The Trends of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, and Systemic Immunoinflammatory Index in Patients with Intracerebral Hemorrhage and Clinical Value in Predicting Pneumonia 30 Days After Surgery.

BACKGROUND: Inflammatory response is closely associated with secondary brain injury and pneumonia in intracerebral hemorrhage (ICH). In this study, we aimed to investigate the value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immunoinflammatory index (SII) in the development of pneumonia in ICH patients 30 days after surgery. METHODS: We retrospectively collected clinical data on patients with ICH who underwent surgical treatment at our institution from January 2016 to December 2022, mainly including NLR, PLR, and SII at different time points. Receiver operating characteristic curves were used to compare the value of different inflammatory indicators in predicting the development of postoperative pneumonia 30 days after surgery in ICH patients, and multivariate logistic regression analyses were used to identify independent risk factors for pneumonia 30 days after surgery. RESULTS: Among 112 patients with ICH undergoing surgical treatment, 31 (27.7%) developed pneumonia postoperatively. The results of the univariate analysis demonstrated that patients in the pneumonia group experienced significantly higher blood glucose, NLR at 72 hours postoperatively, PLR at 72 hours postoperatively, and SII at 72 hours postoperatively (SII3) than those in the nonpneumonia group, and significantly lower admission Glasgow Coma Scale scores than those in the nonpneumonia group (all P < 0.05). NLR, PLR, and SII showed increasing and then decreasing in the disease process of ICH and peaked at 48 hours postoperatively. Multivariable logistic regression analysis revealed that SII3 was an independent risk factor for postoperative pneumonia 30 days after surgery in ICH patients (odds ratio = 1.001, 95% confidence interval: 1.000-1.002, P = 0.008). The area under the curve of the developed nomogram model was 0.895 (95% confidence interval = 0.823-0.967), with a sensitivity and specificity of 0.903 and 0.815, respectively, providing good predictive power. CONCLUSIONS: In the course of ICH, NLR, PLR, and SII increased and then decreased and peaked at 48 hours postoperatively. The SII3 was the best predictor of the occurrence of pneumonia postoperatively in ICH patients.

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.

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.

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.

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.

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.

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.