Cardiometabolic multimorbidity, peripheral biomarkers, and dementia in rural older adults: The MIND-China study.

INTRODUCTION: Evidence has emerged that cardiometabolic multimorbidity (CMM) is associated with dementia, but the underlying mechanisms are poorly understood. METHODS: This population-based study included 5704 older adults. Of these, data were available in 1439 persons for plasma amyloid-ß (Aß), total tau, and neurofilament light chain (NfL) and in 1809 persons for serum cytokines. We defined CMM following two common definitions used in previous studies. Data were analyzed using general linear, logistic, and mediation models. RESULTS: The presence of CMM was significantly associated with an increased likelihood of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) (p < 0.05). CMM was significantly associated with increased plasma Aß40, Aß42, and NfL, whereas CMM that included visceral obesity was associated with increased serum cytokines. The mediation analysis suggested that plasma NfL significantly mediated the association of CMM with AD. DISCUSSION: CMM is associated with dementia, AD, and VaD in older adults. The neurodegenerative pathway is involved in the association of CMM with AD. HIGHLIGHTS: The presence of CMM was associated with increased likelihoods of dementia, AD, and VaD in older adults. CMM was associated with increased AD-related plasma biomarkers and serum inflammatory cytokines. Neurodegenerative pathway was partly involved in the association of CMM with AD.

The lifestyle for brain health index, the cluster of differentiation 33 (CD33) gene, and cognitive function among rural Chinese older adults: A population-based study.

BACKGROUND: We sought to examine the associations of the Lifestyle for Brain Health (LIBRA) index with cognitive function among rural Chinese older adults and to explore the potential role of cluster of differentiation 33 gene (CD33) in the associations. METHODS: This population-based cross-sectional study included 4914 dementia-free participants (age ≥60 years; 56.43 % women) in the 2018 baseline examination of MIND-China. The LIBRA index was generated from 11 factors. We used a neuropsychological test battery to assess episodic memory, verbal fluency, attention, executive function, and global cognition. The CD33(rs3865444) polymorphism was detected using multiple-polymerase chain reaction amplification. Data were analyzed using the general linear regression models. RESULTS: A higher LIBRA index was associated with multivariable-adjusted ß-coefficient (95 %CI) of -0.011(-0.020- -0.001) for global cognitive z-score, -0.020(-0.033- -0.006) for episodic memory, and -0.016(-0.029- -0.004) for verbal fluency. The CD33(rs3865444) was associated with a lower global cognitive z-score in the additive (CA vs. CC: ß-coefficient=0.042; 95 %CI=0.008-0.077), the dominant (CA+AA vs. CC: 0.040; 0.007-0.073), and the over-dominant (CA vs. CC+AA: 0.043; 0.009-0.077) models. Similar results were obtained for verbal fluency and attention. The CD33 gene showed statistical interactions with LIBRA index on cognitive function (Pinteraction<0.05) such that a higher LIBRA index was significantly associated with lower z-scores of global cognition and attention only among CD33 CC carriers (P < 0.05). CONCLUSIONS: This population-based study reveals for the first time that a higher LIBRA index is associated with worse cognitive performance in rural Chinese older adults and that CD33 gene could modify the association.

Associations of Blood Absolute Neutrophil Count and Cytokines With Cognitive Function in Dementia-Free Participants: A Population-Based Cohort Study.

BACKGROUND: The relationships of neutrophils and cytokines with cognitive dysfunction are poorly defined. We aimed to investigate the association of peripheral blood absolute neutrophil count (ANC) with cognitive function in older adults and to further explore the mediating role of serum cytokines in this association. METHODS: This population-based cohort study included 1 666 dementia-free participants (age ≥60 years) derived from baseline examinations (March-September 2018) of the Multimodal Intervention to Delay Dementia and Disability in Rural China (MIND-China); of these, 1 087 participants completed follow-up examinations in October-December 2019. We used a neuropsychological test battery to assess episodic memory, verbal fluency, attention, and executive function at the baseline and follow-up examinations. We used Mindray BC-6800 automated hematology analyzer to measure ANC and Meso Scale Discovery to measure serum interleukin-6 (IL-6) and eotaxin-3. RESULTS: The linear regression analysis of cross-sectional data at baseline (n = 1 666) suggested that increased ANC was significantly associated with a lower episodic memory z score (ß coefficient: -0.149, 95% CI: -0.274 to -0.023) and lower long-delayed free recall z score (-0.216, -0.361 to -0.070). Serum IL-6 and eotaxin-3 could mediate 16.16% to 20.21% and 7.55% to 9.35%, respectively, of these associations. The analysis of longitudinal data (n = 1 087) showed a J-shaped relationship of ANC with decline in episodic memory z score (p for nonlinear = .049), and a U-shaped relationship between ANC and decline in long-delayed free recall z score (p for nonlinear = .043). CONCLUSIONS: Increased neutrophils are associated with poor cognitive performance and accelerated decline in episodic memory, and the cross-sectional association is partly mediated by serum cytokines.

A preliminary study of calcium channel-associated mRNA and miRNA networks in post-traumatic epileptic rats.

The calcium channels are the main pathogenesis and therapeutic target for post-traumatic epilepsy (PTE). However, differentially expressed miRNAs (DEMs) and mRNAs associated with calcium channels in PTE and their interactions are poorly understood. We produced a PTE model in rats and conducted RNA-seq in PTE rats. Gene annotation was used to verify differentially expressed mRNAs related to calcium channels. RNAhybrid, PITA, and Miranda prediction were used to build the miRNA-mRNA pairs. Furthermore, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used for the functional enrichment analysis of DEMs. The quantification changes of mRNA and miRNA were verified by RT-qPCR. There were 431 identified differentially expressed genes (DEGs) in PTE rats compared with the sham group, of which five mRNAs and 7 miRNAs were related to calcium channels. The miRNA-mRNA network suggested a negative correlation between 11 pairs of miRNA-mRNA involved in the p53 signaling pathway, HIF-1 signaling pathway. RT-qPCR verified three upregulated mRNAs in PTE rats, associated with 7 DEMs negatively related to them, respectively. This study has revealed the changes in miRNA-mRNA pairs associated with calcium channels in PTE, which might contribute to the further interpretation of potential underlying molecular mechanisms of PTE and the discovery of promising diagnostics.

Triglyceride-glucose index, Alzheimer's disease plasma biomarkers, and dementia in older adults: The MIND-China study.

Introduction: Population-based studies have rarely explored the associations of the triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, with dementia and plasma biomarkers for amyloid beta (Aß) and neurodegeneration. Methods: This population-based study included 5199 participants (age ≥ 65 years); of these, plasma Aß, total tau, and neurofilament light chain (NfL) were measured in 1287 persons. Dementia and subtypes were diagnosed following the international criteria. TyG index was calculated as ln(fasting triglyceride(mg/dL) × fasting glucose[mg/dL]/2). Data were analyzed using logistic and general linear regression models. Results: Dementia, Alzheimer's disease (AD), and vascular dementia (VaD) were diagnosed in 301, 195, and 95 individuals, respectively. A high TyG index was significantly associated with increased likelihoods of dementia and AD; the significant association with dementia remained among participants without cardiovascular disease or diabetes. In the biomarker subsample, a high TyG index was correlated with elevated plasma Aß, but not with total tau or NfL. Discussion: High TyG index is associated with dementia, possibly via Aß pathology.

CiteSpace-Based Visualization Analysis of Forensic Research in China from 2010 to 2019.

OBJECTIVES: To analyze the research status of forensic medicine in China from 2010 to 2019, obtain the development trend of forensic medicine and explore the hotspots and research frontiers. METHODS: The forensic medical academic papers published on China National Knowledge Infrastructure (CNKI) database from 2010 to 2019 were collected. CiteSpace 5.7.R1, an information visualization analysis software, was used to analyze publication organizations, authors, keywords, and other elements. RESULTS: The majority of the research institutions were universities, provincial and ministerial scientific research and forensic institutions. Forensic pathology was still an important branch of forensic medicine and a popular research direction. The "polymorphism" and "Y chromosome" had been the research hotspots in recent years. "Medical damage" and "standard" were the most novel studies. CONCLUSIONS: In order to provide scientific basis and research direction for forensic research, this paper analyzes the cooperation network, research hotspots and research innovation in forensic research.

Research progress in digital pathology: A bibliometric and visual analysis based on Web of Science.

BACKGROUND: The development of whole slide image and deep neural network technologies has contributed to the paradigm shift in diagnostic pathology and has received much attention from researchers, with related publications increasing yearly and "exploding" in recent years. However, few studies have systematically reviewed "digital pathology" using bibliometric tools. In this study, we will use multiple approaches to visualize and analyze "digital pathology" to provide a comprehensive and objective picture of the field's historical evolution and future development. METHODS: We use VOSviewer, CiteSpace, Gephi, and R to analyze the authors, institutional and national collaboration networks, keyword co-occurrence, and co-citation analysis to visualize the current status of global digital pathology research. RESULTS: Digital pathology-related research is mainly active in "molecular, biological, and immunology" journal groups, "pharmaceutical, medical, and clinical" journal groups, and "psychology, education, and health" journal groups; in addition to "digital pathology," "diagnosis," "deep learning," "histopathology," and "surgical pathology" are also active research topics; the U.S. has significant research results in digital pathology, with the top 10 publishing institutions all coming from the U.S. In the past two decades, global digital pathology-related research can be divided into two major research areas. One is about system verification and optimization of WSI, and the other is about the application and development of artificial intelligence technology in digital pathology. Among them, based on the development of computer technology and the update of the machine learning concept, the research results for deep neural network technologies have been more concentrated in recent years. The robust performance of deep neural networks in feature extraction and image analysis provides a new research direction for improving digital pathology-aided diagnosis systems, which is where the research hotspots have been in recent years. CONCLUSIONS: The bibliometric analysis may help better understand the current status of research within the field of digital pathology and provide references and lessons for future related research.

Mapping the Knowledge of Antipsychotics-Induced Sudden Cardiac Death: A Scientometric Analysis in CiteSpace and VOSviewer.

The drugs on the market for schizophrenia are first-generation and second-generation antipsychotics. Some of the first-generation drugs have more side effects than the other drugs, so they are gradually no longer being applied clinically. Years of research have shown that the risk of sudden cardiac death in psychotic patients is associated with drug use, and antipsychotic drugs have certain cardiotoxicity and can induce arrhythmias. The mechanism of antipsychotic-induced sudden cardiac death is complicated. Highly cited papers are among the most commonly used indicators for measuring scientific excellence. This article presents a high-level analysis of highly cited papers using Web of Science core collection databases, scientometrics methods, and thematic clusters. Temporal dynamics of focus topics are identified using a collaborative network (author, institution, thematic clusters, and temporal dynamics of focus topics are identified), keyword co-occurrence analysis, co-citation clustering, and keyword evolution. The primary purpose of this study is to discuss the visual results, summarize the research progress, and predict the future research trends by bibliometric methods of CiteSpace and VOSviewer. This study showed that a research hotspot is that the mechanisms of cardiotoxicity, the safety monitoring, and the assessment of the risk-benefit during clinical use of some newer antipsychotics, clozapine and olanzapine. We discussed relevant key articles briefly and provided ideas for future research directions for more researchers to conduct related research.

Identification of miRNA-mRNA regulatory network associated with the glutamatergic system in post-traumatic epilepsy rats.

Background: Glutamate is one of the most important excitatory neurotransmitters in the mammalian brain and is involved in a variety of neurological disorders. Increasing evidence also shows that microRNA (miRNA) and mRNA pairs are engaged in a variety of pathophysiological processes. However, the miRNA and mRNA pairs that affect the glutamatergic system in post-traumatic epilepsy (PTE) remain unknown. Methods: PTE rats were induced by injecting 0.1 mol/L, 1 µL/min FeCl2 solution. Behavioral scores and EEG monitoring were used to evaluate whether PTE was successfully induced. RNA-seq was used to obtain mRNA and miRNA expression profiles. Bioinformatics analysis was performed to screen differentially expressed mRNAs and miRNAs associated with the glutamatergic system and then predict miRNA-mRNA interaction pairs. Real-time quantitative reverse transcription PCR was used to further validate the expression of the differential miRNAs and mRNAs. The microRNA-mRNA was subject to the Pearson correlation analysis. Results: Eight of the 91 differentially expressed mRNAs were associated with the glutamatergic system, of which six were upregulated and two were downregulated. Forty miRNAs were significantly differentially expressed, with 14 upregulated and 26 downregulated genes. The predicted miRNA-mRNA interaction network shows that five of the eight differentially expressed mRNAs associated with the glutamatergic system were targeted by multiple miRNAs, including Slc17a6, Mef2c, Fyn, Slc25a22, and Shank2, while the remaining three mRNAs were not targeted by any miRNAs. Of the 40 differentially expressed miRNAs, seven miRNAs were found to have multiple target mRNAs associated with the glutamatergic system. Real-time quantitative reverse transcription PCR validation and Pearson correlation analysis were performed on these seven targeted miRNAs-Slc17a6, Mef2c, Fyn, Slc25a22, and Shank2-and six additional miRNAs selected from the literature. Real-time quantitative reverse transcription PCR showed that the expression levels of the mRNAs and miRNAs agreed with the predictions in the study. Among them, the miR-98-5p-Slc17a6, miR-335-5p-Slc17a6, miR-30e-5p-Slc17a6, miR-1224-Slc25a22, and miR-211-5p-Slc25a22 pairs were verified to have negative correlations. Conclusions: Our results indicate that miRNA-mRNA interaction pairs associated with the glutamatergic system are involved in the development of PTE and have potential as diagnostic biomarkers and therapeutic targets for PTE.

Knowledge atlas of post-traumatic epilepsy research: Based on citespace visualization analysis.

The mechanism of posttraumatic epilepsy (PTE) is complicated and the treatment and prognostic effects are not satisfactory. In this study, CiteSpace and VOSviewer are used to analyze the literature related to PTE (January 2000-June 2020). The aspects of the cooperative network (author, institution, and country), keywords co-occurrence, document co-citation clustering, and journal dual-map overlay were analyzed, and the atlas was constructed. The United States, Finland, and other research institutions have frequently published PTE-related articles, thus having richer research results. The relevant research was mostly published in journals, such as Journal of Neurotrauma, Journal of Neuroscience, Brain Research, Neurobiology of Disease. Quantitative diffusion MRI plays a critical role in PTE research. The study on the susceptibility to seizures and the underlying mechanism of PTE received different degrees of attention. The present study provided an in-depth understanding of the research foundation, relevant research results, the current research frontiers, and the main research focus in the PTE field. Herein, we briefly discussed relevant key articles and also provided ideas for future research directions.

Identification of MicroRNA-Potassium Channel Messenger RNA Interactions in the Brain of Rats With Post-traumatic Epilepsy.

Background: Dysregulated expression of microRNAs and potassium channels have been reported for their contributions to seizure onset. However, the microRNA-potassium channel gene interactions in traumatic brain injury-induced post-traumatic epilepsy (PTE) remain unknown. Methods: PTE was induced in male rats by intracranial injection with ferrous chloride (0.1 mol/L, 1 µl/min) at the right frontal cortex. Electroencephalography was recorded at 60 min, as well as day 1, 7, and 30, and the behavioral seizures were assessed before injection and at different time points after injection. Rats were killed on day 30 after injection. The right frontal cortex samples were collected and subjected to high throughput messenger RNA (mRNA) and microRNA sequencing. A network of differentially expressed potassium channel mRNAs and microRNAs was constructed using OryCun2.0 and subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The differential mRNA and microRNA expressions were verified using quantitative real-time-PCR. The microRNA-mRNA was subject to the Pearson correlation analysis. Results: A PTE rat model was successfully established, as evidenced by behavioral seizures and epileptiform discharges on electroencephalography in PTE rats compared with sham rats. Among the 91 mRNAs and 40 microRNAs that were significantly differentially expressed in the PTE rat brain, 4 mRNAs and 10 microRNAs were associated with potassium channels. Except for potassium calcium-activated channel subfamily N member 2, the other three potassium channel mRNAs were negatively correlated with seven microRNAs. These microRNA-mRNA pairs were enriched in annotations and pathways related to neuronal ion channels and neuroinflammation. Quantitative real-time-PCR and correlation analysis verified negative correlations in miR-449a-5p-KCNH2, miR-98-5p-KCNH2, miR-98-5p-KCNK15, miR-19b-3p-KCNK15, and miR-301a-3p-KCNK15 pairs. Conclusion: We identified microRNA-potassium channel mRNA interactions associated with PTE, providing potential diagnostic markers and therapeutic targets for PTE.