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Chronic obstructive pulmonary disease (COPD), characterized by clinical sub-phenotypes such as emphysema (E) and chronic bronchitis (CB), is associated with a greater risk of lung cancer (LC). This study aimed to assess the expression patterns of circRNA and their potential functional involvement in LC patients with COPD. A circRNA microarray was used to characterize differentially expressed circRNAs (DEcircRNAs) profiles. A total of 176, 240, 163, and 243 DEcircRNAs were identified in comparisons between CB vs. LC patients (Con), E vs. Con, E vs. CB, and CBE vs. Con, respectively. DEcircRNAs in all comparison groups were primarily associated with immune-related GO terms and were also enriched in immune and inflammatory pathways. In total, 49 DEcircRNAs were significantly correlated with the infiltration of multiple immune cells. Among them, hsa-MROH9_0001 and hsa-RP11-35J10_0013 were positively and negatively correlated with plasma cells and T-cell CD4 memory resting cells, respectively; these two DEcircRNA-sponged miRNAs have good diagnostic performance. WGCNA identified six key circRNAs associated with CB progression. The expression patterns of hsa-MROH9_0001 and circRNA_21729 in E and CB groups were confirmed by RT-qPCR. In conclusion, we reported circRNA profiles and the findings demonstrated that hsa-MROH9_0001 and circRNA_21729 may be potential therapeutic targets for LC with COPD.
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Neoplasias Pulmonares , Enfermedad Pulmonar Obstructiva Crónica , ARN Circular , Humanos , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , ARN Circular/genética , ARN Circular/metabolismo , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Proyectos Piloto , Masculino , Femenino , Anciano , Perfilación de la Expresión Génica , Persona de Mediana Edad , Transcriptoma/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
PURPOSE: To investigate the treatment time and efficiency of constricted ears of different severity after correction. MATERIALS AND METHODS: We included the patients with constricted ear presented to our hospital for treatment between December 2021 and December 2023 in this retrospective analysis. The patients were divided into class I, II and III groups based on the severity of the constriction. Then we collected the data on classification of severity from each patient, together with sex, family history, age at initial correction, being informed upon diagnosis after birth, as well as utilization of auricle correction system. Logistic regression analysis was performed to identify the factors associated with the treatment time and efficiency. RESULTS: The correction system yielded a high effective rate in the constricted ears. The treatment time in class II was significantly longer compared with those of class I after adjusting these parameters. Compared with the cases of class I, those with a class III showed significant attenuation in the symptoms and conditions (95 % CI: 0.034, 0.365; P < 0.001), after adjusting the age at initial correction, being informed upon diagnosis after birth, and utilization of auricle correction system. There were no statistical differences between class II and III in the treatment efficiency after correction. CONCLUSIONS: The Amazing Ear Correction System was effective in treating constricted ear, yielding satisfactory treatment efficiency. Patients with class II constriction required longer treatment time compared with those of class I. The treatment outcome in the class I constriction was better than that of class III.
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Índice de Severidad de la Enfermedad , Humanos , Femenino , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Constricción Patológica/terapia , Pabellón Auricular/anomalías , Pabellón Auricular/cirugía , Niño , Preescolar , Factores de Tiempo , Oído Externo/anomalías , Lactante , Enfermedades del Oído/terapia , Enfermedades del Oído/diagnósticoRESUMEN
BACKGROUND: Schizophrenia (SZ), a psychiatric disorder for which there is no precise diagnosis, has had a serious impact on the quality of human life and social activities for many years. Therefore, an advanced approach for accurate treatment is required. NEW METHOD: In this study, we provide a classification approach for SZ patients based on a spatial-temporal residual graph convolutional neural network (STRGCN). The model primarily collects spatial frequency features and temporal frequency features by spatial graph convolution and single-channel temporal convolution, respectively, and blends them both for the classification learning, in contrast to traditional approaches that only evaluate temporal frequency information in EEG and disregard spatial frequency features across brain regions. RESULTS: We conducted extensive experiments on the publicly available dataset Zenodo and our own collected dataset. The classification accuracy of the two datasets on our proposed method reached 96.32% and 85.44%, respectively. In the experiment, the dataset using delta has the best classification performance in the sub-bands. COMPARISON WITH EXISTING METHODS: Other methods mainly rely on deep learning models dominated by convolutional neural networks and long and short time memory networks, lacking exploration of the functional connections between channels. In contrast, the present method can treat the EEG signal as a graph and integrate and analyze the temporal frequency and spatial frequency features in the EEG signal. CONCLUSION: We provide an approach to not only performs better than other classic machine learning and deep learning algorithms on the dataset we used in diagnosing schizophrenia, but also understand the effects of schizophrenia on brain network features.
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Electroencefalografía , Redes Neurales de la Computación , Esquizofrenia , Esquizofrenia/diagnóstico , Esquizofrenia/fisiopatología , Humanos , Electroencefalografía/métodos , Procesamiento de Señales Asistido por Computador , Automatización , Diagnóstico por Computador/métodos , Análisis Espacio-TemporalRESUMEN
Chronic obstructive pulmonary disease (COPD) is characterised by persistent airway inflammation even after cigarette smoking cessation. Neutrophil extracellular traps (NETs) have been implicated in COPD severity and acute airway inflammation induced by short-term cigarette smoke (CS). However, whether and how NETs contribute to sustained airway inflammation in COPD remain unclear. This study aimed to elucidate the immunoregulatory mechanism of NETs in COPD, employing human neutrophils, airway epithelial cells (AECs), dendritic cells (DCs), and a long-term CS-induced COPD mouse model, alongside cyclic guanosine monophosphate-adenosine monophosphate synthase and toll-like receptor 9 knockout mice (cGAS--/-, TLR9-/-); Additionally, bronchoalveolar lavage fluid (BALF) of COPD patients was examined. Neutrophils from COPD patients released greater cigarette smoke extract (CSE)-induced NETs (CSE-NETs) due to mitochondrial respiratory chain dysfunction. These CSE-NETs, containing oxidatively-damaged DNA (NETs-DNA), promoted AECs proliferation, nuclear factor kappa B (NF-κB) activation, NF-κB-dependent cytokines and type-I interferons production, and DC maturation, which were ameliorated/reversed by silencing/inhibition of cGAS/TLR9. In the COPD mouse model, blocking NETs-DNA-sensing via cGAS-/- and TLR9-/- mice, inhibiting NETosis using mitoTEMPO, and degrading NETs-DNA with DNase-I, respectively, reduced NETs infiltrations, airway inflammation, NF-κB activation and NF-κB-dependent cytokines, but not type-I interferons due to IFN-α/ß receptor degradation. Elevated NETs components (myeloperoxidase and neutrophil elastase activity) in BALF of COPD smokers correlated with disease severity and NF-κB-dependent cytokine levels, but not type-I interferon levels. In conclusion, NETs-DNA promotes NF-κB-dependent autoimmunity via cGAS/TLR9 in long-term CS exposure-induced COPD. Therefore, targeting NETs-DNA and cGAS/TLR9 emerges as a potential strategy to alleviate persistent airway inflammation in COPD.
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Trampas Extracelulares , FN-kappa B , Neutrófilos , Nucleotidiltransferasas , Enfermedad Pulmonar Obstructiva Crónica , Receptor Toll-Like 9 , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/inmunología , Enfermedad Pulmonar Obstructiva Crónica/patología , Receptor Toll-Like 9/genética , Receptor Toll-Like 9/inmunología , Trampas Extracelulares/inmunología , Trampas Extracelulares/genética , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/inmunología , Animales , Humanos , FN-kappa B/genética , FN-kappa B/inmunología , FN-kappa B/metabolismo , Ratones , Neutrófilos/inmunología , Neutrófilos/patología , Ratones Noqueados , Autoinmunidad/genética , Masculino , ADN/genética , ADN/inmunología , Femenino , Modelos Animales de Enfermedad , Persona de Mediana EdadRESUMEN
Endometriosis is a benign gynecological disease that shares some common features of malignancy. Autophagy plays vital roles in endometriosis and influences endometrial cell metastasis, and hypoxia was identified as the initiator of this pathological process through hypoxia inducible factor 1 alpha (HIF-1α). A newly discovered circular RNA FOXO3 (circFOXO3) is critical in cell autophagy, migration, and invasion of various diseases and is reported to be related to hypoxia, although its role in endometriosis remains to be elucidated up to now. In this study, a lower circFOXO3 expression in ectopic endometrium was investigated. Furthermore, we verified that circFOXO3 could regulate autophagy by downregulating the level of p53 protein to mediate the migration and invasion of human endometrial stromal cells (T HESCs). Additionally, the effects of HIF-1α on circFOXO3 and autophagy were examined in T HESCs. Notably, overexpression of HIF-1α could induce autophagy and inhibit circFOXO3 expression, whereas overexpressing of circFOXO3 under hypoxia significantly inhibited hypoxia-induced autophagy. Mechanistically, the direct combination between HIF-1α and HIF-1α-binding site on adenosine deaminase 1 acting on RNA (ADAR1) promoter increased the level of ADAR1 protein, which bind directly with circFOXO3 pre-mRNA to block the cyclization of circFOXO3. All these results support that hypoxia-mediated ADAR1 elevation inhibited the expression of circFOXO3, and then autophagy was induced upon loss of circFOXO3 via inhibition of p53 degradation, participating in the development of endometriosis.
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Endometriosis , Femenino , Humanos , Endometriosis/genética , Proteína p53 Supresora de Tumor , ARN , ARN Circular/genética , Autofagia , HipoxiaRESUMEN
Home-based movement neuro-rehabilitation is quite necessary when the patient goes back home from hospital. Due to lack of supervision from doctors, rehabilitation at home is often forgotten. As an alternate to doctor-supervision, in this research, we explore the wireless device-free localization technique to assist the rehabilitation procedure. The localization technique can judge whether the patient is near the rehabilitation equipment and even obtain the movement trajectory. The most challenging problem in the wireless device-free localization system is that the received-signal-strength (RSS) of the electromagnetic-wave is unpredictable, which increases the localization error. How to select the informative RSS is pretty important. This research proposes a new criterion (i.e., fluctuation-level) to select the informative RSS. Experimental results show the effectiveness of the proposed fluctuation-level in reducing the localization error.
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The cognitive impairment in schizophrenia (SZ) is characterized by significant deficits in working memory task. In order to explore the brain changes of SZ during a working memory task, we performed time-domain and time-frequency analysis of event related potentials (ERP) of SZ during a 0-back task. The P3 wave amplitude was found to be significantly lower in SZ patients than in healthy controls (HC) (p < 0.05). The power in the θ and α bands was significantly enhanced in the SZ group 200 ms after stimulation, while the θ band was significantly enhanced and the ß band was weakened in the HC group. Furthermore, phase lag index (PLI) based brain functional connectivity maps showed differences in the connections between parietal and frontotemporal lobes between SZ and HC (p < 0.05). Due to the natural similarity between brain networks and graph data, and the fact that graph attention network can aggregate the features of adjacent nodes, it has more advantages in learning the features of brain regions. We propose a multi graph attention network model combined with adaptive initial residual (AIR) for SZ classification, which achieves an accuracy of 90.90 % and 78.57 % on an open dataset (Zenodo) and our 0-back dataset, respectively. Overall, the proposed methodology offers promising potential for understanding the brain functional connections of schizophrenia.
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Memoria a Corto Plazo , Esquizofrenia , Humanos , Memoria a Corto Plazo/fisiología , Encéfalo , Mapeo Encefálico/métodos , Potenciales EvocadosRESUMEN
INTRODUCTION: Blood eosinophil count has been shown markedly variable across different populations. However, its distribution in Chinese general population remains unclear. We aimed to investigate blood eosinophil count and its determinants in a Chinese general population. METHODS: In this population-based study, general citizens of Sichuan province in China were extracted from the China Pulmonary Health study. Data on demographics, personal and family history, living condition, lifestyle, spirometry, and complete blood count test were obtained and analyzed. A stepwise multivariate binary logistic regression analysis was performed to identify determinants of high blood eosinophils (>75th percentile). RESULTS: A total of 3,310 participants were included, with a mean age (standard deviation) of 47.0 (15.6) years. In total population, the median blood eosinophil count was 110.0 (interquartile range [IQR]: 67.2-192.9) cells/µL, lower than that in smokers (133.4 cells/µL, IQR: 79.3-228.4) and patients with asthma (140.7 cells/µL, IQR: 79.6-218.2) or post-bronchodilator airflow limitation (141.5 cells/µL, IQR: 82.6-230.1), with a right-skewed distribution. Multivariate analyses revealed that oldness (aged ≥60 years) (odds ratio [OR]: 1.66, 95% confidence interval [CI]: 1.11-2.48), smoking ≥20 pack-years (OR: 1.90, 95% CI: 1.20-3.00), raising a dog/cat (OR: 1.72, 95% CI: 1.17-2.52), and occupational exposure to dust, allergen, and harmful gas (OR: 1.58, 95% CI: 1.15-2.15) were significantly associated with high blood eosinophils. CONCLUSION: This study identifies a median blood eosinophil count of 110.0 cells/µL and determinants of high blood eosinophils in a Chinese general population, including oldness (aged ≥60 years), smoking ≥20 pack-years, raising a dog/cat, and occupational exposure to dust, allergen, and harmful gas.
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Asma , Eosinofilia , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Persona de Mediana Edad , Alérgenos , Asma/epidemiología , Polvo , Eosinofilia/epidemiología , Eosinófilos , Recuento de Leucocitos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Adulto , AncianoRESUMEN
The objective of this study was to investigate IL13Ra2 expression in brainstem glioma (BSG) and its correlation with key markers, functions, and prognostic implications, evaluating its therapeutic potential. A total of 80 tumor samples from BSG patients were analyzed. Multiplex immunofluorescence was used to examine six markers-IL13Ra2, H3.3K27M, CD133, Ki67, HLA-1, and CD4-establishing relationships between IL13Ra2 and these markers. Survival analysis, employing Kaplan-Meier and Cox proportional hazard regression models, encompassed 66 patients with complete follow-up. RNA-Seq data from a previously published study involving 98 patients were analyzed using the DESeq2 library to determine differential gene expression between groups. Gene Ontology (GO) enrichment and single-sample gene set enrichment analysis (ssGSEA) via the clusterProfiler library were used to delineate the gene functions of differentially expressed genes (DEGs). Nearly all the BSG patients displayed varying IL13Ra2 expression, with 45.0% (36/80) exhibiting over a 20% increase. Elevated IL13Ra2 levels were notably observed in pontine gliomas, diffuse intrinsic pontine gliomas (DIPGs), H3F3A-mutant gliomas, and WHO IV gliomas. IL13Ra2 expression was strongly correlated with H3.3K27M mutant protein, Ki67, and CD133. Patients with IL13Ra2 expression >20% showed shorter overall survival compared to those with ≤20% IL13Ra2 expression. The Cox proportional hazard regression model identified H3F3A mutations, rather than IL13Ra2 expression, as an independent prognostic factor. Analysis of RNA-Seq data from our prior cohort confirmed IL13Ra2's correlation with H3.3, CD133, and Ki67 levels. Widespread IL13Ra2 expression in BSG, particularly elevated in the H3F3A mutant group, was strongly correlated with H3F3A mutations, increased proliferation, and heightened tumor stemness. IL13Ra2 represents a promising therapeutic target for BSGs, potentially benefiting patients with H3K27M mutations, DIPGs, WHO Grade IV, and pontine location-specific BSGs, particularly those with H3K27M mutations.
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N6-methyladenosine (m6A) methylation is the most prevalent internal epigenetic posttranscriptional mechanism for regulating mammalian RNA. Despite recent advances in determining the biological functions of m6A methylation, its association with the pathology of ovarian endometriosis remains uncertain. Herein, we performed m6A transcriptome-wide profiling to identify key lncRNAs with m6A modification involved in ovarian endometriosis development by bioinformatics analysis. We found the total m6A level was lower in ovarian endometriosis than in normal endometrium samples, with 9663 m6A peaks associated with 8989 lncRNAs detected in ovarian endometriosis and 9902 m6A peaks associated with 9210 lncRNAs detected in normal endometrium samples. These m6A peaks were primarily enriched within AAACU motifs. Functional enrichment analysis indicated that pathways involving the regulation of adhesion and development were significantly enriched in these differentially methylated lncRNAs. The regulatory relationships among lncRNAs, microRNAs (miRNAs), and mRNAs were identified by competing endogenous RNA (ceRNA) analysis and determination of the network regulating lncRNA-mRNA expression. Several specific lncRNA, including LINC00665, LINC00937, FZD10-AS1, DIO3OS and GATA2-AS1 which were differently expressed and modified by m6A, were validated using qRT-PCR and its interaction with infiltrating immune cells was explored. Furthermore, we found LncRNA DIO3OS promotes the invasion and migration of Human endometrial stromal cells (THESCs) and ALKBH5 regulates the expression of the lncRNA DIO3OS through m6A modification in vitro. Our study firstly revealed the transcriptome-wide map of m6A modification in lncRNAs of ovarian endometriosis. These findings may enable the determination of the underlying mechanism governing the pathogenesis of ovarian endometriosis and provide theoretical basis for further deeper research on the role of m6A in the development of ovarian endometriosis.
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Endometriosis , ARN Largo no Codificante , Femenino , Humanos , Animales , ARN Largo no Codificante/genética , Transcriptoma , Endometriosis/genética , Adenosina , Metilación , MamíferosRESUMEN
This study aims to examine the clinical characteristics and outcomes of clinical myocarditis in pediatric patients in China. This is a multicenter retrospective study. Children diagnosed with clinical myocarditis from 20 hospitals in China and admitted between January 1, 2015, and December 30, 2021, were enrolled. The clinical myocarditis was diagnosed based on the "Diagnostic Recommendation for Myocarditis in Children (Version 2018)". The clinical data were collected from their medical records. A total of 1210 patients were finally enrolled in this study. Among them, 45.6% had a history of respiratory tract infection. An abnormal electrocardiogram was observed in 74.2% of patients. Echocardiography revealed that 32.3% of patients had a left ventricular ejection fraction of less than 50%. Cardiac MRI was performed in 4.9% of children with clinical myocarditis, of which 61% showed localized or diffuse hypersignal on T2-weighted images. Serum levels of cardiac troponin I (cTnI), creatine kinase-MB (CK-MB), and N-terminal B-type natriuretic peptide (NT-proBNP) were higher in patients with fulminant myocarditis than in patients with myocarditis, making them potential risk factors for fulminant myocarditis. Following active treatment, 12.1% of patients were cured, and 79.1% were discharged with improvement. CONCLUSION: Clinical myocarditis in children often presents with symptoms outside the cardiovascular system. CK-MB, cTnI, and NT-proBNP are important indicators for assessing clinical myocarditis. The electrocardiogram and echocardiogram findings in children with clinical myocarditis exhibit significant variability but lack specificity. Cardiac MRI can be a useful tool for screening clinical myocarditis. Most children with clinical myocarditis have a favorable prognosis. WHAT IS KNOWN: ⢠Pediatric myocarditis presents complex clinical manifestations and exhibits varying degrees of severity. Children with mild myocarditis generally have a favorable prognosis, while a small number of children with critically ill myocarditis experience sudden onset, hemodynamic disorders, and fatal arrhythmias. Therefore, early diagnosis and timely treatment of myocarditis are imperative. WHAT IS NEW: ⢠To the best of our knowledge, this multicenter retrospective study is the largest ever reported in China, aiming to reveal the clinical characteristics and outcomes of pediatric clinical myocarditis in China. We provided an extensive analysis of the clinical characteristics, diagnosis, treatment, prognosis, and factors impacting disease severity in pediatric clinical myocarditis in China, which provides insights into the epidemiological characteristics of pediatric clinical myocarditis.
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Miocarditis , Niño , Humanos , Miocarditis/diagnóstico , Miocarditis/terapia , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular Izquierda , Forma MB de la Creatina-Quinasa , Arritmias Cardíacas , China/epidemiologíaRESUMEN
The level of folate receptor (FR) has become one of the independent factors for measuring human tumor diseases. The precise quantification of FR is helpful for the early diagnosis and subsequent treatment of tumors. The modification of electrodes is a key issue in ensuring and enhancing the electrochemical biosensing ability. In this study, we in-situ synthesized a nanocomposite material with excellent conductivity and stability by grafting first-generation poly(amidoamine) dendrimers onto the MXene (Ti3C2TX) as the immobilized matrix (PAMAM@MXene). An electrochemical sensor was developed for FR monitor by loading the PAMAM@MXene on screen-printed carbon electrodes (SPCEs). Scanning electron microscopy (SEM) supported the effective synthesis of PAMAM@MXene. Under optimal conditions, the prepared sensor achieved the quantification of FR with a wide range of concentrations from 10 ng/mL to 1000 ng/mL with a detection limit (LOD) of 5.6 ng/mL. It also exhibited satisfactory selectivity, reproducibility, and stability, which provided the possibility for expanding new pathways in the detection of clinical FR.
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Técnicas Biosensibles , Neoplasias , Nitritos , Elementos de Transición , Humanos , Reproducibilidad de los Resultados , Técnicas Electroquímicas , Electrodos , Ácido FólicoRESUMEN
BACKGROUND: Sleep disorders, including obstructive sleep apnea (OSA), restless leg syndrome (RLS) and insomnia, are present in chronic obstructive pulmonary disease (COPD) with varied prevalence. The aim of this systematic review and meta-analysis was to investigate prevalence of OSA, RLS and insomnia in patients with COPD and summarize their clinical characteristics. METHODS: We searched PubMed, Web of Science and Scopus for eligible articles reporting the prevalence of OSA, RLS, and insomnia in COPD patients. The NewcastleâOttawa scale was applied for quality assessment. Odds ratios or mean differences with 95 % confidence intervals (CIs) were applied for the overall prevalence calculation and clinical characteristics assessment. Sensitivity analysis, subgroup analysis and meta-regression were conducted to evaluate the heterogeneity of the results. RESULTS: Sixty articles reporting the prevalence of sleep disorders in patients with COPD were included, and the prevalence of OSA, RLS, and insomnia reached 29.1 %(95%CI 27.2%-30.9 %), 21.6 %(95%CI 11.8%-33.3 %) and 29.5 %(95%CI 16.9%-44.0 %), respectively. COPD patients with OSA were characterized by male sex (OR 1.631 95 % CI: 1.231-2.161), obesity(kg/m2) (MD 4.435, 95 % CI 3.218-5.652), higher Epworth Sleepiness Scale (MD: 3.741, 95 % CI: 0.655-6.828, p = 0.018), better pulmonary function (MD 5.66, 95 % CI 3.546-7.774) and higher risks of hypertension (OR 1.933 95 % CI 1.382-2.70) and diabetes (OR 1.898 95 % CI 1.264-2.849). COPD patients with RLS were associated with a higher Epworth sleepiness scale (ESS) score (MD 3.444, 95 % CI 1.880-5.008) and a longer COPD duration(year) (MD: 3.656, 95 % CI: 2.209-5.103). COPD patients with insomnia were characterized by female sex(OR 0.556, 95%CI 0.545,0.567, p < 0.001). CONCLUSION: Our study suggests that OSA, RLS and insomnia are common in COPD patients with specific clinical characteristics. Further studies are needed to explore the interactions between COPD and sleep disorders.
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Enfermedad Pulmonar Obstructiva Crónica , Síndrome de las Piernas Inquietas , Apnea Obstructiva del Sueño , Trastornos del Inicio y del Mantenimiento del Sueño , Trastornos del Sueño-Vigilia , Humanos , Masculino , Femenino , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Prevalencia , Somnolencia , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Apnea Obstructiva del Sueño/complicaciones , Apnea Obstructiva del Sueño/epidemiología , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/complicaciones , Síndrome de las Piernas Inquietas/epidemiología , Síndrome de las Piernas Inquietas/complicacionesRESUMEN
BACKGROUND: Endometriosis-related infertility is a common worldwide reproductive health concern. Despite ongoing research, the causes of infertility remain unclear. Evidence suggests that epigenetic regulation is crucial in reproduction. However, the role of N6-methyladenosine (m6A) modification of RNA in endometriosis-related infertility requires further investigation. METHODS: We examined the expression of m6A and methyltransferase-like 3 (METTL3) in endometrial samples taken from normal fertile women in the proliferative phase (the NP group) or the mid-secretory phase (the NS group) or from women with endometriosis-related infertility at the mid-secretory phase (the ES group). We treated primary endometrial stromal cells (ESCs) with medroxyprogesterone acetate and 8-Bromo-cyclic adenosine monophosphate for in vitro decidualization and detected the expression of m6A, METTL3, and decidual markers. We analyzed the expression of m6A, METTL3, and forkhead box O1 (FOXO1) in ESCs from normal fertile women (the ND group) or women with endometriosis-related infertility (the ED group). We also assessed the expression of m6A, METTL3, and decidual markers, as well as the embryo adhesion rate, upon METTL3 overexpression or knockdown. Additionally, we investigated the role of METTL3 in embryo implantation in vivo by applying mice with endometriosis. Furthermore, we performed RNA stability assays, RNA immunoprecipitation (RIP), and methylated RIP assays to explore the mechanisms underlying the regulation of FOXO1 by METTL3-mediated m6A. RESULTS: The expression of m6A and METTL3 was reduced only in the NS group; the NP and ES groups demonstrated increased m6A and METTL3 levels. m6A and METTL3 levels decreased in ESCs with prolonged decidual treatment. Compared to the ND group, m6A and METTL3 levels in the ED group increased after decidual treatment, whereas the expression of FOXO1 decreased. METTL3 overexpression suppressed the expression of decidual markers and embryo implantation in vitro; METTL3 knockdown exhibited the opposite effect. Inhibition of METTL3 promoted embryo implantation in vivo. Furthermore, we observed that METTL3-mediated m6A regulated the degradation of FOXO1 mRNA through YTHDF2, a m6A binding protein. CONCLUSIONS: METTL3-regulated m6A promotes YTHDF2-mediated decay of FOXO1 mRNA, thereby affecting cellular decidualization and embryo implantation. These findings provide novel insights into the development of therapies for women with endometriosis-related infertility.
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Endometriosis , Infertilidad Femenina , Animales , Femenino , Humanos , Ratones , Endometriosis/complicaciones , Endometriosis/genética , Epigénesis Genética , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Metiltransferasas/genética , Metiltransferasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Células del Estroma/metabolismo , Factores de Transcripción/genética , Infertilidad Femenina/metabolismoRESUMEN
Electrocardiogram (ECG) electrodes are important sensors for detecting heart disease whose performance determines the validity and accuracy of the collected original ECG signals. Due to the large drawbacks (e.g., allergy, shelf life) of traditional commercial gel electrodes, textile electrodes receive widespread attention for their excellent comfortability and breathability. This work demonstrated a dry electrode for ECG monitoring fabricated by screen printing silver/silver chloride (Ag/AgCl) conductive ink on ordinary polyester fabric. The results show that the screen-printed textile electrodes have good and stable electrical and electrochemical properties and excellent ECG signal acquisition performance. Furthermore, the resistance of the screen-printed textile electrode is maintained within 0.5 Ω/cm after 5000 bending cycles or 20 washing and drying cycles, exhibiting excellent flexibility and durability. This research provides favorable support for the design and preparation of flexible and wearable electrophysiological sensing platforms.
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The inter-tumor heterogeneity of the tumor microenvironment (TME) and how it correlates with clinical profiles and biological characteristics in brainstem gliomas (BSGs) remain unknown, dampening the development of novel therapeutics against BSGs. The TME status was determined with a list of pan-cancer conserved gene expression signatures using a single-sample gene set enrichment analysis (ssGSEA) and was subsequently clustered via consensus clustering. BSGs exhibited a high inter-tumor TME heterogeneity and were classified into four clusters: "immune-enriched, fibrotic", "immune-enriched, non-fibrotic", "fibrotic", and "depleted". The "fibrotic" cluster had a higher proportion of diffuse intrinsic pontine gliomas (p = 0.041), and "PA-like" tumors were more likely to be "immune-enriched, fibrotic" (p = 0.044). The four TME clusters exhibited distinct overall survival (p < 0.001) and independently impacted BSG outcomes. A four-gene panel as well as a radiomics approach were constructed to identify the TME clusters and achieved high accuracy for determining the classification. Together, BSGs exhibited high inter-tumor heterogeneity in the TME and were classified into four clusters with distinct clinical outcomes and tumor biological properties. The TME classification was accurately identified using a four-gene panel that can potentially be examined with the immunohistochemical method and a non-invasive radiomics method, facilitating its clinical application.
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Recently, convolutional neural networks (CNNs) have been widely applied in brain-computer interface (BCI) based on electroencephalogram (EEG) signals. Due to the subject-specific nature of EEG signal patterns and the multi-dimensionality of EEG features, it is necessary to employ appropriate feature representation methods to enhance the decoding accuracy of EEG. In this study, we proposed a method for representing EEG temporal, frequency, and phase features, aiming to preserve the multi-domain information of EEG signals. Specifically, we generated EEG temporal segments using a sliding window strategy. Then, temporal, frequency, and phase features were extracted from different temporal segments and stacked into 3D feature maps, namely temporal-frequency-phase features (TFPF). Furthermore, we designed a compact 3D-CNN model to extract these multi-domain features efficiently. Considering the inter-individual variability in EEG data, we conducted individual testing for each subject. The proposed model achieved an average accuracy of 89.86, 78.85, and 63.55% for 2-class, 3-class, and 4-class motor imagery (MI) classification tasks, respectively, on the PhysioNet dataset. On the GigaDB dataset, the average accuracy for 2-class MI classification was 91.91%. For the comparison between MI and real movement (ME) tasks, the average accuracy for the 2-class were 87.66 and 80.13% on the PhysioNet and GigaDB datasets, respectively. Overall, the method presented in this paper have obtained good results in MI/ME tasks and have a good application prospect in the development of BCI systems based on MI/ME.
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BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder with complex pathophysiological mechanism. It is reported that even a modest weight loss of 5-10% substantially may improve the reproductive and metabolic profile. This study aims to assess the efficacy of the low dose of liraglutide (0.6 mg QD) combined with metformin (0.85 mg BID) in weight loss in Chinese Han women with PCOS. METHODS: We included clinical data of 102 obese/overweight (≥18 years, body mass index ≥28 kg/m2 or ≥24 kg/m2) women who were diagnosed with PCOS from October 2016 to March 2018 in Wuhan Union Hospital initially. They were treated with dinae-35, low dose of liraglutide (0.6 mg QD) and metformin (0.85 mg BID) for 12 weeks. The demographic and clinical data were retrieved retrospectively, and weight loss was the main outcome measure. Student's paired t-test and Wilcoxon rank sum test were used to compare the differences before and after therapy, p < 0.05 was considered statistically significant. RESULTS: Participants(n = 102)had lost a mean of 7.20 ± 3.42 kg of body weight (95%CI: 6.55-7.86, p < 0.001), and the mean reduction of BMI was 2.87 ± 1.36 kg/m2 (95%CI: 0.02-0.27, p < 0.001). A total of 88.24% of participants lost more than 5% of their body weight. CONCLUSION: The combination of low dose of liraglutide and metformin was associated with significant reduction of body weight in Chinese Han women with PCOS. Additionally, a larger randomized double-blind multicenter controlled clinical trial is needed to confirm that. TRIAL REGISTRATION: The study was registered on http://www.chictr.org.cn as ChiCTR1900024384.
Asunto(s)
Metformina , Síndrome del Ovario Poliquístico , Femenino , Humanos , Peso Corporal , Pueblos del Este de Asia , Hipoglucemiantes/uso terapéutico , Liraglutida/uso terapéutico , Metformina/uso terapéutico , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Estudios Retrospectivos , Pérdida de Peso , AdultoRESUMEN
OBJECT: Pediatric diffuse intrinsic pontine glioma (DIPG) is a radiologically heterogeneous disease entity, here we aim to establish a multimodal imaging-based radiological classification and evaluate the outcome of different treatment strategies under this classification frame. METHODS: This retrospective study included 103 children diagnosed with DIPGs between January 2015 and August 2018 in Beijing Tiantan Hospital (Beijing, China). Multimodal radiological characteristics, including conventional magnetic resonance imaging (MRI), diffuse tensor imaging/diffuse tensor tractography (DTI/DTT), and positron emission tomography (PET) were reviewed to construct the classification. The outcome of different treatment strategies was compared in each DIPG subgroup using Kaplan-Meier method (log-rank test) to determine the optimal treatment for specific DIPGs. RESULTS: Four radiological DIPG types were identified: Type A ("homocentric", n=13), Type B ("ventral", n=41), Type C ("eccentric", n=37), and Type D ("dorsal", n=12). Their treatment modalities were grouped as observation (43.7%), cytoreductive surgery (CRS) plus radiotherapy (RT) (24.3%), RT alone (11.7%), and CRS alone (20.4%). CRS+RT mainly fell into type C (29.7%), followed by type B1 (21.9%) and type D (50%). Overall, CRS+RT exhibited a potential survival advantage compared to RT alone, which was more pronounced in specific type, but this did not reach statistical significance, due to limited sample size and unbalanced distribution. CONCLUSION: We proposed a multimodality imaging-based radiological classification for pediatric DIPG, which was useful for selecting optimal treatment strategies, especially for identifying candidates who may benefit from CRS plus RT. This classification opened a window into image-guided integrated treatment for pediatric DIPG.
Asunto(s)
Neoplasias del Tronco Encefálico , Glioma Pontino Intrínseco Difuso , Glioma , Niño , Humanos , Glioma/diagnóstico por imagen , Glioma/terapia , Estudios Retrospectivos , Neoplasias del Tronco Encefálico/diagnóstico por imagen , Neoplasias del Tronco Encefálico/cirugía , Imagen MultimodalRESUMEN
OBJECTIVES: Studies have suggested contradictory results on the relationship between chronic obstructive pulmonary disease (COPD) and periodontal disease (PD). The aim of this study was to determine whether PD increased the risk of COPD and COPD-related clinical events. DESIGN: A systematic review and meta-analysis. DATA SOURCES: PubMed, Ovid EMBASE and Ovid CENTRAL were searched from inception to 22 February 2023. ELIGIBILITY CRITERIA FOR STUDIES: We included trials and observational studies evaluating association of PD with the risk of COPD or COPD-related events (exacerbation and mortality), with statistical adjustment for smoking. DATA EXTRACTION AND SYNTHESIS: Two investigators independently extracted data from selected studies using a standardised Excel file. Quality of studies was evaluated using the Newcastle-Ottawa Scale. OR with 95% CI was pooled in a random-effect model with inverse variance method. RESULTS: 22 observational studies with 51 704 participants were included. Pooled analysis of 18 studies suggested that PD was weakly associated with the risk of COPD (OR: 1.20, 95% CI 1.09 to 1.32). However, in stratified and subgroup analyses, with strict adjustment for smoking, PD no longer related to the risk of COPD (adjusting for smoking intensity: OR: 1.14, 95% CI 0.86 to 1.51; smokers only: OR: 1.46, 95% CI 0.92 to 2.31; never smokers only: OR: 0.93, 95% CI 0.72 to 1.21). Moreover, PD did not increase the risk of COPD-related exacerbation or mortality (OR: 1.18, 95% CI 0.71 to 1.97) in the pooled result of four studies. CONCLUSIONS: This study demonstrates PD confers no risk for COPD and COPD-related events when strictly adjusted by smoking. Large-scale prospective cohort studies with control of potential confounding factors are warranted to validate the present findings.