RESUMO
BACKGROUND: Previous evidence suggests that higher blood uric acid (UA) levels are associated with adverse cardiovascular outcomes during pregnancy and subsequent birth outcomes. However, it has been relatively unclear whether these associations persist in normotensive pregnant women. METHODS: The study was based on a retrospective analysis of 18,250 mother-infant pairs in a large obstetric center in China. Serum UA concentrations in early pregnancy (median: 17.6, IQR: 16.3, 18.6 gestational weeks) were assessed. Hyperuricemia was defined as ≥ one standard deviation (SD) of the reference value for the corresponding gestational age. Outcomes of gestational diabetes mellitus (GDM), preterm birth (PB), low birth weight (LBW), macrosomia, small for gestational age (SGA) and large for gestational age (LGA) were extracted from the medical records. RESULTS: The mean maternal UA level was 0.22 ± 0.05 mmol/L, and 2,896 (15.9%) subjects had hyperuricemia. After adjustment for several covariates, UA was associated with several adverse outcomes. The ORs (95%CI) per one SD increase in serum UA concentration were 1.250 (1.136, 1.277) for GDM, 1.137 (1.060, 1.221) for PB, 1.134 (1.051, 1.223) for LBW, and 1.077 (1.020, 1.137) for SGA, respectively. Similar adverse associations were found between hyperuricemia and GDM, PB (ORs: 1.394 and 1.385, P < 0.001), but not for LBW, macrosomia, SGA, and LGA. Adverse associations tended to be more pronounced in subjects with higher BMI for outcomes including PB, LBW, and SGA (P interaction = 0.001-0.028). CONCLUSION: Higher UA levels in early pregnancy were associated with higher risk of GDM, PB, LBW, and SGA in normotensive Chinese women.
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Diabetes Gestacional , Hiperuricemia , Nascimento Prematuro , Gravidez , Feminino , Recém-Nascido , Humanos , Diabetes Gestacional/epidemiologia , Macrossomia Fetal/epidemiologia , Macrossomia Fetal/etiologia , Ácido Úrico , Estudos Retrospectivos , Resultado da Gravidez/epidemiologia , Hiperuricemia/epidemiologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Aumento de Peso , Retardo do Crescimento FetalRESUMO
BACKGROUND: Plexiform lesions, which have a dynamic appearance in structure and cellular composition, are the histological hallmark of severe pulmonary arterial hypertension in humans. The pathogenesis of the lesion development remains largely unknown, although it may be related to local inflammation and dysfunction in early progenitor endothelial cells (eEPCs). We tested the hypothesis that eEPCs contribute to the development of plexiform lesions by differentiating into macrophages in the setting of chronic inflammation. METHODS: The eEPC markers CD133 and VEGFR-2, macrophage lineage marker mannose receptor C-type 1 (MRC1), TNFα and nuclear factor erythroid 2-related factor 2 (Nrf2) in plexiform lesions in a broiler model were determined by immunohistochemistry. eEPCs derived from peripheral blood mononuclear cells were exposed to TNFα, and macrophage differentiation and angiogenic capacity of the cells were evaluated by phagocytotic and Matrigel plug assays, respectively. The role of Nrf2 in eEPC-to-macrophage transition as well as in MRC1 expression was also evaluated. Intratracheal installation of TNFα was conducted to determine the effect of local inflammation on the formation of plexiform lesions. RESULTS: Cells composed of the early lesions have a typical eEPC phenotype whereas those in more mature lesions display molecular and morphological characteristics of macrophages. Increased TNFα production in plexiform lesions was observed with lesion progression. In vitro studies showed that chronic TNFα challenge directed eEPCs to macrophage differentiation accompanied by hyperactivation of Nrf2, a stress-responsive transcription factor. Nrf2 activation (Keap1 knockdown) caused a marked downregulation in CD133 but upregulation in MRC1 mRNA. Dual luciferase reporter assay demonstrated that Nrf2 binds to the promoter of MRC1 to trigger its expression. In good agreement with the in vitro observation, TNFα exposure induced macrophage differentiation of eEPCs in Matrigel plugs, resulting in reduced neovascularization of the plugs. Intratracheal installation of TNFα resulted in a significant increase in plexiform lesion density. CONCLUSIONS: This work provides evidence suggesting that macrophage differentiation of eEPCs resulting from chronic inflammatory stimulation contributes to the development of plexiform lesions. Given the key role of Nrf2 in the phenotypic switching of eEPCs to macrophages, targeting this molecular might be beneficial for intervention of plexiform lesions.
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Células Progenitoras Endoteliais , Hipertensão Pulmonar , Animais , Humanos , Células Progenitoras Endoteliais/fisiologia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Fator de Necrose Tumoral alfa , Fator 2 Relacionado a NF-E2 , Proteína 1 Associada a ECH Semelhante a Kelch , Leucócitos Mononucleares , Galinhas , Inflamação , Macrófagos , RNA MensageiroRESUMO
BACKGROUND: Thyroid function is known to be closely linked with type 2 diabetes, but data on the association between thyroid function and gestational diabetes mellitus (GDM) are inconsistent. METHODS: A total of 2849 pregnant women were included in this retrospective study. Serum concentrations of thyroid indicators (free tetraiodothyronine, FT4; thyroid-stimulating hormone, TSH; and thyroid peroxidase antibody, TPO Ab) were obtained from a clinical laboratory. The presence of GDM were drawn from medical records. The clinical subtypes of thyroid function (euthyroidism, subclinical hypothyroidism, hyperthyroidism, and isolated hypothyroxinemia) were categorized according to the thresholds of the 2.5th/97.5th and 10th/90th percentiles of TSH and FT4 concentrations. A concentration of > 34 IU/L was defined as indicating TPO Ab-positivity. RESULTS: Two hundred and thirty-five (8.25%) of the 2849 women were TPO Ab-positive. Higher serum concentrations of FT4 (top vs. bottom tertiles) was found to be negatively associated with the risk of GDM. The corresponding odds (OR) values (top tertile vs. bottom tertile) were 0.71 [95% confidence interval (CI): 0.54, 0.93]. No significant associations were observed between the extremely 2.5th/97.5th or 10th/90th percentiles of FT4 concentration, TSH concentration, thyroid function subtypes (vs. euthyroidism), TPO Ab-positivity (vs. -negativity), and the GDM risk. The corresponding results remained similar when TPO Ab-positive subjects were excluded. CONCLUSIONS: A negative association with the risk of GDM was observed for the highest FT4 concentrations tertile. No significant associations were found between the TSH concentration, thyroid function subtypes, TPO Ab positivity, and the GDM risk.
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Diabetes Gestacional , Doenças da Glândula Tireoide/complicações , Hormônios Tireóideos/sangue , Adulto , Biomarcadores/sangue , China , Feminino , Humanos , Gravidez , Estudos Retrospectivos , Testes de Função TireóideaRESUMO
BACKGROUND: Previous evidence has suggested that lower gestational vitamin D levels might increase the risks of adverse pregnancy and birth outcomes. The results remain inconsistent and require further exploration. METHODS: A total of 2814 Chinese mother-infant pairs were included in this retrospective cohort study. Serum concentrations of 25(OH)D were reviewed in early pregnancy (16.3 ± 2.3 weeks). Outcomes of maternal gestational diabetes mellitus (GDM), cesarean section, fetal distress, preterm birth, low birth weight (LBW), and macrosomia were extracted from the medical records. Cox regression analysis was used to explore these associations. RESULTS: In total, 19.3% of mothers were pregnant at an advanced age (≥35 years), and 40.3% of pregnant women had vitamin D deficiency (< 50 nmol/L). After adjusting for potential covariates, the hazard ratio (HR) (95% CI) per standard deviation (SD) increase of serum 25(OH)D concentrations was 0.86 (0.779, 0.951) for GDM, 0.844 (0.730, 0.976) for preterm birth, and 0.849 (0.726, 0.993) for LBW. Similar protective associations were found for GDM, cesarean section, and preterm birth for a better vitamin D status when compared with vitamin D deficiency. CONCLUSION: Higher early pregnancy vitamin D was associated with a lower risk of GDM, cesarean section, preterm birth, and LBW.
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Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Deficiência de Vitamina D/epidemiologia , Adulto , Cesárea , Estudos de Coortes , Diabetes Gestacional/epidemiologia , Feminino , Sofrimento Fetal/epidemiologia , Macrossomia Fetal/epidemiologia , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Nascimento Prematuro , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoAssuntos
Neoplasias do Sistema Nervoso Central , Lenalidomida , Rituximab , Humanos , Estudos Retrospectivos , Rituximab/efeitos adversos , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Idoso , Masculino , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Feminino , Lenalidomida/administração & dosagem , Lenalidomida/efeitos adversos , Lenalidomida/uso terapêutico , Idoso de 80 Anos ou mais , Pirazinas/administração & dosagem , Pirazinas/uso terapêutico , Pirazinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Pessoa de Meia-Idade , Linfoma/tratamento farmacológico , Resultado do Tratamento , Piperidinas , PiridinasRESUMO
Administration of bevacizumab to patients with brain metastases (BM) is controversial due to concerns about the increased risk of intracranial hemorrhage (ICH). This meta-analysis assessed whether the risk of ICH increases in BM patients receiving treatments that contain bevacizumab versus without. PubMed, Embase, Cochrane Library and annual meeting abstracts of the American Society of Clinical Oncology up to 13 November 2016 were searched for studies that referred to ICH complications due to bevacizumab in patients with BM. Eight studies involving 8713 patients were included in this analysis. Compared with the control arm without bevacizumab, the bevacizumab treatment arm did not exhibit a significant increase in ICH [odds ratio (OR) 1.20; 95% confidence intervals (CI) 0.69-2.09; P = 0.53]. Subgroup analyses with retrospective studies showed a similar result, although subgroup analyses with prospective studies failed. This meta-analysis revealed that bevacizumab does not significantly increase the risk of ICH in solid tumor patients with BM.
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Antineoplásicos Imunológicos/efeitos adversos , Bevacizumab/efeitos adversos , Neoplasias Encefálicas/complicações , Hemorragias Intracranianas/induzido quimicamente , Neoplasias Encefálicas/secundário , Feminino , Humanos , Hemorragias Intracranianas/complicações , Masculino , Razão de Chances , Resultado do TratamentoRESUMO
Human adipose-derived stem cells (hASCs) become an appealing source for regenerative medicine. However, with the multi-passage or cryopreservation for large-scale growth procedures in terms of preclinical and clinical purposes, hASCs often reveal defective cell viability, which is a major obstacle for cell therapy. In our study, the effects of induced pluripotent stem cells-derived conditioned medium (iPS-CM) on the proliferation and anti-apoptosis in hASCs were investigated. hASCs at passage 1 were identified by the analysis of typical surface antigens with flow cytometry assay and adipogenic and osteogenic differentiation. The effect of iPS-CM on the proliferation in hASCs was analyzed by cell cycle assay and Ki67/P27 quantitative polymerase chain reaction analysis. The effect of iPS-CM on the anti-apoptosis of hASCs irradiated by 468 J/m(2) of ultraviolet C was investigated by annexin v/propidium iodide analysis, mitochondrial membrane potential assay, intracellular reactive oxygen species assay, Western blotting and caspase activity assays. The effect of iPS-CM on the surface antigen expressions of hASCs was analyzed using flow cytometry assay. The levels of Activin A and bFGF in culture supernatant of hASCs with different treatments were also detected by enzyme-linked immunosorbent assay. iPS-CM promoted proliferation and inhibited apoptosis of hASCs. This discovery demonstrates that iPS-CM might be used as one of the available means to overcome the propagation obstacle for hASCs and make for large-scale growth procedures in terms of preclinical and clinical purposes.
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Tecido Adiposo/citologia , Meios de Cultivo Condicionados/farmacologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco/efeitos dos fármacos , Ativinas/metabolismo , Antígenos de Superfície/metabolismo , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Fator 2 de Crescimento de Fibroblastos/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Medicina Regenerativa , Células-Tronco/citologia , Células-Tronco/imunologiaRESUMO
To study active secondary metabolites of endophytic fungus Diaporthe longicolla A616 isolated from Pogostemon cablin. Ten compounds were isolated from fermentation product of the strain 616 by silica gel, reverse phase silica gel, Sephadex-LH20, HPLC and so on. Their structures were identified as 1,3-diamino-1,3-dimethylurea(1),(7R,9R)-7-hydroxy-9-propyl-5-nonen-9-olide(2), Ergosta-5,7,22-trien-3ß-ol(3),(22E,24R)-ergosta-4,6,8(14)-22-tetraen-3-one(4),(22E,24R)-3ß,5α-dihydroxy-6ß-ergosta-7,22-diene(5), citreoisocoumarin(6), glycerol monolinoleate(7), 1-(2-hydroxyethoxy)ethyl(E)-octadec-9-enoate(8), cyclo-(L-Pro-L-Ala)(9), cyclo(L)-Pro-(L)-Val(10), respectively, based on extensive spectroscopic analysis and literature comparisons. Compounds 6-10 were isolated from the genus Diaporthe for the first time. All isolated compounds were evaluated for in vitro cytotoxic activities against SF-268, MCF-7, NCI-H460 and HepG-2 tumor cell lines. Compounds 4 and 5 showed potent growth inhibitory activities against the four cell lines with IC50 values of 5.3, 6.5, 12.2, 6.1µmolâ¢L⻹ and 8.2, 5.2, 6.1, 9.4µmolâ¢L⻹, respectively.
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Antineoplásicos/isolamento & purificação , Ascomicetos/química , Pogostemon/microbiologia , Linhagem Celular Tumoral , Endófitos/química , Células Hep G2 , Humanos , Células MCF-7 , Estrutura Molecular , Metabolismo SecundárioRESUMO
OBJECTIVE: To study the value of amino-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting symptomatic patent ductus arteriosus (sPDA) in preterm infants. METHODS: Preterm infants born at a gestational age (GA) of ≤ 32 weeks and diagnosed with patent ductus arteriosus (PDA) by echocardiography within 48 hours after birth between June 2014 and April 2015 were selected as subjects. Their clinical manifestations were observed, and serum NT-proBNP levels were measured and echocardiography was performed at 3 and 5 days after birth. The infants were divided into sPDA group and asymptomatic PDA (asPDA) group based on their clinical manifestations and the results of echocardiography. The correlations between serum NT-proBNP level and echocardiographic indices were analyzed. Serum NT-proBNP levels were compared between the two groups. The receiver operator characteristic (ROC) curve was applied to determine the sensitivity and specificity of serum NT-proBNP in the prediction of sPDA. RESULTS: A total of 69 preterm infants were enrolled in this study, with 13 infants in the sPDA group and 56 infants in the asPDA group. Serum NT-proBNP level was positively correlated with the diameter of the arterial duct (r=0.856; P<0.05)and the ratio of left atrial diameter to aortic root diameter (LA/AO) (r=0.713; P<0.05). At 3 and 5 days after birth, the serum NT-proBNP levels in the sPDA group were significantly higher than those in the asPDA group (P<0.05). The area under the ROC curve (AUC) for the prediction of sPDA by NT-proBNP levels at 3 days after birth was 0.949 (95% CI: 0.892-1.000; P<0.001), with a cut-off value of 27 035 pg/mL (sensitivity: 92.3%; specificity: 94.6%); the AUC for the prediction of sPDA by NT-proBNP levels at 5 days after birth was 0.924 (95% CI: 0.848-1.000; P<0.001), with a cut-off value of 6 411 pg/mL (sensitivity: 92.3%; specificity: 92.9%). CONCLUSIONS: NT-proBNP may be a quantitative index for shunt volume. The measurement of serum NT-proBNP levels on 3 and 5 days after birth may be useful to predict sPDA in preterm infants.
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Permeabilidade do Canal Arterial/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Biomarcadores , Feminino , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Curva ROCRESUMO
OBJECTIVE: To investigate the prevalence, current treatment, and clinical characteristics of asthma, as well as the risk factors for this disease, among children aged 0-14 years in 2010 in urban Zhongshan, China. METHODS: A total of 10 336 children aged 0-14 years were selected from urban Zhongshan by cluster random sampling. The Third National Childhood Asthma Epidemiological Questionnaire 2010 was used to analyze the prevalence, current treatment, and clinical characteristics of childhood asthma, as well as the risk factors for this disease. RESULTS: Asthma was diagnosed in 179 cases (1.73%). The prevalence of asthma in male children was significantly higher than that in female children (2.25% vs 1.16%; P<0.01). Of the 179 patients, severe attacks were common in 104 cases (58.1%), 110 cases (61.5%) had slow onset, 102 cases (57.0%) had gradually relieved conditions, 61 cases (34.1%) suffered from asthma during seasonal transition, and 150 cases (83.8%) developed asthma due to respiratory tract infection. Among all asthmatic children, 71.5% had been treated with inhaled corticosteroids, and 71.5% had been treated with bronchodilator. The multivariate logistic regression analysis showed that a history of penicillin allergy, a family history of allergy, food allergy, eczema, allergic rhinitis, cesarean delivery, family mould, and perinatal passive smoking were independent risk factors for childhood asthma. CONCLUSIONS: The prevalence of childhood asthma in urban Zhongshan is on a high level, and is associated with gender. The treatment of asthma has been standardized, but still needs further improvement. The onset of asthma attack is influenced by various factors.
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Asma/epidemiologia , Adolescente , Asma/etiologia , Criança , Pré-Escolar , China/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Risco , Estações do Ano , Fatores de TempoRESUMO
OBJECTIVE: To study the secondary metabolites of the endophytic fungus Arthrinium sp. A092 from Uvaria microcarpa. METHODS: The compounds were isolated and purified by silica gel column chromatography, reverse silica gel column chromatography, Sephadex LH-20 column chromatography, HPLC, preparative TLC and recrystallization. Their structures were identified by extensive analysis of their spectroscopic data. RESULTS: Ten compounds were isolated from the fermentation broth extract of strain A092 and identified as flemingipanic acid(1), ( - )-gynuraone(2),2-(4-methoxy-phenyl)-ethanol(3),2-hexyl-methymaleic anhydride(4), {1-[(12E, 16E)]-12,16-eicosadienoyl]-2-[ (E, E)-7, 10-octadecadienoyl]-3-stearoylglycerol} (5), mycoediketoperazine (6), libertellenone C(7),4-hydroxymethyl-4, 6-octadiene-2, 3-diol (8), dimethyl phthalate (9), and di-(2-ethyl)-hexylphthalate (10). CONCLUSION: Compounds 1,3 - 5 and 8 - 10 are isolated from the genus Arthrinium for the first time.
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Ascomicetos/química , Uvaria/microbiologia , Cromatografia Líquida de Alta Pressão , Fermentação , Ácidos Ftálicos , Salicilatos , Metabolismo SecundárioRESUMO
OBJECTIVE: To study the alterations of follicular T helper cells (CD4(+)CXCR5(+)Tfh cells, Tfh) on circulating T lymphocytes in children with asthma, and to study the expression of transcription regulatory factors BCL-6 and BLIMP-1 mRNA. METHODS: Sixty-four children with asthma and 25 healthy controls were enrolled in this study. On the basis of the disease, the children with asthma were classified into acute phase group (n=36) and remission phase group (n=28). The flow cytometry was used to detect the proportion of CD4(+)CXCR5(+)Tfh cells on CD4(+)T lymphocytes. Real-time PCR was performed to detect the levels of BCL-6 mRNA and BLIMP-1 mRNA. The double -antibody Sandwich ELISA was used to detect plasma concentrations of total IgE, IL-2, IL-6 and IL-21. RESULTS: The proportion of CD4(+)CXCR5(+)Tfh cells was significantly higher in the acute group than in the control group and the remission group (P<0.05). Transcription levels of BCL-6 mRNA were significantly higher, while the inhibitory factors BLIMP-1 mRNA was significantly lower in the acute group than in the remission group and control group (P<0.05). The plasma concentration of IL-6 in the acute group increased significantly compared with the control group (P<0.05). Plasma concentrations of total IgE and IL-21 increased significantly, in contrast, plasma IL-2 concentration decreased significantly in the acute group, compared with the control group and the remission group (P<0.05). Correlation analysis showed that both IL-21 and IL-6 concentrations were positively correlated with the proportion of CD4(+)CXCR5(+)Tfh cells (r=0.76, r=0.46 respectively; P<0.05), while IL-2 level was negatively correlated with the proportion of Tfh cells (r=-0.68, P<0.05). CONCLUSIONS: The abnormal proportion of CD4(+)CXCR5(+)Tfh cells might be involved in the immunological pathogenesis of acute asthma in children. The increased expression of BCL-6 mRNA and decreased expression of BLIMP-1 mRNA as well as the alterations of plasma total IgE, cytokines IL-2, IL-6 and IL-21 in microenvironment might be account for the increased proportion of CD4(+)CXCR5(+)Tfh cells in children with acute asthma.
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Asma/imunologia , Proteínas de Ligação a DNA/genética , Receptores CXCR5/análise , Proteínas Repressoras/genética , Linfócitos T Auxiliares-Indutores/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Interleucinas/sangue , Masculino , Fator 1 de Ligação ao Domínio I Regulador Positivo , Proteínas Proto-Oncogênicas c-bcl-6 , RNA Mensageiro/análiseRESUMO
OBJECTIVE: To investigate the incidence of wheezing and chronic cough in children aged 3-14 years in different living areas of Zhongshan, China. METHODS: According to the unified program of the 2010 national epidemiological survey of asthmatic children aged 0-14 years, a questionnaire survey of the children aged 3-14 years in rural and urban areas of Zhongshan was conducted. RESULTS: A total of 15 763 children were included in the survey. Among all participants, 8 248 were from the urban area, and 7 515 from the rual area; 8 306 were boys, and 7 457 were girls. The percentage of children with a history of wheezing was significantly higher in the urban group than in the rural group (6.6% vs 3.2%; P<0.05), and it was significantly higher in boys than in girls for each group (P<0.05). The urban group had a significantly higher percentage of individuals who had wheezing in the past one year than the rural group (2.8% vs 1.5%; P<0.05), and this percentage was significantly higher in boys than in girls for each group (P<0.05). Compared with the rural group, the urban group had a significantly higher percentage of individuals who had chronic cough (duration 1 year) (7.9% vs 3.1%; P<0.05). The above indices were relatively high in children under 6 years of age, and all but the percentage of girls who had wheezing in the past one year in both rural and urban areas showed significant differences between all age groups. CONCLUSIONS: The incidence of wheezing and chronic cough varies with age, sex, and living area for children aged 3-14 years in Zhongshan, and it is relatively high under 6 years of age, in the urban area, and among boys.
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Tosse/epidemiologia , Sons Respiratórios , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Doença Crônica , Feminino , Humanos , Incidência , Masculino , Inquéritos e QuestionáriosRESUMO
BACKGROUND: BRII-196 and BRII-198 are two recombinant human immunoglobulin (Ig) G1 monoclonal antibodies (mAbs) that non-competitively target distinct epitope regions within the receptor-binding domain (RBD) of the coronavirus spike glycoproteins. These antibodies are derived directly from human B cells of individuals who recovered from COVID-19. OBJECTIVE: To analyze the efficacy of BRII-196/BRII-198 in the treatment of coronavirus disease 2019 (COVID-19) vaccine breakthrough infections. METHODS: COVID-19 patients at high risk of progressing to severe and critical illness, with an initial SARS-CoV-2 immunoglobulin (Ig) G antibody level < 1.0 S/CO (detected within 24-48 hours post COVID-19 diagnosis), were treated with BRII-196/BRII-198 within three days of symptom onset. Treatment continued until the antibody level exceeded 1.0 S/CO. Patients whose absolute lymphocyte count (ALC) at first detection (within 24-48 h post-diagnosis) was < 0.8 × 109/L received thymalfasin therapy within three days of symptom onset, continuing until the ALC level surpassed 0.8 × 109/L. We determined the correlation of SARS-CoV-2 IgG antibody level and ALC with the condition of COVID-19 patients. Additionally, we analyzed the effects of BRII-196/BRII-198 on SARS-CoV-2 nucleic acid (NA) negative conversion, lymphocyte count recovery, and the change in SARS-CoV-2 IgG antibody level from the first positive NA test for SARS-CoV-2 to negative conversion in COVID-19 patients. RESULTS: A total of 61 cases of breakthrough infections were observed, classified as 10 mild cases, 31 ordinary cases, and 20 severe cases. Among these, 20%, 48.4% and 75% of the patients with mild, ordinary, and severe COVID-19, respectively, had initial SARS-CoV-2 IgG antibody level < 1.0 S/CO. Additionally, 0%, 35% and 70% had initial ALC < 0.8 × 109/L, respectively. Fifteen ordinary and 15 severe COVID-19 patients were treated with BRII-196/BRII-198. In severely infected patients, BRII-196/BRII-198 treatment showed statistically significant differences in NA negative conversion time and changes in SARS-CoV-2 IgG antibody levels (P < 0.05). However, in patients classified with ordinary severity, BRII-196/BRII-198 treatment did not lead to notable differences in NA negative conversion time or changes in SARS-CoV-2 IgG antibody level (P > 0.05). BRII-196/BRII-198 therapy was not associated with lymphocyte count recovery time in patients with either ordinary and/or severe COVID-19 (P > 0.05). CONCLUSIONS: The initial levels of SARS-CoV-2 IgG antibody and lymphocytes in fully vaccinated patients with breakthrough infections are inversely correlated with the severity of the disease. Early treatment with BRII-196/BRII-198 can shorten NA negative conversion time in severe COVID-19 patients and increase in vivo neutralizing antibody levels post-conversion, providing lasting protection. However, BRII-196/BRII-198 does not influence lymphocyte count recovery in patients with either ordinary and/or severe COVID-19.
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Purpose: This study aims to explore the factors linked to the occurrence of acute pulmonary thromboembolism (PE) within a cohort of patients exhibiting hypoxic saturation (oxygen saturation levels falling below 93%), subsequent to undergoing off-pump coronary artery bypass grafting (OPCABG). Methods: A retrospective case-control study was conducted. A total of 296 patients met the inclusion and exclusion criteria, divided into PE group (100 cases) and non-PE group (196 cases) according to whether they had PE or not. The preoperative and postoperative information of patients were collected and statistically analyzed. Results: The results from a multivariate logistic regression analysis indicated the following factors were independently linked to PE following OPCABG: history of smoking (OR = 3.019, 95% CI, 1.437-6.634, P = 0.004), preoperative arterial oxygen partial pressure ≤78.9 mmHg (OR = 3.686, 95% CI, 1.708-8.220, P = 0.001), presence of postoperative lower extremity deep venous thrombosis (OR = 4.125, 95% CI, 1.886-9.310, P < 0.001), elevated postoperative D-dimer levels >6.76 mg/l (OR = 8.078, 95% CI, 3.749-18.217, P<0.001), postoperative NT-BNP levels (OR = 1.001, 95% CI: 1.000-1.001, P = 0.011), and elevated postoperative pulmonary arterial pressure >33.0 mmHg (OR = 10.743, 95% CI: 3.422-37.203, P < 0.001). The developed nomogram exhibited a high predictive accuracy with an area under the curve of 0.913 (95% CI: 0.878-0.948). Conclusion: When patients have a history of preoperative smoking, decreased preoperative arterial oxygen pressure, postoperative lower limb DVT, increased postoperative pulmonary artery pressure, and elevated postoperative D-Dimer and NT pro-BNP levels, it is recommended to take perioperative preventive measures, timely diagnostic evaluation, and if necessary, anticoagulant treatment. In addition, the results of this study may improve the diagnostic sensitivity of medical staff for postoperative PE in OPCABG, thereby increasing the detection rate and potentially reducing the need for excessive medical imaging procedures.
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OBJECTIVE: To study a method for rapidly identifying the saponions components in Ginseng and explore the fragmentation regularity. METHODS: Used ACQUITY UPLC/Q-TOF micro system gradient elute wirh 10 mmol/L ammonium acetate-acetonitrile mobile phase under the ESI negative mode; Data were analyzed by Masslynx 4.1 software. RESULTS: 30 kinds of saponins in Ginseng were analyzed and identified by UPLC/Q-TOF-MS, and the fragmentation regularity of ginseng saponins components were explored. CONCLUSION: A analysis method is established for rapid identification of saponin components.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Panax/química , Saponinas/análise , Saponinas/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Medicamentos de Ervas Chinesas/isolamento & purificação , Estrutura Molecular , Raízes de Plantas/química , Controle de Qualidade , Saponinas/isolamento & purificaçãoRESUMO
Animals living in estuaries suffer from rapid and continuous salinity fluctuations, while the global warming and extreme precipitation aggravate this situation. Osmoregulation is important for estuarine animals adapt to salinity fluctuations. The present study investigated the effects of low salinity stress on osmoregulation and gill transcriptome in two populations of mud crab from Hangzhou Bay and Zhangzhou Bay of China, respectively. Crabs were transferred from salinity 25 ppt to 5 ppt for 96 h. Edematous swelling in gill filaments was caused by low salinity stress and was more serious in Zhangzhou Bay population. Gill Na+/K+-ATPase activity increased (p < 0.01) in both populations under the low salinity stress and was significantly higher (p < 0.01) in Hangzhou Bay population than in Zhangzhou Bay population. According to transcriptome analysis, there were 191 genes differentially expressed under the low salinity stress in gill tissue of both populations. Several ion transport and energy metabolism related pathways, as well as the arginine and proline metabolism pathway, were enriched by these genes. On the other hand, 272 genes were identified to differentially express between two populations under the low salinity stress, but not under the control salinity. The enrichment analysis showed that these genes were mainly related to ion transport, energy metabolism, osmolytes metabolism and methyltransferase activity. In conclusion, the present study suggested that mud crab exploited a combination of extracellular anisosmotic regulation and intracellular isosmotic regulation for osmoregulation under the low salinity stress. Hangzhou Bay population showed a greater osmoregulatory capacity, which is probably due to the enhanced ion transport, energy supply, and osmolytes regulation. Meanwhile, epigenetic modification might also contribute to an inherent osmoregulation ability for Hangzhou Bay population to response to salinity fluctuation rapidly.
Assuntos
Braquiúros , Animais , Braquiúros/genética , Transcriptoma , Osmorregulação , Brânquias/metabolismo , Estresse Salino , SalinidadeRESUMO
Hypoxic-ischemic encephalopathy, which predisposes to neonatal death and neurological sequelae, has a high morbidity, but there is still a lack of effective prevention and treatment in clinical practice. To better understand the pathophysiological mechanism underlying hypoxic-ischemic encephalopathy, in this study we compared hypoxic-ischemic reperfusion brain injury and simple hypoxic-ischemic brain injury in neonatal rats. First, based on the conventional Rice-Vannucci model of hypoxic-ischemic encephalopathy, we established a rat model of hypoxic-ischemic reperfusion brain injury by creating a common carotid artery muscle bridge. Then we performed tandem mass tag-based proteomic analysis to identify differentially expressed proteins between the hypoxic-ischemic reperfusion brain injury model and the conventional Rice-Vannucci model and found that the majority were mitochondrial proteins. We also performed transmission electron microscopy and found typical characteristics of ferroptosis, including mitochondrial shrinkage, ruptured mitochondrial membranes, and reduced or absent mitochondrial cristae. Further, both rat models showed high levels of glial fibrillary acidic protein and low levels of myelin basic protein, which are biological indicators of hypoxic-ischemic brain injury and indicate similar degrees of damage. Finally, we found that ferroptosis-related Ferritin (Fth1) and glutathione peroxidase 4 were expressed at higher levels in the brain tissue of rats with hypoxic-ischemic reperfusion brain injury than in rats with simple hypoxic-ischemic brain injury. Based on these results, it appears that the rat model of hypoxic-ischemic reperfusion brain injury is more closely related to the pathophysiology of clinical reperfusion. Reperfusion not only aggravates hypoxic-ischemic brain injury but also activates the anti-ferroptosis system.
RESUMO
Two electrochemical signals of the MCF-7 cell were simultaneously detected by using multiwall carbon nanotubes and room temperature ionic liquid composite film modified electrode. The signal at +0.726 V due to the oxidation of xanthine and guanine, was obviously improved. And the signal at +1.053 V due to the oxidation of hypoxanthine and adenine was found for the first time. This two-signal electrochemical method is credible to detect cell viability and proliferation.
Assuntos
Eletroquímica/métodos , Catálise , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Eletroquímica/instrumentação , Eletrodos , Humanos , Nanotubos de Carbono/química , TemperaturaRESUMO
OBJECTIVE: To construct the eukaryotic expression vector for Max interacting protein 1 (Mxi1). METHODS: The full length cDNA of Mxi1 gene obtained from fetal lymphocyte and KG1 cells were inserted into plasmid pDs-red2-N1 respectively to generate pDs-red2-N1/Mri1 (wild/mutation type). Then the recombinant vector was transfected into Cos-7 cells via liposome. 48 hours post transfection, mRNA of Mri1 gene was detected by RT-PCR and Mxi1 protein expression was detected by flow cytometry and fluorescence microscope in the Cos-7 cells. RESULTS: The eukaryotic expression vector of Mxi1 was constructed and transfected into eukaryotic cells successfully. The expression of red fluorescence protein in the transfected Cos-7 cells was observed under fluorescence microscope which implied the expression of Mxi1. The transfect efficiency of both wild and mutation type were in a high level in 3 days after transfected, which lasted to 6 d. RT-PCR amplified the total RNA extracted from the transfected Cos-7 cells could find increased mRNA level of Mxi1 gene. CONCLUSION: We successfully constructed the eukaryote expression vector for Mri1 gene; Cos-7 cells transfected with the vector via liposome could express Mxi1 protein. These could be useful for the further study of the Myc gene modulation.