Coarctation of the aorta(CoA)is a relatively common congenital cardiac defect often causing few symptoms and therefore can be challenging to diagnose.The hallmark finding on physical examination is upper extremity hyp...Coarctation of the aorta(CoA)is a relatively common congenital cardiac defect often causing few symptoms and therefore can be challenging to diagnose.The hallmark finding on physical examination is upper extremity hypertension,and for this reason,CoA should be considered in any young hypertensive patient,justifying measurement of lower extremity blood pressure at least once in these individuals.The presence of a significant pressure gradient between the arms and legs is highly suggestive of the diagnosis.Early diagnosis and treatment are important as long-term data consistently demonstrate that patients with CoA have a reduced life expectancy and increased risk of cardiovascular complications.Surgical repair has traditionally been the mainstay of therapy for correction,although advances in endovascular technology with covered stents or stent grafts permit nonsurgical approaches for the management of older children and adults with native CoA and complications.Persistent hypertension and vascular dysfunction can lead to an increased risk of coronary disease,which,remains the greatest cause of long-term mortality.Thus,blood pressure control and periodic reassessment with transthoracic echocardiography and threedimensional imaging(computed tomography or cardiac magnetic resonance)for should be performed regularly as cardiovascular complications may occur decades after the intervention.展开更多
Objective Many physiological and pathological conditions,including cyanotic congenital heart diseases(CCHD),are accompanied by chronic hypoxia,which might interfere with the transcription process.However,the transcrip...Objective Many physiological and pathological conditions,including cyanotic congenital heart diseases(CCHD),are accompanied by chronic hypoxia,which might interfere with the transcription process.However,the transcriptome profile in peripheral blood under hypoxia is still unidentified.The present work aimed to explore the transcriptional profile alteration of peripheral blood in chronic hypoxia.Methods The present study used a chronic hypoxia rat model to simulate the hypoxic state of CCHD patients.Two groups of Sprague-Dawley rats(n=6 per group)were either exposed to hypoxia(10%O2)or normoxia(21%O2)for 3 weeks.Body weight was measured weekly.Peripheral blood was collected and total RNA was extracted for RNA-Seq at the end of the hypoxia treatment.After quality assessment,the library was sequenced by the Illumina Hiseq platform.The differentially expressed genes were screened(false discovery rate<0.05 and fold change>2).The functional annotation analysis and cluster analysis of differentially expressed genes were performed based on the adjusted P-value(padj<0.05).Results Compared with the control group,the body weight of the rats in the hypoxia group was significantly lowered(P<0.01).RNA-Seq results showed that the transcriptome patterns of the two groups had significant differences.In total,872 genes were identified as differentially expressed.Among all,803 genes were downregulated,while only 69 genes were up-regulated in the hypoxia group.The functional enrichment analysis of the 872 genes showed that multiple biological processes involved,such as porphyrin-containing compound metabolic process,hemoglobin complex and oxygen transporter activity.Conclusions Our study demonstrated the transcriptional profile alteration in peripheral blood of chronic hypoxia rat model.This study provided basic data and directions to further understand the physiological and pathological changes in patients with CCHD.展开更多
Histone deacetylase 3 (HDAC3) is a major HDAC, whose enzymatic activity is targeted by small molecule inhibitors for treating a variety of conditions. However, its enzymatic activity is largely dispensable for its fun...Histone deacetylase 3 (HDAC3) is a major HDAC, whose enzymatic activity is targeted by small molecule inhibitors for treating a variety of conditions. However, its enzymatic activity is largely dispensable for its function in embryonic development and hepatic lipid metabolism.HDAC3 plays a pivotal role in regulating muscle fuel metabolism and contractile function. Here, we address whether these muscular functions of HDAC3 require its enzymatic activity. By mutating the NCoR/SMRT corepressors in a knock - in mouse model named NS-DADm, we ablated the enzymatic activity of HDAC3 without affecting its protein levels. Compared to the control mice, skeletal muscles from NS-DADm mice showed lower force generation, enhanced fatigue resistance, enhanced fatty acid oxidation, reduced glucose uptake during exercise, upregulated expression of metabolic genes involved in branchedchain amino acids catabolism, and reduced muscle mass during aging, without changes in the muscle fiber-type composition or mitochondrial protein content. These muscular phenotypes are similar to those observed in the HDAC3-depleted skeletal muscles, which demonstrates that, unlike that in the liver or embryonic development, the metabolic function of HDAC3 in skeletal muscles requires its enzymatic activity. These results suggest that drugs specifically targeting HDAC3 enzyme activity could be developed and tested to modulate muscle energy metabolism and exercise performance.展开更多
Background The fenestration function is by allowing a right-to-left shunt resulting in an increased cardiac index, associated with mild arterial oxygen desaturation. Subsequent transcatheter fenestration closure can b...Background The fenestration function is by allowing a right-to-left shunt resulting in an increased cardiac index, associated with mild arterial oxygen desaturation. Subsequent transcatheter fenestration closure can be performed after haemodynamic assessment. The purpose of this study was to compare the outcomes of extracardiac connection (EC) with or without fenestration. Methods Ninety-five consecutive patients diagnosed with univentricular heart disease underwent EC using Gore-Tax conduits at the Department of Children's Heart Center, Justus-Liebig-University Giessen Germany from June 1996 to July 2007. According to EC with or without fenestration, the patients were assigned to two groups (group A with fenestration and group B without fenestration). Mortality, effusions, postoperative mean pulmonary artery pressure, postoperative oxygen saturation, postoperative thrombosis, postoperative neurological problems, and the postoperative loss of sinus rhythm were compared. In group A, 23 patients had fenestration closed interventionally after a mean time of 20-22 months. Results Mortality and postoperative mean pulmonary artery pressure in group B (3 and (15.1±3.4) mmHg, respectively) were significantly higher than group A (0 and (13.2±2.8) mmHg, respectively). Postoperative oxygen saturation, postoperative thrombosis, postoperative neurological problems, and the postoperative loss of sinus rhythm did not differ between cohorts. Conclusions Fenestrating an extracardiac tunnel seems to improve acute postoperative mortality by rising cardiac output. The induced right-to-left shunt shows no morbidity postoperatively. If a stabilized chronic hemodynamic situation is achieved, an interventional closure of the fenestration can be performed to advance the arterial saturation and improve the exercise tolerance of the patients.展开更多
文摘Coarctation of the aorta(CoA)is a relatively common congenital cardiac defect often causing few symptoms and therefore can be challenging to diagnose.The hallmark finding on physical examination is upper extremity hypertension,and for this reason,CoA should be considered in any young hypertensive patient,justifying measurement of lower extremity blood pressure at least once in these individuals.The presence of a significant pressure gradient between the arms and legs is highly suggestive of the diagnosis.Early diagnosis and treatment are important as long-term data consistently demonstrate that patients with CoA have a reduced life expectancy and increased risk of cardiovascular complications.Surgical repair has traditionally been the mainstay of therapy for correction,although advances in endovascular technology with covered stents or stent grafts permit nonsurgical approaches for the management of older children and adults with native CoA and complications.Persistent hypertension and vascular dysfunction can lead to an increased risk of coronary disease,which,remains the greatest cause of long-term mortality.Thus,blood pressure control and periodic reassessment with transthoracic echocardiography and threedimensional imaging(computed tomography or cardiac magnetic resonance)for should be performed regularly as cardiovascular complications may occur decades after the intervention.
基金the National Science Fund for Distinguished Young Scholars(81525002,2016-2020).
文摘Objective Many physiological and pathological conditions,including cyanotic congenital heart diseases(CCHD),are accompanied by chronic hypoxia,which might interfere with the transcription process.However,the transcriptome profile in peripheral blood under hypoxia is still unidentified.The present work aimed to explore the transcriptional profile alteration of peripheral blood in chronic hypoxia.Methods The present study used a chronic hypoxia rat model to simulate the hypoxic state of CCHD patients.Two groups of Sprague-Dawley rats(n=6 per group)were either exposed to hypoxia(10%O2)or normoxia(21%O2)for 3 weeks.Body weight was measured weekly.Peripheral blood was collected and total RNA was extracted for RNA-Seq at the end of the hypoxia treatment.After quality assessment,the library was sequenced by the Illumina Hiseq platform.The differentially expressed genes were screened(false discovery rate<0.05 and fold change>2).The functional annotation analysis and cluster analysis of differentially expressed genes were performed based on the adjusted P-value(padj<0.05).Results Compared with the control group,the body weight of the rats in the hypoxia group was significantly lowered(P<0.01).RNA-Seq results showed that the transcriptome patterns of the two groups had significant differences.In total,872 genes were identified as differentially expressed.Among all,803 genes were downregulated,while only 69 genes were up-regulated in the hypoxia group.The functional enrichment analysis of the 872 genes showed that multiple biological processes involved,such as porphyrin-containing compound metabolic process,hemoglobin complex and oxygen transporter activity.Conclusions Our study demonstrated the transcriptional profile alteration in peripheral blood of chronic hypoxia rat model.This study provided basic data and directions to further understand the physiological and pathological changes in patients with CCHD.
文摘Histone deacetylase 3 (HDAC3) is a major HDAC, whose enzymatic activity is targeted by small molecule inhibitors for treating a variety of conditions. However, its enzymatic activity is largely dispensable for its function in embryonic development and hepatic lipid metabolism.HDAC3 plays a pivotal role in regulating muscle fuel metabolism and contractile function. Here, we address whether these muscular functions of HDAC3 require its enzymatic activity. By mutating the NCoR/SMRT corepressors in a knock - in mouse model named NS-DADm, we ablated the enzymatic activity of HDAC3 without affecting its protein levels. Compared to the control mice, skeletal muscles from NS-DADm mice showed lower force generation, enhanced fatigue resistance, enhanced fatty acid oxidation, reduced glucose uptake during exercise, upregulated expression of metabolic genes involved in branchedchain amino acids catabolism, and reduced muscle mass during aging, without changes in the muscle fiber-type composition or mitochondrial protein content. These muscular phenotypes are similar to those observed in the HDAC3-depleted skeletal muscles, which demonstrates that, unlike that in the liver or embryonic development, the metabolic function of HDAC3 in skeletal muscles requires its enzymatic activity. These results suggest that drugs specifically targeting HDAC3 enzyme activity could be developed and tested to modulate muscle energy metabolism and exercise performance.
文摘Background The fenestration function is by allowing a right-to-left shunt resulting in an increased cardiac index, associated with mild arterial oxygen desaturation. Subsequent transcatheter fenestration closure can be performed after haemodynamic assessment. The purpose of this study was to compare the outcomes of extracardiac connection (EC) with or without fenestration. Methods Ninety-five consecutive patients diagnosed with univentricular heart disease underwent EC using Gore-Tax conduits at the Department of Children's Heart Center, Justus-Liebig-University Giessen Germany from June 1996 to July 2007. According to EC with or without fenestration, the patients were assigned to two groups (group A with fenestration and group B without fenestration). Mortality, effusions, postoperative mean pulmonary artery pressure, postoperative oxygen saturation, postoperative thrombosis, postoperative neurological problems, and the postoperative loss of sinus rhythm were compared. In group A, 23 patients had fenestration closed interventionally after a mean time of 20-22 months. Results Mortality and postoperative mean pulmonary artery pressure in group B (3 and (15.1±3.4) mmHg, respectively) were significantly higher than group A (0 and (13.2±2.8) mmHg, respectively). Postoperative oxygen saturation, postoperative thrombosis, postoperative neurological problems, and the postoperative loss of sinus rhythm did not differ between cohorts. Conclusions Fenestrating an extracardiac tunnel seems to improve acute postoperative mortality by rising cardiac output. The induced right-to-left shunt shows no morbidity postoperatively. If a stabilized chronic hemodynamic situation is achieved, an interventional closure of the fenestration can be performed to advance the arterial saturation and improve the exercise tolerance of the patients.