Background:Tetralogy of Fallot(TOF)is a very common cyanotic congenital heart disease.Endothelial-to-mesenchymal transition(EndoMT)is recognized as a physiological mechanism involved in embryonic heart development and...Background:Tetralogy of Fallot(TOF)is a very common cyanotic congenital heart disease.Endothelial-to-mesenchymal transition(EndoMT)is recognized as a physiological mechanism involved in embryonic heart development and endothelial formation.However,there is still a gap in the reports related to the mechanism of EndoMT development in TOF.Methods:First,transcriptomic data of single cell nuclei of TOF and Donor were obtained based on the Gene Expression Omnibus(GEO)database,and the data were normalized and clus-tered by dimensionality reduction using the Seurat package.Subsequently,differentially expressed genes(DEGs)between TOF and Donor were screened using the“FindMarkers”function,and the gene sets of interest were enriched.Finally,to characterize the dynamics of EndoMT occurrence in TOF,we performed pseudotime cell tra-jectory inference as well as utilized SCENIC analysis to probe the gene regulatory networks(GRNs)dominated by transcription factors(TFs)in endothelial cells.Results:We identified a total of six cell clusters based on single-cell nuclear transcriptome data from TOF and Donor.We found that 611 genes with up-regulated expression within TOF showed conversion to mesenchyme.By subdividing endothelial cell subtypes,endothelial cells 2 were shown to be involved in cell adhesion,migration and extracellular matrix processes.Pseudo-time and SCENIC analyses showed that endothelial cell 2 has EndoMT potential.In addition,ERG and TEAD1 are TFs that play key reg-ulatory roles in this subtype,and both of their target genes are also highly expressed in TOF.This demonstrates that ERG and TEAD1 effectively promote the EndoMT process.Conclusion:Our study reveals the molecular mechanisms underlying the development of EndoMT in TOF,which demonstrates that manipulating the endothelial-to-mesenchymal transition may offer unprecedented therapeutic potential for the treatment of TOF.展开更多
Tetralogy of Fallot(TOF)with total anomalous pulmonary vein connections(TAPVC)is a rare type of complex congenital heart disease among all TOF cases.Co-presentation of major aortopulmonary collateral arteries(MAPCAs)c...Tetralogy of Fallot(TOF)with total anomalous pulmonary vein connections(TAPVC)is a rare type of complex congenital heart disease among all TOF cases.Co-presentation of major aortopulmonary collateral arteries(MAPCAs)compensates for the lack of central pulmonary bloodflow and decreases the severity of right-to-left shunting in TOF.We present a case of a 2-year-old child with complex diagnoses of TOF,TAPVC,a large secun-dum atrial septal defect(ASD),and intraoperatively identified MAPCAs.She underwent surgery to repair the TAPVC,valve-sparing reconstruction of the right ventricular outflow tract,interventricular defect closure,and the creation of patent foramen ovale(PFO).After the operation,hemodynamic instability happened along with sudden blood pressure drop,desaturation,and increased central venous pressure,which subsided after adminis-tering inhalational nitric oxide(NO).A postoperative pulmonary hypertension crisis was suggested when the patient experienced recurrent symptoms after the termination of NO.Echocardiographicfindings of a D-shaped left ventricle(LV),right-to-left PFO shunt and high tricuspid valve gradientfirmly established the diagnosis.It was subsequently managed with continuous NO inhalation and sildenafil,which rendered a satisfactory outcome.Repaired TOF and TAPVC could be at particular risk of developing pulmonary hypertension crisis,especially in the presence of MAPCAs due to possible remodeling of the pulmonary vasculature.Furthermore,a relatively non-compliant LV function and small left atrial size may exacerbate the risk of developing postcapillary pulmonary hypertension after TAPVC repair.A successful postoperative outcome calls for a meticulous preoperative analysis of the anatomical lesions,as well as careful monitoring.展开更多
<span style="font-family:Verdana;">Congenital cyanogenic heart disease (CCHD) is a malformation of the heart and large vessels characterized by an oxygen desaturation in the arterial blood, responsible...<span style="font-family:Verdana;">Congenital cyanogenic heart disease (CCHD) is a malformation of the heart and large vessels characterized by an oxygen desaturation in the arterial blood, responsible for cyanosis. The general objective was to study the profile of CCHD in Senegalese hospitals. This is a retrospective study carried out over a period of 8 years (January 1, 2010 - December 31, 2017) and including all children aged 0 to 16 years followed for a CCHD. The hospital prevalence was 0.87% for 420 cases collected. The sex ratio was 1.44 and the average age at diagnosis was 16 months. First degree parental consanguinity was noted in </span><span><span style="font-family:Verdana;">36 cases (30.78%). The main reasons for consultation were breathing difficult</span><span style="font-family:Verdana;">y</span></span><span> <span style="font-family:Verdana;">in 242 cases (57.62%) and fever in 136 patients (32.36%). Apart from cyanosis, the clinical signs were dominated by the heart murmur in 313 cases (74.7%), tachycardia in 283 cases (67.38%) and digital hippocratism in 162 cases (38.57%). Cardiomegaly was found in 239 patients (83.36%). The main types of CCHD were tetralogy of Fallot and transposition of the large vessels. In biology, 206 patients (49.05%) presented polyglobulia. A complete surgical cure was carried out in 22 patients (5.24%). Complications were anoxic crisis (52 cases) and hemorrhagic syndrome (17 cases). There were 97 deaths (28.28%) during hospitalization. The diagnosis of CCHD is late in our country and surgical management is poor explaining the high mortality</span><span style="font-family:Verdana;">.</span></span>展开更多
We report a case of an 11-year-old boy with diagnosed but uncorrected tetralogy of Fallot presented to us for brain abscess drainage. The child was managed successfully with scalp block with sedation.
One of the most common types of cyanotic congenital heart disease is Tetralogy of Fallot(ToF).Treatment has constantly increased since the first surgical repair in 1954.Excellent treatment having long-term survival(30...One of the most common types of cyanotic congenital heart disease is Tetralogy of Fallot(ToF).Treatment has constantly increased since the first surgical repair in 1954.Excellent treatment having long-term survival(30 years survival ranges from 68.5%to 90.5%)is available for the ToF.However conventional and frequently required re-interventions include residual issues like right ventricular outflow tract obstruction,pulmonary regurgitation and(ventricular)arrhythmia.Right ventricular dysfunction might lead to longstanding pulmonary regurgitation and/or stenosis.It is important to perform pulmonary valve replacement or relief of pulmonary stenosis prior to irreversible right ventricular dysfunction,though determining optimal timing of pulmonary valve replacement is a problematic task due to various reasons.As seen in longstanding pulmonary regurgitation,the biological mechanisms underlying dysfunction of the right ventricle is often unclear.Various techniques of assessing the right ventricle are used to predict imminent dysfunction.The interventricular,ventriculo-arterial and atrioventricular interactions of right ventricle are not completely explained but play significant role in right ventricle performance.This review focuses on providing a brief overview of the history of ToF,describing the current strategies for treatment and describing the long-term survival,residual lesions and re-interventions following repair.Remaining related challenges and present condition of the art regarding these challenges are also illustrated.展开更多
Background Although most patients with tetralogy of Fallot undergo radical repair during infancy and childhood,patients that remain undiagnosed and untreated until adulthood can still be treated.This study aimed to ev...Background Although most patients with tetralogy of Fallot undergo radical repair during infancy and childhood,patients that remain undiagnosed and untreated until adulthood can still be treated.This study aimed to evaluate longterm outcomes of adult patients with tetralogy of Fallot who were treated surgically,and to determine the predictors of postoperative pulmonary regurgitation.Methods Fifty-six adult patients underwent complete surgical repair.Forty-three patients （76.8%） required a transannular patch.Systolic,diastolic,and mean pressure in the main pulmonary artery were measured after repair.Results The early mortality rate was 3.6%.The 16-year survival rate was （84.4±11.5）%.Late echocardiography revealed 41 patients with transannular patch who had pulmonary regurgitation,consisting of mild pulmonary regurgitation in 28 patients,moderate in eight,and severe regurgitation in five patients.In addition,there was right ventricular outflow tract stenosis in nine patients,moderate/severe tricuspid valve regurgitation in seven,and residual ventricular septal defect in five.Logistic regression analysis demonstrated that the mean pulmonary pressure measured just after repair predicted late pulmonary regurgitation.Conclusions The long-term survival of surgically treated adult patients with tetralogy of Fallot is acceptable.The mean pressure 〉20 mmHg in the main pulmonary artery measured right after surgical repair may be a feasible reference to time the reconstruction of the pulmonary valve.展开更多
Background:Abnormal expression of connexin 43(Cx43)has been reported to play an important role in the development of conotrunccal anomalies.However,less is known about the underlying reason for its abnormal expression...Background:Abnormal expression of connexin 43(Cx43)has been reported to play an important role in the development of conotrunccal anomalies.However,less is known about the underlying reason for its abnormal expression.MicroRNAs(miRNAs),as an important part of gene expression regulation,have been implicated in some cardiac diseases.This study aimed to investigate the expression of Cx43 and its related miRNAs in patients with tetralogy of Fallot(TOF),and illustrate the potential role of abnormal miRNAs regulation to Cx43 expression in the pathology of TOF.Methods:Real-time polymerase chain reaction was used to detect the expression of Cx43 and 10 Cx43-related miRNAs in the myocardium from 30 TOF patients and 10 normal controls.Immunohistochemistry was used to detect Cx43 protein expression.Putative miRNA binding sites in the 3'UTR of Cx43 were examined in 200 TOF patients and 200 healthy individuals,using Sanger sequencing,to exclude sequence variations resulting in binding diffi culties of miRNAs.Results:Cx43 mRNA and protein expression in the myocardium tissue was significantly increased in TOF patients.The expression of MiR-1 and 206 was significantly decreased in the TOF patients as compared with the controls(P<0.05).No obvious difference was observed in the expression of the other 7 miRNAs between the TOF patients and controls(P>0.05).No meaningful sequence variation was detected in the putative miR1/206 binding sites in the 3'UTR of Cx43.Conclusions:This study indicated that miR-1 and 206 is down-regulated in TOF patients,which may cause an up-regulation of Cx43 protein's synthesis.It provided a clue that miR-1 and 206 might be involved in the pathogenesis of TOF,additional experiments are needed to determine if in fact,miR-1 and 206 contribute substantially to TOF.展开更多
Background：The most typical cardiac abnormality is conotruncal defects （CTDs） in patients with 22q11 deletion syndrome （22q11DS）.HIRA （histone cell cycle regulator） gene,as one of the candidate genes located at...Background：The most typical cardiac abnormality is conotruncal defects （CTDs） in patients with 22q11 deletion syndrome （22q11DS）.HIRA （histone cell cycle regulator） gene,as one of the candidate genes located at the critical region of 22q11DS,was reported as possibly relevant to CTD in animal models.This study aimed to analyze the level of expression of the HIRA gene in tetralogy of Fallot （TOF） patients and the potential DNA sequence variations in the promoter region.Methods：The messenger RNA （mRNA） expression was examined with quantitative real-time polymerase chain reaction in 39 myocardial tissues of the right ventricular outflow tract （RVOT） from TOF patients and 4 myocardial tissues of RVOT from noncardiac death children.The protein expression was detected using immunohistochemistry in 12 TOF patients and 4 controls.A total of 100 TOF cases and 200 healthy controls were recruited for DNA sequencing.Results：The mRNA and protein expressions of the HIRA gene in the myocardium of the TOF patients were both significantly lower as compared to the controls （P 〈 0.05）.Five single nucleotide polymorphisms （SNPs）,including g.4111A〉G （rs1128399）,g.4265C〉A （rs4585115）,g.4369T〉G （rs2277837）,g.4371C〉A （rs148516780）,and g.4543T〉C （rs111802956）,were found in the promoter region of the HIRA gene.There were no significant differences of frequencies in these SNPs between the TOF patients and the controls （P 〉 0.05）.Conclusion：The abnormal lower expression of the HIRA gene in the myocardium may participate in the pathogenesis of TOF.展开更多
Tetralogy of Fallot （TOF） is the most common form of cyanotic congenital cardiac disease in humans. With recent advances in corrective surgery early lethality from TOF is rare but long-term sequelae, including arrhy...Tetralogy of Fallot （TOF） is the most common form of cyanotic congenital cardiac disease in humans. With recent advances in corrective surgery early lethality from TOF is rare but long-term sequelae, including arrhythmia, ventricular dysfunction and often life-long disability. Now attention has shifted from immediate outcomes to understanding causation. This review summarizes current knowledge regarding the embryonic and molecular mechanisms involved in cardiac development, with particular attention paid to the role of transcription factors and to their potential usefulness in order to clarify the genetic basis of TOF.展开更多
目的:总结法洛四联症(tetralogy of Fallot,TOF)患儿根治术后早期处理经验,以降低TOF根治术后早期并发症的发生率及病死率。方法:回顾性分析2012年1月至12月完成的TOF根治术188例,将其分为并发症组31例,非并发症组157例。对比两组患儿...目的:总结法洛四联症(tetralogy of Fallot,TOF)患儿根治术后早期处理经验,以降低TOF根治术后早期并发症的发生率及病死率。方法:回顾性分析2012年1月至12月完成的TOF根治术188例,将其分为并发症组31例,非并发症组157例。对比两组患儿年龄、体质量,术前血色素、血氧饱和度、McGoon比值,术中体外循环时间、主动脉阻断时间,术后呼吸机辅助时间、体质量监护室停留时间,正性肌力药物评分以及术后右心室流出道压力差。结果:并发症组术前McGoon比值(1.54±0.21)vs.(2.01±0.42),体外循环时间(112.54±33.32)vs.(97.03±26.1)min、主动脉阻断时间(65.38±15.41)vs.(61.87±15.38)min,呼吸机辅助时间(85.64±35.38)vs.(44.62±21.84)h、监护室停留时间5.0(2.0,7.0)vs.3.0(1.0,5.0)d,正性肌力药物评分(18.21±6.27)vs.(10.16±3.18)与非并发症组比较差异有统计学意义(P<0.05)。术后右心室流出道压力差21.5(12.3,33.8)vs.24.0(17.0,32.0)mmHg(1mmHg=0.133kPa),并发症组与非并发症组比较差异无统计学意义。并发症包括低心排出量综合征(低心排)9例,渗漏综合征12例,心律失常5例,灌注肺损伤2例,感染5例。其中死亡5例(病死率2.66%)。结论:严格把握手术适应证,缩短体外循环时间,术后合理应用正性肌力药物,积极腹膜透析是预防和控制TOF根治术后低心排和渗漏综合征的有效方法。呼吸机辅助通气呼气末正压治疗及高频振荡呼吸机治疗可以控制大多数灌注肺,必要时可介入封堵侧枝。展开更多
基金supported by The National Natural Science Foundation of China(No.82160050)State Key Laboratory of Pathogenesis,Prevention and Treatment of High Incidence Diseases in Central Asia(No.SKL-HIDCA-2021-24).
文摘Background:Tetralogy of Fallot(TOF)is a very common cyanotic congenital heart disease.Endothelial-to-mesenchymal transition(EndoMT)is recognized as a physiological mechanism involved in embryonic heart development and endothelial formation.However,there is still a gap in the reports related to the mechanism of EndoMT development in TOF.Methods:First,transcriptomic data of single cell nuclei of TOF and Donor were obtained based on the Gene Expression Omnibus(GEO)database,and the data were normalized and clus-tered by dimensionality reduction using the Seurat package.Subsequently,differentially expressed genes(DEGs)between TOF and Donor were screened using the“FindMarkers”function,and the gene sets of interest were enriched.Finally,to characterize the dynamics of EndoMT occurrence in TOF,we performed pseudotime cell tra-jectory inference as well as utilized SCENIC analysis to probe the gene regulatory networks(GRNs)dominated by transcription factors(TFs)in endothelial cells.Results:We identified a total of six cell clusters based on single-cell nuclear transcriptome data from TOF and Donor.We found that 611 genes with up-regulated expression within TOF showed conversion to mesenchyme.By subdividing endothelial cell subtypes,endothelial cells 2 were shown to be involved in cell adhesion,migration and extracellular matrix processes.Pseudo-time and SCENIC analyses showed that endothelial cell 2 has EndoMT potential.In addition,ERG and TEAD1 are TFs that play key reg-ulatory roles in this subtype,and both of their target genes are also highly expressed in TOF.This demonstrates that ERG and TEAD1 effectively promote the EndoMT process.Conclusion:Our study reveals the molecular mechanisms underlying the development of EndoMT in TOF,which demonstrates that manipulating the endothelial-to-mesenchymal transition may offer unprecedented therapeutic potential for the treatment of TOF.
基金The report was conducted in accordance with the Nuremberg Code and Declaration of Helsinki,and the protocol was approved by the Institutional Review Board of National Cardiovascular Center Harapan Kita(No.LB.02.01/VII/037/KEP037/2022).
文摘Tetralogy of Fallot(TOF)with total anomalous pulmonary vein connections(TAPVC)is a rare type of complex congenital heart disease among all TOF cases.Co-presentation of major aortopulmonary collateral arteries(MAPCAs)compensates for the lack of central pulmonary bloodflow and decreases the severity of right-to-left shunting in TOF.We present a case of a 2-year-old child with complex diagnoses of TOF,TAPVC,a large secun-dum atrial septal defect(ASD),and intraoperatively identified MAPCAs.She underwent surgery to repair the TAPVC,valve-sparing reconstruction of the right ventricular outflow tract,interventricular defect closure,and the creation of patent foramen ovale(PFO).After the operation,hemodynamic instability happened along with sudden blood pressure drop,desaturation,and increased central venous pressure,which subsided after adminis-tering inhalational nitric oxide(NO).A postoperative pulmonary hypertension crisis was suggested when the patient experienced recurrent symptoms after the termination of NO.Echocardiographicfindings of a D-shaped left ventricle(LV),right-to-left PFO shunt and high tricuspid valve gradientfirmly established the diagnosis.It was subsequently managed with continuous NO inhalation and sildenafil,which rendered a satisfactory outcome.Repaired TOF and TAPVC could be at particular risk of developing pulmonary hypertension crisis,especially in the presence of MAPCAs due to possible remodeling of the pulmonary vasculature.Furthermore,a relatively non-compliant LV function and small left atrial size may exacerbate the risk of developing postcapillary pulmonary hypertension after TAPVC repair.A successful postoperative outcome calls for a meticulous preoperative analysis of the anatomical lesions,as well as careful monitoring.
文摘<span style="font-family:Verdana;">Congenital cyanogenic heart disease (CCHD) is a malformation of the heart and large vessels characterized by an oxygen desaturation in the arterial blood, responsible for cyanosis. The general objective was to study the profile of CCHD in Senegalese hospitals. This is a retrospective study carried out over a period of 8 years (January 1, 2010 - December 31, 2017) and including all children aged 0 to 16 years followed for a CCHD. The hospital prevalence was 0.87% for 420 cases collected. The sex ratio was 1.44 and the average age at diagnosis was 16 months. First degree parental consanguinity was noted in </span><span><span style="font-family:Verdana;">36 cases (30.78%). The main reasons for consultation were breathing difficult</span><span style="font-family:Verdana;">y</span></span><span> <span style="font-family:Verdana;">in 242 cases (57.62%) and fever in 136 patients (32.36%). Apart from cyanosis, the clinical signs were dominated by the heart murmur in 313 cases (74.7%), tachycardia in 283 cases (67.38%) and digital hippocratism in 162 cases (38.57%). Cardiomegaly was found in 239 patients (83.36%). The main types of CCHD were tetralogy of Fallot and transposition of the large vessels. In biology, 206 patients (49.05%) presented polyglobulia. A complete surgical cure was carried out in 22 patients (5.24%). Complications were anoxic crisis (52 cases) and hemorrhagic syndrome (17 cases). There were 97 deaths (28.28%) during hospitalization. The diagnosis of CCHD is late in our country and surgical management is poor explaining the high mortality</span><span style="font-family:Verdana;">.</span></span>
文摘We report a case of an 11-year-old boy with diagnosed but uncorrected tetralogy of Fallot presented to us for brain abscess drainage. The child was managed successfully with scalp block with sedation.
文摘One of the most common types of cyanotic congenital heart disease is Tetralogy of Fallot(ToF).Treatment has constantly increased since the first surgical repair in 1954.Excellent treatment having long-term survival(30 years survival ranges from 68.5%to 90.5%)is available for the ToF.However conventional and frequently required re-interventions include residual issues like right ventricular outflow tract obstruction,pulmonary regurgitation and(ventricular)arrhythmia.Right ventricular dysfunction might lead to longstanding pulmonary regurgitation and/or stenosis.It is important to perform pulmonary valve replacement or relief of pulmonary stenosis prior to irreversible right ventricular dysfunction,though determining optimal timing of pulmonary valve replacement is a problematic task due to various reasons.As seen in longstanding pulmonary regurgitation,the biological mechanisms underlying dysfunction of the right ventricle is often unclear.Various techniques of assessing the right ventricle are used to predict imminent dysfunction.The interventricular,ventriculo-arterial and atrioventricular interactions of right ventricle are not completely explained but play significant role in right ventricle performance.This review focuses on providing a brief overview of the history of ToF,describing the current strategies for treatment and describing the long-term survival,residual lesions and re-interventions following repair.Remaining related challenges and present condition of the art regarding these challenges are also illustrated.
基金This study was supported by a grant from the Natural Science Foundation ofNingbo, Zhejiang （No. 2011A610036）.
文摘Background Although most patients with tetralogy of Fallot undergo radical repair during infancy and childhood,patients that remain undiagnosed and untreated until adulthood can still be treated.This study aimed to evaluate longterm outcomes of adult patients with tetralogy of Fallot who were treated surgically,and to determine the predictors of postoperative pulmonary regurgitation.Methods Fifty-six adult patients underwent complete surgical repair.Forty-three patients （76.8%） required a transannular patch.Systolic,diastolic,and mean pressure in the main pulmonary artery were measured after repair.Results The early mortality rate was 3.6%.The 16-year survival rate was （84.4±11.5）%.Late echocardiography revealed 41 patients with transannular patch who had pulmonary regurgitation,consisting of mild pulmonary regurgitation in 28 patients,moderate in eight,and severe regurgitation in five patients.In addition,there was right ventricular outflow tract stenosis in nine patients,moderate/severe tricuspid valve regurgitation in seven,and residual ventricular septal defect in five.Logistic regression analysis demonstrated that the mean pulmonary pressure measured just after repair predicted late pulmonary regurgitation.Conclusions The long-term survival of surgically treated adult patients with tetralogy of Fallot is acceptable.The mean pressure 〉20 mmHg in the main pulmonary artery measured right after surgical repair may be a feasible reference to time the reconstruction of the pulmonary valve.
基金supported by the National Basic Research Program of China(2010CB529500,2009CB941704)the Natural Science Foundation of China(30930096,30901624)the Shanghai Municipal Science and Technology Commission(11JC1401400).
文摘Background:Abnormal expression of connexin 43(Cx43)has been reported to play an important role in the development of conotrunccal anomalies.However,less is known about the underlying reason for its abnormal expression.MicroRNAs(miRNAs),as an important part of gene expression regulation,have been implicated in some cardiac diseases.This study aimed to investigate the expression of Cx43 and its related miRNAs in patients with tetralogy of Fallot(TOF),and illustrate the potential role of abnormal miRNAs regulation to Cx43 expression in the pathology of TOF.Methods:Real-time polymerase chain reaction was used to detect the expression of Cx43 and 10 Cx43-related miRNAs in the myocardium from 30 TOF patients and 10 normal controls.Immunohistochemistry was used to detect Cx43 protein expression.Putative miRNA binding sites in the 3'UTR of Cx43 were examined in 200 TOF patients and 200 healthy individuals,using Sanger sequencing,to exclude sequence variations resulting in binding diffi culties of miRNAs.Results:Cx43 mRNA and protein expression in the myocardium tissue was significantly increased in TOF patients.The expression of MiR-1 and 206 was significantly decreased in the TOF patients as compared with the controls(P<0.05).No obvious difference was observed in the expression of the other 7 miRNAs between the TOF patients and controls(P>0.05).No meaningful sequence variation was detected in the putative miR1/206 binding sites in the 3'UTR of Cx43.Conclusions:This study indicated that miR-1 and 206 is down-regulated in TOF patients,which may cause an up-regulation of Cx43 protein's synthesis.It provided a clue that miR-1 and 206 might be involved in the pathogenesis of TOF,additional experiments are needed to determine if in fact,miR-1 and 206 contribute substantially to TOF.
基金This work was supported by grants from the Natural Science Foundation of China （No. 81370198, No. 81570283） and National Key Research and Development Program （No. 2016YFC 1000500）.
文摘Background：The most typical cardiac abnormality is conotruncal defects （CTDs） in patients with 22q11 deletion syndrome （22q11DS）.HIRA （histone cell cycle regulator） gene,as one of the candidate genes located at the critical region of 22q11DS,was reported as possibly relevant to CTD in animal models.This study aimed to analyze the level of expression of the HIRA gene in tetralogy of Fallot （TOF） patients and the potential DNA sequence variations in the promoter region.Methods：The messenger RNA （mRNA） expression was examined with quantitative real-time polymerase chain reaction in 39 myocardial tissues of the right ventricular outflow tract （RVOT） from TOF patients and 4 myocardial tissues of RVOT from noncardiac death children.The protein expression was detected using immunohistochemistry in 12 TOF patients and 4 controls.A total of 100 TOF cases and 200 healthy controls were recruited for DNA sequencing.Results：The mRNA and protein expressions of the HIRA gene in the myocardium of the TOF patients were both significantly lower as compared to the controls （P 〈 0.05）.Five single nucleotide polymorphisms （SNPs）,including g.4111A〉G （rs1128399）,g.4265C〉A （rs4585115）,g.4369T〉G （rs2277837）,g.4371C〉A （rs148516780）,and g.4543T〉C （rs111802956）,were found in the promoter region of the HIRA gene.There were no significant differences of frequencies in these SNPs between the TOF patients and the controls （P 〉 0.05）.Conclusion：The abnormal lower expression of the HIRA gene in the myocardium may participate in the pathogenesis of TOF.
基金supported by the Major International Joint Research Project of Ministry of Science and Technology of China(No.2010DFA32660)National Key Technology Research and Development Program of Ministry of Science and Technology of China(2011BAI11B22)National Natural Science Foundation of China(No.81370230)
文摘Tetralogy of Fallot （TOF） is the most common form of cyanotic congenital cardiac disease in humans. With recent advances in corrective surgery early lethality from TOF is rare but long-term sequelae, including arrhythmia, ventricular dysfunction and often life-long disability. Now attention has shifted from immediate outcomes to understanding causation. This review summarizes current knowledge regarding the embryonic and molecular mechanisms involved in cardiac development, with particular attention paid to the role of transcription factors and to their potential usefulness in order to clarify the genetic basis of TOF.
文摘目的:总结法洛四联症(tetralogy of Fallot,TOF)患儿根治术后早期处理经验,以降低TOF根治术后早期并发症的发生率及病死率。方法:回顾性分析2012年1月至12月完成的TOF根治术188例,将其分为并发症组31例,非并发症组157例。对比两组患儿年龄、体质量,术前血色素、血氧饱和度、McGoon比值,术中体外循环时间、主动脉阻断时间,术后呼吸机辅助时间、体质量监护室停留时间,正性肌力药物评分以及术后右心室流出道压力差。结果:并发症组术前McGoon比值(1.54±0.21)vs.(2.01±0.42),体外循环时间(112.54±33.32)vs.(97.03±26.1)min、主动脉阻断时间(65.38±15.41)vs.(61.87±15.38)min,呼吸机辅助时间(85.64±35.38)vs.(44.62±21.84)h、监护室停留时间5.0(2.0,7.0)vs.3.0(1.0,5.0)d,正性肌力药物评分(18.21±6.27)vs.(10.16±3.18)与非并发症组比较差异有统计学意义(P<0.05)。术后右心室流出道压力差21.5(12.3,33.8)vs.24.0(17.0,32.0)mmHg(1mmHg=0.133kPa),并发症组与非并发症组比较差异无统计学意义。并发症包括低心排出量综合征(低心排)9例,渗漏综合征12例,心律失常5例,灌注肺损伤2例,感染5例。其中死亡5例(病死率2.66%)。结论:严格把握手术适应证,缩短体外循环时间,术后合理应用正性肌力药物,积极腹膜透析是预防和控制TOF根治术后低心排和渗漏综合征的有效方法。呼吸机辅助通气呼气末正压治疗及高频振荡呼吸机治疗可以控制大多数灌注肺,必要时可介入封堵侧枝。
