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Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.
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Imagem de Difusão por Ressonância Magnética , Sistema Glinfático , Humanos , Masculino , Feminino , Sistema Glinfático/diagnóstico por imagem , Sistema Glinfático/patologia , Sistema Glinfático/fisiopatologia , Pessoa de Meia-Idade , Estudos Transversais , Idoso , Imagem de Difusão por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Processamento de Imagem Assistida por Computador/métodos , Adulto , Estudos de CoortesRESUMO
OBJECTIVES: Intracranial arterial dolichoectasia (IADE) is characterized by the dilation, elongation, and tortuosity of intracranial arteries. We aimed to investigate the association between variations of the Circle of Willis (COW) and IADE in the general population, as well as estimate the genetic correlation between COW variations and IADE. METHODS: A total of 981 individuals from a population-based cohort were included. Brain magnetic resonance angiography was performed to assess COW variants and measure the diameters of intracranial arteries. IADE was defined as a total intracranial volume-adjusted diameter ≥ 2 standard deviations. Logistic regression models were used to analyze the association between COW variations and IADE. The heritability and genetic correlation were estimated using genome-wide complex trait analysis (GCTA) based on single nucleotide polymorphism (SNP) array data. RESULTS: The prevalence of IADE was 6.2%. Hypoplastic/absent A1 segments were associated with an increase in contralateral ICA diameter (ß ± SE, 0.279 ± 0.049; pâ¯=â¯0.001) and a decrease in ipsilateral ICA diameter (ß ± SE, -0.300 ± 0.050; pâ¯=â¯0.001). Fetal-type posterior cerebral artery (FTP) was associated with a larger ICA diameter (ß ± SE, 0.326 ± 0.048; pâ¯=â¯0.001) and a smaller BA diameter (ß ± SE, -0.662 ± 0.043; pâ¯=â¯0.001). FTP revealed a positive genetic correlation with ICA dilation (rGâ¯=â¯0.259 ± 0.175; pâ¯=â¯0.0009) and a negative genetic correlation with BA dilation (rGâ¯=â¯-0.192 ± 0.153, pâ¯=â¯0.015). CONCLUSIONS: There was an association between COW variations and larger intracranial arterial diameters in the general population. Genetic factors may play a role in the development of intracranial arterial dilation and the formation of COW variants.
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BACKGROUND AND PURPOSE: The circle of Willis (COW) is a circulatory anastomosis located at the base of the brain. Little is known about the association between covert vascular brain injury and COW configurations in the general population. We explored this relationship in a community-based Chinese sample. METHODS: A total of 1,055 patients (mean age, 54.8 ± 8.9 years; 36.0% men) without intracranial arterial stenosis were included in the analysis. Magnetic resonance imaging was performed to evaluate the presence of imaging markers of covert vascular brain injury, including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds (CMBs), enlarged perivascular spaces, and brain atrophy. Magnetic resonance angiography was used to classify the COW configurations according to the completeness, symmetry, and presence of the fetal posterior cerebral artery (FTP). The association between vascular lesions and variations in COW was analyzed. RESULTS: Among the 1,055 patients, 104 (9.9%) had a complete COW. Completeness correlated with age (p = 0.001). Incomplete COW was positively associated with WMH severity (OR = 2.071; 95% CI, 1.004-4.270) and CMB presence (OR = 1.542; 95% CI, 1.012-2.348), independent of age and sex. The presence of FTP was associated with lacunes (OR = 1.878; 95% CI, 1.069-3.298), more severe WMHs (OR = 1.739; 95% CI, 1.064-2.842), and less severe enlarged perivascular spaces (OR = 0.562; 95% CI, 0.346-0.915). CONCLUSIONS: COW configuration was significantly related to various covert vascular brain injuries.
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Traumatismo Cerebrovascular , Círculo Arterial do Cérebro , Humanos , Círculo Arterial do Cérebro/diagnóstico por imagem , Círculo Arterial do Cérebro/patologia , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Angiografia por Ressonância Magnética , Traumatismo Cerebrovascular/patologiaRESUMO
BACKGROUND: Berberine (BBR) is an isoquinoline alkaloid found in the Berberis species. It was found to have protected effects in cardiovascular diseases. Here, we investigated the effect the regulatory function of long noncoding RNAs (lncRNAs) during the treatment of stable coronary heart disease (CHD) using BBR. We performed microarray analyses to identify differentially expressed (DE) lncRNAs and mRNAs between whole blood samples from 5 patients with stable CHD taking BBR and 5 no BBR volunteers. DE lncRNAs and mRNAs were validated by quantitative real-time PCR. RESULTS: A total of 1703 DE lncRNAs and 912 DE mRNAs were identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated DE mRNAs might be associated with mammalian target of rapamycin and mitogen-activated protein kinase pathway. These pathways may be involved in the healing process after CHD. To study the relationship between mRNAs encoding transcription factors (DNA damage inducible transcript 3, sal-like protein 4 and estrogen receptor alpha gene) and CHD related de mRNAs, we performed protein and protein interaction analysis on their corresponding proteins. AKT and apoptosis pathway were significant enriched in protein and protein interaction network. BBR may affect downstream apoptosis pathways through DNA damage inducible transcript 3, sal-like protein 4 and estrogen receptor alpha gene. Growth arrest-specific transcript 5 might regulate CHD-related mRNAs through competing endogenous RNA mechanism and may be the downstream target gene regulated by BBR. Verified by the quantitative real-time PCR, we identified 8 DE lncRNAs that may relate to CHD. We performed coding and non-coding co-expression and competing endogenous RNA mechanism analysis of these 8 DE lncRNAs and CHD-related DE mRNA, and predicted their subcellular localization and N6-methyladenosine modification sites. CONCLUSION: Our research found that BBR may affect mammalian target of rapamycin, mitogen-activated protein kinase, apoptosis pathway and growth arrest-specific transcript 5 in the process of CHD. These pathways may be involved in the healing process after CHD. Our research might provide novel insights for functional research of BBR.
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Berberina , Doença das Coronárias , RNA Longo não Codificante , Berberina/farmacologia , Berberina/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/genética , Receptor alfa de Estrogênio , Humanos , Proteínas Quinases Ativadas por Mitógeno , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Serina-Treonina Quinases TORRESUMO
BACKGROUND: Although inflammation is found to be related to arteriopathy pathogenesis, it is yet to be determined the distinct correlations of specific inflammatory biomarker types contributing to different cerebral large vessel diseases. We aimed to investigate the association between multiple inflammatory biomarkers and cerebral atherosclerosis and dolichoectasia in a community-based sample. METHODS: A total of 960 participants of the Shunyi study were included. A panel of 14 circulatory inflammatory biomarkers was assessed and then grouped in three sets as systemic, endothelial-related, and media-related inflammation, based on underlying different inflammatory cascades. Intracranial atherosclerotic stenosis (ICAS), dolichoectasia estimated by magnetic resonance angiography, and carotid plaques estimated by ultrasound were also performed. RESULTS: Endothelial-related inflammatory group was related to the presence of ICAS (R2 = 0.215, p = 0.024) and carotid plaques (R2 = 0.342, p = 0.013). Backward stepwise elimination showed that E-selectin was prominent (ß = 0.67, 95% CI: 0.54-0.85, p = 0.001; ß = 0.79, 95% CI: 0.68-0.93, p = 0.005). Systemic inflammatory group was associated with an increased basilar artery diameter (R2 = 0.051, p < 0.001), and backward stepwise elimination showed that IL-6 was prominent (ß = 0.07, 95% CI: 0.03-0.11, p < 0.001). CONCLUSION: Different types of inflammatory biomarkers were associated with atherosclerosis and dolichoectasia, respectively, implying dissimilar inflammatory processes. Further confirming of their distinct anti-inflammatory roles as potential therapeutic targets is warrant.
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Aterosclerose , Arteriosclerose Intracraniana , Aterosclerose/complicações , Aterosclerose/diagnóstico por imagem , Aterosclerose/patologia , Artéria Basilar , Biomarcadores , Humanos , Inflamação/complicações , Inflamação/diagnóstico por imagem , Inflamação/patologia , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico por imagemRESUMO
AIMS: This study aimed to assess the clinical characteristics and long-term survival outcome in patients with Takayasu's arteritis-associated pulmonary hypertension (TA-PH). METHODS AND RESULTS: We conducted a nationally representative cohort study of TA-PH using data from the National Rare Diseases Registry System of China. Patients with pulmonary artery involvement who fulfilled the diagnostic criteria of Takayasu's arteritis and pulmonary hypertension were included. The primary outcome was the time from diagnosis of TA-PH to the occurrence of all-cause death. Between January 2007 and January 2019, a total of 140 patients were included, with a mean age of 41.4 years at diagnosis, and a female predominance (81%). Patients with TA-PH had severely haemodynamic and functional impairments at diagnosis. Significant improvements have been found in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and haemodynamic profiles in patients with TA-PH receiving drugs approved for pulmonary arterial hypertension. The overall 1-, 3-, and 5-year survival rates in TA-PH were 94.0%, 83.2%, and 77.2%, respectively. Predictors associated with an increased risk of all-cause death were syncope [adjusted hazard ratio (HR) 5.38 (95% confidence interval 1.77-16.34), P = 0.003], NT-proBNP level [adjusted HR 1.04 (1.03-1.06), P < 0.001], and mean right atrial pressure [adjusted HR 1.07 (1.01-1.13), P = 0.015]. CONCLUSION: Patients with TA-PH were predominantly female and had severely compromised haemodynamics. More than 80% of patients in our cohort survived for at least 3 years. Medical treatment was based on investigators' personal opinions, and no clear risk-to-benefit ratio can be derived from the presented data.
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Hipertensão Pulmonar , Hipertensão Arterial Pulmonar , Arterite de Takayasu , Adulto , Estudos de Coortes , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Estudos Retrospectivos , Arterite de Takayasu/complicações , Arterite de Takayasu/epidemiologiaRESUMO
BACKGROUND AND PURPOSE: Researches on rare variants of NOTCH3 in the general Chinese population are lacking. This study aims to describe the spectrum of rare NOTCH3 variants by whole-exome sequencing in a Chinese community-based cohort and to investigate the association between rare NOTCH3 variants and age-related cerebral small vessel disease. METHODS: The cross-sectional study comprised 1065 participants who underwent whole-exome sequencing and brain magnetic resonance imaging. NOTCH3 variants with minor allele frequency<1% in all 4 public population databases (1000 Genomes, ESP6500siv2_ALL, GnomAD_ALL, and GnomAD_EAS) were defined as rare variants. Multivariable linear and logistic regressions were used to investigate the associations between rare NOTCH3 variants and volume of white matter hyperintensities and cerebral small vessel disease burden. Clinical and imaging characteristics of rare NOTCH3 variant carriers were summarized. RESULTS: Sixty-five rare NOTCH3 variants were identified in 147 of 1065 (13.8%) participants, including 57 missense single nucleotide polymorphisms (SNPs), 5 SNPs in splice branching sites, and 3 frameshift deletions. A significantly higher volume of white matter hyperintensities and heavier burden of cerebral small vessel disease was found in carriers of rare NOTCH3 EGFr (epidermal growth factor-like repeats)-involving variants, but not in carriers of EGFr-sparing variants. The carrying rate of rare EGFr-involving NOTCH3 variants in participants with dementia or stroke was significantly higher than those without dementia or stroke (12.4% versus 6.6%, P=0.041). Magnetic resonance imaging signs suggestive of CADASIL were found in 3.4% (5/145) rare EGFr cysteine-sparing NOTCH3 variant carriers but not in 2 cysteine-altering NOTCH3 variant carriers. CONCLUSIONS: Carriers of rare NOTCH3 variants involving the EGFr domain may be genetically predisposed to age-related cerebral small vessel disease in the general Chinese population.
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Doenças de Pequenos Vasos Cerebrais/genética , Predisposição Genética para Doença/genética , Receptor Notch3/genética , Idoso , Povo Asiático/genética , Estudos de Coortes , Estudos Transversais , Feminino , Variação Genética , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Noninvasive positive-pressure ventilation (NPPV) is recognized as an effective adjuvant therapy for sleep-disordered breathing (SDB) in heart failure patients with reduced ejection fraction (HFrEF + SDB). In recent years, some studies have found that adaptive servo-ventilation (ASV) has a negative impact on survival, especially among patients with central sleep apnea (CSA), the use of which is controversial. This study aims to explore the effects of NPPV on cardiac function and survival in patients with sleep-disordered breathing and chronic congestive heart failure. This meta-analysis was based on literature searches of publications published before August 31, 2019, in the PubMed, EMBASE, Cochrane Library, and Web of Science databases. A total of 88 independent studies were summarized and compared, comprising a sampling of 19,259 subjects. Compared with the nontreatment group, treatment with ASV had no effect on all-cause mortality in patients with HFrEF + CSA (hazard ratio (HR) = 1.13 [0.84, 1.51]). Short-term treatment with ASV, e.g., 3-6 months, was significantly beneficial regarding event-free survival in patients with HFrEF + CSA (HR = 0.13 [0.04, 0.45]). Periodic short-term (e.g., 3-6 months) positive-pressure ventilation can significantly improve cardiac function, which is beneficial for the survival of patients with HFrEF + CSA. Attention should be paid to the length and period of treatment, as prolonged treatment may have negative effects.
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Insuficiência Cardíaca , Síndromes da Apneia do Sono , Apneia do Sono Tipo Central , Pressão Positiva Contínua nas Vias Aéreas , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/terapia , Humanos , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/terapia , Apneia do Sono Tipo Central/terapia , Volume Sistólico , Resultado do TratamentoRESUMO
Pathological mechanisms of pulmonary arterial hypertension (PAH) remain largely unexplored. Effective treatment of PAH remains a challenge. The aim of this study was to discover the underlying mechanism of PAH through functional metabolomics and to help develop new strategies for prevention and treatment of PAH.Metabolomic profiling of plasma in patients with idiopathic PAH was evaluated through high-performance liquid chromatography mass spectrometry, with spermine identified to be the most significant and validated in another independent cohort. The roles of spermine and spermine synthase were examined in pulmonary arterial smooth muscle cells (PASMCs) and rodent models of pulmonary hypertension.Using targeted metabolomics, plasma spermine levels were found to be higher in patients with idiopathic PAH compared to healthy controls. Spermine administration promoted proliferation and migration of PASMCs and exacerbated vascular remodelling in rodent models of pulmonary hypertension. The spermine-mediated deteriorative effect can be attributed to a corresponding upregulation of its synthase in the pathological process. Inhibition of spermine synthase in vitro suppressed platelet-derived growth factor-BB-mediated proliferation of PASMCs, and in vivo attenuated monocrotaline-mediated pulmonary hypertension in rats.Plasma spermine promotes pulmonary vascular remodelling. Inhibiting spermine synthesis could be a therapeutic strategy for PAH.
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Hipertensão Arterial Pulmonar , Animais , Proliferação de Células , Modelos Animais de Doenças , Glicogênio Sintase , Humanos , Miócitos de Músculo Liso , Artéria Pulmonar , Ratos , Espermina , Remodelação VascularRESUMO
BACKGROUND: To investigate the epidemiology and in-hospital mortality of veno-venous (VV) and veno-arterial (VA) extracorporeal membrane oxygenation (ECMO) in Mainland China throughout 2018. METHODS: Patients supported by ECMO from 1700 tertiary hospitals in 31 provinces from January 1 to December 31, 2018, were selected from the National Clinical Improvement System database. RESULTS: The 1700 included hospitals had 2073 cases of ECMO in 2018, including 714 VV and 1359 VA ECMOs. The average patient age was 50 years (IQR 31-63), and 1346 were male. The average hospital stay was 17 days (IQR 7-30), and the average costs per case was $36,334 (IQR 22,547-56,714). The three provinces with the highest number of ECMO cases were Guangdong, Beijing, and Zhejiang; the southeast coastal areas and regions with higher GDP levels had more cases. Overall in-hospital mortality was 29.6%. Mortality was higher among patients who were male, over 70 years old, living in underdeveloped areas, and who were treated during the summer. Mortality in provinces with more ECMO cases was relatively low. The co-existence of congenital malformations, blood system abnormalities, or nervous system abnormalities increased in-hospital mortality. CONCLUSIONS: Mortality and medical expenses of ECMO among patients in China were relatively low, but large regional and seasonal differences were present. Risk factors for higher in-hospital mortality were older age, male sex, in underdeveloped areas, and treatment during the summer. Additionally, congenital malformations and blood system and nervous system abnormalities were associated with in-hospital mortality.
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Estado Terminal/terapia , Oxigenação por Membrana Extracorpórea/normas , Mortalidade Hospitalar/tendências , Resultado do Tratamento , Adolescente , Adulto , Idoso , Pequim/epidemiologia , Criança , Estado Terminal/epidemiologia , Estado Terminal/mortalidade , Estudos Transversais , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Heart failure(HF)is the terminal stage of cardiovascular diseases and has long been one of the most deadly condition due to its high morbidity and mortality.Since the currently available treatment options cannot meet the clinical needs,new therapeutic strategies for HF should be actively explored.Epigenetics does not involve the changes of genetic sequences but focuses on the stable inheritance of genes in different individuals.It is affected by the interaction between genes and environments,which may result in DNA methylation,histone modification,and other changes.This article summarizes the recent research advances in epigenetics in HF.
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Epigênese Genética , Insuficiência Cardíaca/genética , Metilação de DNA , Histonas/química , HumanosRESUMO
BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease with high heritability. Although several predisposing genes have been linked to IPAH, the genetic aetiology remains unknown for a large number of IPAH cases. METHODS: We conducted an exome-wide gene-based burden analysis on two independent case-control studies, including a total of 331 IPAH cases and 10â508 controls. Functional assessments were conducted to analyse the effects of genetic mutations on protein biosynthesis and function. RESULTS: The gene encoding human bone morphogenetic protein 9 (BMP9) was identified as a novel genetic locus displaying exome-wide association with IPAH in the discovery cohort (OR 18.8; p=1.9×10-11). This association was authenticated in the independent replication cohort (p=1.0×10-5). Collectively, the rare coding mutations in BMP9 occurred in 6.7% of cases, ranking this gene second to BMPR2, comprising a combined significance of 2.7×10-19 (OR 21.2). Intriguingly, the patients with BMP9 mutations had lower plasma levels of BMP9 than those without. Functional studies showed that the BMP9 mutations led to reduced BMP9 secretion and impaired anti-apoptosis ability in pulmonary arterial endothelial cells. CONCLUSION: We identify BMP9 as an IPAH culprit gene.
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Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Hipertensão Pulmonar Primária Familiar/genética , Mutação em Linhagem Germinativa , Adolescente , Adulto , Estudos de Casos e Controles , Células Endoteliais/metabolismo , Exoma , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Intracranial arterial dolichoectasia (IADE) is a poorly understood arteriopathy compared with intracranial atherosclerotic stenosis (ICAS). We aimed to investigate the risk factors of IADE and ICAS and their relationship with neuroimaging markers of cerebral small vessel disease in a population-based study. METHODS: This study comprised 1237 participants (aged 57.2±9.4 years, 37.6% men) who underwent brain magnetic resonance imaging and magnetic resonance angiography. IADE was assessed based on basilar artery dolichoectasia (diameter, height of bifurcation, and laterality of basilar artery) and dilation of basilar artery and internal carotid artery (intracranial volume-adjusted diameter ≥2 SD). ICAS was defined as any degree of stenosis in at least 1 intracranial artery. The neuroimaging markers of cerebral small vessel disease, including lacunes, white matter hyperintensities, microbleeds, dilated perivascular spaces, and brain atrophy, were evaluated. RESULTS: Basilar arterial dolichoectasia was observed in 3.6% (45/1237); intracranial arterial dilation in 5.9% (67/1142); and ICAS in 15.7% (194/1237). Older age, higher systolic blood pressure, diabetes mellitus, higher LDL-C (low-density lipoprotein cholesterol) and lower HDL-C (high-density lipoprotein cholesterol) were associated with the presence of ICAS (all P<0.001), whereas only older age was associated with IADE. ICAS was associated with lacunes (odds ratio, 2.91; 95% confidence interval, 1.96-4.34; P<0.001), increased white matter hyperintensities volume (ß±SE, 0.54±0.13; P<0.001), and brain atrophy (ß±SE, -1.16±0.21; P<0.001), whereas basilar arterial dolichoectasia was mainly associated with dilated perivascular spaces in basal ganglia (odds ratio, 2.20; 95% confidence interval, 1.20-4.02; P=0.01) and, to a lesser extent, associated with lacunes and microbleeds. CONCLUSIONS: IADE and ICAS had different risk factor profiles and associated with different imaging phenotypes of cerebral small vessel disease, suggesting different underlying mechanisms.
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Artéria Basilar/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/epidemiologia , Arteriosclerose Intracraniana/epidemiologia , Insuficiência Vertebrobasilar/epidemiologia , Fatores Etários , Idoso , Atrofia , Pressão Sanguínea , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Constrição Patológica , Diabetes Mellitus/epidemiologia , Dilatação Patológica , Feminino , Humanos , Arteriosclerose Intracraniana/diagnóstico por imagem , Leucoaraiose/diagnóstico por imagem , Leucoaraiose/epidemiologia , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neuroimagem , Fenótipo , Fatores de Risco , Insuficiência Vertebrobasilar/diagnóstico por imagem , Substância Branca/diagnóstico por imagemRESUMO
In the elderly, brain structural deficits and gait disturbances due to cerebral small vessel disease (CSVD) have been well demonstrated. The relationships among CSVD, brain atrophy, and motor impairment, however, are far from conclusive. Particularly, the effect of CSVD on subcortical nuclear atrophy, motor performance of upper extremities, and associating patterns between brain atrophy and motor impairment remains largely unknown. To address these gaps, this study recruited 770 community-dwelling subjects (35-82 years of age), including both CSVD and non-CSVD individuals. For each subject, four motor tests involving upper and lower extremities were completed. High-resolution structural MRI was applied to extract gray matter (GM) volume, white matter volume, cortical thickness, surface area, and subcortical nuclear (caudate, putamen, pallidum, and thalamus) volumes. The results showed worse motor performance of lower extremities but relatively preserved performance of upper extremities in the CSVD group. Intriguingly, there was a significant association between the worse performance of upper extremities and atrophy of whole-brain GM and pallidum in the CSVD group but not in the non-CSVD group. In addition, mediation analysis confirmed a functional CSVD-to-"brain atrophy"-to-"motor impairment" pathway, that is, a mediating role of thalamic atrophy in the CSVD effect on walking speed in the elderly, indicating that CSVD impairs walking performance through damaging the integrity of the thalamus in aging populations. These findings provide important insight into the functional consequences of CSVD and highlight the importance of evaluating upper extremities functions and exploring their brain mechanisms in CSVD populations during aging.
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Encéfalo/diagnóstico por imagem , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Transtornos dos Movimentos/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Atrofia , Encéfalo/patologia , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/patologia , Estudos de Coortes , Feminino , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Transtornos dos Movimentos/etiologia , Transtornos dos Movimentos/patologia , Tamanho do Órgão , Substância Branca/patologiaRESUMO
Cardiomyocyte apoptosis correlates with the pathogenesis of heart disease. Long noncoding RNA (LncRNA) emerges as a class of noncoding RNAs that regulate gene expression and participate in various cellular processes. However, the role of lncRNAs in cardiomyocyte apoptosis remains to be elucidated. In our study, we found that lncRNA FTX is significantly down-regulated upon ischemia/reperfusion injury and hydrogen peroxide treatment. Enhanced expression of FTX inhibits cardiomyocyte apoptosis induced by hydrogen peroxide. miR-29b-1-5p was found to interact with FTX and regulate the expression of Bcl2l2. Inhibition of miR-29b-1-5p attenuated cardiomyocyte apoptosis upon hydrogen peroxide treatment. We then found that FTX functions as endogenous sponge for miR-29b-1-5p and regulates the activity of miR-29b-1-5p. The results demonstrate that FTX regulates cardiomyocyte apoptosis through modulating the expression of Bcl2l2 which is mediated by miR-29b-1-5p. Our findings reveal a novel regulatory model which is composed of FTX, miR-29b-1-5p and Bcl2l2. Manipulating of their levels may become a new approach to tackling cardiomyocyte apoptosis related heart diseases.
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Proteínas Reguladoras de Apoptose/genética , Apoptose/genética , Apoptose/fisiologia , MicroRNAs/genética , Miócitos Cardíacos/fisiologia , RNA Longo não Codificante/genética , Animais , Células Cultivadas , Regulação da Expressão Gênica/genética , Masculino , Camundongos , Miócitos Cardíacos/citologiaRESUMO
Objective To analyze the effectiveness and safety of laparoscopic sleeve gastrectomy (LSG) in treating obesity and its co-morbidities.Methods The clinical data of obese patients undergoing LSG in Peking Union Medical College Hospital from August 2012 to August 2017 were retrospectively analyzed. Medium-term outcome measures included excess weight loss (%EWL),co-morbidity improvement,and complications.Results Seventy-five obese patients comprising 28 men[ body mass index(BMI):(47.3±7.5)kg/m 2) ] and 47 women [BMI (41.1±7.0) kg/m 2] were enrolled in this analysis. The common co-morbidities were liver dysfunction (53.3%),dyslipidemia (52.0%),obstructive sleep apnea (45.3%),type 2 diabetes mellitus (38.7%),and arterial hypertension (37.3%),which were improved by 75.0%,58.3%,83.3%,75.0% and 58.3% three years after surgery. The mean %EWL at 1,2,and 3 years after surgery was 81.6±34.7,80.9±30.2 and 79.7±30.8,respectively. The proportions of patients achieving successful weight loss were 81.7% (n=49),81.0% (n=34),and 79.3% (n=23) at 1,2,and 3 years (%EWL>50%). Early severe complications (Clavien-Dindo classification>2) occurred in 2.6% of patients,and the most common late complications was gastroesophageal reflux disease,which could be relieved by acid suppressants.Conclusion LSG is effective and safe in treating obesity and its co-morbidities.
Assuntos
Gastrectomia , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Dislipidemias/complicações , Feminino , Humanos , Hipertensão/complicações , Laparoscopia , Hepatopatias/complicações , Masculino , Estudos Retrospectivos , Apneia Obstrutiva do Sono/complicações , Resultado do Tratamento , Redução de PesoRESUMO
BACKGROUND Leukocyte telomere length (LTL) is regarded as a potential marker of biological aging. Oxidative stress plays a major role in the rate of telomeric DNA loss. The aim of this study was to explore whether the LTL was shorter in Chinese patients with premature coronary artery disease (PCAD) than in non-CAD controls and to determine the relationship between oxidative stress and LTL shortening in this population. MATERIAL AND METHODS Patients for coronary angiography were recruited. In total, 128 patients with PCAD and 128 non-CAD controls were enrolled. Samples of circulating leukocytes and plasma were collected. The mean LTL was measured using a polymerase chain reaction-based assay and expressed as the ratio of telomere repeat copies to single-copy gene (SCG) copies (T/S ratio). Reactive oxygen species (ROS) levels and total antioxidant capacity (T-AOC) were determined in plasma. RESULTS Both the T/S ratio (0.88±0.86 vs. 1.10±0.57, P=0.015) and telomere base pairs (4.97±1.37 kb vs. 5.32±0.91 kb, P=0.015) were significantly shorter in the PCAD group than in non-CAD controls. The T-AOC levels of the PCAD group were significantly lower than those of the non-CAD controls (0.482 mM [0.279, 0.603 mM]) vs. 0.778 mM [0.421, 0.924 mM], P=0.000). The ratio of T-AOC to ROS in the PCAD patients was significantly decreased compared to that of the non-CAD controls (0.1026±0. 1587 [Mm*ml/ng] vs. 0.1435±0.1946 [Mm*ml/ng], P=0.013). CONCLUSIONS The results point to a potential link between reduced LTLs in patients with PCAD and early onset of atherosclerosis. The decline in antioxidant capacity may play an important role in accelerating the attrition of telomeres in PCAD patients.