Development of biodegradable occluders in the treatment for congenital heart diseases / 中华实用儿科临床杂志

Percutaneous intervention with occluder has become the preferred radical therapy for most of common congenital heart diseases, such as atrial septal defect (ASD), ventricular septal defect and patent ductus arteriosus.At present, most occluders for clinical use are made of nitinol, which will permanently exist in human body after implantation, and lead to the risk of severe complications such as chronic inflammation, cardiac perforation and high-grade atrioventricular block.Biodegradable occluder will be gradually replaced by body tissues after implantation.Investigators are exploring to develop biodegradable occluder with different biodegradable materials.In particular, a completely biodegradable atrial septum occlusion system (Absnow™) developed by the team of professor Zhang Zhiwei has been approved for clinical trial by China Food and Drug Administration (CFDA) in 2018, which is the first completely biodegradable atrial septal defect occluder entered the clinical trial phase in the world.The results of human trial test demonstrated the initial safety and effectiveness of this occluder.However, multi-center clinical trials are needed for evaluation and verification.Currently, selecting suitable materials for developing new biodegradable occluders, and the effectiveness and safety of occluders are the focuses and development trend of studies on biodegradable occluders in the treatment of congenital heart diseases.

Transthoracic echocardiographic diagnosis for partial anomalous pulmonary venous connection in children / 中华实用儿科临床杂志

Objective:To investigate the cause of missed diagnosis by transthoracic echocardiography (TTE) based on the characteristics of partial anomalous pulmonary venous connection (PAPVC), and to improve the ultrasonic diagnostic accuracy of PAPVC in children.Methods:The TTE results of 252 children under 12 years old who were confirmed with PAPVC at Guangdong Provincial People′s Hospital from January 2011 to June 2019 were reviewed retrospectively.The types of PAPVC and the associated atrial septal defects (ASD) as well as the confirmed and missed cases by TTE were analyzed.Results:PAPVC was right-sided in 238 patients (94.4%), left-sided in 8 patients (3.2%), and bilateral in 6 patients (2.4%). There were 177 cases (70.2%) whose pulmonary veins were abnorma-lly connected to the right atrium(RA), 37 cases (14.7%) to the junction of the RA and the superior vena cava (SVC), 27 cases (10.7%) to the distal SVC, and 6 cases (2.4%) to the inferior vena cava.Besides, pulmonary veins of 5 cases (2.0%) flew back to the RA through the coronary sinus.One hundred and ninety PAPVC cases were combined with sinus venous defects (SVD) and 53 cases combined with secondum ASD.Two hundred and twenty-one cases were accurately diagnosed while 31 cases were underestimated by TTE.The omission diagnostic rates of right superior pulmonary veins connecting to the distal SVC, 1 or 2 right pulmonary veins connecting to the RA or the junction of the RA and SVC, and left-sided PAPVC were 8 out of 18 (44.4%), 22 out of 215 (10.2%) and 1 out of 8 (12.5%), respectively.Among 54 cases with right superior pulmonary veins anomalously connected to the RA or the junction of the RA and SVC, 88.9% of them (48/54 cases) were combined with superior SVD.Among 161 cases with the right inferior pulmonary veins or 2 right pulmonary veins connected to the RA, 78.2% of them (126/161 cases) were combined with inferior SVD.There were statistically significant differences in ASD types between the 2 right-sided PAPVC groups.Conclusions:SVD is often associated with 1 or 2 right pulmonary veins connected to the RA or the junction of the RA and SVC.The cases with right superior pulmonary veins connected to the distal SVC are prone to be underestimated by TTE.Whether there is abnormal blood flowing into SVC should be noticed during superior sternal fossa examinations.Each pulmonary vein should be examined in detail in the TTE test and accurate diagnosis of PAPVC can be made in most cases.

Development of biodegradable occluders in the treatment for congenital heart diseases / 中华实用儿科临床杂志

Percutaneous intervention with occluder has become the preferred radical therapy for most of common congenital heart diseases,such as atrial septal defect (ASD),ventricular septal defect and patent ductus arteriosus.At present,most occluders for clinical use are made of nitinol,which will permanently exist in human body after implantation,and lead to the risk of severe complications such as chronic inflammation,cardiac perforation and high-grade atrioventricular block.Biodegradable occluder will be gradually replaced by body tissues after implantation.Investigators are exploring to develop biodegradable occluder with different biodegradable materials.In particular,a completely biodegradable atrial septum occlusion system (AbsnowTM) developed by the team of professor Zhang Zhiwei has been approved for clinical trial by China Food and Drug Administration (CFDA) in 2018,which is the first completely biodegradable atrial septal defect occluder entered the clinical trial phase in the world.The results of human trial test demonstrated the initial safety and effectiveness of this occluder.However,multi-center clinical trials are needed for evaluation and verification.Currently,selecting suitable materials for developing new biodegradable occluders,and the effectiveness and safety of occluders are the focuses and development trend of studies on biodegradable occluders in the treatment of congenital heart diseases.

Outcome and follow-up analysis of transcatheter or surgical therapy for neonates with pulmonary atresia with intact ventricular septum and critical pulmonary stenosis / 中华实用儿科临床杂志

Objective@#To evaluate the safety and effectiveness of transcatheter or surgical procedure for neonates diagnosed with pulmonary atresia with intact ventricular septum (PA/IVS) or critical pulmonary stenosis (CPS) by retrospectively analyzina the clinical data, thus to discuss the clinical strategy decision.@*Methods@#From November 2006 to August 2018, 105 neonates (PA/IVS 51 cases, CPS 54 cases) went through transcatheter or surgical procedure in Guangdong Provincial Cardiovascular Institute (transcatheter procedure 43 cases, surgery 62 cases). All cases manifested mild to moderate right ventricular dysplasia.Transcatheter procedure included pulmonary radio frequency perforation and percutaneous balloon pulmonary valvuloplasty (PBPV). Surgical procedure included reconstruction of right ventricular outflow tract (transannular patch), pulmonary valvotomy and closed transventricular pulmonary valvuloplasty, while Aortic-Pulmonary shunt was performed in certain cases.Average follow-up period was (40.1±36.9) months.Hospitalization and follow-up data were analyzed to evaluate the safety and efficacy of transcatheter and surgical procedure.@*Results@#Operative time, hospital stay, complication rate were lower in transcatheter procedure group than those of surgery group[(107.8±61.6) min vs.(183.3±36.8) min, (18.6±7.9) d vs.(31.1±13.4) d, 30.2% vs.80.6%], and the differences were significant(all P=0.000). In transcatheter procedure group, 2 cases (4.7%) died and biventricular circulation is obtained in all survival cases.In surgery group, 5 cases (8.1%) died.Of the survival cases from surgery group, 39 cases (69.6%) obtained biventricular circulation, 3 cases (5.4%) obtained one and a half ventricular circulation while other 14 cases (25.0%) were candidates for biventricular repair.@*Conclusions@#Biventricular circulation can be achieved in most PA/IVS or CPS neonates with mild-moderate right ventricular dysplasia.PBPV turns out to be a safe and effective therapy for neonates with CPS while perforation of right ventricular outflow tract remains a nonnegligible complication in transcatheter therapy for PA/IVS.

Outcome and follow _up analysis of transcatheter or surgical therapy for neonates with pulmonary atresia with intact ventricular septum and critical pulmonary stenosis / 中华实用儿科临床杂志

Objective To evaluate the safety and effectiveness of transcatheter or surgical procedure for neo_nates diagnosed with pulmonary atresia with intact ventricular septum(PA/IVS)or critical pulmonary stenosis(CPS) by retrospectively analyzina the clinical data,thus to discuss the clinical strategy decision. Methods From November 2006 to August 2018,105 neonates(PA/IVS 51 cases,CPS 54 cases)went through transcatheter or surgical procedure in xuangdong Provincial Cardiovascular Institute(transcatheter procedure 43 cases,surgery 62 cases). All cases mani_fested mild to moderate right ventricular dysplasia. Transcatheter procedure included pulmonary radio frequency perfora_tion and percutaneous balloon pulmonary valvuloplasty( PBPV). Surgical procedure included reconstruction of right ventricular outflow tract(transannular patch),pulmonary valvotomy and closed transventricular pulmonary valvuloplas_ty,while Aortic _Pulmonary shunt was performed in certain cases. Average follow _up period was(40. 1 ± 36. 9) months. Hospitalization and follow_up data were analyzed to evaluate the safety and efficacy of transcatheter and surgi_cal procedure. Results Operative time,hospital stay,complication rate were lower in transcatheter procedure group than those of surgery group[(107. 8 ± 61. 6)min υs.(183. 3 ± 36. 8)min,(18. 6 ± 7. 9)d υs.(31. 1 ± 13. 4)d, 30. 2% υs. 80. 6%],and the differences were significant(all P=0. 000). In transcatheter procedure group,2 cases (4. 7%)died and biventricular circulation is obtained in all survival cases. In surgery group,5 cases(8. 1%)died. Of the survival cases from surgery group,39 cases(69. 6%)obtained biventricular circulation,3 cases(5. 4%)obtained one and a half ventricular circulation while other 14 cases( 25. 0%) were candidates for biventricular repair. Conclusions Biventricular circulation can be achieved in most PA/IVS or CPS neonates with mild_moderate right ventricular dysplasia. PBPV turns out to be a safe and effective therapy for neonates with CPS while perforation of right ventricular outflow tract remains a nonnegligible complication in transcatheter therapy for PA/IVS.

Different interventions in treatment of children with congenital aortic stenosis / 中华实用儿科临床杂志

Objective To evaluate the efficacy and safety of percutaneous balloon aortic valvuloplasty (PBAV) in retrograde,antegrade way or right ventricular pacing in children.Methods This was retrospective clinical study included 32 children who were treated with PBAV for congenital aortic stenosis from January 2008 to June 2017 in Guangdong Cardiovascular Institute.The general clinical data including residual stenosis and aortic stenosis again,and degree of artery injury,aortic regurgitation were particularly assessed.Results A total of 32 patients consisting of 27 boys and 5 girls underwent the procedure,with age of (55.8 ± 52.0) months (ranging from 20 days to 15 years) and body weight (18.2 ± 14.0) kg (ranging from 3.5 kg to 59.0 kg).Two infants accepted left cardiac catheterization through femoral vein and one with interventional indication then accepted PBAV through the patent foramen ovale.The others underwent the retrograde way,including 24 cases with rapid right ventricular pacing.The catheter-measured peak systolic the aortic valve gradient decreased from (81.6 ± 28.0) mmHg(1 mmHg =0.133 kPa) to (41.4 ± 19.0) mmHg immediately after percutaneous interventional treatment,and the difference was statistically significant (t =9.543,P =0.000).The peak systolic valve gradient mea-sured pre-PBAV and on the second day after PBAV measured by Doppler echocardiography decreased from (82.7 ±23.0) mmHg to (44.6 ± 18.0) mmHg,and the difference was statistically significant (t =11.732,P =0.000).The diameters of the aortic valve were (13.8 ± 3.0) mm(ranging from 6.5 mm to 21.0 mm) and the balloons were (14.1 ±4.0) mm(ranging from 6 mm to 23 mm).The follow-up period was 1 to 72 months.The peak systolic valve gradient measured by Doppler echocardiography increased from (44.6 ±18.0) mmHg to (58.6 ± 30.0) mmHg,and the difference was statistically significant (t =-2.549,P =0.016).During the procedure,5 children (14.7％) accepted surgery for restenosis or regurgitation.Seven had regurgitation,one had femoral artery embolism and one died on the second day after the procedure.Conclusions With the diversification of procedures and the continuous improvement of interventional devices,PBAV can play a very good role in alleviating congenital aortic stenosis in children,and the safety has been continuously improved.

Evaluation of middle-term effect of percutaneous intervention therapy for muscular ventricular septal defect in children / 中华实用儿科临床杂志

Objective To evaluate the safety and efficacy of percutaneous closure for muscular ventricular septal defect(MVSD).Methods Fifty-one patients diagnosed as MVSD from October 2011 to July 2016 at Guangdong General Hospital were enrolled including 32 males and 19 females,ranging from 1 to 16 (5.12 ±3.52) years in age,weight (20.19 ± 10.55) kg.The diameter of the MVSD was (4.82 ± 2.51) mm which was measured by transthoracic echocardiography (TTE),and multiple defects were found in 10 patients.The choice of plugging device and transport system depended on the size,position and status of MVSD.TTE and left ventricular (LV) angiography were performed before and after release of the device to evaluate the therapeutic effects.Electrocardiogram and TTE were performed during follow-up period at 24 h,1 month,3 months,6 months and 12 months after operation and yearly thereafter.Results Eight cases showed no hemodynamic significance through standard catheter examination then the interventional therapy was stopped.Cardiac arrest was found in 1 case when the long sheath was transported along the track,and the procedure was terminated immediately,and the selective surgical operation was performed after successful rescue.The devices were successfully placed in the rest of 42 patients (97.6％) with operation time (90.68 ± 36.42) min and fluoroscopy time (18.67 ± 10.89) min.The average of follow-up time was (13.82 ± 13.84) months ranging from 1 to 48 months.It was found that mild residual shunts showed in 4 cases during operation,mild tricuspid regurgitation showed in 2 cases and trivial aortic regurgitation showed in 1 case at 6 months after operation,but there was no need to intervene anymore.Conclusions Percutaneous closure of MVSD in children is safe and effective with high successful rate and low incidence of complication.The middle-term follow-up findings were satisfactory.

Feasibility of diagnosis of perimembranous ventricular septal defect with right aortic valve prolapse by ul-trasonic echocardiography / 实用医学杂志

Objectives To explore the feasibility ofdiagnosis of Perimembranous Ventricular Septal Defect with Right Aortic Valve Prolapse by ultrasonic echocardiography. Methods 131 VSD patients aged 1 to 22 years, weight 8.0 to 54.0 kg, underwent transthoracic echocardiography (TTE) and left ventricular angiography to show the diameter of VSD and the degree of AVP. Results Among 131 patients, 87 cases were diagnosed as VSD,14 as VSD with slight AVP, 12 as, VSD with middle AVP, and 18 as VSD with severe AVP by ultrasonic echocardiography respectively. After the left ventricular angiography and aortic root angiography , it proved that positive rate of VSD was 44.8%, positive rate of VSD with slight AVP was 42.86%, positive rate of VSD with middle AVP was 58.3%,and positive rate of VSD with severe AVP was 83.3%. Conclusion The transthoracic echocardiography (TTE) contributes to diagnosis of severe degree of AVP,while TTE evaluates the slight degree of AVP incorrectly enough. Left ventricular angiography and aortic root angiography are needed to realize the di-agnosis of AVP.

Follow-up results of heart conduct block after transcatheter closure of ventricular septal defect surgery / 实用医学杂志

Objective To study the prevalence and risk factors of heart conduct block after transcatheter closure of ventricular septal defect (VSD)surgery. Methods A total of 1 069 cases underwent transcatheter closure VSD were retrospectively analyzed. The risk factors were assessed by multivariable logistical analysis. Results The median follow-up time was 2.2 (1 to 4.16) years. The early post-procedure heart conduct block was 20.5 %(219 cases), and 35 cases underwent severe conduct block (3.3%). During the follow-up, there were 43 late onset heart conduct block (4.0%), including 4 (0.4%) complete atrioventricular block. Multivariable logistic analysis showed that implanted of asymmetrical occluder from foreign company was the risks factors for early onset severe conduct block, with longer procedure time. Placement of thin-waist-big-side occluder were risk factor for the late onset conduct block. Conclusions Heart conduct block after transcatheter closure VSD is common , light and recovery. The late onset severe conduct block is minor. Symmetrical occluder should be chosen in transcatheter closure VSD if possible.

Analysis on causes of failed procedure of transcatheter closure for ventricular septal defects in children / 中华实用儿科临床杂志

Objective To analyze the causes of failed transcatheter closure for ventricular septal defects (VSD)in children. Methods One thousand two hundred and eighty children aged 13 to 141 months who underwent transcatheter closure from June 2009 to September 2013 in Guangdong General Hospital were selected. There were 43 failures(3. 36% ). The clinical data including transthoracic echocardiograph( TTE),radiography,interventional ap-proach and surgical findings were analyzed. Results Forty - three patients included 25 male and 18 female. The pa-tients' ages ranged from 13 to 141(43. 0 ± 31. 9)months and their weight ranged from 10 to 35(16. 3 ± 5. 59)kg. The causes of failure including doubly committed subarterial VSD misdiagnosed as perimembranous VSD(PMVSD)or intracristal VSD were in 6 patients. The size of occluder was too small in 13 cases,and there were statistical differences between three measurements of size of VSD(F = 19. 134,P = 0. 001). The size of VSD measured by left ventricular an-giography was significantly smaller than that measured by TTE,and there was statistical difference[(4. 78 ± 1. 11) mm vs(6. 48 ± 1. 43)mm,t = 4. 50,P = 0. 001]. The dimension of VSD measured by left ventricular angiography was significantly smaller than that measured by surgical findings,and there was statistical difference[(4. 78 ± 1. 11) mm vs(7. 02 ± 1. 08)mm,t = 5. 92,P = 0. 001]. But,the size of VSD measured by TTE had no significant difference compared with that measured by surgical findings(t = 1. 42,P = 0. 168). Aortic regurgitation occurred in 14 cases;atrioventricular block or left bundle branch block in 3 patients;tricuspid stenosis in 2 cases and residual shunt in 5 pa-tients. Conclusions Doubly committed subarterial VSD may be misdiagnosed as PMVSD or intracristal VSD. In the ca-ses of VSD concomitant with aortic valve prolapse,size of the occluders should be referred to VSD dimensions measured by TTE. In the cases of VSD adjacent to aortic valve,suitable occluders should be selected and operation technique should be improved to avoid aortic regurgitation.

Evaluation for the clinical effect of duct occluder in treatment of intracristal ventricular septal defect / 中华实用儿科临床杂志

Objective To evaluate the clinical effect for transcatheter closure of intracristal ventricular septal defects (IVSD) using duct occluder.Methods Between Jun.2012 and Sep.2013,implantaion of duct occluder was conducted in 27 IVSD pmients,which was compmed with acentric ventricular septal occluder attempted in 53 IVSD patients.The transthoracic echocardiography,electrocardiography,and clinical examination were observed at 24 hours,and after 1,3,6 and 12 months follows-up.Results Implantation of duct occluders were achieved in 26 (96.23 ％) patients and implantation of acentric ventricular septal occluder in 42 (79.25％) patients.The mean follow-up time was 6.78 months (1-17 months).The procedure time,fluoroscopic time and residual shunt were not statistically different between the 2 groups (all p ＞ 0.05).The size of VSD (t =-3.124,P =0.003) and occluder diameter (t =-4.285,P ＜0.001)were smaller and the procedure success rate was higher in the duct occluder group (x2 =9.099,P =0.011).Left ventricular end diastolic dimension,left atrial diameter,left ventricular end diastolic dimension,right ventricular end diastolic dimension and pulmonary artery diameter were decreased significantly (F =57.62,5.002,4.754,2.782,P =0.000,0.033,0.001,0.030) after surgical procedure compared with those before procedure,except for the right atrial diameter and left ventricular ejection fraction.No new serious aortic regurgitation or increased mitral regurgitation,tricuspid regurgitation was shown after procedure in 2 groups.Complete left bundle branch block occurred in 2 patients respectively,pericardial effusion and thromboembolism of right femoral artery occurred in 1 patient in the acentric ventricular septal occluder group.Conclusions The duct occluder for IVSD closure has presented a good result,without serious complications,which provides a new method for IVSD closure.Further studies are necessary to determine the long-term results in a larger population of patients.

An analyze of medium and long term follow-up of arrhythmias after transcatheter closure of ventricular ;septal defect in children / 临床儿科杂志

Objective To observe and analyze the medium and long term follow-up data of arrhythmias after transcatheter closure of children with ventricular septal defect (VSD). Methods Retrospectively analyzed the clinical data of 1071 children with VSD, who successfully underwent transcatheter device closure, at l, 3, 6, 12 months and ev-ery year post procedure from March 2002 to December 2010. Results Of all 1071 children, 272 cases (25.4%) were ob-served of having arrhythmias within 1 month after intervention, mainly including atrioventricular block (AVB), branch block, junctional tachycardia, atrial and ventricular tachycardia, frequent contractions, etc. Among them, 22 cases (2.1%) had above II degree AVB, complete left bundle branch block (CLBBB) and other causes of serious arrhythmias. After treatment, all cases got better and no permanent pacemaker was necessary. After 1 to 107 months (2.8±1.7 years) fol-low-up, 161 cases (18.2%) were observed of having persistent abnormal ECG mainly caused by AVB and branch block, including 10 cases (1.1%) with serious arrhythmias. In 4 cases with late-onset AVB, 3 cases had already appeared AVB in early postoperative, 1 case had recurrence CLBBB, left ventricle enlarge, and died of heart failure during follow up. Four cases were implanted permanent pacemaker. Conclusion During follow-up, serious arrhythmias after VSD closure, such as AVB or CLBBB, have high risk of recurring. Conduction block arrhythmias may reappear or worsen, while arrhythmias like tachycardia and premature heart rhythm mostly return to normal.

Prevalence and risk factors of arrhythmias after transcatheter closure of ventricular septal defect in children / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the prevalence and risk factors of arrhythmia after transcatheter closure of ventricular septal defect (VSD) in children.</p><p><b>METHODS</b>A total 1 069 children (583 males, mean age (7.7 ± 3.6) years) underwent transcatheter closure of VSD from January 2002 to December 2010 in our hospital were enrolled and retrospectively analyzed.VSD diameters were (4.0 ± 1.8)mm, 336 cases accompanied membranous aneurysm. Electrocardiogram were performed at 1, 3 days after the procedure.Once arrhythmias recorded, electrocardiogram was performed daily till discharge. All cases were followed up by ECG at 1, 3, 6, 12 months after the procedure in outpatient department and then in a year interval. The risk factors were identified by multivariable logistical analysis.</p><p><b>RESULTS</b>All VSDs were closed successfully and the diameters of occluder was (7.2 ± 2.1)mm. The median follow-up time was 2.2 (1.0-4.2) years. Mortality was zero during follow up.Incidence of early ( < 1 month) post-procedure arrhythmias was 24.6 % (263 cases), and severe arrhythmias were recorded in 50 cases (4.7%). There were 43 late ( ≥ 1 month) post-procedure arrhythmias (4.0%) including 4 (0.4%) complete atrioventricular block. Multivariable logistic analysis revealed that VSD treated with thin-waist-big-side occluder (OR = 2.426, 95%CI:1.835-3.208, P < 0.001) , male gender (OR = 1.267, 95%CI:1.055-1.523, P = 0.011) were the risk factors while higher body weight (OR = 0.838, 95%CI:0.737-0.951, P = 0.006) was protective factor for early onset arrhythmia. Placement of asymmetrical occluder (OR = 4.777, 95%CI:2.079-10.978, P < 0.001) , longer procedure time (OR = 1.011, 95%CI:1.002-1.020, P = 0.012) , occluder from foreign countries (OR = 2.621, 95%CI:1.143-6.014, P = 0.021) were the risks factors for early onset severe conduct block. Treatment with thin-waist-big-side occluder (OR = 2.654, 95%CI: 1.042-6.760, P = 0.041) was the risk factor while higher body weight (OR = 0.373, 95%CI:0.159-0.875, P = 0.023) was a protective factor for late onset conduct block.</p><p><b>CONCLUSIONS</b>Arrhythmia after transcatheter closure of VSD is common in children, and late onset severe conduct block is rare. The weight of patients should not too light and symmetrical occluder should be chosen if possible in the transcatheter closure VSD procedure to minimize the risk of late onset conduct block.</p>

Potential biomarkers predicting risk of pulmonary hypertension in congenital heart disease: the role of homocysteine and hydrogen sulfide / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Pulmonary hypertension (PH) is a common complication of congenital heart disease (CHD). Although risk stratification is vital for prognosis and therapeutic guidance, the need for understanding the role of novel biomarkers cannot be overlooked. The aim of the present study was to investigate the changes of homocysteine and hydrogen sulfide levels and find potential biomarkers for early detection and treatment.</p><p><b>METHODS</b>Between September 2012 and April 2013, we prospectively collected data on 158 pediatric patients with left to right shunt CHD at our institution. Standard right heart catheterizations were performed in all cases. Seventy-seven cases were associated with PH. The levels of homocysteine and hydrogen sulfide were detected with fluorescence polarization immunoassay and a sensitive silver-sulphur electrode, respectively. Enzyme-linked immunosorbent assay was used to determine the expression of methylenetetrahydrofolate reductase (MTHFR), cystathionine β-synthase (CBS), and cystathionine gamma-lyase (CSE). Radioimmunoassays were used to obtain folic acid and vitamin B12 levels.</p><p><b>RESULTS</b>The difference in the levels of homocysteine, folic acid, vitamin B12, hydrogen sulfide, as well as the MTHFR and CSE expression between patients with PH and without PH were statistically significant (all P < 0.05). Homocysteine had the best sensitivity and specificity to predict PH (P < 0.001). Subgroup analysis showed that the levels of homocysteine and hydrogen sulfide, and the expression of CSE and MTHFR between patients with dynamic and obstructive PH were significantly different (all P < 0.05). Based on the ROC curve, homocysteine had the best sensitivity and specificity to predict obstructive PH (P = 0.032), while CSE had the most significant sensitivity and specificity to predict the dynamic PH (P = 0.008).</p><p><b>CONCLUSIONS</b>Increased levels of homocysteine and decreased levels of hydrogen sulfide were significantly negatively correlated in PH associated with CHD. The underlying mechanism involved the decreased expression of MTHFR and CSE along with vitamin B12 deficiency. Homocysteine and hydrogen sulfide are potential biomarkers to predict PH.</p>

Tissue inhibitors of metalloproteinase-1 and -2 (TIMP-1 and TIMP-2) mRNA and antigens location in the liver of patients with cirrhosis / 中华传染病杂志

Objective To study the expression and distribution of TIMP 1 and TIMP 2 in liver tissue of cirrhosis patient and to investigate the roles and pathogenesis of TIMP 1 and TIMP 2 in liver cirrhosis. Methods TIMP 1 and TIMP 2 proteins and mRNA were detected with immunohistochemistry and in situ hybridization methods using monoclonal antibodies and cDNA probes. Results mRNA and proteins of TIMP 1 and TIMP 2 were detected in all the liver tissues from 40 liver cirrhosis patients, all in cytoplasm but not nucleus. TIMP 1 and TIMP 2 were found co exist in all samples, while TIMP 1 concentration was higher. Conclusions mRNA and protein of TIMP 1 and TIMP 2 are found in all the cirrhosis patient samples. Liver TIMP 1 and TIMP 2 concentrations increase with the progression of liver cirrhosis, decrease the degradation of extracellular matrix proteins, resulting in the initiation and the development of liver fibrosis and liver cirrhosis.

Inhibiting effect of antisense oligonucleotides phosphorothioate on gene and protein expression of TIMPs in rat liver fibrosis / 中华传染病杂志

Objective To observe the inhibition of asON phosphorothioate to the TIMP-1 gene and protein expression in the liver tissue of immune- induced hepatic fibrosis rats. Methods According to the analysis of modulator, structure protein, encoding sequence of TIMP-1 genome, we designed four different groups of asONs. These asONs were injected into the hepatic fibrosis rat models through coccygeal vein. The results were observed by RT-PCR, immunohistochemistry and in situ hybridization with collagen Ⅰ、Ⅲ, special staining of collagen fiber, electron microscope. Results The asON phosphorothioate of TIMP-1 could be expressed in vivo, and could block the TIMP-1 gene and protein expression in the liver of immune- induced hepatic fibrosis rats on the level of mRNA, which could promote the degradation of collagen Ⅰ、Ⅲ(P

A new homemade secundum atrial septal defect closure device / 中国介入心脏病学杂志

Objective To evaluate the feasibility, safety and efficacy of a new homemade device for percutaneous closure of secundum atrial septal defects (ASDs) Methods Percutaneous closure of surgically created fossa ovalis ASD was attempted in 8 piglets The device was braided from Nitinol wires in the shape of two flat discs with a short connecting waist with a diameter corresponding to that of the defect to be closed Polyethylene filling was implanted to enhance thrombogenicity Pulmonary arteriography with levo phase was obtained before closure and immediately after closure Transthoracic echocardiography with color Doppler was used in all animals during closure and in follow up examinations The animals were killed at various intervals up to 6 months after occlusion for microscopic examination Results Successful placement of the device was achieved in all the 8 animals All ASDs were completely occluded in 1 month, observed by transthoracic echocardiography Postmortem gross and microscopic examination of the 8 specimens 1 to 6 months after placement showed complete or near complete fibrous neoendocardium coverage of both the right and left atrial discs Conclusion These observations show the feasibility of occlusion of secundum ASDs by the homemade device with the advantages of easy placement and repositionability in piglets

THE LOCALIZATION AND EXPRESSION OF TIMP-2 IN EXPERIMENTAL HEPATIC FIBROSIS IN RAT / 解放军医学杂志

An experimental immunity hepatic fibrosis rat model was prepared by means of immunologic assault with human serum albumin, and normal rats served as a control group. The immunohistochemistry methods and in situ hybridization were respectively used to detect TIMP 2 mRNA and related antigens in the liver,and to investigate the localization and expression of TIMP 2 in the liver of both normal and experimental hepatic fibrosis rats. The results showed that TIMP 2 mRNA and related antigens in the livers of experimental group were expressed in myofibroblasts and fibroblasts, especially in the portal area and fibrous septum. The positive signal was located in the cytoplasm, but not in the nucleus. On the other hand, there was a high level of expression of TIMP 2 in the liver of the experimental group.It is suggested that in the process of hepatic fibrosis, fibroblasts and myofibroblasts are the major cells expressing TIMP 2. The severer the hepatic fibrosis in the injured liver is, the higher the levels of TIMP 2 related antigens and gene expression are.