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BACKGROUND AND PURPOSE: Unawareness of the risk factors is one of the most important issues that need to be settled for stroke prevention. We aimed to evaluate the awareness of risk factors for cerebrovascular diseases (CVDs) among acute ischemic stroke patients and to investigate the characteristics of patients who were unaware of their risk factors in Shenzhen, China. METHODS: Registered data on awareness of CVD risk factors of patients with confirmed acute ischemic stroke (AIS) from June 2020 to December 2022 were analyzed in May 2023. The data were extracted from the database of Shenzhen Quality Control Center for Management of Cerebrovascular Diseases. RESULTS: Totally, there were 5147 AIS patients with complete data eligible for this study. AIS patients' awareness regarding existing hypertension, diabetes, dyslipidemia, and atrial fibrillation (AF) was 76.1%, 76.2%, 24.2%, and 53.4%, respectively. Patients who were lack of awareness of the CVD risk factors were more likely to be males, individuals with younger ages, and those without medical insurance or a CVD history. CONCLUSIONS: The overall awareness of the CVD risk factors was suboptimal among AIS patients in Shenzhen, especially for the existing dyslipidemia. The health education of AIS should be further improved in males as well as individuals without medical insurance or any CVD histories. Age was an independent factor associated with the lack of awareness of the CVD risk factors. The stroke screening program should be extended to younger people.
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Cardiovascular disease remains the leading cause of mortality on a global scale. Individuals who possess risk factors for cardiovascular disease, such as high blood pressure (BP) and obesity, face an elevated risk of experiencing organ-specific pathophysiological changes. This damage includes pathophysiological changes in the heart and peripheral vascular systems, such as ventricular hypertrophy, arterial stiffening, and vascular narrowing and stenosis. Consequently, these damages are associated with an increased risk of developing severe cardiovascular outcomes including stroke, myocardial infarction, heart failure, and coronary heart disease. Among all the risk factors associated with cardiovascular disease, high blood pressure emerges as the most prominent. However, conventional resting BP measurement methods such as auscultatory or oscillometric methods may fail to identify many individuals with asymptomatic high BP. Recently, exercise BP has emerged as a valuable diagnostic tool for identifying real (high) blood pressure levels and assessing underlying cardiovascular risk, in addition to resting BP measurements in adults. Furthermore, numerous established factors, such as low cardiorespiratory fitness and high body fatness, have been confirmed to contribute to exercise BP and the associated cardiovascular risk. Modifying these factors may help reduce high exercise BP and, consequently, alleviate the burden of cardiovascular disease. A significant body of evidence has demonstrated cardiovascular disease in later life have their origins in early life. Children and adolescents with these cardiovascular risk factors also possess a greater propensity to develop cardiovascular diseases later in life. Nevertheless, the majority of previous studies on the clinical utility of exercise BP have been conducted in middle-to-older aged populations, often with pre-existing clinical conditions. Therefore, there is a need to investigate further of the factors influencing exercise BP in adolescence and its association with cardiovascular risk in early life. Our previously published work showed that exercise BP is a potential useful method to detect adolescents with increased cardiovascular risk. Children and adolescents with cardiovascular risk factors are more likely to develop cardiovascular diseases later in life. However, previous studies on the clinical utility of exercise BP have largely focused on middle-to-older aged populations with pre-existing clinical conditions. Therefore, there is a need to investigate further the factors influencing exercise BP in adolescence and its association with future cardiovascular risk. Our previous studies, which focused on exercise BP measured at submaximal intensity, have shown that exercise BP is a potentially useful method for identifying adolescents at increased cardiovascular risk. Our previous findings suggest that improving cardio-respiratory fitness and reducing body fatness may help to reduce the risk of developing cardiovascular disease and improve overall cardiovascular health. These findings have important implications for the development of effective prevention and early detection strategies, which can contribute to improved public health outcomes.
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Pressão Sanguínea , Aptidão Cardiorrespiratória , Doenças Cardiovasculares , Exercício Físico , Humanos , Criança , Adolescente , Aptidão Cardiorrespiratória/fisiologia , Pressão Sanguínea/fisiologia , Fatores de Risco , Masculino , Fatores de Risco de Doenças Cardíacas , FemininoRESUMO
As the resident immune cells in the central nervous system, microglia exhibit a 'sensitized' or 'primed' phenotype with dystrophic morphology and dysregulated functions in aged brains. Although studies have demonstrated the inflammatory profile of aged microglia in several neurological diseases, this issue is largely uncertain in stroke. Consequently, this study investigated the effects of primed and repopulated microglia on post-ischemic brain injury in aged mice. We replaced primed microglia with newly repopulated microglia through pharmacological administration and withdrawal of the colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX3397. Further, we performed a series of behavioral tests and flow cytometry in mouse models of middle cerebral artery occlusion (MCAO) to study the effects of microglial replacement on ischemic injury in the aged brain. With depletion and subsequent repopulation of microglia in MCAO mice, microglial replacement in aged mice improved neurological function and decreased brain infarction. This protective effect was accompanied by the reduction of peripheral immune cells infiltrating into brains. We showed that the repopulated microglia expressed elevated neuroprotective factors (including Cluster of Differentiation 206, transforming growth factor-ß, and interleukin-10) and diminished expression of inflammatory markers (including Cluster of Differentiation 86, interleukin-6, and tumor necrosis factor α). Moreover, microglial replacement protected the blood-brain barrier and relieved neuronal death in aged mice subjected to 60 min of MCAO. These results imply that the replacement of microglia in the aged brain may alleviate brain damage and neuroinflammation, and therefore, ischemic brain damage. Thus, targeting microglia could be a promising therapeutic strategy for ischemic stroke.
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Envelhecimento , Infarto da Artéria Cerebral Média , Camundongos Endogâmicos C57BL , Microglia , Doenças Neuroinflamatórias , Fármacos Neuroprotetores , Animais , Microglia/efeitos dos fármacos , Microglia/imunologia , Masculino , Camundongos , Infarto da Artéria Cerebral Média/imunologia , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/patologia , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Pirróis/farmacologia , Pirróis/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Encéfalo/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Modelos Animais de Doenças , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Barreira Hematoencefálica/efeitos dos fármacosRESUMO
Background: In the field of medical imaging, the rapid rise of convolutional neural networks (CNNs) has presented significant opportunities for conserving healthcare resources. However, with the wide spread application of CNNs, several challenges have emerged, such as enormous data annotation costs, difficulties in ensuring user privacy and security, weak model interpretability, and the consumption of substantial computational resources. The fundamental challenge lies in optimizing and seamlessly integrating CNN technology to enhance the precision and efficiency of medical diagnosis. Methods: This study sought to provide a comprehensive bibliometric overview of current research on the application of CNNs in medical imaging. Initially, bibliometric methods were used to calculate the frequency statistics, and perform the cluster analysis and the co-citation analysis of countries, institutions, authors, keywords, and references. Subsequently, the latent Dirichlet allocation (LDA) method was employed for the topic modeling of the literature. Next, an in-depth analysis of the topics was conducted, and the topics in the medical field, technical aspects, and trends in topic evolution were summarized. Finally, by integrating the bibliometrics and LDA results, the developmental trajectory, milestones, and future directions in this field were outlined. Results: A data set containing 6,310 articles in this field published from January 2013 to December 2023 was complied. With a total of 55,538 articles, the United States led in terms of the citation count, while in terms of the publication volume, China led with 2,385 articles. Harvard University emerged as the most influential institution, boasting an average of 69.92 citations per article. Within the realm of CNNs, residual neural network (ResNet) and U-Net stood out, receiving 1,602 and 1,419 citations, respectively, which highlights the significant attention these models have received. The impact of coronavirus disease 2019 (COVID-19) was unmistakable, as reflected by the publication of 597 articles, making it a focal point of research. Additionally, among various disease topics, with 290 articles, brain-related research was the most prevalent. Computed tomography (CT) imaging dominated the research landscape, representing 73% of the 30 different topics. Conclusions: Over the past 11 years, CNN-related research in medical imaging has grown exponentially. The findings of the present study provide insights into the field's status and research hotspots. In addition, this article meticulously chronicled the development of CNNs and highlighted key milestones, starting with LeNet in 1989, followed by a challenging 20-year exploration period, and culminating in the breakthrough moment with AlexNet in 2012. Finally, this article explored recent advancements in CNN technology, including semi-supervised learning, efficient learning, trustworthy artificial intelligence (AI), and federated learning methods, and also addressed challenges related to data annotation costs, diagnostic efficiency, model performance, and data privacy.
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BACKGROUND: Pre-hospital delay in China is a serious issue with unclear relevant reasons, seriously impeding the adoption of appropriate measures. Herein, we analyzed the onset-to-door time (ODT) in Chinese patients with acute ischemic stroke (AIS) and its influencing factors. METHODS: We prospectively recruited 3,459 patients with AIS from nine representative tertiary general hospitals in China between January and June 2022. Patients were divided into ODT ≤ 3 h and ODT > 3 h groups. Following single-factor analysis, binary logistic regression analysis was performed to evaluate the risk factors leading to pre-hospital delay. RESULTS: In total, 763 (21.83%) patients arrived at the hospital within 3 h of onset. After adjusting for confounding factors, the risk factors for ODT were residence in rural areas (odds ratio [OR]: 1.478, 95% credibility interval [CI]: 1.024-2.146) and hospital transfer (OR: 7.479, 95% CI: 2.548-32.337). The protective factors for ODT were location of onset ≤ 20 km from the first-visit hospital (OR: 0.355, 95% CI: 0.236-0.530), transportation by emergency medical services (OR: 0.346, 95% CI: 0.216-0.555), history of atrial fibrillation (OR: 0.375, 95% CI: 0.207-0.679), moderate stroke (OR: 0.644, 95% CI: 0.462-0.901), and severe stroke (OR: 0.506, 95% CI: 0.285-0.908). CONCLUSIONS: Most patients with AIS fail to reach a hospital within the critical 3-h window. The following measures are recommended to reduce pre-hospital delays: reasonable distribution of hospitals accessible to nearby residents, minimizing interhospital transfer, paying attention to patients with mild stroke, and encouraging patients to use ambulance services. Pre-hospital delays for patients can be reduced by implementing these measures, ultimately improving the timeliness of treatment and enhancing patient prognosis. This study was carried out amid the COVID-19 pandemic, which presented challenges and constraints.
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COVID-19 , AVC Isquêmico , Tempo para o Tratamento , Humanos , COVID-19/epidemiologia , Feminino , Masculino , China/epidemiologia , Estudos Prospectivos , AVC Isquêmico/epidemiologia , AVC Isquêmico/terapia , Idoso , Pessoa de Meia-Idade , Tempo para o Tratamento/estatística & dados numéricos , Fatores de Risco , SARS-CoV-2 , Idoso de 80 Anos ou mais , População do Leste AsiáticoRESUMO
BACKGROUND: Irregular sleep patterns have been associated with inflammation. Galectin-3, a novel biomarker, plays an important role in inflammation. We investigated the relationship between sleep patterns and galectin-3 in a Chinese population. METHODS: A total of 1,058 participants from the Shenzhen-Hong Kong United Network on Cardiovascular Disease study were included in the analysis. Age and sex-adjusted linear regression models were employed to investigate the relationship between galectin-3 level and traditional metabolic biomarkers. Logistic regression models were used to estimate the association among sleep disturbance, nighttime sleep duration, and daytime napping duration and elevated galectin-3, with elevated galectin-3 defined as galectin-3 level > 65.1 ng/ml. RESULTS: Of study participants, the mean age was 45.3 years and 54.3% were women. Waist circumference, natural logarithm (ln)-transformed triglyceride, and ln-transformed high sensitivity C-reactive protein were positively associated with galectin-3 level (age and sex-adjusted standardized ß [95% confidence interval (CI)], 0.12 [0.04, 0.21], 0.11 [0.05, 0.17], and 0.08 [0.02, 0.14], respectively). Sleep disturbance was associated with elevated galectin-3 (odds ratio [95% CI], 1.68 [1.05, 2.68], compared to those without sleep disturbance) after adjusting for traditional metabolic biomarkers. No interaction was observed between galectin-3 and age, sex, obesity, hypertension, and diabetes on sleep disturbance. No association was found between nighttime sleep duration or daytime napping duration and elevated galectin-3. CONCLUSIONS: Our study provides evidence of a significant association between sleep disturbance and elevated galectin-3 level, independent of traditional metabolic biomarkers. Screening and interventions on galectin-3 could assist in preventing sleep disturbance-induced inflammatory disease.
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Biomarcadores , Galectina 3 , Transtornos do Sono-Vigília , Sono , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Galectina 3/sangue , Biomarcadores/sangue , Adulto , Sono/fisiologia , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/sangue , China/epidemiologia , Hong Kong/epidemiologia , População do Leste AsiáticoRESUMO
Noninvasive and effortless diagnosis of Alzheimer's disease (AD) remains challenging. Here we report the multiplexed profiling of extracellular vesicle (EV) surface proteins at the single EV level in five types of easily accessible body fluids using a proximity barcoding assay (PBA). A total of 183 surface proteins were detected on the EVs from body fluids collected from APP/PS1 transgenic mice and patients with AD. The AD-associated differentially expressed EV proteins could discriminate between the control and AD/AD model samples with high accuracy. Based on machine learning predictive models, urinary EV proteins exhibited the highest diagnostic potential compared to those on other biofluid EVs, both in mice and humans. Single EV analysis further revealed AD-associated EV subpopulations in the tested body fluids, and a urinary EV subpopulation with the signature proteins PLAU, ITGAX and ANXA1 could diagnose patients with AD in blinded datasets with 88% accuracy. Our results suggest that EVs and their subpopulations from noninvasive body fluids, particularly urine, are potential diagnostic biomarkers for AD.
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Doença de Alzheimer , Líquidos Corporais , Vesículas Extracelulares , Humanos , Camundongos , Animais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/metabolismo , Vesículas Extracelulares/metabolismo , Biomarcadores/metabolismo , Camundongos Transgênicos , Proteínas de Membrana/metabolismo , Líquidos Corporais/metabolismoRESUMO
BACKGROUND: The hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN1) is predominantly located in key regions associated with epilepsy, such as the neocortex and hippocampus. Under normal physiological conditions, HCN1 plays a crucial role in the excitatory and inhibitory regulation of neuronal networks. In temporal lobe epilepsy, the expression of HCN1 is decreased in the hippocampi of both animal models and patients. However, whether HCN1 expression changes during epileptogenesis preceding spontaneous seizures remains unclear. OBJECTIVE: The aim of this study was to determine whether the expression of HCN1 is altered during the epileptic prodromal phase, thereby providing evidence for its role in epileptogenesis. METHODS: We utilized a cobalt wire-induced rat epilepsy model to observe changes in HCN1 during epileptogenesis and epilepsy. Additionally, we also compared HCN1 alterations in epileptogenic tissues between cobalt wire- and pilocarpine-induced epilepsy rat models. Long-term video EEG recordings were used to confirm seizures development. Transcriptional changes, translation, and distribution of HCN1 were assessed using high-throughput transcriptome sequencing, total protein extraction, membrane and cytoplasmic protein fractionation, western blotting, immunohistochemistry, and immunofluorescence techniques. RESULTS: In the cobalt wire-induced rat epilepsy model during the epileptogenesis phase, total HCN1 mRNA and protein levels were downregulated. Specifically, the membrane expression of HCN1 was decreased, whereas cytoplasmic HCN1 expression showed no significant change. The distribution of HCN1 in the distal dendrites of neurons decreased. During the epilepsy period, similar HCN1 alterations were observed in the neocortex of rats with cobalt wire-induced epilepsy and hippocampus of rats with lithium pilocarpine-induced epilepsy, including downregulation of mRNA levels, decreased total protein expression, decreased membrane expression, and decreased distal dendrite expression. CONCLUSIONS: Alterations in HCN1 expression and distribution are involved in epileptogenesis beyond their association with seizure occurrence. Similarities in HCN1 alterations observed in epileptogenesis-related tissues from different models suggest a shared pathophysiological pathway in epileptogenesis involving HCN1 dysregulation. Therefore, the upregulation of HCN1 expression in neurons, maintenance of the HCN1 membrane, and distal dendrite distribution in neurons may represent promising disease-modifying strategies in epilepsy.
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Modelos Animais de Doenças , Epilepsia , Hipocampo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização , Canais de Potássio , Ratos Sprague-Dawley , Animais , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/metabolismo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Masculino , Epilepsia/metabolismo , Epilepsia/induzido quimicamente , Epilepsia/genética , Epilepsia/fisiopatologia , Ratos , Hipocampo/metabolismo , Canais de Potássio/metabolismo , Canais de Potássio/genética , Pilocarpina/toxicidade , Cobalto/farmacologia , Eletroencefalografia , Neurônios/metabolismo , Neocórtex/metabolismoRESUMO
BACKGROUND: Stroke is prevalent in hypertensive population. It has been suggested that unsaturated fatty acids (USFA) have protective effect on stroke. The effect of saturated fatty acids (SFAs) on stroke is still unclear. Therefore, we studied the relationship between circulating fatty acids and acute ischemic stroke (AIS) in hypertensive patients. METHODS: Eighty-nine pairs including 100 men and 78 women matched by sex and age were recruited. Each pair included a hypertensive patient within 48h of AIS onset and a hypertensive patient without stroke. Six circulating fatty acids were methylated before concentration determination which was repeated twice with percent recovery estimated. RESULTS: There were differences in educational level (P = 0.002) and occupation (P < 0.001) between stroke and non-stroke participants. All the 6 fatty acid levels were higher in non-stroke participants (P = 0.017 for palmitoleic acid, 0.001 for palmitic acid, <0.001 for linoleic acid, <0.001 for behenic acid, <0.001 for nervonic acid and 0.002 for lignoceric acid). In logistic regression analysis, AIS was inversely associated with fatty acid levels except for lignoceric acid. After adjustment for education and occupation, the palmitoleic acid and palmitic acid levels were no longer inversely associated with AIS. After further adjustment for systolic blood pressure, smoking, drinking, total cholesterol and triglyceride, the inverse associations of linoleic acid (OR = 0.965, 95%CI = 0.942-0.990, P = 0.005), behenic acid (OR = 0.778, 95%CI = 0.664-0.939, P = 0.009), nervonic acid (OR = 0.323, 95%CI = 0.121-0.860, P = 0.024) with AIS remained significant. CONCLUSIONS: Circulating fatty acids except lignoceric acid were inversely associated with AIS. Both USFAs and SFAs may have beneficial effect on stroke prevention in hypertensive population.
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Ácidos Graxos , Hipertensão , Acidente Vascular Cerebral , Humanos , Feminino , Masculino , Hipertensão/sangue , Hipertensão/epidemiologia , Hipertensão/complicações , Ácidos Graxos/sangue , Pessoa de Meia-Idade , Idoso , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Fatores de RiscoRESUMO
Context: The coexistence of hypertension and elevated homocysteine (Hcy) levels has a mutually reinforcing impact on the susceptibility to cardio-cerebrovascular disease. Objective: The aim was to assess the prevalence, clinical correlation, and demographic characteristics of hyperhomocysteinemia (HHcy) within the Chinese urban population with hypertension. Methods: A cohort of 473 individuals with hypertension were selected from four communities in Shenzhen, China. Demographic attributes, clinical profiles, and lifestyle behaviors were gathered and compared between individuals with and without HHcy. A logistic regression model was employed to examine potential factors associated with the prevalence of HHcy. Correlation between Hcy levels and clinical characteristics was assessed through multiple linear regression analysis. Results: The prevalence of HHcy in the population with hypertension was 31.3%. In comparison to individuals without HHcy, those with HHcy exhibited a higher proportion of males, a higher prevalence of smoking and alcohol consumption, and a higher proportion of cases with the homozygous (TT) genotype at the MTHFR C677T polymorphism. Moreover, individuals with HHcy had lower levels of folic acid (FA), and lower fruit and vitamin B12 intake. Furthermore, the risk factors for HHcy were male (B = 1.430, OR = 4.179) and MTHFR (TT) (B = 1.086, OR = 2.961). In addition, the multiple linear regression analysis revealed a significant association between Hcy levels and gender (B = -2.784, P = 0.004), MTHFR genotypes (B = 1.410, P = 0.005), and FA levels (B = -0.136, P = 0.030). Conclusion: The high prevalence of HHcy among hypertensive patients in this Chinese urban population underscores the necessity for interventions targeting modifiable risk factors such as dietary choices and lifestyle practices.
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Hiper-Homocisteinemia , Hipertensão , Humanos , Masculino , Feminino , População Urbana , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/epidemiologia , Prevalência , Hipertensão/epidemiologia , China/epidemiologiaRESUMO
Background: Ischemic stroke (IS) is one of most common causes of disability in adults worldwide. However, there is still a lack of effective and reliable diagnostic markers and therapeutic targets in IS. Furthermore, immune cell dysfunction plays an important role in the pathogenesis of IS. Hence, in-depth research on immune-related targets in progressive IS is urgently needed. Methods: Expression profile data from patients with IS were downloaded from the Gene Expression Omnibus (GEO) database. Then, differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed to identify the significant modules and differentially expressed genes (DEGs). Key genes were obtained and used in functional enrichment analyses by overlapping module genes and DEGs. Next, hub candidate genes were identified by utilizing three machine learning algorithms: least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE). Subsequently, a diagnostic model was constructed based on the hub genes, and receiver operating characteristic (ROC) curves were constructed to validate the performances of the predictive models and candidate genes. Finally, the immune cell infiltration landscape of IS was explored with the CIBERSORT deconvolution algorithm. Results: A total of 40 key DEGs were identified based on the intersection of the DEGs and module genes, and we found that these genes were mainly enriched in the regulation of lipolysis in adipocytes, neutrophil extracellular trap formation and complement and coagulation cascades. Based on the results from three advanced machine learning algorithms, we obtained 7 hub candidate genes (ABCA1, ARG1, C5AR1, CKAP4, HMFN0839, SDCBP and TLN1) as diagnostic biomarkers of IS and developed a reliable nomogram with high predictive performance (AUC = 0.987). In addition, immune cell infiltration dysregulation was implicated in IS, and compared with those in the normal group, IS patients had increased fractions of gamma delta T cells, monocytes, M0 macrophages, M2 macrophages and neutrophils and clearly lower percentages of naive B cells, CD8 T cells, CD4+ memory T cells, follicular helper T cells, regulatory T cells (Tregs) and resting dendritic cells. Furthermore, correlation analysis indicated a significant correlation between the hub genes and immune cells in progressive IS. Conclusion: In conclusion, our study identified 7 hub genes as diagnostic biomarkers and established a reliable model to predict the occurrence of IS. Meanwhile, we explored the immune cell infiltration pattern and investigated the relationship between candidate genes and immune cells in the pathogenesis of IS. Hence, our study provides new insights into the diagnosis and treatment of IS.
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Ischemic stroke is a prominent contributor to global morbidity and mortality rates. The intricate and diverse mechanisms underlying ischemia-reperfusion injury remain poorly comprehended. RNA methylation, an emerging epigenetic modification, plays a crucial role in regulating numerous biological processes, including immunity, DNA damage response, tumorigenesis, metastasis, stem cell renewal, adipocyte differentiation, circadian rhythms, cellular development and differentiation, and cell division. Among the various RNA modifications, N6-methyladenosine (m6A) modification stands as the most prevalent in mammalian mRNA. Recent studies have demonstrated the crucial involvement of m6A modification in the pathophysiological progression of ischemic stroke. This review aims to elucidate the advancements in ischemic stroke-specific investigations pertaining to m6A modification, consolidate the underlying mechanisms implicated in the participation of m6A modification during the onset of ischemic stroke, and deliberate on the potential of m6A modification as a viable therapeutic target for ischemic stroke.
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BACKGROUND: Patients with severe thalassemia may experience adverse effects from transfusion such as fever, rash, and iron overload after long-term transfusion therapy. Severe headaches as a side effect of blood transfusion in patients with thalassemia are not commonly observed, especially when combined with superficial siderosis of the central nervous system, which is easily misdiagnosed and requires excessive examination and treatment. CASE PRESENTATION: A 31-year-old woman was admitted with severe headache and vomiting over 3 days following blood transfusion. She was diagnosed with intermediate α-thalassemia at 2 years of age and had a history of irregular blood transfusions. Physical examination revealed horizontal nystagmus with no other abnormal neurological signs. Magnetic resonance (MR) imaging, MR venography, MR arteriography, and cerebrospinal fluid analysis were normal. However, susceptibility-weighted imaging showed abnormal signals in the bilateral and fourth ventricles. Initial antibiotics, antivirals, decompression of intracranial pressure, iron chelation, and symptomatic treatments were administered; subsequently, small intermittent blood transfusions were cautiously administered for severe anemia. The patient's headache was gradually relieved, and she was discharged on day 9. At the 5-month follow-up, the patient's headache recurred following another transfusion. CONCLUSIONS: Severe post-transfusion headache in patients with thalassemia has not been fully recognized and is easily misdiagnosed, leading to excessive examination and treatment. Understanding the clinical features of transfusion-related headaches can help identify this complication, but the exact pathophysiological mechanism requires further research.
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Nistagmo Patológico , Siderose , Talassemia , Feminino , Humanos , Adulto , Siderose/complicações , Siderose/diagnóstico por imagem , Sistema Nervoso Central , Talassemia/complicações , Talassemia/terapia , Cefaleia/etiologia , Cefaleia/terapiaRESUMO
BACKGROUND: Whether minor ischemic stroke (MIS) patients can benefit from intravenous thrombolysis (IVT) remains controversial. The association between the efficacy of IVT and baseline National Institute of Health Stroke Scale (NIHSS) score is unclear in MIS, while the association in moderate and severe stroke is known. This study aimed to explore the effect of IVT in patients with MIS and analyze its efficacy in patients with different baseline NIHSS scores. METHODS: Patients with a NIHSS score ≤5 within 4.5 h of stroke onset were screened in 32 centers. Patients with and without IVT were matched to a ratio of 1:1 with propensity scores. An excellent outcome was defined as a modified Rankin Scale (mRS) score ≤1 at three months after stroke onset. Safety outcomes included mortality and symptomatic intracranial hemorrhage (sICH). Multivariate analysis was used to compute the adjusted odds ratio (OR) for excellent outcomes. The effect of IVT was further analyzed in subgroups according to the baseline NIHSS score. RESULTS: Of the 23,853 screened, 3336 patients with MIS who arrived at the hospital within 4.5 h of onset were included. The 1163 patients treated with IVT were matched with 1163 patients without IVT. IVT in minor strokes generated an adjusted OR of 1.38 (95% CI: 1.09-1.75, p = 0.009) for excellent outcomes. There were no significant differences in mortality (0.17% vs. 0.09%, p = 1.000) and sICH (0.69% vs. 0.86%, p = 0.813) between patients with and without IVT. Subgroup analysis showed that there was no significant effect of IVT in the baseline NIHSS 0-1 or 2-3 subgroups, with adjusted OR of 0.816 (95% CI 0.437-1.53, p = 0.525) and1.22 (95% CI 0.845-1.77, p = 0.287), respectively. In patients with NIHSS score of 4-5, IVT was significantly effective, with an adjusted OR of 1.53 (95% CI 1.02-2.30, p = 0.038). CONCLUSION: IVT can improve MIS outcomes. The risks of sICH and mortality did not increase, especially in patients with NIHSS scores 4 to 5, who could benefit from IVT significantly.
Overall, intravenous thrombolysis can improve the outcomes of patients with minor stroke.Minor stroke patients with a baseline NIHSS score of 4-5 can benefit the most from intravenous thrombolysis.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Fibrinolíticos/efeitos adversos , Terapia Trombolítica/efeitos adversos , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/etiologia , Resultado do Tratamento , Acidente Vascular Cerebral/etiologia , AVC Isquêmico/tratamento farmacológicoRESUMO
Rheumatoid arthritis (RA) is a multifaceted autoimmune disease characterized by systemic inflammation, affecting both articular and extra-articular structures. This condition results in inflammation of joints and synovial membranes, accompanied by the development of systemic comorbidities. Despite extensive research, the precise pathogenic mechanisms responsible for RA have yet to be completely understood. RNA methylation, a burgeoning epigenetic alteration, assumes a pivotal function in the regulation of a myriad of biological phenomena, encompassing immunity, DNA damage response, tumorigenesis, metastasis, stem cell renewal, adipocyte differentiation, circadian rhythms, cellular development and differentiation, and cell division. The N6-methyladenosine (m6A) modification is the most prevalent among the various RNA modifications found in mammalian mRNA. Recent studies have provided evidence of the significant role played by m6A modification in the pathophysiological progression of RA. This review aims to provide a comprehensive analysis of the progress made in research focused on m6A modification in the context of RA, consolidate the underlying mechanisms involved in m6A modification during the initiation of RA and discuss the potential of targeting m6A modification as a viable therapeutic approach for RA.
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Artrite Reumatoide , Doenças Autoimunes , Animais , Artrite Reumatoide/genética , Inflamação , Metilação de RNA , MamíferosRESUMO
RATIONALE: Myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD) represents a demyelinating neurological syndrome characterized by the presence of serum IgG antibodies directed against myelin oligodendrocyte glycoprotein (MOG-IgG). Concurrently, giant cell arteritis (GCA) constitutes a systemic autoimmune vasculitis. PATIENT CONCERNS: In this case, we describe an elderly female patient who presented with the sudden onset of a severe headache, unilateral blindness, and clinical manifestations resembling those of GCA. DIAGNOSIS: Upon conducting a comprehensive analysis of serum antibodies, the diagnosis of MOGAD was established due to the presence of detectable serum MOG-IgG. INTERVENTIONS: Subsequently, the patient was administered intravenous methylprednisolone therapy, commencing 27 days after the initial onset of symptoms. OUTCOMES: It is noteworthy that patients afflicted by MOGAD typically manifest severe visual impairment, which, in many instances, exhibits significant improvement following immunotherapeutic interventions. However, this particular patient did not experience any amelioration in visual function despite glucocorticoid therapy. LESSONS: This unique case illustrates that the clinical presentation resembling GCA may precede the inaugural manifestation of MOGAD. This suggests the possibility of immune-mediated arterial involvement. The significance of glucocorticoid therapy in the context of immune-related diseases warrants further scrutiny, particularly in cases where MOG-IgG screening should be promptly considered.
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Arterite de Células Gigantes , Idoso , Humanos , Feminino , Arterite de Células Gigantes/complicações , Arterite de Células Gigantes/diagnóstico , Arterite de Células Gigantes/tratamento farmacológico , Glicoproteína Mielina-Oligodendrócito , Glucocorticoides/uso terapêutico , Cegueira/diagnóstico , Cegueira/etiologia , Imunoglobulina G , AutoanticorposRESUMO
Objective: This study aims to elucidate the potential links between the GLU/GABA to GLN metabolic cycle disruptions and the onset of depressive and insomnia disorders following a stroke. We particularly focus on understanding if these disorders share a common underlying pathogenic mechanism. Methods: We examined 63 patients with post-stroke insomnia, 62 patients with post-stroke depression, and 18 healthy individuals. The study involved assessing insomnia using the Acute Insomnia Scale (AIS) and depression using the Hamilton Depression Rating Scale. We measured serum concentrations of GLN, GLU, and GABA and analyzed their correlations with AIS and HAMD scores. Results: Our results indicate no significant difference in the serum levels of GLN, GLU, and GABA between the post-stroke insomnia and depression groups. However, these levels were notably lower in both patient groups compared to the healthy control group. A negative correlation between AIS scores and GABA levels was observed in the post-stroke insomnia group, suggesting a potential link between GABAergic disturbances and insomnia. Conversely, no significant correlation was found between Hamilton Depression Rating Scale scores and the levels of GABA, GLU, or GLN in the post-stroke depression group. Conclusion: The study highlights that abnormalities in the GLU/GABA to GLN metabolic cycle, particularly the levels of GLN, GABA, and GAD, might be intricately linked to the pathogenesis of post-stroke insomnia and depression. Our findings suggest that GABAergic imbalances could be indicative of post-stroke insomnia, serving as potential biological markers for differential diagnosis in clinical settings. Further research is warranted to explore these relationships in greater depth, potentially leading to new diagnostic and therapeutic approaches for post-stroke neuropsychiatric disorders.
RESUMO
Early detection and drug intervention with the appropriate timing and dosage are the main clinical challenges for ischemic stroke (IS) treatment. The conventional therapeutic agents relay fluorescent signals, which require real-time external light excitation, thereby leading to inevitable autofluorescence and poor tissue penetration. Herein, we report endogenous peroxynitrite (ONOO-)-activated BDP-4/Cur-CL NPs that release NIR afterglow signals (λmax 697 nm) for real-time monitoring of the progression of ischemia reperfusion (I/R) brain injury while releasing curcumin for the safe treatment of IS. The BDP-4/Cur-CL NPs exhibited bright NIR afterglow luminescence (maximum 732-fold increase), superb sensitivity (LOD = 82.67 nM), high energy-transfer efficiency (94.6%), deep tissue penetration (20 mm), outstanding antiapoptosis, and anti-inflammatory effects. The activated NIR afterglow signal obtained in mice with middle cerebral artery occlusion (MCAO) showed three functions: (i) the BDP-4/Cur-CL NPs are rapidly activated by endogenous ONOO-, instantly illuminating the lesion area, distinguishing I/R damage from normal areas, which can be successfully used for endogenous ONOO- detection in the early stage of IS; (ii) real-time reporting of in situ generation and dynamic fluctuations of endogenous ONOO- levels in the lesion area, which is of great value in monitoring the evolutionary mechanisms of IS; and (iii) dynamic monitoring of the release of curcumin drug for safe treatment. Indeed, the released curcumin effectively decreased apoptosis, enhanced survival, alleviated neuroinflammation, reduced brain tissue loss, and improved the cognition of MCAO stroke mice. This work is the first example of afterglow luminescence for early diagnosis, real-time reporting, drug tracing, and treatment for IS.
Assuntos
Curcumina , AVC Isquêmico , Nanopartículas , Camundongos , Animais , AVC Isquêmico/tratamento farmacológico , Curcumina/farmacologia , Curcumina/uso terapêutico , Luminescência , EncéfaloRESUMO
BACKGROUND: At present, the pathogenesis of post-stroke insomnia (PSI) is still inconclusive. OBJECTIVE: To explore the changes and significance of serum cholecystokinin-8 (CCK-8), substance P (SP), and 5-hydroxytryptamine (5-HT) in patients with PSI. METHODS: Ninety-one patients with stroke were selected as the research subjects, and according to the score of the Athens Insomnia Scale (AIS), they were divided into the insomnia group and the non-insomnia group. The serum levels of CCK-8, SP, and 5-HT in the two groups were compared to explore their relationships with PSI. RESULTS: Among the 91 patients, 56 were in the insomnia group and 35 were in the non-insomnia group, and the incidence of insomnia was 61.5%. There was no significant difference in the serum levels of CCK-8, SP, and 5-HT between the two groups (P= 0.696, 0.980, and 0.809, respectively). One-way analysis of variance showed that there was no significant correlation between the serum levels of CCK-8, SP, 5-HT, and the AIS score (P= 0.7393, 0.9581, and 0.5952, respectively). CONCLUSION: The incidence of PSI was relatively high, but it could not be proved that CCK-8, SP, and 5-HT were involved in the pathogenesis of PSI. There might exist other neurotransmitters involved in the pathophysiological process of PSI, which should be further explored.