hcy group was significantly lower (median: 0.5 vs. 2.5, P < 0.001). The relapse rate differed significantly between these groups (30.6 vs. 50.0%, P = 0.023). Multivariate analysis showed that the initial EDSS score (odds ratio [OR] 3.03, 95% confidence interval [CI] 2.07-4.45, P < 0.001) and serum Hcy level (OR 1.13, 95%CI 1.04-1.22, P = 0.002) were significantly associated with poor prognosis in NMOSD patients. Additionally, multivariate analysis showed that serum Hcy level (hazard ratio 1.06, 95%CI 1.04-1.09, P < 0.001) was an independent predictor of the risk for relapse in NMOSD. The 12-month relapse rate of the high Hcy group was 34.8%, and 50% of high Hcy patients relapsed within 35 months after the first onset. A serum Hcy level exceeding 14.525 µmol/L indicated a high risk of relapse, with a sensitivity of 43.7%, specificity of 90.0%, and area under the ROC curve of 0.674 (95%CI 0.59-0.76, P < 0.001). Conclusion: Serum Hcy level is an independent predictor of relapse and poor prognosis in first-attack NMOSD patients. Early monitoring and reduction of serum Hcy levels may be of great significance in the prevention of disease relapse and severe disability.

Induced Pluripotent Stem Cells for Ischemic Stroke Treatment.

Ischemic stroke is one of the main central nervous system diseases and is associated with high disability and mortality rates. Recombinant tissue plasminogen activator (rt-PA) and mechanical thrombectomy are the optimal therapies available currently to restore blood flow in patients with stroke; however, their limitations are well recognized. Therefore, new treatments are urgently required to overcome these shortcomings. Recently, stem cell transplantation technology, involving the transplantation of induced pluripotent stem cells (iPSCs), has drawn the interest of neuroscientists and is considered to be a promising alternative for ischemic stroke treatment. iPSCs are a class of cells produced by introducing specific transcription factors into somatic cells, and are similar to embryonic stem cells in biological function. Here, we have reviewed the current applications of stem cells with a focus on iPSC therapy in ischemic stroke, including the neuroprotective mechanisms, development constraints, major challenges to overcome, and clinical prospects. Based on the current state of research, we believe that stem cells, especially iPSCs, will pave the way for future stroke treatment.

Neutrophil-to-Lymphocyte Ratio on Admission is an Independent Risk Factor for the Severity of Neurological Impairment at Disease Onset in Patients with a First Episode of Neuromyelitis Optica Spectrum Disorder.

PURPOSE: To investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the severity of neurological impairment at disease onset in patients with a first episode of neuromyelitis optica spectrum disorder (NMOSD). PATIENTS AND METHODS: This retrospective study included 259 patients with newly diagnosed NMOSD who were hospitalized at our institution between January 2013 and January 2020 (NMOSD group) and 169 healthy control subjects who underwent a physical examination at our hospital during the same period (control group). The clinical data collected included general information, past medical history, biochemical test results, imaging findings, NLR, AQP-4 antibody status, and initial Expanded Disability Status Scale score. A logistic regression model was used to analyze NLR as an independent risk factor for the severity of neurological impairment at disease onset in the NMOSD group. Receiver-operating characteristic curve analysis was used to evaluate the ability of the NLR to predict the severity of neurological impairment at disease onset in the NMOSD group and to determine its critical value. RESULTS: The NLR was significantly higher in the NMOSD group than in the control group (P<0.001). In the NMOSD group, neurological impairment at disease onset was more severe in those with a high NLR than in those with a low NLR (P<0.001). At onset of disease, patients with severe neurological impairment had a more significant increase in NLR than those with mild-to-moderate neurological impairment (P<0.001). Both univariate (OR 1.180, 95% CI 1.046-1.331, P=0.007) and multivariate (OR 1.146, 95% CI 1.003-1.308, P=0.044) logistic regression analyses showed that the NLR was positively correlated with the severity of neurological impairment at onset of disease in the NMOSD group. The area under the receiver-operating characteristic curve was 0.687. CONCLUSION: The NLR is an independent risk factor for the severity of neurological impairment at disease onset in patients with a first episode of NMOSD.

Clinical and Radiological Characteristics of Children and Adults With First-Attack Myelin Oligodendrocyte Glycoprotein Antibody Disease and Analysis of Risk Factors for Predicting the Severity at Disease Onset in Central China.

Objective: To analyze and compare different clinical, laboratory, and magnetic resonance imaging characteristics between pediatric and adult patients with first-attack myelin oligodendrocyte glycoprotein antibody disease (MOGAD) and to explore predictive factors for severity at disease onset. Methods: Patients diagnosed with MOGAD at the First Affiliated Hospital of Zhengzhou University from January 2013 to August 2021 were enrolled in this retrospective study. Age at disease onset, sex, comorbidities, laboratory tests, magnetic resonance imaging (MRI) characteristics, and Expanded Disability Status Scale (EDSS) scores were collected and analyzed. The association between risk factors and initial EDSS scores at disease onset was analyzed using logistic regression models and Spearman correlation analyses. A receiver-operating characteristic (ROC) curve analysis was used to evaluate the predictive ability of the uric acid and homocysteine (Hcy) levels for the severity of neurological dysfunction at the onset of MOGAD. Results: Sixty-seven patients (female, n=34; male, n=33) with first-attack MOGAD were included in this study. The mean age at onset was 26.43 ± 18.22 years (range: 3-79 years). Among patients <18 years of age, the most common presenting symptoms were loss of vision (36.0%), and nausea and vomiting (24.0%), and the most common disease spectrum was acute disseminated encephalomyelitis (ADEM) (40.0%). Among patients aged ≥18 years, the most common presenting symptoms were loss of vision (35.7%), paresthesia (33.3%), and paralysis (26.2%), and the most common disease spectrum was optic neuritis (35.7%). The most common lesions were cortical gray matter/paracortical white matter lesions in both pediatric and adult patients. Uric acid [odds ratio (OR)=1.014; 95% confidence interval (CI)=1.006-1.022; P=0.000] and serum Hcy (OR=1.125; 95% CI=1.017-1.246; P=0.023) levels were significantly associated with the severity of neurological dysfunction at disease onset. Uric acid levels (r=0.2583; P=0.035) and Hcy levels (r=0.3971; P=0.0009) were positively correlated with initial EDSS scores. The areas under the ROC curve were 0.7775 (95% CI= 0.6617‒0.8933; P<0.001) and 0.6767 (95% CI=0.5433‒0.8102, P=0.014) for uric acid and Hcy levels, respectively. Conclusion: The clinical phenotype of MOGAD varies in patients of different ages. The most common disease spectrum was ADEM in patients aged<18 years, while optic neuritis was commonly found in patients aged ≥18 years. The uric acid and Hcy levels are risk factors for the severity of neurological dysfunction at disease onset in patients with first-attack MOGAD.

NLRP3 in the Cerebrospinal Fluid as a Potential Biomarker for the Diagnosis and Prognosis of Community-Acquired Bacterial Meningitis in Adults.

OBJECTIVE: To discover the levels of NLR family pyrin domain-containing 3 (NLRP3) in the cerebrospinal fluid (CSF) from adult patients with community-acquired bacterial meningitis (CABM). METHODS: We enrolled 34 patients with CABM, 20 patients with viral meningitis (VM), and 25 patients with non-inflammatory neurological disease. Data on standard clinical parameters, scores, and outcomes were obtained from clinical records, and inflammasome levels in the CSF were measured by an enzyme-linked immunosorbent assay. The area under the receiver operating characteristic curve (AUROC) was used to quantify the diagnostic and prognostic performance of CSF NLRP3 as a biomarker of CABM. RESULTS: The levels of NLRP3 were elevated in the CSF of patients with CABM, but levels for ASC, caspase-1, or other inflammasomes did not vary significantly. CSF NLRP3 was positively correlated with clinical severity and with the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte count, albumin quotient (Qalb), and immunoglobulin G quotient (QIgG). Patients with unfavorable outcomes had higher levels of NLRP3 in the CSF, which were correlated with several blood indicators, including NLR, PLR, and lymphocyte and monocyte counts. CONCLUSIONS: Our results suggested that the level of CSF NLRP3 could represent the severity of CABM in adults. CSF NLRP3 may be a good biomarker for the diagnosis of CABM and for the discrimination between CABM and VM. It may also be a better biomarker for predicting the prognosis of adult patients with CABM when compared to the NLR or the lymphocyte and monocyte counts.

Triglyceride Level Is an Independent Risk Factor in First-Attacked Neuromyelitis Optica Spectrum Disorders Patients.

Objective: To investigate prospective associations between triglyceride (TG) level and prognosis of first-attacked patients with neuromyelitis optica spectrum disorders (NMOSD). Methods: This retrospective study included 196 patients newly diagnosed with NMOSD from June 2014 to December 2018. Data of clinical parameters, including age of onset, sex, BMI, blood lipid levels, anti-aquaporin-4 status, serum glucose level, therapy regimens, comorbidities, initial Expanded Disability Status Scale (EDSS), relapses, and outcomes were collected. We used logistic regression models to examine the associations among relevant clinical factors and outcomes, and statistical analyses were performed using the SPSS 23.0 software. Results: Compared with the high TG group, residual EDSS was relatively lower in the normal TG group (median 1.0 vs. 2.0, P = 0.002). In the univariate analysis, TG level was positively correlated with outcomes (OR 1.75, 95% CI 1.18-2.60, P = 0.005) and relapses (OR 1.57, 95% CI 1.07-2.31, P = 0.02). Our stratified analysis suggested that patients with normal BMI (OR 4.90, 95% CI 2.10-11.44, P = 0.001) were closely correlated with poor recovery owing to increased TG level. In the multivariate analysis, a statistically significant association still existed between TG level and outcomes (OR 3.44, 95% CI 1.02-11.64; P = 0.040) after adjusting for various variables. Conclusions: In first-attacked NMOSD patients, TG level was positively associated with poor recovery. Early monitoring and treatment of elevated TG level in NMOSD patients are important.

Lin28B regulates the fate of grafted mesenchymal stem cells and enhances their protective effects against Alzheimer's disease by upregulating IGF-2.

Mesenchymal stem cells (MSCs) transplantation has emerged as a potential therapeutic approach for Alzheimer's disease (AD). However, the poor proliferation capacity and low survival rate of engrafted MSCs in the hostile microenvironment of AD limit their therapeutic efficiency. Lin28B is a conserved RNA-binding protein associated with cell self-renewal and survival. The purpose of the present study was to explore whether lin28B might influence the functions of implanted MSCs and strengthen their neuroprotective potential in AD. A gain-of-function assay was used to upregulate lin28B expression in MSCs by lentiviral transfection. Our in vitro results indicated that lin28B promoted MSCs proliferation and migration, and protected MSCs against Aß1-42-induced cell death by upregulating insulin-like growth factor-2 (IGF-2). Blockage of IGF-2 partially abrogated the above effects of lin28B. After intracerebroventricular injection into amyloid precursor protein/presenilin 1 mice, implanted MSCs were monitored using bioluminescence imaging. We observed that administration of MSCs transfected with lin28B significantly stimulated their proliferation and prolonged cell retention after delivery. Moreover, administration of the transfected MSCs markedly mitigated cognitive deficits, promoted amyloid plaque clearance, decreased the activation of microglia, and reduced neuronal cell death. The data above confirmed our hypothesis that lin28B is a crucial modulator determining the fate of transplanted MSCs by regulating IGF-2-associated pathways and thereby enhancing their protective effects against AD.