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OBJECTIVES: To explore the relationship between adverse childhood experiences and falls in older adults, and the mediating effects of depression on such associations. METHODS: This is a prospective study used survey data from the China Health and Retirement Longitudinal Study. Twelve expanded ACEs obtained from the 2014 Life History Survey. Depression levels were assessed using the Centre for Epidemiologic Studies Depression Scale-10. Self-reported outcomes of falling evaluated based on "Have you fallen down since the last survey?" and "How many times have you fallen down seriously enough to need medical treatment?" Logistic regression models were used to explore the relationship between ACEs with falls and recurrent falls. Poisson regression models were used to explore the relationship between ACEs and number of severe falls. Besides, mediation analysis was used to explore whether depression mediates the relationship between ACEs and falls in older adults. RESULTS: The more adverse childhood experiences experienced, the higher the risk of fall and recurrent falls, and the more severe the falls. Additionally, depression partially mediated the relationship between adverse childhood experiences and falls. Besides, middle-aged individuals were more susceptible to the impact of adverse childhood experiences on falls than older individuals, especially males. CONCLUSIONS: Exposure to adverse childhood experiences is associated with falls in older adults, and depression partially mediates this association. Middle-aged adults were more susceptible to the impact of adverse childhood experiences on falls. These offer important information for clinical practice and public health interventions to prevent falls and reduce fall-related injuries among older adults.
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Chordoma is a rare bone cancer with variable clinical outcomes. Here, we recruited 184 sporadic chordoma patients from the US and Canada and collected their clinical and treatment data. The average age at diagnosis was 45.5 years (Range 5-78) and the chordoma site distribution was 49.2% clivus, 26.2% spinal, and 24.0% sacral. Most patients (97.5%) received surgery as the primary treatment, among whom 85.3% also received additional treatment. Except for the most prevalent cancers like prostate, lung, breast, and skin cancer, there was no discernible enrichment for any specific cancer type among patients or their family members. Among a subset of patients (N = 70) with tumor materials, we conducted omics analyses and obtained targeted panel sequencing and SNP array genotyping data for 51 and 49 patients, respectively. The most recurrent somatic driver mutations included PIK3CA (12%), followed by chromatin remodeling genes PBRM1 and SETD2. Amplification of the 6q27 region, containing the chordoma susceptibility gene TBXT, was detected in eight patients (16.3%). Clival patients appeared to be less likely to carry driver gene mutations, chromosome arm level deletion events (e.g., 5p, 5p, and 9p), or 6q27 amplification compared to sacral patients. After adjusting for age, sex, tumor site, and additional treatment, patients with somatic deletions of 14q (OR = 13.73, 95% CI 1.96-96.02, P = 0.008) and 18p (OR = 13.68, 95% CI 1.77-105.89, P = 0.012) were more likely to have persistent chordoma. The study highlights genomic heterogeneity in chordoma, potentially linked to location and clinical progression.
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Cordoma , Humanos , Cordoma/genética , Cordoma/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Adolescente , Adulto Joven , Niño , Preescolar , Proteínas de Unión al ADN/genética , Mutación , Fosfatidilinositol 3-Quinasa Clase I/genética , Proteínas de Dominio T Box/genética , Factores de Transcripción/genética , Proteínas Nucleares/genética , Neoplasias de la Base del Cráneo/genética , Neoplasias de la Base del Cráneo/patología , Neoplasias de la Columna Vertebral/genética , Neoplasias de la Columna Vertebral/patología , Canadá , Polimorfismo de Nucleótido Simple , Proteínas Fetales , N-Metiltransferasa de Histona-LisinaRESUMEN
ABSTRACT: Interpreting genes of interest is essential for identifying molecular mechanisms, but acquiring such information typically involves tedious manual retrieval. To streamline this process, the fanyi package offers tools to retrieve gene information from sources like National Center for Biotechnology Information (NCBI), significantly enhancing accessibility. Additionally, understanding the latest research advancements and sharing achievements are crucial for junior researchers. However, language barriers often restrict knowledge absorption and career development. To address these challenges, we developed the fanyi package, which leverages artificial intelligence (AI)-driven online translation services to accurately translate among multiple languages. This dual functionality allows researchers to quickly capture and comprehend information, promotes a multilingual environment, and fosters innovation in academic community. Meanwhile, the translation functions are versatile and applicable beyond biomedicine research to other domains as well. The fanyi package is freely available at https://github.com/YuLab-SMU/fanyi .
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Inteligencia Artificial , Humanos , Barreras de Comunicación , LenguajeRESUMEN
PURPOSE: The transverse relaxation time T 2 $$ {}_2 $$ holds significant relevance in clinical applications and research studies. Conventional T 2 $$ {}_2 $$ mapping approaches rely on spin-echo sequences, which require lengthy acquisition times and involve high radiofrequency (RF) power deposition. An alternative gradient echo (GRE) phase-based T 2 $$ {}_2 $$ mapping method, utilizing steady-state acquisitions at one small RF spoil phase increment, was recently demonstrated. Here, a modified magnitude- and phase-based T 2 $$ {}_2 $$ mapping approach is proposed, which improves T 2 $$ {\mathrm{T}}_2 $$ estimations by simultaneous fitting of T 1 $$ {\mathrm{T}}_1 $$ and signal amplitude ( A â P D $$ A\propto PD $$ ) at three or more RF spoiling phase increments, instead of assuming a fixed T 1 $$ {\mathrm{T}}_1 $$ value. METHODS: The feasibility of the magnitude-phase-based method was assessed by simulations, in phantom and in vivo experiments using skipped-CAIPI three-dimensional-echo-planar imaging (3D-EPI) for rapid GRE imaging. T 2 $$ {\mathrm{T}}_2 $$ , T 1 $$ {\mathrm{T}}_1 $$ and PD estimations obtained by our method were compared to T 2 $$ {\mathrm{T}}_2 $$ of the phase-based method and T 1 $$ {\mathrm{T}}_1 $$ and PD of spoiled GRE-based multi-parameter mapping using a multi-echo version of the same sequence. RESULTS: The agreement of the proposed T 2 $$ {\mathrm{T}}_2 $$ with ground truth and reference T 2 $$ {\mathrm{T}}_2 $$ values was higher than that of phase-based T 2 $$ {\mathrm{T}}_2 $$ in simulations and in phantom data. While phase-based T 2 $$ {\mathrm{T}}_2 $$ overestimation increases with actual T 2 $$ {\mathrm{T}}_2 $$ and T 1 $$ {\mathrm{T}}_1 $$ , the proposed method is accurate over a large range of physiologically meaningful T 2 $$ {\mathrm{T}}_2 $$ and T 1 $$ {\mathrm{T}}_1 $$ values. At the same time, precision is improved. In vivo results were in line with these observations. CONCLUSION: Accurate magnitude-phase-based T 2 $$ {}_2 $$ mapping is feasible in less than 5 min scan time for 1 mm nominal isotropic whole-head coverage at 3T and 7T.
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OBJECTIVE: Osteosarcopenia adversely affects the quality of life and physical health of older adults. We sought to explore the association between dietary patterns and osteosarcopenia in community-dwelling older adults. METHODS: This is a cross-sectional study from Northeast China, in which, we included older community adults aged 60 and above. Through face-to-face interviews, we collected dietary information from participants using a food frequency questionnaire. Subsequently, principal component analysis (PCA) was used to obtain the dietary patterns of the participants. Through physical examination, we obtained the participants' information on osteosarcopenia, which was defined by the coexist of osteopenia and sarcopenia. We analysed the association between dietary patterns and dietary compositions with ostesarcopenia. RESULTS: In this study, a total of 9429 participants were included, and the prevalence of osteosarcopenia in community-dwelling older adults was 6.2%. PCA identified three main dietary patterns, and the lacto-ovo-vegetarian dietary pattern was inversely associated with osteosarcopenia. Compared to the lowest lacto-ovo-vegetarian quartile (Q1), the Q4 group (OR = 0.64, 95% CI:0.49-0.83) was inversely associated with osteosarcopenia. Through the weighted quantile sum regression model, we also found that the overall effect of the lacto-ovo-vegetarian dietary components was inversely associated with osteosarcopenia (OR = 0.58, 95% CI: 0.37-0.92); the largest contributors were vegetables, fresh milk, eggs, and dairy products. CONCLUSION: Overall, we found that a lacto-ovo-vegetarian dietary pattern, particularly the consumption of vegetables, fresh milk, eggs, and dairy products, was inversely associated with osteosarcopenia in older adults. And this might provide new insights for the prevention and treatment of osteosarcopenia.
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Dieta Vegetariana , Calidad de Vida , Humanos , Anciano , Estudios Transversales , Dieta/efectos adversos , VerdurasRESUMEN
OBJECTIVES: To examine the relationships between adverse childhood experiences (ACEs) and developing sarcopenia in older adults and the modifying effects of active social participation. METHODS: This prospective cohort study used survey data from the China Health and Retirement Longitudinal Study, including baseline surveys from 2011, follow-up data from 2013, follow-up data from 2015, and information on ACEs from the 2014 Life History Survey. Information concerning 10 ACEs, including five threat-related ACEs and five deprivation-related ACEs before 17 years of age was obtained by questionnaires through face-to-face interviews. Sarcopenia status was assessed according to the Asian Working Group for Sarcopenia 2019 algorithm, consisted of low muscle mass, and low muscle strength, or poor physical performance. The relationship between ACEs, social participation, and sarcopenia was evaluated using Cox proportional hazard regression models. RESULTS: The study population comprised 6859 older adults in main analyses. Having experienced ≥ 3 ACEs led to an increased 31% risk of developing sarcopenia (hazard ratio [HR]:1.31, 95% confidence interval [CI]:1.10-1.56). Participants having experienced ≥ 2 threat-related ACEs (HR:1.22, 95%CI:1.04-1.43) or deprivation-related ACEs (HR:1.22, 95%CI:1.02-1.46) had a 22% higher risk of developing sarcopenia. Active social participation significantly modified the association between ACEs (p < 0.05), especially threat-related ACEs (p < 0.05), and sarcopenia. CONCLUSIONS: ACEs were associated with the development of sarcopenia; however, social participation had a modifying effect. These findings provide insights for early identification of vulnerable groups, advance intervention timing, and highlight the benefits of promoting active social participation among individuals with sarcopenia who have experienced ACEs.
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Experiencias Adversas de la Infancia , Sarcopenia , Humanos , Anciano , Estudios de Cohortes , Sarcopenia/epidemiología , Estudios Longitudinales , Estudios Prospectivos , Participación SocialRESUMEN
BACKGROUND: Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined. METHODS: High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter. In vivo 2-photon imaging, behavioral tests, immunofluorescence, transmission electron microscopy, Western blot analysis, vascular leakage assay, and single-cell RNA sequencing were performed to clarify the phenotype and elucidate the molecular mechanism. RESULTS: Monocytes expressed high-level CTSD in patients with type 2 diabetes. The transgenic mice expressing human CTSD in the monocytes showed increased brain microvascular permeability resembling the diabetic microvascular phenotype, accompanied by cognitive deficit. Mechanistically, the monocytes release nonenzymatic pro-CTSD to upregulate caveolin expression in brain endothelium triggering caveolae-mediated transcytosis, without affecting the paracellular route of brain microvasculature. The circulating pro-CTSD activated the caveolae-mediated transcytosis in brain endothelial cells via its binding with low-density LRP1 (lipoprotein receptor-related protein 1). Importantly, genetic ablation of CTSD in the monocytes exhibited a protective effect against the diabetes-enhanced brain microvascular transcytosis and the diabetes-induced cognitive impairment. CONCLUSIONS: These findings uncover the novel role of circulatory pro-CTSD from monocytes in the pathogenesis of cerebral microvascular lesions in diabetes. The circulatory pro-CTSD is a potential target for the intervention of microvascular complications in diabetes.
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Catepsina D , Diabetes Mellitus Tipo 2 , Monocitos , Animales , Humanos , Ratones , Encéfalo/metabolismo , Catepsina D/metabolismo , Catepsina D/farmacología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Células Endoteliales/metabolismo , Endotelio Vascular/metabolismo , Precursores Enzimáticos , Ratones Transgénicos , Monocitos/metabolismo , Transcitosis/fisiologíaRESUMEN
Primary cilia are distributed extensively within the corneal epithelium and endothelium. However, the presence of cilia in the corneal stroma and the dynamic changes and roles of endothelial and stromal cilia in corneal homeostasis remain largely unknown. Here, we present compelling evidence for the presence of primary cilia in the corneal stroma, both in vivo and in vitro. We also demonstrate dynamic changes of both endothelial and stromal cilia during corneal development. In addition, our data show that cryoinjury triggers dramatic cilium formation in the corneal endothelium and stroma. Furthermore, depletion of cilia in mutant mice lacking intraflagellar transport protein 88 compromises the corneal endothelial capacity to establish the effective tissue barrier, leading to an upregulation of α-smooth muscle actin within the corneal stroma in response to cryoinjury. These observations underscore the essential involvement of corneal endothelial and stromal cilia in maintaining corneal homeostasis and provide an innovative strategy for the treatment of corneal injuries and diseases.
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Cilios , Sustancia Propia , Endotelio Corneal , Homeostasis , Animales , Ratones , Actinas/metabolismo , Cilios/metabolismo , Lesiones de la Cornea/metabolismo , Lesiones de la Cornea/patología , Lesiones de la Cornea/terapia , Sustancia Propia/citología , Sustancia Propia/crecimiento & desarrollo , Sustancia Propia/metabolismo , Endotelio Corneal/citología , Endotelio Corneal/crecimiento & desarrollo , Endotelio Corneal/metabolismo , Homeostasis/fisiología , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Supresoras de Tumor/genética , Ciliopatías/metabolismo , Ciliopatías/patología , Ciliopatías/terapiaRESUMEN
Objective: The study aimed to explore the association between the site of interictal epileptic discharges (IEDs) on postoperative electroencephalogram (EEG) and seizure recurrence after antiepileptic drug (AED) withdrawal. The study hypothesizes that the concordance of IED sites with surgical sites indicates incomplete resection of epileptic focus, while non-concordance of IED sites with surgical sites indicates postoperative changes or cortical stimulation. The former has a higher risk of seizure recurrence. Methods: We retrospectively analyzed the postoperative EEG pattern of 182 consecutive children who underwent resection surgery. To identify the risk factors for seizure recurrence, we compared the attributes of seizure recurred and seizure-free groups by univariate and multivariate analyses. AED tapering was standardized, involving a 25% reduction in the dose of a single type of AED every 2 weeks, independent of the presurgical AED load. Results: We attempted AED withdrawal in 116 (63.7%) children. Twenty-eight (24.1%) children experienced seizure recurrence during or after AED withdrawal. A greater number of AEDs used at the time of surgery (p=0.005), incomplete resection (p=0.001), and presence of IED on postoperative EEG (p=0.011) are predictors of seizure recurrence. The completeness of resection and seizure recurrence after AED withdrawal were related to the presence of IED on the EEG, but not to the concordance of IED with surgical sites. Conclusion: For children with abnormal EEG, the decision to discontinue AED should be made more cautiously, regardless of the relative location of the discharge site and the surgical site.
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OBJECTIVE: People with epilepsy desire to acquire accurate information about epilepsy and actively engage in its management throughout the long journey of living with seizures. ChatGPT is a large language model and we aimed to assess the accuracy and consistency of ChatGPT in responding to the common concerns of people with epilepsy and to evaluate its ability to provide emotional support. METHODS: Questions were collected from the International League against Epilepsy and the China Association against Epilepsy. The responses were independently assessed by two board-certified epileptologists from the China Association against Epilepsy, and a third reviewer resolved disagreements. The reviewers assessed its ability to provide emotional support subjectively. RESULTS: A total of 378 questions related to epilepsy and 5 questions related to emotional support were included. ChatGPT provided "correct and comprehensive" answers to 68.4% of the questions. The model provided reproducible answers for 82.3% questions. The model performed poorly in answering prognostic questions, with only 46.8% of the answers rated as comprehensive. When faced with questions requiring emotional support, the model can generate natural and understandable responses. SIGNIFICANCE: ChatGPT provides accurate and reliable answers to patients with epilepsy and is a valuable source of information. It also provides partial emotional support, potentially assisting those experiencing emotional distress. However, ChatGPT may provide incorrect responses, leading users to inadvertently accept incorrect and potentially dangerous advice. Therefore, the direct use of ChatGPT for medical guidance is not recommended and its primary use at present is in patients education.
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Epilepsia , Humanos , Epilepsia/terapia , Convulsiones , Certificación , China , LenguajeRESUMEN
Gut microbiota, widely populating the mammalian gastrointestinal tract, plays an important role in regulating diverse pathophysiological processes by producing bioactive molecules. Extensive detection of these molecules contributes to probing microbiota function but is limited by insufficient identification of existing analytical methods. In this study, a systematic strategy was proposed to detect and annotate gut microbiota-related metabolites on a large scale. A pentafluorophenyl (PFP) column-based liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method was first developed for high-coverage analysis of gut microbiota-related metabolites, which was verified to be stable and robust with a wide linearity range, high sensitivity, satisfactory recovery, and repeatability. Then, an informative database integrating 968 knowledge-based microbiota-related metabolites and 282 sample-sourced ones defined by germ-free (GF)/antibiotic-treated (ABX) models was constructed and subsequently used for targeted extraction and annotation in biological samples. Using pooled feces, plasma, and urine of mice for demonstration application, 672 microbiota-related metabolites were annotated, including 21% neglected by routine nontargeted peak detection. This strategy serves as a useful tool for the comprehensive capture of the intestinal flora metabolome, contributing to our deeper understanding of microbe-host interactions.
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Microbioma Gastrointestinal , Metabolómica , Ratones , Animales , Metabolómica/métodos , Metaboloma , Espectrometría de Masas/métodos , Cromatografía Liquida/métodos , MamíferosRESUMEN
Cardiac fibrosis is associated with aging, for which no targeted therapies are available. With aging, the levels of nerve growth factor-induced gene B (Nur77) are reduced during cardiac remodelling; however, its role in cardiac fibrosis in aging remains unclear. Here, we found that Nur77 knockout increased cardiac structure abnormalities, systolic and diastolic dysfunction, cardiac hypertrophy, and fibrotic marker expression in 15-month-old mice. Furthermore, Nur77 deficiency induced collagen type I (Col-1) and α-smooth muscle actin overproduction in transforming growth factor beta (TGF-ß) treated H9c2 cells, whereas Nur77 overexpression attenuated this effect. Nur77 deficiency in vivo and in vitro downregulated glycogen synthase kinase (GSK)-3ß expression and increased ß-catenin activity, while its overexpression increased GSK-3ß expression. GSK-3ß knockdown counteracted the anti-fibrotic effect of Nur77 on TGF-ß-treated H9c2 cells. Chromatin immunoprecipitation and luciferase reporter assay results suggested GSK-3ß as the direct target of Nur77. Our findings suggest that Nur77 directly initiates GSK-3ß transcription and age-related cardiac fibrosis partly through the GSK-3ß/ß-catenin pathway. This study proposes a novel mechanism for Nur77 regulating cardiac fibrosis and suggests Nur77 as a target for the prevention and treatment of aging-associated cardiac fibrosis and heart failure.
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Corazón , beta Catenina , Animales , Ratones , beta Catenina/metabolismo , Fibrosis , Glucógeno Sintasa Quinasa 3 beta , Factor de Crecimiento Transformador betaRESUMEN
As the most prevalent chronic liver disease globally, NAFLD encompasses a pathological process that ranges from simple steatosis to NASH, fibrosis, cirrhosis, and HCC, closely associated with numerous extrahepatic diseases. While the initial etiology was believed to be hepatocyte injury caused by lipid toxicity from accumulated triglycerides, recent studies suggest that an imbalance of cholesterol homeostasis is of greater significance. The role of nuclear receptors in regulating liver cholesterol homeostasis has been demonstrated to be crucial. This review summarizes the roles and regulatory mechanisms of nuclear receptors in the 3 main aspects of cholesterol production, excretion, and storage in the liver, as well as their cross talk in reverse cholesterol transport. It is hoped that this review will offer new insights and theoretical foundations for the study of the pathogenesis and progression of NAFLD and provide new research directions for extrahepatic diseases associated with NAFLD.