Synthesis of a COF-on-MOF hybrid nanomaterial for enhanced colorimetric biosensing.

The construction of hybrid materials is significant for the exploration of functionalities in colorimetric biosensing due to its structural designability and synergy effects. In this work, a COF-on-MOF hybrid nanomaterial has been newly synthesized for colorimetric biosensing. Experimental results reveal that on-surface synthesis of COF on MOF brings nanoscale proximity between COF and MOF, which exhibits more than two folds of peroxidase-like activity as compared to single Fe-MOF. Therefore, by using the MCA@Fe-MOF nanomaterial with the assist of a specific acetyl-peptide, MCA@Fe-MOF can serve as an efficient signal reporter for colorimetric assay of histone deacetylase (HDAC), and the limit of detection (LOD) can be as low as 0.261 nM. Looking forward, the demand for diverse and promising COF-on-MOF nanomaterials with varied functionalities is anticipated, propelling further exploration of their role in colorimetric biosensing.

Colorectal cancer and its attributable risk factors in East Asia, 1990-2030.

BACKGROUND: The disease burden of colorectal cancer in East Asia has been at a high level. However, the epidemiological characteristics of the disease burden in this region have not been systematically studied. METHOD: Data were obtained from the Global Burden of Disease 2019 program. Joinpoint analysis was used to identify long-term trends in mortality of colorectal cancer. Independent effects of age, period, and cohort were detected by the age-period-cohort model. The Bayesian age-period-cohort model was performed to predict the burden of colorectal cancer across East Asia by 2030. RESULTS: From 1990 to 2019, the average annual percentage change (AAPC) showed upward trends in mainland China (1.05 [95% confidence interval (CI)], 0.82, 1.28) as well as Taiwan Province of China (1.81 [95% CI], 1.51, 2.10) but downward in Japan (-0.60 [95% CI], -0.70, -0.49) (P < 0.05). Attributable risk factors for colorectal cancer in East Asia remained stable over 30 years, while the risk of metabolic factors is noteworthy in the future. In the next decade, the age-standardized death rate (ASDR) of colorectal cancer in China was predicted to surpass that of Japan and South Korea in expectation. CONCLUSION: The mortality of colorectal cancer is escalating in developing countries, while it is gradually declining in high-income countries across East Asia. Nonetheless, the disease burden of colorectal cancer in high-income countries remains substantial level.

Preparation of Well-Constructed and Metal-Modified Covalent Organic Framework Nanoparticles for Biosensing Design with Cascade Catalytic Capability.

Uniform covalent organic framework nanoparticles (COF NPs) with a well-defined pore structure may provide a robust platform for scaffolding enzymes. Herein, bipyridine-based spherical COF NPs have been successfully prepared in this work through the Schiff base condensation reaction. Moreover, they are functionalized by metal modification and are further used for biosensor fabrication. Experimental results reveal that the metal-modified COF NPs also display impressive peroxidase-like catalytic activities, while they can load enzymes, such as glucose oxidase (GOx) and sarcosine oxidase (SOx), to develop a cascade catalysis system for design of various kinds of biosensors with very well performance. For example, the optimized GOx@Fe-COFs can achieve a sensitive detection of glucose with a low limit of detection (LOD) of 12.8 µM. Meanwhile, the enzymes also exhibit a commendable preservation of 80% enzymatic activity over a span of 14 days under ambient conditions. This work may pave the way for advancing cascade catalysis and the analysis of different kinds of biological molecules based on COF NPs.

Genome-wide identification and expression analysis of the KCS gene family in soybean (Glycine max) reveal their potential roles in response to abiotic stress.

Very long chain fatty acids (VLCFAs) are fatty acids with chain lengths of 20 or more carbon atoms, which are the building blocks of various lipids that regulate developmental processes and plant stress responses. 3-ketoacyl-CoA synthase encoded by the KCS gene is the key rate-limiting enzyme in VLCFA biosynthesis, but the KCS gene family in soybean (Glycine max) has not been adequately studied thus far. In this study, 31 KCS genes (namely GmKCS1 - GmKCS31) were identified in the soybean genome, which are unevenly distributed on 14 chromosomes. These GmKCS genes could be phylogenetically classified into seven groups. A total of 27 paralogous GmKCS gene pairs were identified with their Ka/Ks ratios indicating that they had undergone purifying selection during soybean genome expansion. Cis-acting element analysis revealed that GmKCS promoters contained multiple hormone- and stress-responsive elements, indicating that GmKCS gene expression levels may be regulated by various developmental and environmental stimuli. Expression profiles derived from RNA-seq data and qRT-PCR experiments indicated that GmKCS genes were diversely expressed in different organs/tissues, and many GmKCS genes were found to be differentially expressed in the leaves under cold, heat, salt, and drought stresses, suggesting their critical role in soybean resistance to abiotic stress. These results provide fundamental information about the soybean KCS genes and will aid in their further functional elucidation and exploitation.

Investigating the ID3/SLC22A4 as immune-related signatures in ischemic stroke.

BACKGROUND: Ischemic stroke (IS) is a fearful disease that can cause a variety of immune events. Nevertheless, precise immune-related mechanisms have yet to be systematically elucidated. This study aimed to identify immune-related signatures using machine learning and to validate them with animal experiments and single cell analysis. METHODS: In this study, we screened 24 differentially expressed genes (DEGs) while identifying immune-related signatures that may play a key role in IS development through a comprehensive strategy between least absolute shrinkage and selection operation (LASSO) regression, support vector machine (SVM) and immune-related genes. In addition, we explored immune infiltration using the CIBERSORT algorithm. Finally, we performed validation in mouse brain tissue and single cell analysis. RESULTS: We identified 24 DEGs for follow-up analysis. ID3 and SLC22A4 were finally identified as the better immune-related signatures through a comprehensive strategy among DEGs, LASSO, SVM and immune-related genes. RT-qPCR, western blot, and immunofluorescence revealed a significant decrease in ID3 and a significant increase in SLC22A4 in the middle cerebral artery occlusion group. Single cell analysis revealed that ID3 was mainly concentrated in endothelial_2 cells and SLC22A4 in astrocytes in the MCAO group. A CIBERSORT finds significantly altered levels of immune infiltration in IS patients. CONCLUSIONS: This study focused on immune-related signatures after stroke and ID3 and SLC22A4 may be new therapeutic targets to promote functional recovery after stroke. Furthermore, the association of ID3 and SLC22A4 with immune cells may be a new direction for post-stroke immunotherapy.

Dual DNA recycling amplifications coupled with Au NPs@ZIF-MOF accelerator for enhanced electrochemical ratiometric sensing of pathogenic bacteria.

Sensitive and accurate quantification of pathogenic bacteria is vastly significant to the related food safety. Herein, a sensitive ratiometric electrochemical biosensor was developed for the detection of Staphylococcus aureus (S. aureus) based on dual DNA recycling amplifications and Au NPs@ZIF-MOF accelerator. Gold nanoparticles-loaded Zeolitic imidazolate metal-organic framework (Au NPs@ZIF-MOF) as electrode substrate possessed a large specific surface area for nucleic acid adsorption, and as an accelerator promoted the transfer of electrons. The strong recognition of aptamer to target S. aureus could initiate the padlock probe-based exponential rolling circle amplification (P-ERCA, as the first DNA recycling amplification), generating large numbers of trigger DNA strands. The released trigger DNA further activated the catalytic hairpin assembly (CHA, as the second DNA recycling amplification) on electrode surface. Consequently, P-ERCA and CHA continuously brought about one target to many signal transduction, leading to an exponential amplification. To achieve the accuracy of detection, the signal ratio of methylene blue (MB) and ferrocene (Fc) (IMB/IFc) was applied for intrinsic self-calibrating. Taking advantages of dual DNA recycling amplifications and Au NPs@ZIF-MOF, the proposed sensing system displayed high sensitivity for S. aureus quantification with a linear range of 5-108 CFU/mL, and the limit of detection was 1 CFU/mL. Moreover, this system represented excellent reproducibility, selectivity, and practicability for S. aureus analysis in foods.

An electrochemical biosensor to identify the phenotype of aggressive breast cancer cells.

Identifying the phenotype of aggressive breast cancer (BC) cells is vital for the effectiveness of surgical intervention and standard-of-care therapy. HER-2 is overexpressed in aggressive BC and MMP-2 is a crucial indicator of invasiveness and metastasis of BC, so we have proposed an electrochemical biosensor in this work to identify the phenotype of aggressive BC cells via detection of HER-2 together with MMP-2 by designing a dual-trapping peptide and a metal organic framework (MOF)-based probe. Specifically, the designed peptide contains both a HER-2 recognition sequence and MMP-2-specific substrate, while the MOF-based probe (AuNPs@HRP@ZIF-8), prepared by loading horseradish peroxidase (HRP) and gold nanoparticles (AuNPs) on ZIF-8, can also combine with the peptide. Consequently, sensitive and specific detection of both HER-2 and MMP-2 can be achieved in the wide range from 50 fg mL-1 to 50 ng mL-1 and 10 fg mL-1 to 10 ng mL-1, respectively, and the biosensor can distinguish HER-2+ BC cells and evaluate the invasion capability, which might be extended to provide a method for the accurate identification of tumor features in BC subtypes.

Engineering m6A demethylation-activated DNAzyme for visually and sensitively sensing fat mass and obesity-associated protein.

Fat mass and obesity-associated protein (FTO) regulating the N6-methyladenine (m6A, the most pervasive epigenetic modification) levels within the nucleus has been identified as a potential biomarker for cancer diagnosis and prognosis. However, current methods for FTO detection are complicated or/and not sensitive enough for practical application. Herein, we propose a colorimetric biosensor for detecting FTO based on a delicate design of m6A demethylation-activated DNAzyme. Specifically, an m6A-blocked DNAzyme is constructed as a switch of the biosensor that can be turned on by target FTO. The decreased thermal stability resulting from substrate cleavage leads to a DNAzyme recycling to produce multiple primers. Then the rolling circle amplification (RCA) reactions can be initiated to generate G-quadruplex-DNAzymes catalyzing 2,2-azino-bis-(3-ethylben-zthiazoline-6-sulfonic acid (ABTS) oxidation which can be readily observed by the naked eye. Quantitative detection can also be achieved with a limit of detection (LOD) down to 69.9 fM, exhibiting higher sensitivity than previous reports. Therefore, this biosensor opens a simple and sensitive way to achieve visual assay of FTO via triple signal amplification. In addition, our biosensor has been successfully applied to FTO detection in clinical samples, which shows great potential in clinical molecular diagnostics.

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.

Covalent organic frameworks (COFs)-based biosensors for the assay of disease biomarkers with clinical applications.

Covalent organic frameworks (COFs) are an emerging type of porous crystalline polymers that are built by light elements (typically H, B, C, N, O and Si) via organic covalent bonds. Currently, COFs have been exploited for biomedical application due to their unique properties, such as structural diversity, intrinsic stability, ordered porosity, tailor-made functions, and excellent adsorption features. In particular, COFs are increasingly popular in the construction of biosensors for the detection of various disease biomarkers, and have been extended to the clinical applicability for early diagnostics, medication instruction and prognostic monitoring of diseases. In this review, we mainly summarize the recent advances on COFs-based biosensors for the assay of disease biomarkers with clinical applications. According to the features of molecular structure, disease biomarkers are classified into four categories, including small biological ions/molecules, proteins, nucleic acids, and cancer cells/exosomes. Impressively, COFs-based biosensors present a bright prospect in clinical diagnosis of diseases in both hospital-end and household-end utilization.

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.

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.

Monocyte to High-Density Lipoprotein Ratio: A Novel Predictive Marker of Disease Severity and Prognosis in Patients With Neuromyelitis Optica Spectrum Disorders.

Background and Purpose: To investigate the association of monocyte to high-density lipoprotein ratio (MHR) with disease severity and prognosis in patients with neuromyelitis optica spectrum disorders (NMOSD). Methods: This retrospective study included 125 patients with NMOSD. Demographic and clinical parameters, including the MHR, were assessed. The initial Expanded Disability Status Scale (EDSS) score and relapse rate were used to evaluate disease severity and prognosis, respectively. Correlations between MHR and disease severity and relapse rate were analyzed. The predictive value of MHR for prognosis was evaluated using receiver operating characteristic (ROC) curve analysis. Results: Compared with the low MHR group, the initial EDSS score (median 4.5 vs. 5.5%, P = 0.025) and relapse rate (51.61 vs. 30.16%, P = 0.015) were significantly higher in the high MHR group. MHR was positively correlated with the initial EDSS score (r = 0.306, P = 0.001). Multivariate analysis showed that MHR was significantly associated with severity (odds ratio = 7.90, 95% confidence interval [CI] = 1.08-57.82, P = 0.041), and it was a significant predictor of disease prognosis (hazard ratio = 3.12, 95% CI = 1.02-9.53, P = 0.046). The median relapse interval of the high MHR group was 24.40 months. When the MHR was higher than 0.565, the risk of relapse was high [sensitivity, 33.3%; specificity, 91.9%; area under the ROC curve, 0.642 (95% CI = 0.54-0.74, P = 0.007)]. Conclusion: MHR is a novel predictive marker of disease severity and prognosis in patients with NMOSD. Early monitoring and reduction of MHR may allow earlier intervention and improved prognosis.

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.

Effect of Low Complement C4 on Clinical Characteristics of Patients with First-Episode Neuromyelitis Optica Spectrum Disorder.

PURPOSE: To describe and compare the clinical features of patients with first-episode neuromyelitis optica spectrum disorder (NMOSD) in a normal complement C4 group and a low complement C4 group, and explore the mechanism by which low complement C4 affects the clinical features of patients with NMOSD. PATIENTS AND METHODS: We retrospectively analyzed clinical data of 169 aquaporin-4 (AQP4) antibody positive patients with NMOSD from the First Affiliated Hospital of Zhengzhou University from December 2013 to March 2021. Prior to treatment, the blood was drawn for detection, and the patients underwent a 3.0 Tesla MRI examination. A low complement C4 level was defined as a serum complement C4 level <0.14 g/L. Depending on whether the complement C4 level was reduced, it was divided into the normal complement C4 group and low complement C4 group. The basic demographics, clinical manifestations, laboratory examinations, and imaging findings of the two groups were compared. RESULTS: Among the 169 AQP4 antibody positive patients, 54 were low-complement C4 patients and 115 were normal. There were no significant differences in the demographics, clinical manifestations, treatment options, or admission Expanded Disability Status Scale (EDSS) score between two groups (P > 0.05). The median of discharged EDSS was the same (4 vs 4), but the difference between the two was statistically significant (P = 0.019). Compared with the normal complement C4 group, the blood uric acid level (225 vs 179; P = 0.001) and the C3 level (1.06 vs 0.87, P = 0.000) of the low complement C4 group were significantly lower. The incidence of brainstem lesions in patients with low complement C4 was higher (53.7% vs 33%, P = 0.01). CONCLUSION: The treatment effect of the first-episode AQP4 antibody positive NMOSD low complement C4 group was poor, the blood-brain barrier was more severely damaged, and the disease changes were likely to involve the brainstem.

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.

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.