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BACKGROUND: Previous studies suggested only the radial artery and the No-touch (NT) technique were effective in reducing graft occlusion after coronary artery bypass grafting (CABG) surgery. However, there is no randomized trial comparing these 2 graft conduits. The optimum second conduit for CABG remains undetermined. MATERIALS AND METHODS: This study is a prospective, single-center randomized clinical trial, aiming to compare the graft patency between the radial artery and the NT vein graft. All patients undergoing isolated CABG with left internal mammary artery (LIMA) plus at least 2 additional grafts will be considered eligible. About 774 cases (516 in the radial artery group and 258 in the NT vein group) will be enrolled in over 1 to 2 years. Participants will be randomized and allocated to two bypass strategies: the LIMA plus 1 radial artery and 1 conventional vein graft, or the LIMA plus 2 NT vein grafts. The primary outcome is graft occlusion at 1 year after CABG evaluated by CT angiography. The secondary outcomes include graft occlusion at 3 and 5 years and major adverse cardiac or cerebrovascular events at 1, 3, and 5 years follow-ups. DISCUSSION: This study will define whether or not the NT vein has a lower graft occlusion rate than the radial artery in short and mid-term follow-ups, and provide new evidence for the second conduit choice in CABG surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT06014047. Registered on October 15th, 2023.
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Puente de Arteria Coronaria , Oclusión de Injerto Vascular , Arteria Radial , Vena Safena , Grado de Desobstrucción Vascular , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Angiografía por Tomografía Computarizada/métodos , Angiografía Coronaria/métodos , Puente de Arteria Coronaria/métodos , Puente de Arteria Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/cirugía , Oclusión de Injerto Vascular/prevención & control , Oclusión de Injerto Vascular/etiología , Arterias Mamarias/trasplante , Estudios Prospectivos , Arteria Radial/trasplante , Ensayos Clínicos Controlados Aleatorios como Asunto , Vena Safena/trasplanteRESUMEN
In plant species, anthocyanin accumulation is specifically regulated by light signaling. Although the CONSTITUTIVELY PHOTOMORPHOGENIC1/SUPPRESSOR OF PHYA-105 (COP1/SPA) complex is known to control anthocyanin biosynthesis in response to light, the precise mechanism underlying this process remains largely unknown. Here, we report that Increase in BONSAI Methylation 1 (IBM1), a JmjC domain-containing histone demethylase, participates in the regulation of light-induced anthocyanin biosynthesis in Arabidopsis. The expression of IBM1 was induced by high light (HL) stress, and loss-of-function mutations in IBM1 led to accelerated anthocyanin accumulation under HL conditions. We further identified that IBM1 is directly associated with SPA1/3/4 chromatin in vivo to establish a hypomethylation status on H3K9 and DNA non-CG at these loci under HL, thereby releasing their expression. Genetic analysis showed that quadruple mutants of IBM1 and SPA1/3/4 resemble spa134 mutants. Overexpression of SPA1 in ibm1 mutants complements the mutant phenotype. Our results elucidate the significance and mechanism of IBM1 histone demethylase in the epigenetic regulation of anthocyanin biosynthesis in Arabidopsis under HL conditions.
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Antocianinas , Proteínas de Arabidopsis , Epigénesis Genética , Regulación de la Expresión Génica de las Plantas , Histona Demetilasas con Dominio de Jumonji , Luz , Antocianinas/biosíntesis , Antocianinas/genética , Arabidopsis/genética , Arabidopsis/efectos de la radiación , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Cromatina/metabolismo , Metilación de ADN/genética , Histonas/metabolismo , Histona Demetilasas con Dominio de Jumonji/metabolismo , Histona Demetilasas con Dominio de Jumonji/genética , Mutación/genética , FenotipoRESUMEN
Objective: Nucleotide excision repair (NER) plays a vital role in maintaining genome stability, and the effect of NER gene polymorphisms on hepatoblastoma susceptibility is still under investigation. This study aimed to evaluate the relationship between NER gene polymorphisms and the risk of hepatoblastoma in Eastern Chinese Han children. Methods: In this five-center case-control study, we enrolled 966 subjects from East China (193 hepatoblastoma patients and 773 healthy controls). The TaqMan method was used to genotype 19 single nucleotide polymorphisms (SNPs) in NER pathway genes, including ERCC1, XPA, XPC, XPD, XPF, and XPG. Then, multivariate logistic regression analysis was performed, and odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized to assess the strength of associations. Results: Three SNPs were related to hepatoblastoma risk. XPC rs2229090 and XPD rs3810366 significantly contributed to hepatoblastoma risk according to the dominant model (adjusted OR=1.49, 95% CI=1.07-2.08, P=0.019; adjusted OR=1.66, 95% CI=1.12-2.45, P=0.012, respectively). However, XPD rs238406 conferred a significantly decreased risk of hepatoblastoma under the dominant model (adjusted OR=0.68, 95% CI=0.49-0.95; P=0.024). Stratified analysis demonstrated that these significant associations were more prominent in certain subgroups. Moreover, there was evidence of functional implications of these significant SNPs suggested by online expression quantitative trait loci (eQTLs) and splicing quantitative trait loci (sQTLs) analysis. Conclusions: In summary, NER pathway gene polymorphisms (XPC rs2229090, XPD rs3810366, and XPD rs238406) are significantly associated with hepatoblastoma risk, and further research is required to verify these findings.
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INTRODUCTION: The necessity of complete bi-atrial lesion created by radiofrequency clamp and pen for nonparoxysmal atrial fibrillation (AF) in patients with rheumatic mitral valve disease (RMVD) remains unclear. METHODS: From January 2014 to December 2018, patients with RMVD concomitant with nonparoxysmal AF who underwent mitral valve surgery concomitant surgical ablation were retrospectively enrolled. We divided patients into Group A (complete bi-atrial lesion set created by radiofrequency clamp and pen) and Group B (simplified lesion sets created by radiofrequency clamp alone including bi-atrial ablation with incomplete mitral isthmus line and stand-alone left atrial ablation) according to the surgical ablation lesion sets. Propensity score matching was applied to analyze freedom from atrial tachyarrhythmias between the two groups. RESULTS: Two hundred eight (38.5%) and 332 (61.5%) patients were divided into Group A and Group B, respectively. In Group B, the proportion of patients with recurrent atrial flutter in the subgroup of bi-atrial ablation with incomplete mitral isthmus line was higher than that in Group A (p = .044). After propensity score matching, there were 203 patients in each group. Better freedom from atrial tachyarrhythmias without antiarrhythmic drugs was obtained in Group A (83.1%, 79.6%, and 65.4%) than Group B (73.1%, 68.4%, and 52.7%) at 12, 36, and 60 months after operation (p = .012). CONCLUSION: The application of radiofrequency clamp and pen to create complete bi-atrial lesion set in surgical ablation for nonparoxysmal AF in RMVD was associated with superior long-term efficacy.
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Fibrilación Atrial , Ablación por Catéter , Enfermedades de las Válvulas Cardíacas , Humanos , Válvula Mitral/diagnóstico por imagen , Válvula Mitral/cirugía , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Fibrilación Atrial/complicaciones , Estudios Retrospectivos , Estudios de Seguimiento , Enfermedades de las Válvulas Cardíacas/diagnóstico , Enfermedades de las Válvulas Cardíacas/diagnóstico por imagen , Ablación por Catéter/efectos adversos , Ablación por Catéter/métodos , Resultado del TratamientoRESUMEN
BACKGROUND: Exploring the mechanisms of valvular heart disease at the cellular level may be useful to identify new therapeutic targets; however, the comprehensive cellular landscape of nondiseased human cardiac valve leaflets remains unclear. METHODS: The cellular landscapes of nondiseased human cardiac valve leaflets (5 aortic valves, 5 pulmonary valves, 5 tricuspid valves, and 3 mitral valves) from end-stage heart failure patients undergoing heart transplantation were explored using single-cell RNA sequencing. Bioinformatics was used to identify the cell types, describe the cell functions, and investigate cellular developmental trajectories and interactions. Differences among the 4 types of cardiac valves at the cellular level were summarized. Pathological staining was performed to validate the key findings of single-cell RNA sequencing. An integrative analysis of our single-cell data and published genome-wide association study-based and bulk RNA sequencing-based data provided insights into the cell-specific contributions to calcific aortic valve diseases. RESULTS: Six cell types were identified among 128 412 cells from nondiseased human cardiac valve leaflets. Valvular interstitial cells were the largest population, followed by myeloid cells, lymphocytes, valvular endothelial cells, mast cells, and myofibroblasts. The 4 types of cardiac valve had distinct cellular compositions. The intercellular communication analysis revealed that valvular interstitial cells were at the center of the communication network. The integrative analysis of our single-cell RNA sequencing data revealed key cellular subpopulations involved in the pathogenesis of calcific aortic valve diseases. CONCLUSIONS: The cellular landscape differed among the 4 types of nondiseased cardiac valve, which might explain their differences in susceptibility to pathological remodeling and valvular heart disease.
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Estenosis de la Válvula Aórtica , Calcinosis , Insuficiencia Cardíaca , Enfermedades de las Válvulas Cardíacas , Humanos , Estenosis de la Válvula Aórtica/patología , Válvula Aórtica/patología , Calcinosis/metabolismo , Células Endoteliales/metabolismo , Estudio de Asociación del Genoma Completo , Células Cultivadas , Enfermedades de las Válvulas Cardíacas/genética , Enfermedades de las Válvulas Cardíacas/cirugía , Enfermedades de las Válvulas Cardíacas/complicaciones , Insuficiencia Cardíaca/metabolismoRESUMEN
BACKGROUND: Migration of human aortic smooth muscle cells (HASMCs) contributes to the pathogenesis of atherosclerosis. This study aims to functionally characterize long noncoding RNA TPRG1-AS1 (tumor protein p63 regulated 1, antisense 1) in HASMCs and reveal the underlying mechanism of TPRG1-AS1 in HASMCs migration, neointima formation, and subsequent atherosclerosis. METHODS: The expression of TPRG1-AS1 in atherosclerotic plaques was verified a series of in silico analysis and quantitative real-time polymerase chain reaction analysis. Northern blot, rapid amplification of cDNA ends and Sanger sequencing were used to determine its full length. In vitro transcription-translation assay was used to investigate the protein-coding capacity of TPRG1-AS1. RNA fluorescent in situ hybridization was used to confirm its subcellular localization. Loss- and gain-of-function studies were used to investigate the function of TPRG1-AS1. Furthermore, the effect of TPRG1-AS1 on the pathological response was evaluated in carotid balloon injury model, wire injury model, and atherosclerosis model, respectively. RESULTS: TPRG1-AS1 was significantly increased in atherosclerotic plaques. TPRG1-AS1 did not encode any proteins and its full length was 1279nt, which was bona fide a long noncoding RNA. TPRG1-AS1 was mainly localized in cytoplasmic and perinuclear regions in HASMCs. TPRG1-AS1 directly interacted with MYH9 (myosin heavy chain 9) protein in HASMCs, promoted MYH9 protein degradation through the proteasome pathway, hindered F-actin stress fiber formation, and finally inhibited HASMCs migration. Vascular smooth muscle cell-specific transgenic overexpression of TPRG1-AS1 significantly reduced neointima formation, and attenuated atherosclerosis in apolipoprotein E knockout (Apoe-/-) mice. CONCLUSIONS: This study demonstrated that TPRG1-AS1 inhibited HASMCs migration through interacting with MYH9 protein and consequently suppressed neointima formation and atherosclerosis.
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Aterosclerosis , MicroARNs , Placa Aterosclerótica , ARN Largo no Codificante , Humanos , Ratones , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Músculo Liso Vascular/metabolismo , Neointima/metabolismo , Placa Aterosclerótica/metabolismo , Actinas/metabolismo , Complejo de la Endopetidasa Proteasomal/metabolismo , ADN Complementario/metabolismo , ADN Complementario/farmacología , Hibridación Fluorescente in Situ , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismo , Proliferación Celular , Miocitos del Músculo Liso/metabolismo , Movimiento Celular , Aterosclerosis/genética , Aterosclerosis/prevención & control , Aterosclerosis/metabolismo , MicroARNs/genética , Proteínas del Citoesqueleto/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas/metabolismoRESUMEN
Secondary wall thickening in the sclerenchyma cells is strictly controlled by a complex network of transcription factors in vascular plants. However, little is known about the epigenetic mechanism regulating secondary wall biosynthesis. In this study, we identified that ARABIDOPSIS HOMOLOG of TRITHORAX1 (ATX1), a H3K4-histone methyltransferase, mediates the regulation of fiber cell wall development in inflorescence stems of Arabidopsis thaliana. Genome-wide analysis revealed that the up-regulation of genes involved in secondary wall formation during stem development is largely coordinated by increasing level of H3K4 tri-methylation. Among all histone methyltransferases for H3K4me3 in Arabidopsis, ATX1 is markedly increased during the inflorescence stem development and loss-of-function mutant atx1 was impaired in secondary wall thickening in interfascicular fibers. Genetic analysis showed that ATX1 positively regulates secondary wall deposition through activating the expression of secondary wall NAC master switch genes, SECONDARY WALL-ASSOCIATED NAC DOMAIN PROTEIN1 (SND1) and NAC SECONDARY WALL THICKENING PROMOTING FACTOR1 (NST1). We further identified that ATX1 directly binds the loci of SND1 and NST1, and activates their expression by increasing H3K4me3 levels at these loci. Taken together, our results reveal that ATX1 plays a key role in the regulation of secondary wall biosynthesis in interfascicular fibers during inflorescence stem development of Arabidopsis.
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Proteínas de Arabidopsis/fisiología , Arabidopsis/metabolismo , Pared Celular/metabolismo , Regulación de la Expresión Génica de las Plantas/fisiología , Código de Histonas , N-Metiltransferasa de Histona-Lisina/fisiología , Histonas/genética , Inflorescencia/metabolismo , Proteínas de Plantas/genética , Tallos de la Planta/metabolismo , Factores de Transcripción/fisiología , Transcriptoma , Proteínas de Arabidopsis/biosíntesis , Proteínas de Arabidopsis/genética , Inmunoprecipitación de Cromatina , Regulación de la Expresión Génica de las Plantas/genética , Ontología de Genes , Genes de Plantas , Histonas/metabolismo , Lignina/metabolismo , Proteínas de Plantas/metabolismo , Tallos de la Planta/ultraestructura , ARN de Planta/biosíntesis , ARN de Planta/genética , Factores de Transcripción/biosíntesis , Factores de Transcripción/genética , Xilanos/metabolismoRESUMEN
BACKGROUND: Vein graft occlusion is deemed a major challenge in coronary artery bypass grafting. Previous studies implied that the no-touch technique for vein graft harvesting could reduce occlusion rate compared with the conventional approach; however, evidence on the clinical benefit and generalizability of the no-touch technique is scare. METHODS: From April 2017 to June 2019, we randomly assigned 2655 patients undergoing coronary artery bypass grafting at 7 hospitals in a 1:1 ratio to receive no-touch technique or conventional approach for vein harvesting. The primary outcome was vein graft occlusion on computed tomography angiography at 3 months and the secondary outcomes included 12-month vein graft occlusion, recurrence of angina, and major adverse cardiac and cerebrovascular events. The generalized estimate equation model was used to account for the cluster effect of grafts from the same patient. RESULTS: During the follow-up, 2533 (96.0%) participants received computed tomography angiography at 3 months after coronary artery bypass grafting and 2434 (92.2%) received it at 12 months. The no-touch group had significantly lower rates of vein graft occlusion than the conventional group both at 3 months (2.8% versus 4.8%; odds ratio, 0.57 [95% CI, 0.41-0.80]; P<0.001) and 12 months (3.7% versus 6.5%; odds ratio, 0.56 [95% CI, 0.41-0.76]; P<0.001). Recurrence of angina was also less common in the no-touch group at 12 months (2.3% versus 4.1%; odds ratio, 0.55 [95% CI, 0.35-0.85]; P<0.01). Rates of major adverse cardiac and cerebrovascular events were of no significant difference between the 2 groups. The no-touch technique was associated with higher rates of leg wound surgical interventions at 3-month follow-up (10.3% versus 4.3%; odds ratio, 2.55 [95% CI, 1.85-3.52]; P<0.001). CONCLUSIONS: Compared with the conventional vein harvesting approach in coronary artery bypass grafting, the no-touch technique significantly reduced the risk of vein graft occlusion and improved patient prognosis. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03126409.
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Puente de Arteria Coronaria/métodos , Procedimientos Quirúrgicos Vasculares/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
For woody plants, clonal propagation efficiency is largely determined by adventitious root (AR) formation at the bases of stem cuttings. However, our understanding of the molecular mechanisms contributing to AR morphogenesis in trees remains limited, despite the importance of vegetative propagation, currently the most common practice for tree breeding and commercialization. Here, we identified Populus-specific miR476a as a regulator of wound-induced adventitious rooting that acts by orchestrating mitochondrial homeostasis. MiR476a exhibited inducible expression during AR formation and directly targeted several Restorer of Fertility like (RFL) genes encoding mitochondrion-localized pentatricopeptide repeat proteins. Genetic modification of miR476a-RFL expression revealed that miR476a/RFL-mediated dynamic regulation of mitochondrial homeostasis influences AR formation in poplar. Mitochondrial perturbation via exogenous application of a chemical inhibitor indicated that miR476a/RFL-directed AR formation depends on mitochondrial regulation that acts via auxin signaling. Our results thus establish a microRNA-directed mitochondrion-auxin signaling cascade required for AR development, providing insights into the role of mitochondrial regulation in the developmental plasticity of plants.
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Populus , Regulación de la Expresión Génica de las Plantas , Ácidos Indolacéticos/metabolismo , Mitocondrias , Fitomejoramiento , Raíces de Plantas/genética , Raíces de Plantas/metabolismo , Populus/genéticaRESUMEN
Trichomes are specialized epidermal cells that contribute to plant resistance against herbivores. Their formation is controlled precisely by multiple genetic and environmental signals. Previous studies have shown that microRNA319 (miR319) and gibberellin (GA) signaling are involved in trichome development in Arabidopsis, but little is known about their interaction between these factors. Here we reported that the miR319a/TEOSINTE BRANCHED/CYCLOIDEA/PCF (TCP) module participates in trichome initiation synergistically with GA signaling in Populus tomentosa. We demonstrated that overexpression of miR319a decreased transcription levels of its targeted TCPs and significantly elevated leaf trichome density in transgenic poplar, resulting in decreasing insect herbivory. Conversely, repressing miR319a by short tandem target mimics (STTM) elevated TCP expression levels and decreased trichome density in transgenic plants. The trichome phenotype of 35S:miR319a plants could be abolished by introducing a miR319a-resistant form of TCP19. Furthermore, the miR319a-targeted TCP19 interacted directly with REPRESSOR OF ga1-3 (RGA), a downstream repressor of GA signaling. TCP19 and RGA synergistically inhibited the GLABROUS1 (GL1)-induced expression of trichome marker gene GLABRA2 (GL2), thereby repressing leaf trichome initiation. Our results provide an insight into the molecular mechanism by which miR319/TCP19 module and GA signaling coordinated regulating trichome initiation in P. tomentosa.
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Proteínas de Arabidopsis , Populus , Animales , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Insectos/metabolismo , Populus/genética , Populus/metabolismo , Tricomas/metabolismo , Zea mays/metabolismoRESUMEN
Anthocyanins are involved in several aspects of development and defence in poplar (Populus spp.). Although, over the past decades, significant progress has been made in uncovering these anthocyanin biosynthetic and regulatory mechanisms, the fundamental understanding of the epigenetic regulation in this pathway is still largely unclear. Here, we isolated a histone H3K9 demethylase gene JMJ25 from Populus and characterized its role in anthocyanin biosynthesis by genetic and biochemical approaches. JMJ25 was induced by continuous dark treatment. Overexpression of JMJ25 led to downregulated expression of anthocyanin biosynthetic genes in transgenic poplar, resulting in a significant reduction in anthocyanin content. ChIP-qPCR assays showed that JMJ25 could directly associate with MYB182 chromatin and dynamically demethylate at H3K9me2. Furthermore, JMJ25 also affected the DNA methylation levels of MYB182. By contrast, knockout of JMJ25 by CRISPR/Cas9 resulted in ectopic anthocyanin accumulation under dark condition and increased expression of anthocyanin biosynthetic genes. Our results support a model in which JMJ25 directly affects MYB182 expression by altering the histone methylation status of its chromatin and DNA methylation, resulting in repression of anthocyanin accumulation. This study uncovered an epigenetic mechanism that modulates anthocyanin biosynthesis in poplar.
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Antocianinas/biosíntesis , Histona Demetilasas/metabolismo , Proteínas de Plantas/metabolismo , Populus/metabolismo , Cromatina/metabolismo , Metilación de ADN , Regulación de la Expresión Génica de las Plantas/genética , Histona Demetilasas/genética , Histona Demetilasas/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/fisiología , Plantas Modificadas Genéticamente , Populus/enzimología , Populus/genéticaRESUMEN
BACKGROUND: Vein graft failure is a crucial challenge in coronary artery bypass graft (CABG) surgery. Previous studies have suggested a patency benefit of the No-Touch vein harvesting technique, but only with small sample sizes. MATERIALS AND METHODS: This study is a prospective, multicenter randomized clinical trial with a large sample size, aiming to investigate the efficacy of the No-Touch technique compared with the conventional approach. All patients requiring isolated CABG with left internal mammary artery plus at least one saphenous vein graft will be considered for entry into the study. Two thousand cases (1000 in each arm) will be enrolled over 1 to 2 years in 7 hospitals in China. Participants will be randomized in equal proportions between two surgical strategies: the No-Touch or conventional technique. The primary endpoint is graft vessel occlusion at 3 months after CABG surgery by CT coronary angiography. Secondary outcomes are major adverse cardiac or cerebrovascular events at 3 and 12 months post-operation and graft vessel occlusion at 1 year. DISCUSSION: This study will define the role of the No-Touch vein harvesting technique in CABG surgery and provide strong evidence to answer whether this technique could reduce vein graft occlusion.
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Puente de Arteria Coronaria , Oclusión de Injerto Vascular/diagnóstico por imagen , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Recolección de Tejidos y Órganos/métodos , Grado de Desobstrucción Vascular , China , Angiografía Coronaria , Humanos , Análisis de Intención de Tratar , Arterias Mamarias/trasplante , Estudios Prospectivos , Tamaño de la Muestra , Vena Safena/trasplante , Factores de Tiempo , Recolección de Tejidos y Órganos/efectos adversosRESUMEN
INTRODUCTION: The effect of red blood cell distribution width (RDW) on long-term major cardiac and cardiovascular event (MACCE) in patients with off-pump coronary artery bypass (OPCAB) has not been adequately studied. We investigated the relationship between RDW and the risk of MACCE in patients who underwent OPCAB. METHODS: We retrospectively analyzed the data of 440 consecutive, nonanemic patients (362 males; 82.27% and mean age 60.8 ± 8.9 years) who underwent OPCAB between October 2009 and September 2012 in Fuwai Hospital. Long-term follow-up was obtained through phone calls, hospital records, and clinic visits. MACCE (death, ST elevated infarction, repeat coronary revascularization, stroke) was determined. RESULTS: Over a median of 7.0-year follow-up, 80 incident MACCE events were identified. The RDW levels on admission were significantly higher in MACCE group than non-MACCE group (13.1 ± 0.7 vs 12.8 ± 0.7; P = .005). Using the Cox proportional hazards models, we found that per 1% increment of RDW, the incident of MACCE was increased in different models (hazard ratio [HR] was 1.520, 1.532, and 1.795, respectively; P = .002, .004, and .002). The receiver-operating characteristic analysis revealed an RDW cut-off value of 13% predicting MACCE. Therefore, patients were grouped on this cut-off value. The Kaplan-Meier plot revealed significantly lower event-free survival in the higher RDW group (P = .0158). Compared with subjects in the RDW <13% in full model, subjects in the RDW ≥13% had an HR of 1.829 (95% confidence interval, 1.103-3.032; P = .019). CONCLUSIONS: An RDW level greater than 13% in hospital admission is independently associated with an increased incidence of long-term MACCE after OPCAB.
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Puente de Arteria Coronaria Off-Pump/métodos , Enfermedad de la Arteria Coronaria/cirugía , Eritrocitos/citología , Complicaciones Posoperatorias/epidemiología , China/epidemiología , Enfermedad de la Arteria Coronaria/sangre , Recuento de Eritrocitos , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/sangre , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
KEY MESSAGE: AtDIV2 integrates ABA signaling to negatively regulate salt stress in Arabidopsis. AmDIV (DIVARICATA) is a functional MYB transcription factor (TF) that regulates ventral identity during floral development in Antirrhinum. There are six members of DIV homologs in Arabidopsis; however, the functions of these proteins are largely unknown. Here, we characterized an R-R-type MYB TF AtDIV2, which is involved in salt stress responses and abscisic acid (ABA) signaling. Although universally expressed in tissues, the nuclear-localized AtDIV2 appeared not to be involved in seedling development processes. However, upon exposure to salt stress and exogenous ABA, the transcripts of AtDIV2 are markedly increased in wild-type (Wt) plants. The loss-of-function mutant div2 displayed much more tolerance to salt stress, and several salt-responsive genes were up-regulated. In addition, the div2 mutant showed higher sensitivity to ABA during seed germination. And the germination variance between the Wt and div2 mutant cannot be rectified by treatment with both ABA and sodium tungstate at the same time. ELISA results showed that the endogenous ABA content in the div2 mutant is clearly increased than that in Wt plants. Furthermore, the transcriptional expressions of several ABA-related genes, including ABA1 and ABI3, were elevated. Taken together, our results suggest that the R-R-type MYB TF AtDIV2 plays negative roles in salt stress and is required for ABA signaling in Arabidopsis.
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Ácido Abscísico/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Proteínas de Unión al ADN/metabolismo , Reguladores del Crecimiento de las Plantas/metabolismo , Transducción de Señal , Factores de Transcripción/metabolismo , Arabidopsis/fisiología , Proteínas de Arabidopsis/genética , Proteínas de Unión al ADN/genética , Germinación , Mutación , Salinidad , Semillas/genética , Semillas/fisiología , Estrés Fisiológico , Factores de Transcripción/genéticaRESUMEN
We aimed to elucidate the effects of hepatoma-derived growth factor (HDGF) on growth and metastasis of hepatocellular carcinoma (HCC) cells. Tissue microarrays with 236 HCC specimens and 18 extrahepatic metastases were utilized to detect the HDGF expression by immunohistochemistry. Meanwhile, HDGF expressions in HCC cell lines with different metastatic potentials were examined using immunofluorescence staining, real-time PCR and western blotting. After HDGF silencing, the growth and metastatic potentials of HCC cells were evaluated by soft agar assay, invasion assay, together with tumorigenicity assay in nude mice. The gelatin zymography was performed by detecting MMP-2 and MMP-9 levels. Additionally, western blotting was conducted to determine the levels of total and phosphorylated ERK1/2, JNK, p38 and Akt. The results showed that HDGF was overexpressed in HCC metastasis tumour, and the expression increased with the differentiation degree of tumours (Grade I 44.0%, Grade II 48.4% and Grade III 65.6%). Consistently, HDGF levels were positively associated with the metastatic capability of HCC cells (MHCC97L < MHCC97H < HCCLM3). The growth and metastasis were suppressed by HDGF-siRNA. Gelatinolytic activities were enhanced in the three metastatic HCC cell lines, but had no significant difference among them. The tumourigenicity and metastatic capability of HCCLM3 cells in nude mice were inhibited after silencing HDGF. Meanwhile, HDGF-siRNA specifically suppressed the total and phosphorylated protein levels of ERK1/2, while not JNK, p38 and Akt. In conclusion, HDGF was overexpressed in HCC patients and cells, and HDGF might be closely correlated with HCC metastasis via regulating ERK signalling pathway. Copyright © 2016 John Wiley & Sons, Ltd.
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Carcinoma Hepatocelular/patología , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Neoplasias Hepáticas/patología , Adulto , Animales , Carcinogénesis/patología , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Proliferación Celular , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , Péptidos y Proteínas de Señalización Intercelular/genética , Neoplasias Hepáticas/genética , Masculino , Ratones Desnudos , Persona de Mediana Edad , Metástasis de la Neoplasia , Fosforilación , ARN Interferente Pequeño/metabolismo , Análisis de Matrices TisularesRESUMEN
Wood is the most abundant biomass in perennial woody plants and is mainly made up of secondary cell wall. R2R3-MYB transcription factors are important regulators of secondary wall biosynthesis in plants. In this study, we describe the identification and characterization of a poplar MYB transcription factor PtoMYB92, a homolog of Arabidopsis MYB42 and MYB85, which is involved in the regulation of secondary cell wall biosynthesis. PtoMYB92 is specifically expressed in xylem tissue in poplar. Subcellular localization and transcriptional activation analysis suggest that PtoMYB92 is a nuclear-localized transcriptional activator. Overexpression of PtoMYB92 in poplar resulted in an increase in secondary cell wall thickness in stems and ectopic deposition of lignin in leaves. Quantitative real-time PCR showed that PtoMYB92 specifically activated the expression of lignin biosynthetic genes. Furthermore, transient expression assays using a ß-glucuronidase (GUS) reporter gene revealed that PtoMYB92 is an activator in the lignin biosynthetic pathway during secondary cell wall formation. Taken together, our results suggest that PtoMYB92 is involved in the regulation of secondary cell wall formation in poplar by controlling the biosynthesis of monolignols.
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Vías Biosintéticas/genética , Pared Celular/metabolismo , Lignina/biosíntesis , Proteínas de Plantas/metabolismo , Populus/genética , Populus/metabolismo , Transactivadores/metabolismo , Secuencia de Aminoácidos , Núcleo Celular/metabolismo , Regulación de la Expresión Génica de las Plantas , Datos de Secuencia Molecular , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/genética , Proteínas de Plantas/aislamiento & purificación , Plantas Modificadas Genéticamente , Regiones Promotoras Genéticas , Transporte de Proteínas , Alineación de SecuenciaRESUMEN
BACKGROUND: Spleen-preserving laparoscopic distal pancreatectomy is technically challenging. New surgical robotic systems are now available and show promising outcomes but were very recently implemented in China. METHODS: Seven patients underwent laparoscopic distal pancreatectomy using the da Vinci Robotic System (RDP) for benign or borderline malignant pancreatic tumors. Spleen preservation rate, blood loss, and operative complications were assessed. RESULTS: Mean age was 44.6 ± 13.7 years. Surgery was uneventful in all patients, without conversion to laparotomy. The surgical time (including anesthesia induction, robot docking, operation, and postoperative awaking time) was 460 ± 154 min, while the operation time was 368 ± 126 min. Blood losses were 200 ± 110 mL. The minor (Clavien I+II) complication rate was 14.3%, and the major (Clavien III+IV) complication rate was 14.3 %, including hemorrhage and pancreatic leakage. The spleen preservation rate was 100%. All complications were successfully managed and cured. Intraoperative laparoscopic ultrasound examination successfully identified the correct surgical resection margins. Mean postoperative hospitalization was 8.7 ± 6.6 days. No patient had to undergo a second pancreas surgery. Patients were followed up for a median of 6.8 months (range, 6 to 22 months). All patients survived and reported few discomforts. CONCLUSIONS: RDP is feasible and allows the preservation of the splenic vessels.
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Laparoscopía , Tratamientos Conservadores del Órgano/métodos , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Procedimientos Quirúrgicos Robotizados , Adulto , Anciano , China , Femenino , Estudios de Seguimiento , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Pancreáticas/patología , PronósticoRESUMEN
Dextrocardia requires alterations in techniques during coronary artery bypass graft (CABG) surgery. We report two cases undergoing off-pump coronary artery bypass graft (OPCAB) surgery and discuss techniques for the operative management of these patients.
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Puente de Arteria Coronaria Off-Pump/métodos , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/cirugía , Dextrocardia/complicaciones , Dextrocardia/cirugía , Anciano , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Dextrocardia/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
BACKGROUND: The implantation of left ventricular assist devices (LVADs) as a bridge to transplantation or as destination therapy in end-stage heart failure patients is frequently complicated by the emergence of ventricular arrhythmias (VAs). These arrhythmias have been implicated in precipitating deleterious clinical outcomes, increased mortality rates and augmented healthcare expenditures. CASE PRESENTATION: We present a challenging case of a 49-year-old male with a history of dilated cardiomyopathy who received an LVAD. Post-implantation, the patient suffered from intractable VAs, leading to multiple rehospitalizations and hemodynamic deterioration. Despite exhaustive medical management and electrical cardioversion attempts, the patient's VAs persisted, ultimately necessitating prioritization for cardiac transplantation. DISCUSSION: This case highlights the challenges in managing VAs in LVAD patients and the importance of multidisciplinary collaboration. While pharmacological intervention is the initial strategy, catheter ablation may be considered in selected cases when medication is insufficient. In instances of intractable VAs, expeditious listing for heart transplantation as a high-priority candidate is advisable when feasible.
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Insuficiencia Cardíaca , Corazón Auxiliar , Masculino , Humanos , Persona de Mediana Edad , Corazón Auxiliar/efectos adversos , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/cirugía , Arritmias Cardíacas/etiología , Hemodinámica , Cardioversión Eléctrica , Resultado del TratamientoRESUMEN
The critical role of auxin on secondary vascular development in woody plants has been demonstrated. The concentration gradient of endogenous indole-3-acetic acid and the cellular and molecular pathways contributing to the auxin-directed vascular organization and wood growth have been uncovered in recent decades. However, our understanding of the roles and regulations of auxin influx in wood formation in trees remains limited. Here, we reported that a microRNA, miR7833, participates in the negative regulation of stem cambial cell division and secondary xylem development in Populus tomentosa. The miR7833 is mainly expressed in the vascular cambium during stem radical growth and specifically targets and represses two AUX/LAX family auxin influx carriers, AUX5 and AUX6, in poplar. We further revealed that poplar AUX6, the most abundant miR7833 target in the stem, is preferentially enriched in the developing xylem and is a positive regulator for cell division and differentiation events during wood formation. Moreover, inhibition of auxin influx carriers by 1-naphthoxyacetic acids abolished the regulatory effects of miR7833 and AUX6 on secondary xylem formation in poplar. Our results revealed the essential roles of the miR7833-AUX6 module in regulating cellular events in secondary xylem development and demonstrated an auxin influx-dependent mechanism for wood formation in poplar.