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OBJECTIVES: Both obesity and non-alcoholic fatty liver disease (NAFLD) increase the risk of metabolic abnormalities. However, the metabolic status of children suffering from NAFLD and exhibiting various subtypes of obesity is currently unclear. We aimed to explore the association between NAFLD and metabolic abnormalities in children with different weight statuses. METHODS: We included 6086 participants aged 6-18 years from the China Child and Adolescent NAFLD Study (CCANS), all of whom had undergone ultrasonography or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) to identify NAFLD and metabolic abnormalities, including hyperglycemia, high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C), high low-density lipoprotein cholesterol, high total cholesterol, and hyperuricemia. RESULTS: Among the participants, there were 2408 children with obesity and NAFLD, 174 with NAFLD, 2396 with obesity, and 1108 without obesity and NAFLD. The odds ratios (ORs) of suffering from individual metabolic abnormalities were significantly greater in children with obesity and NAFLD than in children without obesity and NAFLD, with ORs ranging from 6.23 (95% CI: 4.56, 8.53) to 1.77 (95% CI: 1.06, 2.94). The ORs of metabolic abnormalities, except for low HDL-C, were greater in children with NAFLD alone than in children without obesity or NAFLD, with ORs ranging from 4.36 (95% CI: 2.77, 6.84) to 2.08 (95% CI: 1.14, 3.78). Notably, obesity and NAFLD had a multiplicative effect on overall metabolic abnormalities, high TG levels, and low HDL-C levels. CONCLUSIONS: Children with obesity and NAFLD could be at a significantly increased risk of metabolic abnormalities. Even for children without obesity, NAFLD appears to be associated with an increased risk of experiencing a worsened metabolic status.
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Objective: To investugate the unique electrocardiogram (ECG) characteristics of fulminant myocarditis (FM) patients and provide important clues for the diagnosis of FM. Methods: This was a retrospective study. Patients diagnosed with acute myocarditis at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from February 2017 to April 2022 were enrolled and divided into fulminant myocarditis group (FM) and non-fulminant myocarditis group (NFM) according to clinical diagnosis. A total of 246 healthy people who underwent physical examination in the Health examination Center of Tongji Hospital at the same period were selected as the control group. The clinical data and ECG characteristics of the above 3 groups were analyzed and compared. Logistic regression model was used to analyze the influence of ECG parameters on left ventricular ejection fraction in FM patients. Receiver operating curves were constructed to evaluate the predictive value of different ECG parameters for FM. Results: A total of 180 patients were included in this study (FM group: n=123; NFM group: n=57), with an age of (35.0±16.2) years and 106 males (58.89%). Compared with NFM group, ECG was significantly abnormal in FM group, with a higher incidence of sinus tachycardia, ventricular tachycardia or ventricular fibrillation, escape rhythm, right bundle branch block, third degree atrioventricular block, ST-segment elevation, low voltage, prolonged QTc interval, and widened QRS wave in the FM group (all P<0.05). The ECG parameters showed that the amplitude of the full lead QRS wave in FM group was lower than that in NFM group (P<0.01). The average heart rate and QTc interval of FM group were significantly higher than those of NFM and control groups (all P<0.05). Although ST-segment elevation had a higher incidence in the FM group, ECG parameters showed that except for leads â ¢ and aVF, the ST segment levels in all leads in the FM group were lower than those in the control group (all P<0.05). There was a statistically significant difference in some ST segment changes between FM and NFM groups, while there was no statistical difference between the NFM and control groups. Multivariate regression analysis showed that widened QRS wave and increased heart rate were the influencing factors for left ventricular systolic dysfunction in FM patients (OR=16.914, 95%CI: 1.367-209.224, P=0.028; OR=1.026, 95%CI: 1.010-1.042, P=0.001). Receiver operating curve analysis showed that heart rate>86.90 beat/min, QTc>431.50 ms, and RV5+SV1<1.72 mV had certain predictive value for FM diagnosis. Conclusions: FM patients displayed marked and severe ECG abnormalities, and characteristic changes in ECG can provide important first clues for the diagnosis of FM.
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Eletrocardiografia , Miocardite , Humanos , Miocardite/fisiopatologia , Miocardite/diagnóstico , Masculino , Eletrocardiografia/métodos , Feminino , Estudos Retrospectivos , Adulto , Pessoa de Meia-Idade , Doença Aguda , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/diagnósticoAssuntos
Atrofia Muscular Espinal , Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Atrofia Muscular Espinal/terapia , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/tratamento farmacológico , Atrofias Musculares Espinais da Infância/terapia , Atrofias Musculares Espinais da Infância/genética , Atrofias Musculares Espinais da Infância/diagnóstico , Atrofias Musculares Espinais da Infância/tratamento farmacológico , Proteína 2 de Sobrevivência do Neurônio Motor/genética , Criança , Éxons , OligonucleotídeosRESUMO
AIM: To investigate the application value of dual-layer detector computed tomography (CT) single-energy spectral images for reducing artefacts in the lower cervical spine. MATERIALS AND METHODS: Sixty-three patients who underwent neck examination using spectral CT between March 2022 and January 2023 were selected as the participants. Conventional mixed-energy images and spectral imaging data at 40-200 KeV were obtained from the spectral CT scans. The standard deviation (SD), signal-to-noise ratio (SNR), |CTdifference| (the difference in CT value between the C6-7 and C3-4 artefact regions), and contrast-to-noise ratio (CNR) of the C6-7 spinal canal were measured. The image quality of the artefact region in the conventional and single images were compared. RESULTS: The SDintervertebral disc value was highest in the single-level 40 KeV images and lowest in the 120 KeV images (P<0.05). The SNR was lowest in the 40 KeV images (2.07 ± 2.74) and highest in the 120 KeV images (6.20 ± 5.26) (P<0.05). The CTdifference was highest in the 40 KeV images and lowest in the 120 KeV images (108.38 vs. 10.63 ± 8.58). The subjective image quality scores were lowest in the 40 KeV images and highest in the 120 KeV images. CONCLUSION: Our findings suggest that single-energy 120 KeV images may offer benefits such as low SDintervertebral disc, elevated SNR, higher CNR, and improved image quality.
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The number of adults living with cystic fibrosis (CF) has already increased significantly because of drastic improvements in life expectancy attributable to advances in treatment, including the development of highly effective modulator therapy. Chronic airway inflammation in CF contributes to morbidity and mortality, and aging processes like inflammaging and cell senescence influence CF pathology. Our results show that single-cell RNA sequencing data, human primary bronchial epithelial cells from non-CF and CF donors, a CF bronchial epithelial cell line, and Cftr-knockout (Cftr-/-) rats all demonstrated increased cell senescence markers in the CF bronchial epithelium. This was associated with upregulation of fibroblast growth factor receptors (FGFRs) and mitogen-activated protein kinase (MAPK) p38. Inhibition of FGFRs, specifically FGFR4 and to some extent FGFR1, attenuated cell senescence and improved mucociliary clearance, which was associated with MAPK p38 signaling. Mucociliary dysfunction could also be improved using a combination of senolytics in a CF ex vivo model. In summary, FGFR/MAPK p38 signaling contributes to cell senescence in CF airways, which is associated with impaired mucociliary clearance. Therefore, attenuation of cell senescence in the CF airways might be a future therapeutic strategy improving mucociliary dysfunction and lung disease in an aging population with CF.
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Senescência Celular , Fibrose Cística , Mucosa Respiratória , Fibrose Cística/metabolismo , Fibrose Cística/patologia , Fibrose Cística/genética , Fibrose Cística/tratamento farmacológico , Humanos , Animais , Ratos , Mucosa Respiratória/metabolismo , Mucosa Respiratória/patologia , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/genética , Células Epiteliais/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/genética , Masculino , Modelos Animais de Doenças , Linhagem Celular , Brônquios/patologia , Brônquios/metabolismo , Transdução de Sinais , FemininoRESUMO
OBJECTIVE: This work aimed to parse out the role of changing environments on body composition, total energy expenditure, and physical activity in the Mexican Pima, a population experiencing rapid industrialization. METHODS: Using doubly labeled water, we compared energy expenditure and physical activity in a longitudinal cohort of Mexican Pima (n = 26; female: 12) in 1995 and 2010. Body mass and composition were assessed by bioimpedance analysis. To determine the effects of environmental factors on body weight independent of age, we compared the 1995 longitudinal cohort with an age- and sex-matched cross-sectional cohort (n = 26) in 2010. RESULTS: Body mass, fat mass, and fat-free mass all significantly increased between 1995 and 2010. Despite a 13% average increase in body weight, weight-adjusted total daily energy expenditure decreased significantly. Measured physical activity levels also decreased between 1995 and 2010, after we adjusted for weight. CONCLUSIONS: Our results suggest that the recent industrialization of the Maycoba region in Sonora, Mexico, has contributed to a decrease in physical activity, in turn contributing to weight gain and metabolic disease among the Mexican Pima.
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Composição Corporal , Metabolismo Energético , Humanos , Metabolismo Energético/fisiologia , Feminino , Masculino , México , Estudos Transversais , Adulto , Estudos Longitudinais , Índice de Massa Corporal , Pessoa de Meia-Idade , Atividade Motora/fisiologia , Peso Corporal , Exercício Físico/fisiologia , Aumento de Peso/fisiologia , Adulto Jovem , Meio Ambiente , Obesidade/epidemiologiaRESUMO
Netrin-1 (NTN-1) plays a vital role in the progress of nervous system development and inflammatory diseases. However, the role and underlying mechanism of NTN-1 in inflammatory pain (IP) are unclear. BV2 microglia were treated with LPS to mimic the cell status under IP. Adeno-associated virus carrying the NTN-1 gene (AAV-NTN-1) was used to overexpress NTN-1. Complete Freund's Adjuvant (CFA)-induced mouse was recruited as an in vivo model. MTT and commercial kits were utilized to evaluate cell viability and cell death of BV2 cells. The mRNA expressions and secretions of cytokines were measured using the ELISA method. Also, the pyroptosis and activation of BV2 cells were investigated based on western blotting. To verify the role of Rac1/NF-kappaB signaling, isochamaejasmin (ISO) and AAV-Rac1 were presented. The results showed that NTN-1 expression was decreased in LPS-treated BV2 microglia and spinal cord tissues of CFA-injected mice. Overexpressing NTN-1 dramatically reversed cell viability and decreased cell death rate of BV2 microglia under lipopolysaccharide (LPS) stimulation, while the level of pyroptosis was inhibited. Besides, AAV-NTN-1 rescued the activation of microglia and inflammatory injury induced by LPS, decreasing IBA-1 expression, as well as iNOS, IL-1beta and IL-6 secretions. Meanwhile AAV-NTN-1 promoted the anti-inflammation response, including increases in Arg-1, IL-4 and IL-10 levels. In addition, the LPS-induced activation of Rac1/NF-kappaB signaling was depressed by NTN-1 overexpression. The same results were verified in a CFA-induced mouse model. In conclusion, NTN-1 alleviated IP by suppressing pyroptosis and promoting M2 type activation of microglia via inhibiting Rac1/NF-?B signaling, suggesting the protective role of NTN-1 in IP. Keywords: Netrin-1, Inflammatory pain, Pyroptosis, Microglia M2 activation, Rac1/NF-kappaB.
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Inflamação , Microglia , NF-kappa B , Netrina-1 , Neuropeptídeos , Piroptose , Transdução de Sinais , Proteínas rac1 de Ligação ao GTP , Animais , Piroptose/fisiologia , Piroptose/efeitos dos fármacos , Microglia/metabolismo , Camundongos , Netrina-1/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , NF-kappa B/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos Endogâmicos C57BL , Dor/metabolismo , Linhagem Celular , LipopolissacarídeosRESUMO
To find a way to control the electron-bunching process and the bunch-emitting directions when an ultraintense, linearly polarized laser pulse interacts with a nanoscale target, we explored the mechanisms for the periodical generation of relativistic attosecond electron bunches. By comparing the simulation results of three different target geometries, the results show that for nanofoil target, limiting the transverse target size to a small value and increasing the longitudinal size to a certain extent is an effective way to improve the total electron quantity in a single bunch. Then the subfemtosecond electronic dynamics when an ultrashort ultraintense laser grazing propagates along a nanofoil target was analyzed through particle-in-cell simulations and semiclassical analyses, which shows the detailed dynamics of the electron acceleration, radiation, and bunching process in the laser field. The analyses also show that the charge separation field produced by the ions plays a key role in the generation of electron bunches, which can be used to control the quantity of the corresponding attosecond radiation bunches by adjusting the length of the nanofoil target.
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This review assesses interventions to reduce loneliness in Chinese older adults, analyzing 36 studies involving 3965 participants. Focusing on individuals aged 50 and over, the meta-analysis reveals a significant overall effect size (Hedges' g = 0.937, 95% CI [0.71,1.16], p<0.001), highlighting the effectiveness of psychological and mixed-method approaches. Despite promising results, methodological concerns suggest cautious interpretation. Future research should aim to refine intervention quality and examine the impact of technology-supported methods on loneliness.
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Objective: To analysis the incidence rate and mortality rate of endometrial cancer in China from 2004 to 2017 according to the data from China Cancer Registry Annual Report. Methods: The incidence and mortality data of endometrial cancer were extracted from the China Cancer Registry Annual Report 2004 to 2017, and the incidence, mortality, number of new cases, number of deaths were extracted according to the region (national, urban, rural and eastern, middle and western areas) and the age composition of population to estimate the incidence and mortality of endometrial cancer nationwide. The age-standardized incidence rate and mortality rate were calculated based on the Chinese standard population in 2000 (ASIRC, ASIRW) and Segi's world population (ASMRC, ASMRW). Join Point regression was used to calculate the annual percentage change of morbidity rate, and Cochran-Armitage trend test was used to analyze the changing trend of morbidity and mortality. Results: From 2004 to 2017, the number of women covered by the China Cancer Registry Annual Report has increased from 35 571 657 to 215 201 995, and the total population of the covered areas has increased from 5.53% to 31.39%. The crude incidence rate of endometrial cancer increased from 6.20/100 000 to 10.06/100 000, and showed an upward trend over time (P<0.001). After adjusting for age, ASIRC increased from 5.75/100 000 in 2004 to 6.79/100 000 in 2017, and ASIRW increased from 5.60/100 000 in 2004 to 6.56/100 000 in 2017, both showing an upward trend over time (all P<0.001). The crude incidence rates in urban area and rural area were respectively 10.89/100 000 and 9.25/100 000 in 2017, and the ASIRC was higher in urban than rural areas (7.14/100 000 vs 6.43/100 000) after adjusting for age. The ASIRW was higher in eastern areas than middle areas and western areas (7.16/100 000 vs 6.44/100 000 vs 5.60/100 000). The incidence rate in rural areas showed more significant growth than urban areas [annual percent change (APC): 3.2% vs 0.7%, P<0.001]. The age-specific incidence rate increased with age and reached a peak in the age group of 50-54 years (25.70/100 000). Incidence rate in the under-40 age group increased more in rural areas than in urban areas (69.84% vs-7.09%). From 2004 to 2017, the age-standardized mortality rate shows a decreasing trend, with the ASMRC from 1.83/100 000 to 1.47/100 000, and the ASMRW from 1.81/100, 000 to 1.46/100, 000. There was no significant difference between urban and rural areas in mortality of endometrial cancer. Age-specific mortality rates increased with age, reaching a peak in the age group 85 years and older (13.16/100 000). Conclusions: Recent years, there was an increasing incidence rate of endometrial cancer in China. Especially in rural areas, the incidence rate of endometrial cancer is increasing rapidly in young women under 40 years of age. There were differences between urban and rural areas and regions in the incidence rate of endometrial cancer. The incidence rates of endometrial cancer in some high-income cities have occupied the first place of female reproductive system malignant cancers. The age-standardized mortality rate of endometrial cancer shows a decreasing trend.
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Neoplasias do Endométrio , Neoplasias dos Genitais Femininos , Humanos , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Incidência , População Urbana , Neoplasias do Endométrio/epidemiologia , População Rural , Sistema de Registros , China/epidemiologiaRESUMO
Epigenetic modifications are involved in fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF), and contribute to the silencing of anti-fibrotic genes. H3K27me3, a key repressive histone mark, is catalysed by the methyltransferase enhancer of Zeste homologue 2 (EZH2), which is regulated by the post-translational modification, O-linked N-Acetylglucosamine (O-GlcNAc). In this study, we explored the effects of O-GlcNAc and EZH2 on the expression of antifibrotic genes, cyclooxygenase-2 (Cox2) and Heme Oxygenase (Homx1). The expression of Cox2 and Hmox1 was examined in primary IPF or non-IPF lung fibroblasts with or without EZH2 inhibitor EZP6438, O-GlcNAc transferase (OGT) inhibitor (OSMI-1) or O-GlcNAcase (OGA) inhibitor (thiamet G). Non-IPF cells were also subjected to TGF-ß1 with or without OGT inhibition. The reduced expression of Cox2 and Hmox1 in IPF lung fibroblasts is restored by OGT inhibition. In non-IPF fibroblasts, TGF-ß1 treatment reduces Cox2 and Hmox1 expression, which was restored by OGT inhibition. ChIP assays demonstrated that the association of H3K27me3 is reduced at the Cox2 and Hmox1 promoter regions following OGT or EZH2 inhibition. EZH2 levels and stability were decreased by reducing O-GlcNAc. Our study provided a novel mechanism of O-GlcNAc modification in regulating anti-fibrotic genes in lung fibroblasts and in the pathogenesis of IPF.
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Histonas , Fibrose Pulmonar Idiopática , Humanos , Histonas/metabolismo , Acetilglucosamina/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Pulmão/metabolismo , Fibroblastos/metabolismo , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismoRESUMO
Intestinal epithelial expression of the tight junction protein claudin-2, which forms paracellular cation and water channels, is precisely regulated during development and in disease. Here, we show that small intestinal epithelial claudin-2 expression is selectively upregulated in septic patients. Similar changes occurred in septic mice, where claudin-2 upregulation coincided with increased flux across the paracellular pore pathway. In order to define the significance of these changes, sepsis was induced in claudin-2 knockout (KO) and wild-type (WT) mice. Sepsis-induced increases in pore pathway permeability were prevented by claudin-2 KO. Moreover, claudin-2 deletion reduced interleukin-17 production and T cell activation and limited intestinal damage. These effects were associated with reduced numbers of neutrophils, macrophages, dendritic cells, and bacteria within the peritoneal fluid of septic claudin-2 KO mice. Most strikingly, claudin-2 deletion dramatically enhanced survival in sepsis. Finally, the microbial changes induced by sepsis were less pathogenic in claudin-2 KO mice as survival of healthy WT mice injected with cecal slurry collected from WT mice 24 h after sepsis was far worse than that of healthy WT mice injected with cecal slurry collected from claudin-2 KO mice 24 h after sepsis. Claudin-2 upregulation and increased pore pathway permeability are, therefore, key intermediates that contribute to development of dysbiosis, intestinal damage, inflammation, ineffective pathogen control, and increased mortality in sepsis. The striking impact of claudin-2 deletion on progression of the lethal cascade activated during sepsis suggests that claudin-2 may be an attractive therapeutic target in septic patients.
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Claudina-2 , Sepse , Animais , Humanos , Camundongos , Claudina-2/genética , Claudina-2/metabolismo , Disbiose/genética , Disbiose/metabolismo , Função da Barreira Intestinal , Mucosa Intestinal/metabolismo , Permeabilidade , Sepse/metabolismo , Junções Íntimas/metabolismo , Regulação para CimaRESUMO
To explore screening tools for children with autism spectrum disorder (ASD), which are convenient for primary hospitals, it can provide basic data for formulating ASD prevention policies. This was a cross-sectional study by cluster sampling. Huyi District and Xincheng District were extracted for investigation in Xi'an City. From July 2021 to September 2022, all children aged from 3 months to 36 months who live in the two districts were subjected to primary screening. The child care physician used the routine screening tool "warning signs checklist for screening psychological, behavioral and developmental problems of children" and cartoon pictures of "early high-risk warning signs of autism", the children who were positive in the initial screening were referred to the district level maternal and child health hospital for re-screening, and those who were positive in the re-screening were referred to Xi 'an Children's Hospital for diagnosis. The results showed that a total of 17 905 children aged from 3 months to 36 months were initially screened in the two districts, including 10 588 children aged from 18 months to 36 months, 50 children who were positive in the initial screening and 50 children who were re-screened. 23 children (18 boys and 5 girls) were diagnosed with ASD. The prevalence rate of ASD in children was 2.17 (95% confidence interval:1.29-3.06). 42 children were positive for "warning signs checklist" at the preliminary screening, and 19 were confirmed as ASD. 27 children were positive for "cartoon pictures" in the preliminary screening, and 23 were confirmed with ASD. The "cartoon pictures" in the preliminary screening and diagnosis of consistent rate was higher than the "warning signs checklist", two kinds of screening methods comparison were statistically significant difference in the odds of consistent (χ2=11.01, P=0.001). In conclusion, relying on the three-level network of maternal and child health care, it is conducive to the whole process management of screening and diagnosis of children with ASD, and to guide the formulation of prevention policies. The cartoon pictures of "early high-risk warning signs of autism" can assist the identification of children with ASD based on the "warning signs checklist", which is simple, effective and suitable for promotion in the community health care.
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Transtorno do Espectro Autista , Transtorno Autístico , Masculino , Feminino , Humanos , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Estudos Transversais , Programas de Rastreamento/métodos , PrevalênciaRESUMO
BACKGROUND: Previous studies only focused on changes in the global age-specific incidence and mortality for Alzheimer's disease and other dementias, failed to distinguish between cohort and period effects, and did not discuss risk factors separately. METHODS: In this study, Alzheimer's disease disability-adjusted life years (DALYs) data to estimate the burden by gender, age, locations, and social-demographic status for 21 regions from 1990 to 2019. Additionally, trend analysis was performed using the age-period-cohort (APC) model and Join-point model. RESULTS: In most regions, indicators (incidence, mortality, and DALYs) increased steadily with socio-demographic index(SDI) increased. The age effects for Alzheimer's disease and other dementias showed a significant increase from 40 to 95 years. The cohort effects rate ratios (RRs) had a rapid reduction attributed to smoking, high fasting plasma glucose, and high body mass index (BMI). CONCLUSIONS: Countries in middle-low and low SDI regions have higher levels of risk factor exposure. As a result, rapid and effective government responses are necessary to control dementia risk factors and reduce the disease burden in these countries.
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Doença de Alzheimer , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Carga Global da Doença , Estilo de Vida , Fatores SocioeconômicosRESUMO
The use of cosmetics in the crowd has the long-term characteristics. The adverse reactions of cosmetics reported in other country in the world suggest that human patch tests and short-term human using test may not be sufficient to evaluate the safety of high-risk new cosmetic raw ingredients, and long-term human using test should be conducted for evaluation. Therefore, this article reviews the key factors that affect long-term human trial trials, such as site of use, single-use amount, frequency of use, duration of use, and subject conditions, providing supportive evidence for standardized safety evaluation standards for long-term human using test of cosmetics.
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Cosméticos , Experimentação Humana , HumanosRESUMO
OBJECTIVE: To explore the effects of sulforaphane (SFN) and Aß25-35 fibers (fAß25-35) on M1/M2 polarization of BV-2 cells and neuroinflammation-mediated programmed necrosis of neural stem cells. METHODS: BV-2 cells treated with different concentrations of fAß25-35 and SFN were examined for changes in cell viability using the CCK-8 kit. The effect of fAß25-35 alone or in combination with SFN or SB203580 on expressions of IL-6 and TNF-α mRNA and proteins were assessed in BV-2 cells using RT-qPCR and ELISA. CD16/32 and CD206 in the treated cells were analyzed with flow cytometry, and the cellular expressions of p-p38 and p-p65 protein were detected with Western blotting. C17.2 cells co-cultured with BV-2 cells for 24 h were examined for p-mlkl protein expression using Western blotting. RESULTS: fAß25-35 at the concentration of 6.25 µmol/L significantly increased the viability of BV-2 cells (P < 0.01) whereas fAß25-35 beyond 50 µmol/L decreased the cell viability (P < 0.0001). Treatment of BV-2 cells with SFN below 10 µmol/L for 24 h did not significant affect the cell viability (P > 0.05). BV-2 cells treated with fAß25-35 alone, as compared with the cells in the other 3 groups, showed significantly increased IL-6 and TNF-α mRNA and protein expressions (P < 0.001), enhanced CD16/32 expression (P < 0.05), lowered CD206 expression (P < 0.01), and increased protein expressions of p-p38 and p- p65 (P < 0.01). C17.2 cells co-cultured with BV-2 cells treated with fAß25-35, compared with the combined treatments, showed a significant reduction in the protein expression of p-mlkl (P < 0.05). CONCLUSION: SFN reverses M1 type microglia polarization and neuroinflammation-mediated programmed necrosis of neural stem cells by downregulating the MAPK/NF-κB signaling pathway in Aß25-35-activated BV-2 cells.
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NF-kappa B , Células-Tronco Neurais , Humanos , Interleucina-6 , Microglia , Necroptose , Doenças Neuroinflamatórias , Fator de Necrose Tumoral alfa , Transdução de Sinais , Necrose , RNA MensageiroRESUMO
MicroRNAs (miRNAs) may be important mediators of the profound molecular and cellular changes that occur after traumatic brain injury (TBI). However, the changes and possible roles of miRNAs induced by voluntary exercise prior to TBI are still not known. In this report, the microarray method was used to demonstrate alterations in miRNA expression levels in the cerebral cortex of TBI mice that were pretrained on a running wheel (RW). Voluntary RW exercise prior to TBI: i) significantly decreased the mortality rate and improved the recovery of the righting reflex in TBI mice, and ii) differentially changed the levels of several miRNAs, upregulating some and downregulating others. Furthermore, we revealed global upregulation of miR-21, miR-92a, and miR-874 and downregulation of miR-138, let-7c, and miR-124 expression among the sham-non-runner, TBI-non-runner, and TBI-runner groups. Quantitative reverse transcription polymerase chain reaction data (RT-qPCR) indicated good consistency with the microarray results. Our microarray-based analysis of miRNA expression in mice cerebral cortex after TBI revealed that some miRNAs such as miR-21, miR-92a, miR-874, miR-138, let-7c, and miR-124 could be involved in the prevention and protection afforded by voluntary exercise in a TBI model.
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Humanos , Anti-Infecciosos/uso terapêutico , Revisão de Uso de Medicamentos , Anti-Infecciosos/economia , Custos de Medicamentos , Revisão de Uso de Medicamentos/organização & administraçãoRESUMO
To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis.