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BACKGROUND: For adolescents, abnormal dipping patterns in blood pressure (BP) are associated with early-onset organ damage and a higher risk of cardiovascular disorders in adulthood. Obesity is one of the most common reasons for abnormal BP dipping in young people. However, it is unknown whether the severity of obesity is associated with BP dipping status and whether this association is sex-dependent. METHODS: 499 participants between 12 and 17 years old with overweight or obesity underwent ambulatory blood pressure monitoring (ABPM) between April 2018 and January 2019 in Beijing and Baoding. Participants were grouped by body mass index (BMI) into overweight (BMI 85th-95th percentile), obese (BMI ≥ 95th percentile) and severely obese (BMI ≥ 120% of 95th percentile or ≥ 35 kg/m2) groups. Non-dipping was defined as a < 10% reduction in BP from day to night. The interaction effect between sex and obesity degree was also analyzed. RESULTS: 326 boys and 173 girls were included, of whom 130 were overweight, 189 were obese, and 180 were severely obese. Girls with severe obesity had a higher prevalence of non-dipping, but boys showed no significant differences in BP dipping status between obesity categories. In addition, as obesity severity went up, a more evident increase in night-time SBP was observed in girls than in boys. CONCLUSIONS: Severely obese is associated with a higher prevalence of non-BP dipping patterns in girls than in boys, which suggests that the relationship between the severity of obesity and BP dipping status might be sex-specific.
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Hipotensão , Obesidade Infantil , Adolescente , Humanos , Masculino , Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano , Hipotensão/epidemiologia , Obesidade Infantil/patologia , Prevalência , Caracteres Sexuais , FemininoRESUMO
OBJECTIVE: The goal of this study was to investigate the relationship between polymorphisms in interleukin (IL)-12, IL-12R, IL-23, and IL-23R genes and Takayasu arteritis (TA) in a Chinese population. METHODS: A case-control study was performed to investigate the associations of 19 single nucleotide polymorphisms (SNPs) mapping to IL12A, IL12B, IL12RB1, IL12RB2 and IL23R with susceptibility to TA in 145 Chinese TA patients and 300 healthy controls. Genotype identification was performed with the MassARRAY system from Sequenom. The statistical analysis was conducted by Chi square test and unconditional logistic regression with plink. RESULTS: No significant differences were found for the distribution of allele and genotype frequencies of these SNPs between TA patients and healthy controls. However, a trend for IL12A rs582054 and IL23R rs1004819 in association with the TA phenotype was detected. TA patients carrying the rs582054/rs568408 haplotype (P' = 0.019) appeared less likely to progress to a more severe form of disease. And the C allele (P' = 0.082) of IL23R rs1004819 appeared to be a protective factor to refractory disease. CONCLUSIONS: These findings suggest that the polymorphisms of IL12A, IL12B, IL12RB1, IL12RB2 and IL23R might make no contribution to the susceptibility of TA in the Chinese population.
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Subunidade p35 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/genética , Interleucina-23/genética , Receptores de Interleucina-12/genética , Receptores de Interleucina/genética , Arterite de Takayasu/genética , Adolescente , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Arterite de Takayasu/epidemiologia , Adulto JovemRESUMO
The development of single-cell RNA sequencing (scRNA-seq) technology has opened up a new perspective for us to study disease mechanisms at the single cell level. Cell clustering reveals the natural grouping of cells, which is a vital step in scRNA-seq data analysis. However, the high noise and dropout of single-cell data pose numerous challenges to cell clustering. In this study, we propose a novel matrix factorization method named NLRRC for single-cell type identification. NLRRC joins non-negative low-rank representation (LRR) and random walk graph regularized NMF (RWNMFC) to accurately reveal the natural grouping of cells. Specifically, we find the lowest rank representation of single-cell samples by non-negative LRR to reduce the difficulty of analyzing high-dimensional samples and capture the global information of the samples. Meanwhile, by using random walk graph regularization (RWGR) and NMF, RWNMFC captures manifold structure and cluster information before generating a cluster allocation matrix. The cluster assignment matrix contains cluster labels, which can be used directly to get the clustering results. The performance of NLRRC is validated on simulated and real single-cell datasets. The results of the experiments illustrate that NLRRC has a significant advantage in single-cell type identification.
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Algoritmos , Análise de Célula Única , Humanos , Análise por Conglomerados , Perfilação da Expressão Gênica/métodosRESUMO
Single-cell RNA sequencing technology provides a tremendous opportunity for studying disease mechanisms at the single-cell level. Cell type identification is a key step in the research of disease mechanisms. Many clustering algorithms have been proposed to identify cell types. Most clustering algorithms perform similarity calculation before cell clustering. Because clustering and similarity calculation are independent, a low-rank matrix obtained only by similarity calculation may be unable to fully reveal the patterns in single-cell data. In this study, to capture accurate single-cell clustering information, we propose a novel method based on a low-rank representation model, called KGLRR, that combines the low-rank representation approach with K-means clustering. The cluster centroid is updated as the cell dimension decreases to better from new clusters and improve the quality of clustering information. In addition, the low-rank representation model ignores local geometric information, so the graph regularization constraint is introduced. KGLRR is tested on both simulated and real single-cell datasets to validate the effectiveness of the new method. The experimental results show that KGLRR is more robust and accurate in cell type identification than other advanced algorithms.
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Algoritmos , Análise por ConglomeradosRESUMO
Nitric oxide (NO)-dependent pathways may play a significant role in the decline of synaptic and cognitive functions in Alzheimer's disease (AD). However, whether NO in the hippocampal dentate gyrus (DG) is involved in the spatial learning and memory impairments of AD by affecting the glutamate (Glu) response during these processes is not well-understood. Here, we prepared an AD rat model by long-term i.p. of D-galactose into ovariectomized rats, and then the effects of L-NMMA (a NO synthase inhibitor) on Glu concentration and amplitude of field excitatory postsynaptic potential (fEPSP) were measured in the DG region during the Morris water maze (MWM) test in freely-moving rats. During the MWM test, compared with the sham group, the escape latency was increased in the place navigation trial, and the percentage of time spent in target quadrant and the number of platform crossings were decreased in the spatial probe trial, in addition, the increase of fEPSP amplitude in the DG was significantly attenuated in AD group rats. L-NMMA significantly attenuated the spatial learning and memory impairment in AD rats, and reversed the inhibitory effect of AD on increase of fEPSP amplitude in the DG during the MWM test. In sham group rats, the Glu level in the DG increased significantly during the MWM test, and this response was markedly enhanced in AD rats. Furthermore, the response of Glu in the DG during spatial learning was recovered by microinjection of L-NMMA into the DG. Our results suggest that NO in the DG impairs spatial learning and memory and related synaptic plasticity in AD rats, by disturbing the Glu response during spatial learning.
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Doença de Alzheimer , Comportamento Animal , Giro Denteado , Inibidores Enzimáticos/farmacologia , Potenciais Pós-Sinápticos Excitadores , Ácido Glutâmico/metabolismo , Aprendizagem em Labirinto , Óxido Nítrico Sintase/antagonistas & inibidores , Óxido Nítrico/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Giro Denteado/efeitos dos fármacos , Giro Denteado/metabolismo , Giro Denteado/fisiopatologia , Modelos Animais de Doenças , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Aprendizagem em Labirinto/fisiologia , Ovariectomia , Ratos , Ratos Sprague-Dawley , ômega-N-Metilarginina/farmacologiaRESUMO
OBJECT: To explore the effects of occupational aluminum exposure on workers' cognitive function and blood glucose concentration, and to analyze whether blood glucose concentration can mediate the cognitive changes caused by aluminum. METHOD: Our study recruited 375 workers from an aluminum factory in northern China. We collected the fasting elbow venous blood of the workers, measured their fasting blood glucose concentration (FBG), and used ICP-MS to determine plasma aluminum concentration (P-Al) as an indicator of internal exposure. The Montreal Cognitive Assessment (MoCA), was used to assess the cognitive function of workers. Generalized linear model was used to analyze the association of P-Al with cognitive function and blood glucose concentration, and the restricted cubic spline model was used to fit the dose-response relationship. We also conducted a mediation effect analysis. RESULT: We observed the dose-response relationship, that is, as the P-Al increased, sum of MoCA, visuospatial/executive, naming, language, and abstraction scores decreased, and the blood glucose concentration increased. For every e-fold increase in P-Al, sum of MoCA, visuospatial/executive, naming, language, and abstraction scores decreased by 0.328 points, 0.120 points, 0.059 points, 0.060 points, and 0.083 points, respectively, and FBG rose by 0.109 mmol/L. FBG has a significant mediating effect between P-Al and sum of MoCA (P for mediator=0.042), and it could explain 10.7% of the effect of cognitive level related to P-Al. CONCLUSION: Occupational aluminum exposure negatively affected the cognitive function of workers and positively affected FBG. FBG may partially explain the impact of occupational aluminum exposure on workers' cognitive function.
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Disfunção Cognitiva , Exposição Ocupacional , Alumínio/toxicidade , Glicemia , Cognição , Disfunção Cognitiva/etiologia , Humanos , Idioma , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análiseRESUMO
OBJECTIVE: To establish immortalized lymphoblastoid cell lines of a Miao core pedigree with Bardet-Biedl syndrome (BBS), in order to provide a long-term source of material for research. METHODS: With Epstein-Barr virus transformation of B cells and addition of cyclosporine A to inhibit the activity of T cells, fresh anticoagulated blood samples with heparin were collected from 12 members of the core pedigree, and were used to establish the immortalized lymphoblastoid cell lines of B lymphocytes. RESULTS: Twelve immortalized lymphoblastoid cell lines of the core BBS pedigree were obtained successfully. CONCLUSION: The immortalized B lymphoblastoid cell lines of the Miao pedigree with BBS can preserve the whole genome information and provide long-term research materials for BBS study.
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Linfócitos B/citologia , Síndrome de Bardet-Biedl/sangue , Síndrome de Bardet-Biedl/genética , Transformação Celular Viral , Etnicidade/genética , Linhagem Celular , Linhagem Celular Transformada , China/etnologia , Herpesvirus Humano 4 , Humanos , LinhagemRESUMO
OBJECTIVE: To observe the effects of Benzo(a)pyrene (BaP) on apoptosis of neuronal cells and expression of Bcl-2 and Bax proteins and to explore the mechanism of neurotoxicity induced by BaP in rats. METHODS: A total of 32 SD rats were divided randomly into 4 groups, i.e. 3 BaP (126.2, 63.1 and 31.5 µg/kg) groups and a solvent control (50 µg/kg olive oil) group. All rats were exposed to BaP or olive oil by lateral cerebral ventricle micro-injection 1 time a week for 3 weeks. The apoptosis of neuronal cells was detected with TdT-mediated dUTP-biotin nicked labeling (TUNEL) assay and the expression levels of Bcl-2 and Bax were measured with SABC immunohistochemistry in the cerebral cortex and hippocampus tissues of rats. RESULTS: The results of TUNEL assay showed that apoptosis bodies on the surface of the neurons in the cerebral cortex and hippocampus were clearly observed and the number of apoptosis bodies increased with BaP. Apoptosis indexes (AIs) of the rat cerebral cortex and hippocampus in high exposure group were significantly higher than those in control group (P < 0.05 or P < 0.01). The analysis of immunohistochemistry showed that the Bcl-2 expression levels significantly decreased, the Bax expression levels obviously increased and the ratio of Bcl-2 to Bax decreased in the rat cerebral cortex and hippocampus of medium and high exposure groups, as compared with control group (P < 0.05 or P < 0.01). In the rat cerebral cortex and hippocampus, there were the negative correlation (r = -0.927, P < 0.01; r = -0.934, P < 0.01) between AI and Bcl-2, the positive correlation (r = 0.858, P < 0.01; r = 0.847, P < 0.01) between AI and Bax and the negative correlation (r = -0.939, P < 0.01; r = -0.942, P < 0.01) between AI and Bcl-2/Bax. CONCLUSION: BaP could induce the apoptosis of neuronal cells in the rat cerebral cortex and hippocampus. Bcl-2 and Bax protein expression may play an important role in the apoptosis of neuronal cells induced by BaP.
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Apoptose/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Encéfalo/metabolismo , Neurônios/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Masculino , Neurônios/metabolismo , Neurônios/patologia , Ratos , Ratos Sprague-DawleyRESUMO
This research offers a theoretical model to measure the impact of social media usage on social capital in the agricultural system of China. Furthermore, this research also investigates the relationship between agricultural policies related to entrepreneurship training and social media usage. A total of 589 questionnaires were distributed in the training courses of Fujian Agricultural Vocational Technology College, and, Fuzhou, Quanzhou, Jianning, and Liancheng counties and cities in Fujian during winter and summer vacations to target new vocational farmers. The results show that social use, hedonic use, and cognitive use of social media significantly impacted both bridging and bonding social capital. Furthermore, the results of the study suggest that entrepreneurs who have participated in the training have significantly higher levels of social use and cognitive use than those who have not been trained. The findings of this paper have implications for the digital transformation by agricultural entrepreneurs in recognition of the role of sustainable education and learning in entrepreneurial activities and the utilization of social and cognitive functions of social media to acquire and accumulate social capital and provide support for sustainable agriculture and rural development. Furthermore, the concepts of sustainability-driven agriculture in the digital transformational framework were also studied and it was indicated that transformed agriculture can effectively deal with the present challenges.
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Social capital, which is derived from psychological research, has an important value in the construction of network relationships in enterprises. It influences the direction and tendency of network connections in start-up enterprises and has gradually become an important factor in the study of entrepreneurship by scholars. However, the relationship between this and the effectiveness of innovation is unclear. In this study, the social capital is divided into bonding social capital and bridging social capital, and specific data of agricultural entrepreneurs are collected through questionnaire surveys. The results show that both bonding and bridging social capital have a significant positive effect on agricultural entrepreneurship performance. The entrepreneurial capacity of agricultural entrepreneurs regulates the relationship between social capital and creative performance. In the relationship between integrated social capital and creative performance, operational competency plays a positive role and opportunity recognition plays a negative role. On the other hand, in the relationship between bridging social capital and creative performance, the opportunity recognition plays a positive role and the operational competency plays a negative role. Finally, based on the above findings, this study proposes theoretical and practical implications and suggestions for follow-up research.
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BACKGROUND: The prevalence of Fabry disease (FD) in Chinese patients with hypertrophic cardiomyopathy (HCM) is unclear. We aimed to evaluate the prevalence, clinical characteristics, and outcomes of FD in Chinese patients with HCM. METHODS: Of 217 patients with HCM, FD probands were screened by next-generation sequencing at Fuwai Hospital. Medical data from α-galactosidase A activity, electrocardiography, echocardiography, coronary angiography, cardiac magnetic resonance, pathological examination, and follow up was analyzed. RESULTS: Two FD probands were observed (0.93% of patients with HCM), both of which were diagnosed with symptomatic obstructive HCM at 49 years of age. One proband had a GLA mutation (c.887T>C [p.M296T]) with a late-onset cardiac variant, which was characterized by dual ventricular hypertrophy and conduction disease with a permanent pacemaker. The other patient had a GLA mutation (c.758T>C [p.I253T]) with a classic phenotype and dual ventricular hypertrophy, atrioventricular block, renal failure, and recurrent cerebral infarction. Both probands had late gadolinium enhancement mainly in the basal segment of the inferolateral wall. Follow up revealed no exertional symptoms or outflow obstruction after surgical septal myectomy in the two probands, and stable renal function was observed after 6 months of migalastat therapy in the later one. A family study revealed six female carriers and three sudden cardiac deaths. CONCLUSIONS: FD is not uncommon in Chinese patients with HCM. Multiple organic involvement, dual ventricular hypertrophy, and conduction disease provide clinical clues for suspected FD, and early genetic screening is necessary. Surgical septal myectomy and migalastat improve the long-term prognosis of patients with FD.
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Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/epidemiologia , Doença de Fabry/diagnóstico por imagem , Doença de Fabry/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cardiomiopatia Hipertrófica/genética , China/epidemiologia , Ecocardiografia/métodos , Eletrocardiografia/métodos , Doença de Fabry/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Prevalência , Adulto JovemRESUMO
OBJECTIVE: To explore the effects of occupational aluminium(Al) exposure on workers' cognition through a longitudinal study. METHODS: The study population consisted of 276 workers in an Al factory. In 2014, we used inductively coupled plasma mass spectrometry (ICP-MS) to determine the plasma aluminium (P-Al) concentration of the workers, and a combined questionnaire to test the workers' cognitive function. Followed-up in 2016, the workers were tested again for cognitive function. Generalized linear regression was used to assess the association between P-Al concentration and cognitive scores, and multivariable logistic regression was used to assess the risk of cognitive decline caused by Al exposure. RESULTS: Generalized linear regression results showed that a non-significant association was found between the P-Al concentration and cognitive test scores (P > 0.05) in 2014. Two years later, each 10-fold increase in P-Al concentration was inversely associated with the score of Mini-Mental state examination (MMSE) (ß: -0.53, 95% CI: -0.86, -0.20) and Fuld object memory evaluation (FOME) (ß: -0.93, 95% CI: -1.62, -0.24). Each 10-fold increase in P-Al concentration was inversely associated with MMSE2016-2014 (ß: -0.38, 95% CI: -0.74, -0.01) and FOME2016-2014 (ß: -1.20, 95% CI: -1.95, -0.45). There was a statistically significant difference in the average annual rate of change of MMSE and FOME with the tertile of P-Al concentration increase (P < 0.05). The multivariable logistic regression results showed that as the P-Al concentration increased, the risk of a FOME score decline increased (Ptrend = 0.009). CONCLUSIONS: Continuous occupational Al exposure can damage workers' overall cognitive ability, especially episodic memory function.
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Transtornos Cognitivos , Exposição Ocupacional , Alumínio/toxicidade , Cognição , Humanos , Estudos Longitudinais , Testes Neuropsicológicos , Exposição Ocupacional/efeitos adversosRESUMO
To evaluate the different characteristics of cognitive impairment caused by occupational aluminium exposure at different ages, we surveyed 1660 workers in Shanxi Aluminium Plant, China, and assessed their cognitive function and plasma aluminium concentration. In multiple linear regression, the scores of the digit-span test (DST) and digit-span backward test (DSBT) were negatively correlated with plasma aluminium concentration when concentration reached 34.52 µg/L in younger group (ï¼40 years), while in the middle-aged group (≥40 years) only found when concentration reached 42.25 µg/L (ß<0, P < 0.05). In logistic regression, when plasma aluminum concentration reached 42.25µg/L, odds ratios (95 % confidence interval) were 1.695 (1.062-2.705) and 3.270 (1.615-6.620) for DST, 7.644 (3.846-15.192) and 15.308 (4.180-56.059) for DSBT in middle-aged group and younger group, respectively. These results showed that aluminium exposures were associated with cognitive impairment among aluminium-exposed workers, particularly for young workers who were more susceptible.
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Poluentes Ocupacionais do Ar/efeitos adversos , Alumínio/efeitos adversos , Cognição/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Adulto , Poluentes Ocupacionais do Ar/sangue , Alumínio/sangue , Monitoramento Biológico , Disfunção Cognitiva/sangue , Estudos Transversais , Humanos , Masculino , Metalurgia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Exposição Ocupacional/análise , Adulto JovemRESUMO
Progressive cardiac conduction defect (PCCD) is an inherited autosomal dominant cardiac disorder characterized by an agedependent cardiac electrical conduction block. Several genes have been associated with the genetic pathogenesis of PCCD. The present study aimed to identify the causal mutation of PCCD and to investigate the association between genotype and phenotype in a Chinese family with PCCD. A total of 39 family members were included in the present study. All subjects participated in physical, biochemical, electrocardiography and echocardiography examinations. Wholeexome sequencing was performed for four individuals from the same generation, including three patients with PCCD and one normal control with no cardiovascular disease. Sanger sequencing and in silico analysis were used to identify the causal mutation. Wholeexome sequencing and variant identification revealed a candidate nonsense mutation (c.1443C>A, p.Tyr481*) in lamin A/C (LMNA). The mutation was identified in seven patients (including the proband) and two asymptomatic mutation carriers, but it was not detected in 100 control subjects of matched ancestry. Clinical examinations identified typical symptoms in patients with PCCD, including bradycardia and various types of conduction defect, and excluded other phenotypes related to the LMNA mutation. The genotype and phenotype were coassociated among all participants. In the present study, the c.1443C>A mutation in the LMNA gene was identified as a potential cause of PCCD. In silico analysis predicted that the identified mutation was damaging through its effect on the lamin tail domain of LMNA. From the present study, it could be suggested that genetic screening and family counseling, early pacemaker implantation or a sudden death in the family may be essential for risk stratification and treatment of patients with PCCD.
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Doença do Sistema de Condução Cardíaco/diagnóstico , Bloqueio Cardíaco/diagnóstico , Lamina Tipo A/genética , Adolescente , Adulto , Idoso , Sequência de Bases , Doença do Sistema de Condução Cardíaco/genética , Códon sem Sentido , Eletrocardiografia , Feminino , Genótipo , Bloqueio Cardíaco/genética , Humanos , Lamina Tipo A/química , Pessoa de Meia-Idade , Linhagem , Estrutura Terciária de Proteína , Sequenciamento do Exoma , Adulto JovemRESUMO
Angiogenesis and the tumor microenvironment (TME) play important roles in tumorigenesis. Forkhead box Q1 (FOXQ1) is a well-established oncogene in multiple tumors, including colorectal cancer (CRC); however, whether FOXQ1 contributes to angiogenesis and TME modification in CRC remains largely uncharacterized. Here, we demonstrate an essential role of FOXQ1-induced angiogenesis and macrophage recruitment in CRC that is related to its ability to promote the migration of endothelial cells and macrophages through activation of the EGF/PDGF pathway and the Twist1/CCL2 axis. We also provide evidence showing that the clinical significance between FOXQ1, Twist1, CCL2, and macrophage infiltration is associated with reduced 8-year survival in CRC patients. Our findings suggest FOXQ1 plays critical roles in the malignancy and progression of CRC, Therefore, FOXQ1 may serve as a therapeutic target for inhibiting angiogenesis and reducing macrophage recruitment in CRC.
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BACKGROUND: Liddle syndrome (LS), an autosomal dominant disorder, is a common monogenic hypertension in pediatrics. In this study, we reported a novel SCNN1G variant in a Chinese family with pediatric LS, and conduct a systematic review of epithelial sodium channel (ENaC)-gene-positive LS cases to conclude the clinical genetic features of LS in childhood. METHODS: Next-generation sequencing and in silico analysis were performed in the proband to discover candidate variants. Sanger sequencing was used to identify the predicted likely pathogenic variant. LS patients in this family were treated with amiloride. The Medline database was searched to summarize clinical features of pediatric LS cases whose age at genetic diagnosis was not more than 18 years. RESULTS: Genetic analysis identified a novel SCNN1G missense variant (c.1874C>T, p.Pro625Leu) in the proband with LS in childhood. In silico analysis revealed this heterozygous variant was highly conserved and deleterious. A total of 38 publications described pediatric LS associated with 25 pathogenic variants in SCNN1B and SCNN1G in 54 children. Despite the phenotypic heterogeneity, early-onset hypertension is the most common feature. All LS patients in this family or the reviewed cases showed significantly improvements in hypertension and hypokalemia after treatment with ENaC inhibitors. CONCLUSIONS: This study identified a novel SCNN1G missense variant in a patient with pediatric LS, expanding the genetic spectrum of SCNN1G and demonstrating the PY motif of γ-ENaC as a potential mutant region. Early identification and specific management of LS in children and adolescents are important to prevent the development of hypertensive end-organ disease.
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Canais Epiteliais de Sódio/genética , Hipertensão/genética , Síndrome de Liddle/genética , Adolescente , Povo Asiático , Humanos , Masculino , LinhagemRESUMO
PURPOSE: Apparent mineralocorticoid excess (AME) is an ultrarare autosomal recessive disorder resulting from deficiency of 11ß-hydroxysteroid dehydrogenase type 2 (11ßHSD2) caused by mutations in HSD11B2. The purpose of this study was to identify novel compound heterozygous HSD11B2 mutations in a Chinese pedigree with AME and conduct a systematic review evaluating the AME clinical features associated with HSD11B2 mutations. METHODS: Next-generation sequencing was performed in the proband, and Sanger sequencing was used to identify candidate variants in family members, 100 hypertensives, and 100 healthy controls. A predicted structure of 11ßHSD2 was constructed by in silico modeling. A systematic review was used to identify cases of HSD11B2-related AME. Data for genotyping and clinical characterizations and complications were extracted. RESULTS: Next-generation sequencing showed novel compound heterozygous mutations (c.343_348del and c.1099_1101del) in the proband with early-onset hypertension and hypokalemia. Sanger sequencing verified the monoallelic form of the same mutations in five other relatives but not in 100 hypertensives or 100 healthy subjects. In silico structural modeling showed that compound mutations may simultaneously perturb the substrate and coenzyme binding pocket. A systematic review of 101 AME patients with 54 HSD11B2 mutations revealed early-onset hypertension, hypokalemia and homozygous mutations as common features. The homozygous HSD11B2 mutations correlated with low birth weight (r = 0.285, P = 0.02). CONCLUSIONS: We report novel compound heterozygous HSD11B2 mutations in a Chinese teenager with early-onset hypertension, and enriched genotypic and phenotypic spectrums in AME. Genetic testing helps early diagnosis and treatment for AME patients, which may avoid target organ damage.
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Hipertensão , Hipopotassemia , Síndrome de Excesso Aparente de Minerolocorticoides , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética , Adolescente , Humanos , Hipertensão/genética , Síndrome de Excesso Aparente de Minerolocorticoides/genética , Mutação , Síndrome de Excesso Aparente de MinerolocorticoidesRESUMO
BACKGROUND: Tuberculosis (TB) infection has been reported to have a possible relationship with the occurrence and clinical course of Takayasu arteritis (TA). We aimed to describe the characteristics of TB in a large population of TA patients. METHODS: We included a total of 1105 patients with TA, who were hospitalized between January 1992 and December 2017. Comparisons of clinical features were made according to the presence of TB. RESULTS: Among the 1105 patients, 109 (9.9%) had TB, including 53 patients (48.6%) diagnosed with TB before the onset of TA, 23 (21.1%) with a concurrent diagnosis of TB and TA, and 24 patients (22.0%) who developed TB after TA. Pulmonary TB was the most frequently identified (97 patients, 89.0%). Patients with TB had more frequent involvement of the pulmonary artery and experienced more chest discomfort and constitutional symptoms but had less interventional treatment. Demographic characteristics, comorbid diseases, and use of steroids were similar between patients with and without TB. CONCLUSIONS: The proportion of Chinese TA patients with TB was not low, and about half of the patients had TB before TA. Pulmonary TB was the most common. Pulmonary artery involvement and pulmonary hypertension was more frequent in TA patients with TB.
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OBJECTIVE: To explore the effect of polycyclic aromatic hydrocarbons on the neurobehavioral function of coke oven workers. METHODS: 200 healthy adult male coke oven workers were selected from a coke plant of a state-owned steel enterprise in Taiyuan City. 88 controls occupationally unexposed to polycyclic aromatic hydrocarbons (PAHs) were selected from the same enterprise. All the subjects participated in this investigation voluntarily in their consent. Concentration of B(a)P in the working environment was monitored by High Performance Liquid Chromatography (HPLC). Urine samples were sampled immediately after working shifts. The level of urinary 1-hydroxypyrene was determined by HPLC. General information of workers correlated with the investigation was collected in a questionnaire according to the same criteria by well-trained investigators. Neurobehavioral core test battery (NCTB) recommended WHO was performed on coke oven workers and controls to test the neurobehavioral changes and the mood state. RESULTS: the concentration of B(a)P at oven bottom,oven side and oven top were 0.0195 microg/m3, 0.186 microg/m3 and 1.624 microg/m3 respectively, that at oven side and oven top being higher than the one stipulated by the occupational hygiene criterion. Urinary 1-hydroxypyrene was significantly different between the exposure group (3.42 +/- 0.98 micromol/mol creatinine) and control group (2.75 +/- 1.09 micromol/mol creatinine). No significant differences were found between exposure group and control group of age, working years, smoking, drinking and unhealthy food consumption; however, compared to the controls, the scores of total digital span, the forward digital span, and right dotting in the coke oven workers were lower, but that of total dotting was higher, with a statistical significance. According to urinary 1-hydroxypyrene concentration, all the subjects were divided into three groups. (<3.10 micromol/mol creatinine, 3.10 micromol/mol creatinine, >3.87 micromol/mol creatinine). Significant differences of the total digital span, the forward digital span, backward digital span, digit symbol and Benton visual retentions existed in different urinary 1-hydroxypyrene concentration groups and showed a dose-response tendency. Results of multiple stepwise regression analysis and correlation analysis showed that the level of urinary 1-hydroxypyrene affected memory and perception of coke oven workers and negative correlations between the level of urinary 1-hydroxypyrene and changes in neurobehavioral function were found. CONCLUSION: PAHs mainly causes decrease of memory and perception in coke oven workers.
Assuntos
Poluentes Ocupacionais do Ar/análise , Coque , Memória , Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos/urina , Adulto , Humanos , Masculino , Testes NeuropsicológicosRESUMO
OBJECTIVE: To study the role of lipid peroxidation injury and endoplasmic reticulum stress in Al-induced apoptosis. METHODS: Neurons from 0-3 day rats were cultured and treated with different concentrations of AlCl3.6H2O. Morphologic changes of neurons and endoplasmic reticulum were observed under fluorescent and transmission electron microscope; activities of superoxide dismutase (SOD), malondialdehyde (MDA) and ATP enzymes were detected. RESULTS: Typical morphologic changes in neurons apoptosis and endoplasmic reticulum were found under fluorescent and transmission electron microscope; SOD enzyme viability and ATP enzyme viability were significantly increased in the low-dosage group, but reduced in mid and high-dosage group (P < 0.01), whereas MDA levels decreased in the low-dosage group, but increased in mid and high-dosage group (P < 0.01). CONCLUSION: Aluminum may induce neurons apoptosis, and lipid peroxidation injury in endoplasmic reticulum plays an important role in the apoptosis progression.