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INTRODUCTION: The bidirectional relationship between the brain cortex and cardiovascular diseases (CVDs) remains inadequately explored. METHODS: This study used bidirectional Mendelian randomization (MR) analysis to explore the interactions between nine phenotypes associated with hypertension, heart failure, atrial fibrillation (AF), and coronary heart disease (CHD), and brain cortex measurements. These measurements included total surface area (SA), average thickness (TH), and the SA and TH of 34 regions defined by the Desikan-Killiany atlas. The nine traits were obtained from sources such as the UK Biobank and FinnGen, etc., while MRI-derived traits of cortical structure were sourced from the ENIGMA Consortium. The primary estimate was obtained using the inverse-variance weighted approach. A false discovery rate adjustment was applied to the p-values (resulting in q-values) in the analyses of regional cortical structures. RESULTS: A total of 1,260 two-sample MR analyses were conducted. Existing CHD demonstrated an influence on the SA of the banks of the superior temporal sulcus (bankssts) (q=0.018) and the superior frontal lobe (q=0.018), while hypertension was associated with changes in the TH of the lateral occipital region (q=0.02). Regarding the effects of the brain cortex on CVD incidence, total SA was significantly associated with the risk of CHD. Additionally, 16 and 3 regions exhibited significant effects on blood pressure and AF risk, respectively (q<0.05). These regions were primarily located in the frontal, temporal, and cingulate areas, which are associated with cognitive function and mood regulation. CONCLUSION: The detection of cortical changes through MRI could aid in screening for potential neuropsychiatric disorders in individuals with established CVD. Moreover, abnormalities in cortical structure may predict future CVD risk, offering new insights for prevention and treatment strategies.
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To establish functional circuitry, neurons settle down in a particular spatial domain by spacing their cell bodies, which requires proper positioning of the soma and establishing of a zone with unique connections. Deficits in this process are implicated in neurodevelopmental diseases. In this study, we examined the function of EphB6 in the development of cerebral cortex. Overexpression of EphB6 via in utero electroporation results in clumping of cortical neurons, while reducing its expression has no effect. In addition, overexpression of EphrinB2, a ligand of EphB6, also induces soma clumping in the cortex. Unexpectedly, the soma clumping phenotypes disappear when both of them are overexpressed in cortical neurons. The mutual inhibitory effect of EphB6/ EphrinB2 on preventing soma clumping is likely to be achieved via interaction of their specific domains. Thus, our results reveal a combinational role of EphrinB2/EphB6 overexpression in controlling soma spacing in cortical development.
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Efrina-B2 , Receptor EphB6 , Receptor EphB6/metabolismo , Efrina-B2/genética , Efrina-B2/metabolismo , Cuerpo Celular/metabolismo , Neuronas/metabolismoRESUMEN
The accurate expression of postsynaptic AMPA receptors (AMPARs) is critical for information processing in the brain, and ubiquitination is a key regulator for this biological process. However, the roles of E3 ubiquitin ligases in the regulation of AMPARs are poorly understood. Here, we find that RNF220 directly interacts with AMPARs to meditate their polyubiquitination, and RNF220 knockout specifically increases AMPAR protein levels, thereby enhancing basal synaptic activity while impairing synaptic plasticity. Moreover, depending on its E3 ubiquitin ligase activity, RNF220 represses AMPAR-mediated excitatory synaptic responses and their neuronal surface expression. Furthermore, learning and memory are altered in forebrain RNF220-deficient mice. In addition, two neuropathology-related RNF220 variants fail to repress excitatory synaptic activity because of the incapability to regulate AMPAR ubiquitination due to their attenuated interaction. Together, we identify RNF220 as an E3 ubiquitin ligase for AMPARs and establish its substantial role in excitatory synaptic transmission and brain function.
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OBJECTIVES: Despite of strenuous research in the past decades, the etiology of schizophrenia (SCZ) still remains incredibly controversial. Previous genetic analysis has uncovered a close association of Unc-51 like kinase 4 (ULK4), a family member of Unc-51-like serine/threonine kinase, with SCZ. However, animal behavior data which may connect Ulk4 deficiency with psychiatric disorders, particularly SCZ are still missing. METHODS: We generated Emx1-Cre:Ulk4flox/flox conditional knockout (CKO) mice, in which Ulk4 was deleted in the excitatory neurons of cerebral cortex and hippocampus. RESULTS: The cerebral cellular architecture was maintained but the spine density of pyramidal neurons was reduced in Ulk4 CKO mice. CKO mice showed deficits in the spatial and working memories and sensorimotor gating. Levels of p-Akt and p-GSK-3α/ß were markedly reduced in the CKO mice indicating an elevation of GSK-3 signaling. Mechanistically, Ulk4 may regulate the GSK-3 signaling via putative protein complex comprising of two phosphatases, protein phosphatase 2A (PP2A) and 1α (PP1α). Indeed, the reduction of p-Akt and p-GSK-3α/ß was rescued by administration of inhibitor acting on PP2A and PP1α in CKO mice. CONCLUSIONS: Our data identified potential downstream signaling pathway of Ulk4, which plays important roles in the cognitive functions and when defective, may promote SCZ-like pathogenesis and behavioral phenotypes in mice.
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Proteínas Serina-Treonina Quinasas , Esquizofrenia , Animales , Cognición , Eliminación de Gen , Glucógeno Sintasa Quinasa 3/metabolismo , Ratones , Ratones Noqueados , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Esquizofrenia/genética , Esquizofrenia/patología , Transducción de SeñalRESUMEN
Brain community detection is an efficient method to represent the communities of brain networks. However, time-variable functions of the brain and the intricate brain community structure impose a great challenge on it. In this paper, a time-sequential graph adversarial learning (TGAL) framework is proposed to detect brain communities and characterize the structure of communities from brain networks. In the framework, a novel time-sequential graph neural network is designed as an encoder to extract efficient graph representations by spatio-temporal attention mechanism. Since it is difficult to capture the community structure, the measurable modularity loss is used to optimize by maximizing the modularity of the community. In addition, the framework employs an adversarial scheme to guide the learning of representation. The effectiveness of our model is shown through experiments on the real-world brain network datasets, and the great performance of brain community detection demonstrates the advantage of the proposed framework.
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Encéfalo , Aprendizaje , Encéfalo/diagnóstico por imagen , Redes Neurales de la ComputaciónRESUMEN
Soma spacing and dendritic arborization during brain development are key events for the establishment of proper neural circuitry and function. Transcription factor Satb2 is a molecular node in regulating the development of the cerebral cortex, as shown by the facts that Satb2 is required for the regionalization of retrosplenial cortex, the determination of callosal neuron fate, and the regulation of soma spacing and dendritic self-avoidance of cortical pyramidal neurons. In this study, we explored downstream effectors that mediate the Satb2-implicated soma spacing and dendritic self-avoidance. First, RNA-seq analysis of the cortex revealed differentially expressed genes between control and Satb2 CKO mice. Among them, EphA7 transcription was dramatically increased in layers II/III of Satb2 CKO cortex. Overexpression of EphA7 in the late-born cortical neurons of wild-type mice via in utero electroporation resulted in soma clumping and impaired self-avoidance of affected pyramidal neurons, which resembles the phenotypes caused by knockdown of Satb2 expression. Importantly, the phenotypes by Satb2 knockdown was rescued by reducing EphA7 expression in the cortex. Finally, ChIP and luciferase reporter assays indicated a direct suppression of EphA7 expression by Satb2. These findings provide new insights into the complexity of transcriptional regulation of the morphogenesis of cerebral cortex.
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Corteza Cerebral , Neuronas , Animales , Cuerpo Celular/metabolismo , Corteza Cerebral/metabolismo , Proteínas de Unión a la Región de Fijación a la Matriz , Ratones , Neuronas/metabolismo , Células Piramidales/metabolismo , Receptor EphA7 , Factores de Transcripción/metabolismoRESUMEN
BACKGROUND: Strict countermeasures for coronavirus disease (COVID-19) were undertaken in China without knowing their influence on asthma. OBJECTIVE: To investigate the associations between the frequencies of asthma exacerbations and respiratory infections and air pollutants before and during the COVID-19 pandemic, which were direct consequences of countermeasures undertaken for the pandemic. METHODS: Asthma exacerbations and respiratory infections among hospitalized children in the permanent population of Guangzhou City, China, from February to June 2016-2019 (before the pandemic) to February to June 2020 (during the pandemic) were collected in this cross-sectional study in Guangzhou. RESULTS: The number of asthma exacerbation cases per month documented in the Guangzhou Women and Children's Hospital before (median: 13.5; range: 0-48) and during (median: 20; range: 0-34) the mitigative response to the COVID-19 pandemic was similar. The frequency of severe asthma exacerbation cases per month decreased, whereas that of mild asthma exacerbation cases per year increased (p = .004). The number of patients hospitalized with infectious respiratory diseases decreased from 146 (range: 90-172) per month before the pandemic to 42 (range: 33-57) per month during the pandemic (p = .004). Most pathogens and air pollutants decreased during the COVID-19 pandemic. The frequency of severe asthma exacerbations positively correlated to that of respiratory infections in children, but did not correlate to air pollutants. CONCLUSION: Strict countermeasures undertaken for the pandemic were associated with a decreased the frequency of infectious respiratory diseases and severe asthma exacerbations among urban children.
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Asma/epidemiología , COVID-19/epidemiología , SARS-CoV-2 , Adolescente , Contaminantes Atmosféricos , COVID-19/prevención & control , Niño , Preescolar , China/epidemiología , Estudios Transversales , Progresión de la Enfermedad , Femenino , Hospitalización , Hospitales Pediátricos , Humanos , Masculino , PandemiasRESUMEN
PURPOSE: We investigated whether increased expression of activated mitogen-activated protein kinase (MAPK) kinases 1 (MEK1) restores ischemic post-conditioning (IPostC) protection in hypertrophic myocardium following ischemia/reperfusion (I/R) injury. METHODS: C57Bl/6 mice received recombinant adeno-associated virus type 9 (rAAV9)-mediated activated MEK1 gene delivery systemically, then following the induction of cardiac hypertrophy via transverse aortic constriction for 4 weeks. In a Langendorff model, hypertrophic hearts were subjected to 40 min/60 min I/R or with IPostC intervention consisting of 6 cycles of 10 s reperfusion and 10 s no-flow before a 60-min reperfusion. Hemodynamics, infarct size (IS), myocyte apoptosis and changes in expression of reperfusion injury salvage kinase (RISK) pathway were examined. RESULTS: rAAV9-MEK1 gene delivery led to a 4.3-fold and 2.7-fold increase in MEK1 mRNA and protein expression in the heart versus their control values. I/R resulted in a larger IS in hypertrophic than in non-hypertrophic hearts (52.3 ± 4.7% vs. 40.0 ± 2.5%, P < 0.05). IPostC mediated IS reduction in non-hypertrophic hearts (27.6 ± 2.6%, P < 0.05), while it had no significant effect in hypertrophic hearts (46.5 ± 3.1%, P=NS) compared with the IS in non-hypertrophic or hypertrophic hearts subjected to I/R injury only, respectively. Hemodynamic decline induced by I/R was preserved by IPostC in non-hypertrophic hearts but not in hypertrophic hearts. rAAV9-MEK1 gene delivery restored IPostC protection in hypertrophic hearts evidenced by reduced IS (32.0 ± 2.8% vs. 46.5 ± 3.1%) and cardiac cell apoptosis and largely preserved hemodynamic parameters. These protective effects were associated with significantly increased phosphorylation of ERK1/2 and ribosomal protein S6 kinases (p70S6K), but it had no influence on Akt and glycogen synthase kinase-3ß. CONCLUSION: These results demonstrated that rAAV9-mediated activated MEK1 expression restores IPostC protection in the hypertrophic heart against I/R injury through the activation of ERK pathway.
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Dependovirus/genética , Técnicas de Transferencia de Gen , Vectores Genéticos , Hipertrofia Ventricular Izquierda/terapia , Poscondicionamiento Isquémico , MAP Quinasa Quinasa 1/biosíntesis , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/enzimología , Animales , Apoptosis , Modelos Animales de Enfermedad , Inducción Enzimática , Hipertrofia Ventricular Izquierda/enzimología , Hipertrofia Ventricular Izquierda/genética , Hipertrofia Ventricular Izquierda/patología , Preparación de Corazón Aislado , MAP Quinasa Quinasa 1/genética , Masculino , Ratones Endogámicos C57BL , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Infarto del Miocardio/enzimología , Infarto del Miocardio/genética , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , Fosforilación , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismoRESUMEN
Noradrenaline belongs to the monoamine system and is involved in cognition and emotional behaviors. Phox2a and Phox2b play essential but non-redundant roles during development of the locus coeruleus (LC), the main noradrenergic (NA) neuron center in the mammalian brain. The ubiquitin E3 ligase Rnf220 and its cofactor Zc4h2 participate in ventral neural tube patterning by modulating Shh/Gli signaling, and ZC4H2 mutation is associated with intellectual disability, although the mechanisms for this remain poorly understood. Here, we report that Zc4h2 and Rnf220 are required for the development of central NA neurons in the mouse brain. Both Zc4h2 and Rnf220 are expressed in developing LC-NA neurons. Although properly initiated at E10.5, the expression of genes associated with LC-NA neurons is not maintained at the later embryonic stages in mice with a deficiency of either Rnf220 or Zc4h2 In addition, we show that the Rnf220/Zc4h2 complex monoubiquitylates Phox2a/Phox2b, a process required for the full transcriptional activity of Phox2a/Phox2b. Our work reveals a role for Rnf220/Zc4h2 in regulating LC-NA neuron development, and this finding may be helpful for understanding the pathogenesis of ZC4H2 mutation-associated intellectual disability.
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Neuronas Adrenérgicas/fisiología , Proteínas de Homeodominio/metabolismo , Péptidos y Proteínas de Señalización Intracelular/fisiología , Neurogénesis/fisiología , Proteínas Nucleares/fisiología , Factores de Transcripción/metabolismo , Ubiquitina-Proteína Ligasas/fisiología , Ubiquitinación/genética , Neuronas Adrenérgicas/metabolismo , Animales , Diferenciación Celular/genética , Embrión de Pollo , Embrión de Mamíferos , Femenino , Células HEK293 , Humanos , Masculino , Ratones , Ratones Transgénicos , Norepinefrina/metabolismoRESUMEN
The retrosplenial cortex (Rsp) is a transitional cortex located between the neocortex and archicortex, but the molecular mechanism specifying Rsp from the archicortex remains elusive. We here report that the transcription factor Satb2 is required for specifying Rsp identity during its morphogenesis. In Satb2 CKO mice, the boundary between the Rsp and archicortex [i.e., subiculum (SubC)] disappears as early as E17.5, and Rsp efferent projection is aberrant. Rsp-specific genes are lost, whereas SubC-specific genes are ectopically expressed in Rsp of Satb2 CKO mice. Furthermore, cell-autonomous role of Satb2 in maintaining Rsp neuron identity is revealed by inactivation of Satb2 in Rsp neurons. Finally, Satb2 represses the transcription of Nr4a2. The misexpression of Nr4a2 together with Ctip2 induces expression of SubC-specific genes in wild-type Rsp, and simultaneous knockdown of these two genes in Rsp Satb2-mutant cells prevents their fate transition to SubC identity. Thus, Satb2 serves as a determinant gene in the Rsp regionalization by repressing Nr4a2 and Ctip2 during cortical development.
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Moléculas de Adhesión Celular Neuronal/metabolismo , Giro del Cíngulo/metabolismo , Animales , Linaje de la Célula , Regulación de la Expresión Génica , Células HEK293 , Humanos , Ratones Noqueados , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares/metabolismo , Proteínas Represoras/metabolismo , Proteínas Supresoras de Tumor/metabolismoAsunto(s)
Asma , Leucocitos Mononucleares , Alérgenos , Humanos , Células Asesinas Naturales , Análisis de Secuencia de ARNRESUMEN
OBJECTIVE: To investigate the use of antibiotics in children with community-acquired pneumonia (CAP) in multiple regions of China, and to provide a reference for CAP standard treatment and rational antibiotic use in children. METHODS: The medical data of 1 383 children with CAP who were hospitalized in the department of pediatrics in 10 grade A tertiary hospitals from 9 cities between April 14, 2014 and January 1, 2016 were reviewed, to analyze the status of antibiotic use in hospitalized children in North China, Northeast China, East China, and South China. RESULTS: The overall rate of antibiotic use in children with CAP was 89.08%, with 88.7% in North China, 95.5% in Northeast China, 83.3% in East China, and 86.6% in South China. The main types of antibiotics used were cephalosporins, macrolides, compound preparations of ß-lactam antibiotics, polyphosphoric broad-spectrum antibiotics and other ß-lactam antibiotics. The selection of antibiotics was generally rational, but antibiotics were still used in some patients with viral infection alone or a combined use of ≥2 kinds of antibiotics were noted in some patients with infection caused by one kind of pathogen. Irrational antibiotic use was observed in 131 children (10.63%). CONCLUSIONS: There are high rates of antibiotic use and irrational use of antibiotics among children with CAP. Standard management of antibiotic use in children with CAP should be strengthened.
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Infecciones Comunitarias Adquiridas , Antibacterianos/uso terapéutico , Niño , Niño Hospitalizado , China , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , HumanosRESUMEN
BACKGROUND: Many spinning patents and technologies have been explored to produce diverse types of nanomaterials for different applications. As a novel method, the blown bubble-spinning is a one-step process for fabrication of nanofibrous bundles. METHOD: In this study, polyamide6/66(PA6/66) nanofibrous bundles filled with different concentrations of multi-walled carbon nanotubes (MWCNTs) were prepared by the blown bubble-spinning. The dispersion of MWCNT in nanofibers under different treatments was investigated and a detailed characterization focusing on the influence of the presence of MWCNT on the morphology, thermal property and electrical property was carried out. RESULTS: The results showed that MWCNTs treated by Tween60 and ultrasonication were embedded in the PA6/66 nanofibers with uniform dispersion. In addition, it was observed that thermal stability and electrical conductivity of nanofibrous bundles increased with an increase in MWCNT content. CONCLUSION: The PA6/66/MWCNT nanofibrous bundles fabricated by the blown bubble spinning have the great potential applications in sensors and supercapacitors.
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Electrospinning is now commercially used for the fabrication of nano/micro fibers. Compared with spider dragline silk, artificial fibers have poor mechanical properties. Unlike natural silk, which has a hierarchical structure with an approximate 3-fold symmetry, the molecular structure of spun fiber has neither folding nor orientation. To date, it is almost impossible to control molecule orientation during the spinning process. Here, we show that macromolecule orientation can be easily controlled using the laminar flow of fluid mechanics. A lasting laminar flow in a long needle can order macromolecules. We find that the orientation of macromolecules can greatly affect the morphology and mechanical properties of fibers. We expect our technology to be helpful for more sophisticated fabrication of fibers with ordered macromolecules and DNA-like twists.
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BACKGROUND: Asthma is a significant chronic health problem worldwide. Management aims at disease control by reducing functional impairment and exacerbations and improving quality of life (QoL). We report a multi-center study to survey asthma control and QoL in four cities in the Pearl River Delta. METHODS: The conjoint survey involved ten Hong Kong pediatric hospitals/units, two Shenzhen hospitals, two Macau hospitals, and two Guangzhou hospitals on asthma control (using Asthma Control Test) and QoL (Pediatric Allergic Disease Quality of Life Questionnaire, PADQLQ). Acceptability of a treatment is graded as very good/good/fair/poor. RESULTS: Good asthma control was only reported in 80% subjects in Hong Kong, but higher in sister cities (85-94%, P < 0.001). Allergic rhinitis, "incense burning", and "smoker in family" were prevalent among the four cities. Logistic regression showed better control of asthma was associated with better PADQLQ (B = - 0.029, P < 0.001), better acceptability of bronchodilator (B = - 1.488, P = 0.025), negatively with "smoker in family" (B = - 0.83, P = 0.015) and various PADQLQ domains. Conversely, worse PADQLQ was associated with allergic rhinitis severity (B = 4.77, P < 0.001), poor control of asthma (B = 7.56, P < 0.001), increased frequency of traditional Chinese medicine use (B = 1.7, P < 0.05), increased frequency of bronchodilator usage (B = 1.05, P < 0.05), "smoker in family" (B = 4.05, P < 0.05), and incense burning at home (B = 3.9, P < 0.05). CONCLUSIONS: There are some clinical and cultural differences among the four southern Chinese cities within the Guangdong province. This study identifies potentially modifiable environmental and treatment factors associated with poor asthma control and QoL for health-care interventions. Having a smoker in the family is independently associated with poor asthma control and QoL.
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Asma/diagnóstico , Asma/terapia , Terapias Complementarias/métodos , Calidad de Vida , Encuestas y Cuestionarios , Adolescente , Asma/psicología , Niño , Ciudades , Estudios Transversales , Femenino , Hong Kong , Humanos , Modelos Logísticos , Masculino , Análisis Multivariante , Pediatría , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Población UrbanaRESUMEN
Electrospinning is always used to fabricate one-dimensional nanofibers. Cylindrical fibers are formed during the spinning process due to the minimal-surface principle. However, when the moving jet has high rigidity, which can counteract the surface tension for a minimal surface, beltlike fibers can be obtained. Using the Hallâ»Petch effect, the rigidity of the moving jet can be greatly enhanced by adding nanoparticles. Polyethylene glycol with a nanometric crystallite size of 4 nm and ZrO2 nanoparticles are used as additives in the experiment, a theoretical analysis is carried out, and the theoretical predictions are verified experimentally.
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BACKGROUND: Inhaled corticosteroids (ICSs) for treating asthma are controversial because of their negative effects on the growth of asthmatic children and without clearly defined withdrawal strategy. A 2-year ICS step-down and withdrawal strategy has been developed for asthmatic children receiving 3-year subcutaneous immunotherapy (SCIT). METHODS: Eleven children were included into the SCIT group and 13 children into the ICS group. ICSs were discontinued when children met the following criteria: requiring only 1 puffper day, with good control, for at least 6 months; having a forced expiratory volume in 1 second (FEV1)/forced vital capacity ≥80%; and SCIT discontinued for ≥24 months. The main endpoints were the results of both the childhood asthma control test (C-CAT) and the methacholine bronchial provocation test. RESULTS: In the SCIT group, all the 11 children had ICS discontinued, with one child developed asthma attack after pneumonia and received ICS again after completion of SCIT. In the ICS group, five children discontinued ICS and developed asthma attacks later and received ICS again; the other eight children developed severe symptoms during ICS step-down. Thus, the discontinuation of ICS was only achieved in the SCIT group. The dose of methacholine that caused a decrease of 20% in FEV1 continued to improve after discontinuation of ICS for the SCIT group and presented better results than the ICS group (P=0.050). After completion of SCIT, the C-CAT had improved significantly after 30 months of treatment compared with the ICS group (P<0.05). CONCLUSIONS: In the present study, we developed a 2-year step-down and withdrawal strategy from ICSs strategy for allergic asthma children receiving SCIT; the strategy was efficacious and safe.
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Corticoesteroides/administración & dosificación , Asma/diagnóstico , Asma/tratamiento farmacológico , Inmunoterapia/métodos , Privación de Tratamiento , Administración por Inhalación , Corticoesteroides/efectos adversos , Niño , Preescolar , Estudios de Cohortes , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Inmunosupresores/administración & dosificación , Inyecciones Subcutáneas , Masculino , Seguridad del Paciente , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Estadísticas no Paramétricas , Factores de TiempoRESUMEN
The aim of the study is to investigate the association between the human hepatocyte nuclear factor 4 gamma (HNF4G) gene and hyperuricemia in Chinese Han population. A total of 414 hyperuricemia patients and 406 gender and age-matched normouricemic controls were enrolled. Four single nucleotide polymorphisms were genotyped as genetic markers for the human HNF4G gene (rs2977939, rs1805098, rs2941484, rs4735692). Data were analyzed for two separate groups: men and women. For rs2941484, the genotype distribution frequency in hyperuricemic subjects and was significantly different from that in normouricemic controls in men (P = 0.038). Meanwhile, in recessive model of rs2941484, the distribution frequency of TT genotype and CC+CT genotypes also differed significantly between the hyperuricemia men and normouricemic men (P = 0.011). For the other 3 SNPs in both men and women, there was no difference in the genotype and allele and distribution frequency between the hyperuricemia patients and normouricemic controls. In men, after adjustments for BMI, SBP, DBP, fasting glucose, total cholesterol, triglycerides, low density lipoprotein cholesterol and creatinine, the men with the TT genotype of rs2941484 were found to have significantly higher probability of suffering from hyperuricemia than the ones with CT and CC genotypes (OR = 2.170, P < 0.001). Therefore, TT genotype of rs2941484 in the human HNF4G gene might be a gender-specific genetic marker for hyperuricemia in Chinese Han men.
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Alelos , Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Genotipo , Factor Nuclear 4 del Hepatocito/genética , Hiperuricemia/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Biomarcadores , China , Factores de Confusión Epidemiológicos , Femenino , Estudios de Asociación Genética , Sitios Genéticos , Humanos , Hiperuricemia/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: We tested the ability of the SYNTAX score (SS) to predict 1-year adverse outcomes for patients with non-ST segment elevation acute coronary syndromes (NSTE-ACS) who undergo coronary artery bypass graft (CABG) surgery. BACKGROUND: The SS effectively risk stratifies patients who undergo percutaneous coronary intervention, but not patients with stable coronary disease who undergo CABG. METHODS: We calculated the SS for 457 patients with NSTE-ACS in the angiographic substudy of the ACUITY (Acute Catheterization and Urgent Intervention Triage StrategY) trial who underwent CABG. We stratified and compared patients according to SS tertiles. We tested the ability of the SS, as a linear covariate, to predict adverse events by univariate analyses and by univariate and multivariable Cox proportional hazards model. We also tested the predictive abilities of the Age, Creatinine Clearance, and Ejection Fraction (ACEF) score, the clinical SS, and the logistic clinical SS. RESULTS: The median SS was 23 (interquartile range, 15-30). Baseline clinical characteristics were similar among the groups. One-year mortality and major adverse cardiovascular events (all-cause death, myocardial infarction, any stroke, or urgent revascularization) were similar between the groups (P=.13 and P=.62, respectively). Receiver operating characteristic curves, net reclassification indices, and integrated discrimination indices did not improve with SS, clinical SS, or logistic clinical SS compared with the ACEF score. CONCLUSIONS: The anatomical SS does not appear to be useful in risk stratifying patients with NSTE-ACS who undergo CABG. Clinical variables may better risk stratify patients with complex coronary artery disease considered for CABG.
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Síndrome Coronario Agudo/cirugía , Puente de Arteria Coronaria/métodos , Electrocardiografía , Complicaciones Posoperatorias/epidemiología , Medición de Riesgo/métodos , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/mortalidad , Angiografía Coronaria , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Tasa de Supervivencia/tendencias , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: To determine whether TG/HDL-C ratio, which has been shown to be an indicator of the metabolic syndrome (MetS) and insulin resistance (IR), can predict cardiovascular risk factors in the Chinese Han population in Xinjiang. METHODS: The cardiovascular risk survey (CRS) was conducted from October 2007 to March 2010. A total of 14,618 representative participants were selected using a four-stage stratified sampling method. A total of 5757 Han participants were included in the study. The present statistical analysis was restricted to the 5595 Han subjects who had complete anthropometric data. The sensitivity, specificity, and distance on the receiver operating characteristic (ROC) curve in each TG/HDL level were calculated. The shortest distance in the ROC curves was used to determine the optimal cutoff of the TG/HDL-C ratio for detecting cardiovascular risk factors. RESULTS: The prevalence of hypertension, hypercholesterolemia, and hypertriglyceridemia was higher with higher TG/HDL-C ratio for both men and women. The TG/HDL-C ratio was positively associated with systolic blood pressure, diastolic blood pressure, and serum concentrations of total cholesterol. The optimal TG/HDL-C ratio cutoffs for predicting hypertension, dyslipidemia, diabetes, and ≥2 of these risk factors for Han adults in Xinjiang were 1.3, 1.3, 1.4, and 1.4 in men and 0.9, 1.0, 1.0, and 1.1 in women, respectively. CONCLUSIONS: The evaluation of TG/HDL-C ratio should be considered for one of cardiovascular risk factor predictors among Han adults in Xinjiang.