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The NAC transcription factors play important roles in regulating plant growth, development, and senescence, and responding to biotic and abiotic stressors in plants. A novel coding sequence (1,059 bp) was cloned from hexaploid triticale in this study. The putative protein (352 amino acids) encoded by this sequence was over 95% similar to the amino acid sequence of a NAC protein from Aegilops tauschii (XP020161331), and it formed a clade with Ae. tauschii, durum wheat, and barley. The putative protein contained a conserved nature actomyosin (NAM) domain (129 consecutive amino acids) between the 20th and 148th amino acids at the N-terminus and three transcription activation regions at the C-terminus. The novel gene was identified as a triticale NAC gene localized in the nucleus and designated as TwNAC01 (GenBank accession MG736919). The expression levels of TwNAC01 were the highest in roots, followed by leaves and stems when triticale lines were exposed to drought, polyethylene glycol 6,000 (PEG6000), NaCl, cold, methyl jasmonate (MeJA), and abscisic acid (ABA). Transgenic Arabidopsis thaliana overexpressing TwNAC01 had significantly lower leaf water loss rates and longer roots than wild-type (WT) A. thaliana. Virus-induced silencing of the TwNAC01 gene in triticale delayed root development and decreased length of primary root. Under drought stress, leaves of TwNAC01-silenced triticale had higher levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2), but lower relative water content (RWC), net photosynthetic rate, stomatal conductance, intercellular CO2 concentration, and transpiration rate than the leaves of the WT. Gene overexpression and silencing experiments suggested that TwNAC01 improves plant stress tolerance by increasing root length, regulating the water content of plant leaves by reducing MDA and H2O2 content, and adjusting respiration rate. The results suggest that TwNAC01 is a novel NAC transcription factor gene that can be exploited for triticale and cereal improvement.
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Background: Glutathione S-transferase mu 1 (GSTM1) is one of the major glutathione conjugation enzymes. Its expression and activity have been suggested to correlate with the occurrence of colon cancer; however, the role of GSTM1 in tumor immunity remains unclear. Methods: Relevant data downloaded from The Cancer Genome Atlas (TCGA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) was used to perform a multi-dimensional expression analysis of GSTM1 in colon adenocarcinoma (COAD). The correlation between GSTM1 and tumor immunity was analyzed with multiple online tools. Then protein-protein interaction (PPI) network and functional enrichment analyses of GSTM1-associated immunomodulators were performed. Further, we developed the Cox regression model based on the GSTM1-related immunomodulators. Finally, a GSTM1-based clinical nomogram and a calibration curve was established to predict the probability and accuracy of long-term survival. Result: GSTM1 was significantly downregulated in COAD versus normal tissues. Infiltration levels of B cells, CD8+ T cells, and dendritic cells were closely correlated to GSTM1 gene copy number deletion, and GSTM1 expression levels in COAD positively correlated with dendritic cell, B cell, neutrophil, and macrophage infiltration. Functional enrichment analysis indicated 36 GSTM1-related immunomodulators are involved in immune-related pathways of regulating T cell activation and lymphocytic activation. A 2-gene prognostic risk signature based on the 36 GSTM1-related immunomodulators was built using the Cox regression model, and the risk signature in combination with stage had an area under the curve (AUC) value of 0.747 by the receiver operating characteristic method. patients with higher risk scores-calculated based on 2 gene prognostic risk characteristics and further identified as an independent prognostic factor-were associated with worse survival using the Kaplan-Meier analysis. Together, the clinical nomogram and calibration curve based on GSTM1 suggested a good prediction accuracy for long-term survival probability. Conclusions: Our study provided evidence supporting the significant role of GSTM1 in COAD immunity and suggests GSTM1 as a potential novel target for COAD immunotherapy.
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BACKGROUND: Ultra-processed foods have now become dominant in the global food system. Whether their consumption is associated with cardiovascular mortality remains controversial. Moreover, data on ultra-processed foods and cardiovascular outcomes are scarce in the US population. We aimed to examine the association of ultra-processed food consumption with cardiovascular mortality in a US population. METHODS: A population-based cohort of 91,891 participants was identified from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary data were collected through a validated 137-item food frequency questionnaire. Ultra-processed foods were defined by the NOVA classification. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cardiovascular mortality. Restricted cubic spline regression was used to test nonlinearity. Subgroup analyses were conducted to identify the potential effect modifiers. RESULTS: After an average follow-up of 13.5 years (1,236,049.2 person-years), 5490 cardiovascular deaths were documented, including 3985 heart disease deaths and 1126 cerebrovascular deaths. In the fully adjusted model, participants in the highest vs. the lowest quintiles of ultra-processed food consumption had higher risks of death from cardiovascular disease (HRquintile 5 vs. 1, 1.50; 95% CI, 1.36-1.64) and heart disease (HRquintile 5 vs. 1, 1.68; 95% CI, 1.50-1.87) but not cerebrovascular disease (HRquintile 5 vs. 1, 0.94; 95% CI, 0.76-1.17). A nonlinear dose-response pattern was observed for overall cardiovascular and heart disease mortality (all Pnonlinearity < 0.05), with a threshold effect observed at ultra-processed food consumption of 2.4 servings/day and 2.3 servings/day, respectively; below the thresholds, no significant associations were observed for these two outcomes. Subgroup analyses showed that the increased risks of mortality from ultra-processed foods were significantly higher in women than in men (all Pinteraction < 0.05). CONCLUSIONS: High consumption of ultra-processed foods is associated with increased risks of overall cardiovascular and heart disease mortality. These harmful associations may be more pronounced in women. Our findings need to be confirmed in other populations and settings.
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Enfermedades Cardiovasculares/mortalidad , Dieta/estadística & datos numéricos , Comida Rápida/estadística & datos numéricos , Humanos , Estudios Prospectivos , Estados UnidosRESUMEN
Epidemiological studies on magnesium intake and primary liver cancer (PLC) are scarce, and no prospective studies have examined the associations of magnesium intake with PLC incidence and mortality. We sought to clarify whether higher magnesium intake from diet and supplements was associated with lower risks of PLC incidence and mortality in the US population. Magnesium intake from diet and supplements was evaluated through a food frequency questionnaire in a cohort of 104,025 participants. Cox regression was employed to calculate hazard ratios for PLC incidence and competing risk regression was employed to calculate subdistribution hazard ratios for PLC mortality. Restricted cubic spline regression was employed to test nonlinearity. We documented 116 PLC cases during 1,193,513.5 person-years of follow-up and 100 PLC deaths during 1,198,021.3 person-years of follow-up. Total (diet + supplements) magnesium intake was found to be inversely associated with risks of PLC incidence (hazard ratiotertile 3 vs. 1 : 0.44; 95% confidence interval: 0.24, 0.80; ptrend = 0.0065) and mortality (subdistribution hazard ratiotertile 3 vs. 1 : 0.37; 95% confidence interval: 0.19, 0.71; ptrend = 0.0008). Similar results were obtained for dietary magnesium intake. Nonlinear inverse dose-response associations with PLC incidence and mortality were observed for both total and dietary magnesium intakes (all pnonlinearity < 0.05). In summary, in the US population, a high magnesium intake is associated with decreased risks of PLC incidence and mortality in a nonlinear dose-response manner. These findings support that increasing the consumption of foods rich in magnesium may be beneficial in reducing PLC incidence and mortality.
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Encuestas sobre Dietas/estadística & datos numéricos , Conducta Alimentaria , Neoplasias Hepáticas/epidemiología , Deficiencia de Magnesio/dietoterapia , Magnesio/administración & dosificación , Anciano , Suplementos Dietéticos , Detección Precoz del Cáncer/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/prevención & control , Deficiencia de Magnesio/complicaciones , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de Riesgo , Análisis de SupervivenciaRESUMEN
Our previous studies identified that the expression of microRNA29c (miR29c3p) was significantly increased in the serum of pregnant women carrying fetuses with congenital heart disease (CHD) compared with in that of normal pregnant women. However, the mechanism by which miR29c3p affects development of the embryonic heart remained unclear. The aim of the present study was to investigate the effect and potential molecular mechanism of miR29c3p overexpression on P19 cell proliferation, apoptosis and differentiation. miR29c3poverexpression and protein kinase Bγ (Akt3)knockdown cell lines were constructed using transfection technology. The function of miR29c3p and Akt3 in cardiomyocyte development was investigated by determining the proliferation, apoptosis and differentiation of P19 cells, which can differentiate into cardiomyocytes induced by dimethylsulfoxide. Bioinformatic analysis and luciferase assays were performed to explore the association between Akt3 and miR29c3p. The results of the present study revealed that miR29c3p overexpression and Akt3 knockdown suppressed proliferation, and promoted apoptosis and differentiation in P19 cells. Akt3 was also demonstrated to be a target of miR29c3p. Therefore, overexpression of miR29c3p may inhibit proliferation, and promote apoptosis and differentiation in P19 cells by inhibiting the expression of Akt3. miR29c3p may be a potential therapeutic target for the treatment of CHD.
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Regulación de la Expresión Génica , Cardiopatías Congénitas/etiología , MicroARNs/genética , Proteínas Proto-Oncogénicas c-akt/genética , Interferencia de ARN , Animales , Biomarcadores , Puntos de Control del Ciclo Celular , Línea Celular Tumoral , Proliferación Celular , Cardiopatías Congénitas/metabolismo , Cardiopatías Congénitas/patología , Ratones , Miocitos Cardíacos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transfección , Proteína X Asociada a bcl-2/metabolismoRESUMEN
BACKGROUND: Interleukin-37b (IL-37b), a vital negative regulator of the innate immune system, has been reported to be a tumor inhibitor in different type of cancers. However, little is known about the relationship between IL-37b and hepatocellular carcinoma (HCC). The present study aimed to investigate the potential roles of IL-37b in HCC progression. METHODS: Subjects (nâ¯=â¯237) were recruited, and serum IL-37b was measured using ELISA. The tumor-suppressive capacity and underlying mechanisms of IL-37b in HCC were investigated in vitro and in vivo. RESULTS: Compared to healthy controls, serum IL-37b levels were elevated in chronic hepatitis B (CHB) patients but decreased significantly in HBV-HCC patients, especially for those with portal venous tumor thrombus. Low level serum IL-37b in HBV-HCC patients correlated with high HCC stage and poor overall survival and disease-free survival. In vitro and in vivo, recombinant human IL-37b inhibited proliferation and metastasis in HCC cells. Furthermore, IL-37b inhibited epithelial mesenchymal transition in HCC cells in vitro by downregulating IL-6, pSTAT3 (Y705), N-cadherin, and vimentin expression and by upregulating E-cadherin expression. These effects were partially reversed by transfection of adenovirus encoding human IL-6. CONCLUSIONS: IL-37b inhibits HCC growth, metastasis and epithelial mesenchymal transition by regulating IL-6/STAT3 signaling. Serum IL-37b may be a biomarker for HBV-HCC and its staging.
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Carcinoma Hepatocelular/genética , Transición Epitelial-Mesenquimal/genética , Regulación Neoplásica de la Expresión Génica , Interleucina-1/genética , Neoplasias Hepáticas/genética , Factor de Transcripción STAT3/metabolismo , Adulto , Anciano , Análisis de Varianza , Biopsia con Aguja , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Estudios de Casos y Controles , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Hepatitis B Crónica/sangre , Hepatitis B Crónica/genética , Hepatitis B Crónica/patología , Humanos , Inmunohistoquímica , Interleucina-6/metabolismo , Estimación de Kaplan-Meier , Cirrosis Hepática/sangre , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Pronóstico , Valores de Referencia , Medición de Riesgo , Factor de Transcripción STAT3/genética , Transducción de Señal , Análisis de SupervivenciaRESUMEN
BACKGROUND: Robust evidence is lacking regarding the clinical efficacy, safety and cardiopulmonary performance of perventricular closure. This study investigated the perioperative efficacy, safety and cardiorespiratory performance of perventricular closure of perimembranous ventricular septal defects (pmVSDs). METHODS: Operation-naïve infants and young children aged 5-60 months with isolated pmVSDs were randomised to receive either standard open surgical or minimally invasive perventricular closure via direct entry into the ventricle with a catheter from a subxiphoid incision. The primary outcomes included complete closure at discharge, major and minor adverse events and the changes in perioperative cardiorespiratory performance from baseline. Complete closure was mainly analysed in the modified intention-to-treat (mITT) population, with sensitivity analyses for the ITT, per-protocol (PP) and as-treated (AT) populations (non-inferiority margin -5.0%). RESULTS: We recruited 200 patients with pmVSDs for this study (mean age 24.38 months, range 7-58 months, 104 girls), of whom 100 were randomly allocated to one of the study groups. The non-inferiority of perventricular to surgical closure regarding complete closure at discharge was not shown in the ITT (absolute difference -0.010 (95% CI -0.078 to 0.058)) and mITT populations (-0.010 (95% CI -0.069 to 0.048)), but was shown in the PP (0.010 (95% CI -0.043 to 0.062)) and AT populations (0.048 (95% CI -0.009 to 0.106)). Perventricular closure reduced the rate of compromising cardiac haemodynamics, electrophysiological responses, cardiomyocyte viability, respiratory mechanics, ventilatory and gas exchange function and oxygenation and tissue perfusion compared with surgical closure (all between-group P<0.05). CONCLUSIONS: For infants and young children with pmVSD, perventricular closure reduced the rate of postoperative cardiorespiratory compromise compared with surgical closure, but the non-inferiority regarding complete closure should be interpreted in the context of the specific population. TRIAL REGISTRATION NUMBER: NCT02794584 ;Results.
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Procedimientos Quirúrgicos Cardíacos/métodos , Defectos del Tabique Interventricular/cirugía , Ventrículos Cardíacos/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Dispositivo Oclusor Septal , Preescolar , Ecocardiografía Transesofágica/métodos , Femenino , Estudios de Seguimiento , Defectos del Tabique Interventricular/diagnóstico , Ventrículos Cardíacos/diagnóstico por imagen , Humanos , Lactante , Masculino , Periodo Posoperatorio , Diseño de Prótesis , Resultado del TratamientoRESUMEN
BACKGROUND: Orthotopic liver transplantation (OLT) improves the prognosis of patients with hepatocellular carcinoma (HCC). Moreover, the complement system is a powerful immune effector that can affect liver function and process of liver cirrhosis. However, studies correlating the complement system with tacrolimus metabolism after OLT are scarce. In this study, the role of single nucleotide polymorphisms (SNPs) associated with the sixth complement component (C6) in tacrolimus metabolism was investigated during the early stages of liver transplantation. METHODS: The study enrolled 135 adult patients treated with OLT for HCC between August 2011 and October 2013. Ten SNPs in C6 gene and rs776746 in cytochrome P450 3A5 (CYP3A5) gene were investigated. The tacrolimus levels were monitored daily during 4 weeks after transplantation. RESULTS: Both donor and recipient CYP3A5 rs776746 allele A were correlated with decreased concentration/dose (C/D) ratios. Recipient C6 rs9200 allele G and donor C6 rs10052999 homozygotes were correlated with lower C/D ratios. Recipient CYP3A5 rs776746 allele A (yielded median tacrolimus C/D ratios of 225.90 at week 1 and 123.61 at week 2), C6 rs9200 allele G (exhibited median tacrolimus C/D ratios of 211.31 at week 1, 110.23 at week 2, and 99.88 at week 3), and donor CYP3A5 rs776746 allele A (exhibited median C/D ratios of 210.82 at week 1, 111.06 at week 2, 77.49 at week 3, and 85.60 at week 4) and C6 rs10052999 homozygote (exhibited median C/D ratios of 167.59 at week 2, 157.99 at week 3, and 155.36 at week 4) were associated with rapid tacrolimus metabolism. With increasing number of these alleles, patients were found to have lower tacrolimus C/D ratios at various time points during the 4 weeks after transplantation. In multiple linear regression analysis, recipient C6 rs9200 group (AA vs. GG/GA) was found to be related to tacrolimus metabolism at weeks 1, 2, and 3 (P = 0.005, P = 0.045, and P = 0.033, respectively), whereas donor C6 rs10052999 group (CC/TT vs. TC) was demonstrated to be correlated with tacrolimus metabolism only at week 4 (P = 0.001). CONCLUSIONS: Recipient C6 gene rs9200 polymorphism and donor C6 gene rs10052999 polymorphism are new genetic loci that affect tacrolimus metabolism in patients with HCC after OLT.
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Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/cirugía , Tacrolimus/metabolismo , Adulto , Anciano , Carcinoma Hepatocelular/genética , Citocromo P-450 CYP3A/genética , Femenino , Genotipo , Humanos , Inmunosupresores/metabolismo , Neoplasias Hepáticas/genética , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
In our previous efforts to understand the regulatory mechanisms of cucumber unisexual flower development, we observed a stamen-specific down-regulation of the ethylene receptor CsETR1 in stage 6 female flowers of cucumber (Cucumis sativus L.). This down-regulation is correlated with the primordial anther-specific DNA damage that characterizes inappropriate stamen development in cucumber female flowers. To understand how CsETR1 is down regulated in the stamen, we characterized a cucumber MADS box gene homologous to Arabidopsis AP3, CsAP3. We demonstrated that CsAP3 is functionally equivalent to the Arabidopsis B-class MADS gene AP3. However, three novel characteristics of CsAP3 were found. These include firstly, binding and activating CsETR1 promoter in vitro and in vivo; secondly, containing a GV repeat in its C-terminus, which is conserved in cucurbits and required for the transcription activation; and thirdly, decreased expression as the node number increases, which is similar to that found for CsETR1. These findings revealed not only the conserved function of CsAP3 as a B-class floral identity gene, but also its unique functions in regulation of female flower development in cucumber.
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Cardiopatías Congénitas/etiología , Hemodinámica/fisiología , Técnicas Reproductivas Asistidas/efectos adversos , Preescolar , Diástole/fisiología , Ecocardiografía , Femenino , Cardiopatías Congénitas/diagnóstico por imagen , Cardiopatías Congénitas/fisiopatología , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Embarazo , Sistema de Registros , Estadística como Asunto , Sístole/fisiologíaRESUMEN
BACKGROUND: Prenatal ultrasonography is the most widely available diagnostic test for fetal congenital heart disease (CHD), but the factors influencing its diagnostic accuracy remain uncertain despite extensive research. The aim of the present study was to evaluate the potential role of demographic, clinical and ultrasonographic characteristics on diagnostic yields for detecting CHD. METHODS: A systematic search of PubMed, ISI Web of Science, SinoMed, and the Cochrane Library was performed to identify studies assessing the accuracy of prenatal ultrasound in the detection of CHD. A random effects model was used to generate pooled sensitivity and specificity in addition to summary receiver operating characteristic (SROC) curves. RESULTS: Overall, prenatal ultrasound in the detection of CHD had a moderate sensitivity of 68.1% (95% CI 59.6-75.5) and a favorable specificity of 99.9% (99.7-99.9). Risk level and gestation age were independent predictors of diagnostic performance for detecting CHD (p = 0.004 vs. p = 0.002, respectively). The pooled sensitivities significantly increased to varying extents with the following echocardiographic views: 48.7% (34.8-67.2) for four-chamber view (4CV); 58.0% (40.3-73.9) for a combination of 4CV and outflow tract views (OTV); 73.5% (59.2-84.1) for combination of 4CV, OTV and three vessels and trachea view (3VTV); 77.1% (62.0-87.5) for extensive cardiac echocardiography examination (ECEE); and 89.6% (81.0-94.6) for spatiotemporal image correlation (STIC). CONCLUSIONS: Prenatal ultrasound is a powerful tool for the diagnosis of CHD; however, a single ultrasonographic regime is not definitive on its own and must be interpreted in the context of demographic and clinical characteristics.
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Ecocardiografía , Corazón Fetal/diagnóstico por imagen , Cardiopatías Congénitas/diagnóstico por imagen , Ultrasonografía Prenatal/métodos , Área Bajo la Curva , Corazón Fetal/fisiopatología , Edad Gestacional , Cardiopatías Congénitas/fisiopatología , Humanos , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Reproducibilidad de los ResultadosRESUMEN
AIMS: To examine the pattern and extent of cardiovascular developmental alterations among children conceived by assisted reproductive technology (ART) and its association with potential confounders. METHODS: The present study was a prospective single-blind pilot design lasting 15 months. The ART group was recruited by a non-random, consecutive sample on the basis of the unique personal identification number assigned to ART children, whereas spontaneous conception controls were recruited by a population-based random sample from the same hospital by age. Echocardiography was available for the measurement of 128 ART children and 100 controls with respect to cardiovascular geometric morphology and cardiac function. RESULTS: The majority of cardiac geometric morphology parameters were comparable among the study groups (P>0.05), except for significant increases in left ventricular (LV) relative wall thickness (P=0.038), LV mass index (P=0.005) and LV remodeling index (P=0.005) in ART children after adjustment for age, gender, body surface area and heart rate. The results showed similarity in LV systolic function characterized by ejection fraction (P=0.140) and shortening fraction (P=0.167) between the groups. However, ART children had a significant tendency toward a decrease in mitral A (P=0.008) and mitral E' (P=0.012) compared with controls after adjusting for confounders. Additionally, Cox analysis suggested an independent association (P<0.05) of anthropometrics and perinatal outcomes in addition to the ART procedure itself with the differences in cardiac developmental status. CONCLUSION: Our findings support the presence of remodeling in the left cardiac geometric morphology and diastolic dysfunction and the absence of any change to the aortocoronary morphometry or systolic function in ART children compared with controls, which may be independently associated with the anthropometrics and perinatal outcomes in addition to the ART procedure.
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Corazón/crecimiento & desarrollo , Técnicas Reproductivas Asistidas , Niño , Femenino , Humanos , Masculino , Proyectos Piloto , Método Simple CiegoRESUMEN
INTRODUCTION: Minimally invasive endoscopic biopsy techniques have been widely available as potential alternatives for mediastinal lesions staging in patients with known or suspected lung cancer. Previous efforts have been made to evaluate the diagnostic performance of specific endoscopic modality alone at the level of the mediastinum for staging lung cancer, however, few studies focus on the accuracy of comparisons between different endoscopic modalities, especially at the level of any individual lymph node station. The objective of our study is to determine the diagnostic yields of different endoscopic modalities for staging mediastinal lymphadenopathy in lung cancer, especially concerning the individual lymph node station. METHODS/DESIGN: A systematic electronic search of MEDLINE, EMBASE, SinoMed and ISI Web of Science were performed to identify studies evaluating endoscopic modalities accuracy with restriction of English and Chinese languages from inception to an update until May 2014. Data were extracted with the patient as the unit of analysis with regards to the abilities of different endoscopic modalities at the level of mediastinum and particular lymph node station. The methodological quality was assessed independently according to the Quality Assessment of Diagnostic Accuracy Study (QADAS) criteria. An exact binomial rendition of bivariate mixed-effects regression model was used to estimate the pooled sensitivity and specificity. Also, pre-post probability analysis, publication bias analysis and sensitivity analysis were performed for a synthesis of knowledge of this context. DISSEMINATION: The findings will advance our better available knowledge of optimal clinical decision-making when dealing with staging of mediastinal metastasis in lung cancer. TRIAL REGISTRATION NUMBER: PROSPERO-NIHR Prospective Register of Systematic Reviews (CRD42014009792).
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Biopsia con Aguja/métodos , Endosonografía/métodos , Neoplasias Pulmonares/diagnóstico , Enfermedades Linfáticas/patología , Enfermedades del Mediastino/patología , Estadificación de Neoplasias/métodos , Humanos , Procedimientos Quirúrgicos Mínimamente Invasivos , Estudios Prospectivos , Revisiones Sistemáticas como AsuntoRESUMEN
⢠Production of unisexual flowers is an important mechanism that promotes cross-pollination in angiosperms. We previously identified primordial anther-specific DNA damage and organ-specific ethylene perception responsible for the arrest of stamen development in female flowers, but little is known about how the two processes are linked. ⢠To identify potential links between the two processes, we performed suppression subtractive hybridization (SSH) on cucumber (Cucumis sativus L.) stamens of male and female flowers at stage 6, with stamens at stage 5 of bisexual flowers as a control. ⢠Among the differentially expressed genes, we identified an expressed sequence tag (EST) encoding a cucumber homolog to an Arabidopsis calcium-dependent nuclease (CAN), designated CsCaN. Full-length CsCaN cDNA and the respective genomic DNA sequence were cloned and characterized. The CsCaN protein exhibited calcium-dependent nuclease activity. CsCaN showed ubiquitous expression; however, increased gene expression was detected in the stamens of stage 6 female flowers compared with male flowers. As expected, CsCaN expression was ethylene inducible. It was of great interest that CsCaN was post-translationally modified. ⢠This study demonstrated that CsCaN is a novel cucumber nuclease gene, whose DNase activity is regulated at multiple levels, and which could be involved in the primordial anther-specific DNA damage of developing female cucumber flowers.
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Calcio/farmacología , Cucumis sativus/genética , Desoxirribonucleasas/genética , Etilenos/farmacología , Flores/crecimiento & desarrollo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Clonación Molecular , Cucumis sativus/citología , Cucumis sativus/enzimología , Cucumis sativus/crecimiento & desarrollo , ADN Complementario/genética , Desoxirribonucleasas/metabolismo , Flores/citología , Flores/enzimología , Flores/genética , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Isoenzimas/genética , Isoenzimas/metabolismo , Hibridación de Ácido Nucleico , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Procesamiento Proteico-Postraduccional/genéticaRESUMEN
The aim of this study was to investigate the effects of GATA-4 on the differentiation of P19 cells into cardiomyocytes and to examine the relationship between GATA-4 and cardiomyocytes. We constructed vectors to overexpress and silence GATA-4. These vectors, as well as empty ones were transfected into P19 cells. Subsequently, reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis were performed. The morphology of P19 cells during differentiation was observed using an inverted microscope. Total RNA was extracted from P19 cells. We used real-time PCR to evaluate the expression levels of 6 genes: GATA-4, GATA-6, transthyretin (TTR), alpha-fetoprotein (AFP), Nkx2.5, and alpha-myosin heavy chain (alpha-MHC). The gene expression pattern of these 6 genes is graphically shown for each group. The GATA-4 mRNA level in cells overexpressing GATA-4 was notably higher than that in the controls, whereas the levels in the controls were notably higher than those in the GATA-4-silenced P19 cells. The cell lines overexpressing GATA-4 expressed higher levels of Nkx2.5 and alpha-MHC than the controls. However, the controls expressed higher levels of AFP, GATA-6 and TTR than the cells overexpressing GATA-4. The RNAi group expressed lower levels of TTR, Nkx2.5, and alpha-MHC than the controls, but there were no differences in the RNAi group and the controls with regard to the expression levels of AFP and GATA-6. The gene expression pattern in the cells overexpressing GATA-4 was biased toward the Nkx2.5 and alpha-MHC. On the other hand, the gene expression pattern in GATA-4-silenced cells and the controls was biased toward the TTR and AFP. The overexpression of GATA-4 enhances the differentiation of P19 cells into cardiac myocytes, whereas its down-regulation suppresses this trend.
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Diferenciación Celular/fisiología , Factor de Transcripción GATA4/metabolismo , Miocitos Cardíacos/fisiología , Animales , Biomarcadores/metabolismo , Línea Celular , Forma de la Célula , Factor de Transcripción GATA4/genética , Factor de Transcripción GATA6/genética , Factor de Transcripción GATA6/metabolismo , Expresión Génica , Proteína Homeótica Nkx-2.5 , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Ratones , Miocitos Cardíacos/citología , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismo , Prealbúmina/genética , Prealbúmina/metabolismo , Interferencia de ARN , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , alfa-Fetoproteínas/genética , alfa-Fetoproteínas/metabolismoRESUMEN
OBJECTIVE: To discuss the effectiveness of individualized strategy of surgical management on the great arteries (TGA). METHODS: From March 1998 to October 2009, 127 cases (97 males and 30 females) with TGA were treated. There were 97 male and 30 female, aged from 4 hours old to 17 years old with a mean of (25 ± 37) months, weighted from 2.7 to 47.5 kg with a mean of (8 ± 8) kg. The palliative operations included Glenn operation in 14 cases (3 cases double Glenn procedure), Balalock-Taussing shunt in 14 cases, Banding operation in 8 cases, and atrial septal defect enlarge/Banding/Balalock-Taussing shunt in 15 cases. The end-stage operation included Senning procedure in 5 cases, Switch procedure in 32 cases, 2(nd)-stage Switch procedure in 11 cases, Switch procedure with VSD repairing in 20 cases, Switch procedure with Hybrid in 1 case, Nikaidoh procedure in 3 cases, Rastelli procedure in 13 cases, Fonton procedure in 18 cases, other procedure in 4 cases. Twenty-one cases underwent 2 operations, and 5 cases underwent 3 or more operations. Sixty-six cases underwent delayed sternal closure. RESULTS: There were 12 cases of death operatively in 127 cases. The total operative mortality was 9.4%. There were 5 cases dying of low cardiac output during the operation, 2 of pulmonary hypertension crisis, 2 of hemorrhage, 1 of grafting problem of coronary artery deformation, 1 of renal failure after Fonton procedure and 1 case of newborn dying of spontaneous rupture of liver post-operatively. The patients were followed up for 1 month to 12 years. There were 10 patients with vary degrees complications such as pulmonary stenosis, residual shunt and narrow channel. Three cases underwent reoperation. The rest of survived cases had normal heart function, good growth and development state. CONCLUSIONS: Individualized strategy of surgical management based on anatomical conditions of TGA can significantly improve the success rate of surgery and long-term survival.
Asunto(s)
Transposición de los Grandes Vasos/cirugía , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino , Resultado del TratamientoRESUMEN
OBJECTIVE: To determine the effects of diazoxide on oxygen free radicals and cell apoptosis in brain tissue after deep hypothermia cerebral ischemia reperfusion injury in young rats. METHODS: Fifty-four 3-week-old Sprague-Dawley rats were randomly and equitably divided into sham-operated group, model group and diazoxide group respectively (n = 18). The model of hypothermia cerebral ischemia reperfusion injury was made. After 24 hours of operation, the brains of rats were removed and preserved. The content of superoxide dismutase (SOD) and malonaldehyde (MDA) in brain tissue were detected. Cytosolic C release of cytochrome was confirmed by Western Blot. The protein expression of Caspase-3 was determined by immunohistochemistry. RESULTS: In the model group, the content of SOD was (198 +/- 41) U/mg, lower than the sham-operated group's (321 +/- 36) U/mg (P < 0.01). The content of MDA was (212 +/- 21) nmol/mg, was higher than the sham-operated group's (100 +/- 23) nmol/mg (P < 0.01), and the expressions of cytochrome C (0.72 +/- 0.09) and Caspase-3 (83 +/- 10) were all significantly higher than those in the sham-operated group (0.17 +/- 0.02 and 115 +/- 9) (P < 0.01). Compared with the model group, the content of SOD in the diazoxide group [(264 +/- 34) U/mg] was markedly increased (P < 0.05). In addition, diazoxide provided significant reductions in the content of MDA [(174 +/- 19) nmol/mg] and the expressions of cytochrome C (0.41 +/- 0.05) and Caspase-3 (99 +/- 11) (P < 0.05). CONCLUSIONS: The neuroprotective effects of diazoxide against brain injury induced by deep hypothermia cerebral ischemia reperfusion through inhibiting oxygen free radicals and cell apoptosis. Diazoxide may become a new neuroprotective drug after infant complicated congenital cardiac operation.
Asunto(s)
Apoptosis/efectos de los fármacos , Isquemia Encefálica/metabolismo , Diazóxido/farmacología , Especies Reactivas de Oxígeno/metabolismo , Animales , Encéfalo/metabolismo , Encéfalo/patología , Isquemia Encefálica/etiología , Isquemia Encefálica/patología , Caspasa 3/metabolismo , Paro Circulatorio Inducido por Hipotermia Profunda/efectos adversos , Citocromos c/metabolismo , Modelos Animales de Enfermedad , Femenino , Masculino , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Sprague-Dawley , Reperfusión , Superóxido Dismutasa/metabolismoRESUMEN
To understand the regulatory mechanisms governing unisexual flower development in cucumber, we conducted a systematic morphogenetic analysis of male and female flower development, examined the dynamic changes in expression of the C-class floral organ identity gene CUM1, and assessed the extent of DNA damage in inappropriate carpels of male flowers. Accordingly, based on the occurrence of distinct morphological events, we divided the floral development into 12 stages ranging from floral meristem initiation to anthesis. As a result of our investigation we found that the arrest of stamen development in female flowers, which occurs just after the differentiation between the anther and filament, is mainly restricted to the primordial anther, and that it is coincident with down-regulation of CUM1 gene expression. In contrast, the arrest of carpel development in the male flowers occurs prior to the differentiation between the stigma and ovary, given that no indication of ovary differentiation was observed even though CUM1 gene expression remained detectable throughout the development of the stigma-like structures. Although the male and female reproductive organs have distinctive characteristics in terms of organ differentiation, there are two common features regarding organ arrest. The first is that the arrest of the inappropriate organ does not affect the entirety of the organ uniformly but occurs only in portions of the organs. The second feature is that all the arrested portions in both reproductive organs are spore-bearing parts.
Asunto(s)
Cucumis sativus/crecimiento & desarrollo , Flores/crecimiento & desarrollo , Cucumis sativus/genética , Cucumis sativus/ultraestructura , Flores/metabolismo , Flores/ultraestructura , Regulación del Desarrollo de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Proteínas de Dominio MADS/biosíntesis , Proteínas de Dominio MADS/genética , Proteínas de Plantas/biosíntesis , Proteínas de Plantas/genéticaRESUMEN
OBJECTIVE: To summarize the experience of surgical treatment of newborns with congenital heart diseases. METHODS: The experience of surgical treatment of 8 newborns with critical congenital heart diseases, including 3 cases of D-transposition of great arteries with intact ventricular septum, 2 cases of ventricular septal defect with artrial defect (ASD), one case of complete atrioventricular canal defect, 1 case of obstructed supracardiac total anomalous pulmonary venous drainage with ASD, and 1 case of patent ductus arteriosus (PDA). RESULTS: The case of PDA underwent ligation under normothermic anesthesia and the other 7 cases were operated upon under moderate or deep hypothermic cardiopulmonary bypass. All the 8 cases were observed in ICU for 2 approximately 10 days, and were discharged 7 approximately 15 days after operation. The follow-up after discharge showed a satisfying outcome. The postoperative complications included low cardiac output, infection of mediastinum, and respiratory distress syndrome. CONCLUSION: The critical and complex congenital heart diseases should by diagnosed as early as possible and emergency operation is effective and feasible.