Objective    To compare and investigate the efficacy and differences of modified B-T shunt, central shunt and right ventricle-pulmonary artery (RV-PA) connection in the treatment of pulmonary atresia with ventricular septal defect (PA/VSD). Methods    A total of 124 children with PA/VSD underwent initial palliative repair in Shanghai Children's Medical Center from September 2014 to August 2019, including 63 males and 61 females, aged 7 days to 15 years. They were divided into in a modified B-T shunt group (55 patients), a central shunt group (22 patients) and a RV-PA connection group (47 patients). The clinical data of these children were retrospectively analyzed. Results    There were 9 early deaths after palliation, with an early mortality rate of 7.3%. The mean follow-up time was 26.5±20.3 months, with 5 patients lost to follow-up, 5 deaths during the follow-up period, and 105 survivors. The 1-year and 5-year survival rates were both 89.7%. The monthly increased Nakata index was 5.2 (–0.2, 12.3) mm2/m2, 9.2 (0.1, 23.6) mm2/m2, 6.3 (1.8, 23.3) mm2/m2 in the modified B-T shunt group, the central shunt group, and the RV-PA connection group, respectively, with no statistical difference among the three groups. The 1-year survival rate was 85.3%, 78.4%, 95.2%, and the 5-year (4-year in the central shunt group) survival rate was 85.3%, 58.8%, 95.2% in the three groups, respectively, with a statistical difference among them (P<0.05). The complete repair rate was 36.5%, 19.0% and 67.4% in the three groups, respectively, with a statistical difference among the three groups (P<0.001). Conclusion    All these three palliative surgical approaches can effectively promote pulmonary vascular development. But compared with systemic-pulmonary shunt, RV-PA connection has a lower perioperative mortality rate and can achieve a higher complete repair rate at a later stage, which is beneficial for long-term prognosis.

Objective    To evaluate the effects of anatomic correction for congenitally corrected transposition of the great arteries (ccTGA) and 10-year follow-up. Methods    From January 2008 to December 2018, 48 patients with ccTGA who underwent anatomic correction were reviewed. There were 29 males and 19 females with age of 39.2 (3-91) months. The cohort was divided into two groups: a biventricular anatomic correction group (39 patients) and a 1.5 ventricular anatomic correction group (9 patients). They were followed for in-hospital mortality, late mortality, long-term survival, freedom from reoperation, and heart function. Results    There were 3 early deaths and 2 early re-intervention in the biventricular anatomic correction group, but no death and only one re-intervention in the 1.5 ventricular anatomic correction group. Compared with the biventricular anatomic correction group, the operation time, tracheal intubation and ICU time were significantly reduced or shortened in the 1.5 ventricular anatomic correction group (P<0.05). The patients were followed up for 0.5-10.4 years. Four patients were lost. Two patients died in the biventricular anatomic correction group, and two patients received re-intervention. The 1-year, 5-year and 10-year survival rate was 88.2%, 84.0%, and 84.0%, respectively. There was no death or intervention in the 1.5 ventricular anatomic correction group. The quality of life of the other patients in the medium-term follow-up was satisfactory. Only 2 patients were classified as grade Ⅲ in cardiac function, and the other patients were classified as grade Ⅰ-Ⅱ. Conclusion    According to the different anatomic characteristics of ccTGA, the individualized strategy of anatomic correction can achieve satisfactory surgical results, and the medium-term quality of life was good. Especially, 1.5 ventricular anatomic correction may obtain better therapeutic effects because of its lower operative mortality and less postoperative complications.

Objective    To evaluate the effect of off-pump pulmonary valvulotomy for the patients with pulmonary atresia with intact ventricular septum (PA/IVS). Methods    The clinical data of 61 PA/IVS patients who underwent off-pump right ventricular decompression surgery in our hospital from January 2013 to September 2019 were retrospectively analyzed, including 37 males and 24 females, with an average age of 29.7 (2.0-86.0) d and weight of 4.1 (2.5-6.9) kg. Thirty-nine patients received off-pump pulmonary valvulotomy (an open-view valvulotomy group) and 22 patients received balloon valvuloplasty through the right ventricle pulmonary valve (a hybrid therapy group). The postoperative mortality, early re-intervention, and completion of final operation of the two groups were compared. Results    There were 2 deaths in the study with a mortality rate of 3.3% (2/61), and the mortality rate of the two groups was not significantly different (2.6% vs.4.5%, P=0.68). The rate of early re-intervention in the two groups was 5.3% and 19.0%, respectively (P=0.09). There was no statistical difference in intubation time (56.0±25.9 h vs. 62.0±28.9 h, P=0.41), ICU retention time (4.7±2.9 d vs. 5.5±2.2 d, P=0.23) and postoperative hospital stay time (3.9±0.9 d vs. 4.3±1.1 d, P=0.38) between the two groups. The follow-up time was 45.3 (4.0-84.0) months. There were 5 patients lost to follow-up. During the follow-up period, in the open-view valvulotomy group, 17 patients did not need further operation, 13 patients completed the final operation. In the hybrid therapy group, 7 patients did not need further operation, 8 patients completed the final operation. Heart function classification of all patients was in New York Heart Association class Ⅰ-Ⅱ. Conclusion    Compared with the hybrid therapy, off-pump pulmonary valvulotomy for PA/IVS also has the advantages of simple operation, short operation time and high survival rate, and it may be easier to be promoted in clinical application because of its more economic benefits and relatively lower re-intervention rate.

To evaluate the surgical strategy and follow-up for pulmonary atresia with intact ventricular septum (PA/IVS) in our heart center. Methods    From January 2008 to December 2018, 151 patients with PA/IVS were divided into two groups: a one-stage surgery group (26 patients), including 17 males and 9 females at an average age of 14.7±13.2 months, and a staged surgery group (125 patients) including 72 males and 53 females at an average age of 6.4±6.3 months. The clinical effectiveness of the two groups were analyzed. Results    All patients were followed up for 1-11 years. Eighteen patients died and 19 patients were lost to follow-up. The 1-year, 5-year and 10-year survival rate was 90.2%, 87.0%, and 85.2%, respectively. Two patients died in the one-stage surgery group. Twelve patients died after initial surgery, and 4 patients died after final operation in the staged surgery group. The Z value of tricuspid valve (P=0.013) and severe right ventricular dysplasia (P=0.025) were the risk factors of postoperative death in the patients with PA/IVS. Furthermore, 58 patients completed final operation, and the total number of the final operation (including one-stage radical surgery) accounted for 55.6% (84/151). Five patients accepted the re-operation intervention in the medium-term follow-up. The rest of the patients recovered well. Only 2 patients were classified as grade Ⅲ in cardiac function, and the rest patients were classified as gradeⅠ-Ⅱ. Conclusion    According to the degree of right ventricular hypoplasia, the age at operation and the presence or absence of coronary artery malformation, the individualized surgical strategy could significantly improve the success rate of PA/IVS, and early completion of right ventricular decompression operation is conducive to improve the chance for biventricular repair.

Objective:To summarized the experience of 149 cases of critical pediatric cardiac surgery in a single-center during the epidemic period, for providing a safe and feasible management strategy.Methods:Based on the epidemiological characteristics of COVID-19, a strategy consisting of 14 days of isolation was established for the arrangement of cardiac surgery in children during the epidemic period. Retrospective analysis of clinical data of 149 cases of critical cardiac surgery performed from January 23, 2020 to March 20, 2020 under the guidance of this strategy. The primary composite endpoint was death and suspected or confirmed COVID-19.Results:The median age of the children undergoing surgery was 136 days; 73(49.0%) cases were male. Twenty-one cases (14.1%) came from Shanghai, one case (0.7%) came from Hubei Province, and 127 cases (85.2%) came from areas other than Hubei and Shanghai. One patient (0.7%) outside Shanghai who had been isolated for less than 14 days carried emergency surgery under special protection; other 148 patients (99.3%) underwent elective early repair procedure. One patient (0.7%) died, and no COVID-19 was confirmed or suspected.Conclusion:During the COVID-19 epidemic, pediatric cardiac surgery can be safely performed using a specific management strategy, which can be used as a reference when major public health events occur.

Objective The purpose of this report is to summarize and evaluate the clinical effect and experience of re-intervention for children with pulmonary venous restenosis.Methods The clinical data of 53 patients with pulmonary venous restenosis who received reintervention at SCMC from September 2009 to January 2018 were retrospectively analysed, including 34 males and 19 females with mean age of(15.1 ±13.2)months(2-77 months) and mean weight of(7.9 ±3.3)kg(3.7 -17.3 kg).The mean preoperative pulmonary venous velocity was(2.28 ±0.40)m/s(1.89 -3.07 m/s).Primary disease in-cluded 43 cases of total anomalous of pulmonary venous drainage(14 supracardiac type, 20 infracardiac type, 2 intracardiac type and 7 mix type), 8 cases of partial anomalous of pulmonary venous drainage and 2 cases of primary pulmonary venous ste-nosis.The distribution of reintervention methods were shown as follow:34 cases of sutureless technique(21 cases with pedicle pericardium and 13 cases with left auricle tissue), 10 cases of bovine pericardium enlargement, 5 cases of blunt enlargement, 3 cases of balloon dilatation and 1 case of stent implantation.Results The early postoperative pulmonary venous velocity was (1.12 ±0.23) m/s.There were 4 in-hospital deaths with a mortality of 7.5％.49 survivors were under a follow-up of 3-98 months.The echocardiography showed pulmonary venous anastomosis and diameter have grown after reintervetion with a mean growth speed of(0.022 ±0.014)cm/month(P<0.05) and a mean velocity of(1.25 ±0.28)m/s;4 patients occured varying degrees of pulmonary venous obstruction( >1.6 m/s) but no one need reoperation at present.More than 90％ patients exhibi-ted an improvement of NYHA functional class from Ⅲ or Ⅳ preoperatively to Ⅰ or Ⅱ at follow-up.Conclusion Pulmonary venous restenosis is a common complication after primary pulmonary malformations operation .The reintervetion should be per-formed in early period of pulmonary venous obstruction .Pulmonary venous anastomoses after sutureless technique , bovine peri-cardium enlargement and blunt enlargement have grown obviously; although balloon dilatation has a good effect at early period of postoperation, it also has a high restenosis rate and needs a strict mid-and long-term follow-up.

Complex congenital heart disease; right ventricular outflow tract reconstruction; autologous tissue; extracardiac conduit Objective To assess the mid- and long-term outcomes of right ventricular outflow tract reconstruction for children with congenital heart disease. Methods We retrospectively analyzed the clinical data of 3 138 children with complex congenital heart disease in right heart system admitted to our hospital from January 2007 to January 2017. There were 1 660 males and 1 478 females. The age at surgery was 9 days to 84 months, and the body weight was 2.2 to 28.6 kg. Pulmonary patch enlargement was performed in 2 335 patients (1 477 patients of valve-sparing repair and 858 patients of transannular repair); autologous tissue (direct anastomosis, left auricle or pericardial conduit) was used to connect with right ventricle in 289 patients; extracardiac conduits were used for reconstruction in 514 patients. Results There were 181 in-hospital deaths with a mortality of 5.8%. The early postoperative causes of death were low cardiac output syndrome (LCOS), severe pulmonary hypertension and right heart failure. Fifteen patients died of cardiac insufficiency or sudden death during follow-up (6–27 months postoperatively). The echocardiography showed 408 patients with right ventricular outflow tract obsturction (RVOTO), 340 patients with pulmonary trunk or branches stenosis, 609 with pulmonary regurgitation (morderate or severe). 12.6% (394/3 138) of patients underwent reintervention or reoperation with 39 deaths. About 92.4% of patients exhibited an improvement of New York Heart Association (NYHA) functional class from Ⅲ or Ⅳ preoperatively to Ⅰ or Ⅱ at follow-up. Conclusion The anatomical structure of right ventricular outflow tract is complicated and various, and each operation method has different strengths and favorable outcomes. The operation should be individually designed according to pathological types, anatomical features, clinical symptoms and operation conditions.

Objective: The purpose of this report was to discuss and evaluate the timing and outcome of reintervention for children with postoperative valve disease. Methods: The clinical data of 139 patients with postoperative valve disease who received reintervention at SCMC from Sep. 2004 to Mar. 2019 were retrospectively analysed, including 85 males and 54 females. The age ranged from 8-175 months, and the weight ranged from 6.2-75.9 kg. With a mid-long term follow-up (2-133 months), the echocardiography result showed: 40 cases of aortic valve disease, 49 cases of mitral valve disease, 32 cases of tricuspid valve disease and 18 cases of pulmonary valve disease. All patients underwent reintervetion treatment, the distribution of reintervention methods were shown as follow: 47 cases of valve replacement, 40 cases of valvuloplasty, 23 cases of annuloplasty and 29 case of valve reconstruction. Results: There were 6 in-hospital deaths with a mortality of 4.3%. The death cases included 2 cases of aortic disease, 2 cases of mitral disease, 1 case of tricuspid disease and 1 case of pulmonary disease. The early postoperative causes of death were acute myocardial failure, multiple organ failure and severe hyoxemia. Three delayed deaths occurred 8-26 months after operation because of cardiac insufficiency and cardiac shock. All survivors were under a follow-up of 4-148 months. The echocardiography showed the velocity of 92.3% valve stenosis patients had decreased significantly (P<0.05); the insufficient grades of 84.9% patients had reduced and maintained under morderate degree. 6 cases occurred aggravated insufficiency or stenosis and received reoperation in mid-term follow-up included 3 cases of aortic valve, 2 cases of pulmonary valve and 1 case of mitral valve. The cardiac function of survival patients has been improved after reintervtion, 83.1% patients maintained cardiac function at NYHA Ⅰ/Ⅱ at follow-up. The long-term survival rates of 4 valve disease were all over 90%. Conclusion The anatomical structure of chilidren’s valve is complicated and various, valve insufficiency and stenosis often occured after operation. The timing of reintervetion should focus on clinic symptom and cardiac function.The operation should be individually designed according to valve anatomy, which could effectly correct abnormal valve structure, promote cardiac function and improve living quality.

Objective: To investigate whether CD137-CD137L signaling can affect the autophagy of mouse vascular smooth muscle cells(VSMCs) through JNK signal pathway. Methods: Primary culture of C57BL/6J mouse thoracic aorta VSMCs was performed by tissue block adherence method. VSMCs between the third to fifth passages were isolated and cultured. VSMCs were divided into 4 groups: control group, CD137 agonist group, JNK inhibition group, and DMSO group. VSMCs in CD137 agonist group were treated with recombinant protein of CD137L (10 μg/ml), VSMCs in JNK inhibition group were treated with JNK inhibitor SP600125 (10 μmol/L) for 30 minutes followed by recombinant protein of CD137L (10 μg/ml) and DMSO group was treated with the same amount of DMSO in JNK inhibition group for 30 minutes, then added recombinant protein of CD137L (10 μg/ml). Western blot was used to detect the protein expression of p-JNK, LCⅡ and p62 in each group. Fluorescence microscopy was used to track the changes of autophagy in cells which was infected with adenovirus expressing tandem mRFP-GFP-LC3. Transmission electron microscope (TEM) was used to observe intracellular autophagosomes and autolysosomes. Results: (1) Compared with the control group, stimulating CD137-CD137L axis by recombinant protein of CD137L significantly upregulated the expression of p-JNK, LCⅡ and p62 (1.15±0.19 vs. 0.72±0.21, P<0.05;1.03±0.13 vs. 0.59±0.15, P<0.05, and 1.10±0.19 vs. 0.76±0.15, P<0.05). These effects could be reduced by JNK inhibitor (0.61±0.21 vs. 1.15±0.19, P<0.05;0.74±0.11 vs. 1.03±0.13, P<0.05, and 0.21±0.12 vs. 1.10±0.19, P<0.05). The expression of these proteins in DMSO group remained unchanged compared with CD137 agonist group (P>0.05). (2) Changes of autophagy in cells of various group: the number of total fluorescent spots and yellow fluorescent spots in CD137 agonist group was significantly increased compared to control group (total fluorescent spots:(93.00±14.11)/cell vs. (52.33±9.61)/cell, P<0.05, and (64.33±6.81)/cell vs. (25.67±3.51)/cell, P<0.05), moreover, the number of yellow fluorescent spots was higher than the red fluorescent spots fluorescent spots in CD137 agonist group. Compared with CD137 agonist group, pretreatment with JNK inhibitor significantly reduced the number of total fluorescent spots and yellow fluorescent spots ((53.00±3.17)/cell vs. (93.00±14.11)/cell, P<0.05,and (15.33±4.51)/cell vs. (64.33±6.81)/cell, P<0.05). The red fluorescent spots were higher than the yellow fluorescent spots in JNK inhibition group. The number of total fluorescent spots and yellow fluorescent spots in CD137 agonist group was not affected by pretreatment with DMSO (P>0.05). (3) The number of intracellular autophagosomes and autolysosomes was significantly higher in CD137 agonist group than in control group((17.67±6.03)/cell vs. (5.67±2.52)/cell, P<0.05), and the number of autophagosomes was higher than that of autolysosomes in CD137 agonist group((14.00±4.00)/cell vs. (3.67±2.08)/cell, P<0.05). The number of intracellular autophagosomes and autolysosomes was significantly lower in JNK inhibition group compared to CD137 agonist group((5.67±4.04)/cell vs. (17.67±6.03)/cell, P<0.05) and the number of autophagosomes was lower than that of autolysosomes in JNK inhibition group((1.33±1.53)/cell vs. (4.33±2.52)/cell, P<0.05). The number of intracellular autophagosomes and autolysosomes was similar between DMSO group and CD137 agonist group (P>0.05). Conclusion CD137-CD137L signal may influence autophagy of mouse VSMCs via JNK pathway.

Objective: To explore whether CD137-CD137L interaction could induce mouse vascular smooth muscle cells(VSMCs) calcification via P38 MAPK signaling. Methods: (1) Mouse VSMCs obtained from 8-week old male C57 mice were cultured by using method of tissue piece inoculation.The cells from 3 to 8 passage were divided into 4 groups: control group, agonist-CD137 group(recombinant CD137L protein), anti-P38 group(agonist-CD137 group+P38 inhibitor), single anti-P38 group(P38 inhibitor). The calcification was induced by adding a mixture of 10 mmol/L β-glycerophosphate+10^-8 mol/L dexamethasone+10^-7 mol/L insulin in the culture medium.Immunofluorescence was used to observe the changes of VSMCs markers(α-SMA and OPN).Real time-PCR was used to observe the mRNA expression of OPN and RUNX-2. Western blot was used to observe the protein expression of p-P38, OPN and RUNX-2. The level of cell calcification was observed by detecting alkaline phosphatase activity and calcium concentration. (2) The degeree of local calcium deposition was also tested on Von Kossa staining and Alizarin red staining methods in following 5 mouse VSMCs groups: control group, agonist-CD137 group(recombinant CD137L protein), anti-P38 group (agonist-CD137 group+P38 inhibitor), anti-CD137 group (agonist-CD137 group+CD137 inhibitor),agonist-P38 group(anti-CD137 group+P38 agonist). Results: (1) Compared with the control group, the fluorescence intensity of α-SMA was lower in the agonist-CD137 group(2.79±0.25 vs. 5.42±0.47,P<0.05), while the fluorescence intensity of OPN was higher(4.91±0.23 vs. 1.63±0.26, P<0.05). The fluorescence intensity of α-SMA was partly recovered after adding P38 inhibitor(4.48±0.27 vs. 2.79±0.25,P<0.05),but it was still lower than the control group (4.48±0.27 vs. 5.42±0.47, P<0.05),the fluorescence intensity of OPN decreased(2.66±0.15 vs. 4.91±0.23,P<0.05),but it was still higher than that in the control group (2.66±0.15 vs. 1.63±0.26,P<0.05).The fluorescence intensity of α-SMA and OPN(5.32±0.67 vs. 5.42±0.47,1.82±0.30 vs.1.63±0.26,both P>0.05) was similar between the control group and single anti-P38 group.(2) Compared with the control group, the protein level of p-P38(4.15±0.24 vs. 3.48±0.26, P<0.05), OPN(2.43±0.21 vs. 1.53±0.08, P<0.05), RUNX-2(3.20±0.23 vs. 1.13±0.10, P<0.05) was significantly increased in agonist-CD137 group,the above effects were blocked by adding specific P38 inhibitor SB203580(1.16±0.12 vs. 4.15±0.24, 0.50±0.02 vs. 2.43±0.21,and 1.74±0.14 vs. 3.20±0.23,all P<0.05);the protein level of p-P38(2.93±0.60 vs. 3.48±0.26,P>0.05),OPN (1.4±0.64 vs. 1.53±0.08,P>0.05),RUNX-2(1.26±0.26 vs.1.13±0.10, P>0.05) was similar between single anti-P38 group and the control group. (3) Compared with the control group, the mRNA level of OPN (1.51±0.34 vs. 1, P<0.05) and RUNX-2(2.67±0.19 vs. 1, P<0.05) was significantly upregulated in agonist-CD137 group, and these effects were blocked by adding specific P38 inhibitor SB203580(0.33±0.14 vs. 1 and 0.45±0.03 vs. 1,P<0.05);the mRNA level of OPN (1.05±0.09 vs. 1, P>0.05) and RUNX-2(1.18±0.10 vs. 1, P>0.05) was similar between the single anti-P38 group and the control group.(4) Compared with the control group,the ALP activity and calcium concentration(2.40±0.25 vs. 1.40±0.21,5.51±0.33 vs. 3.15±0.31,both P<0.05) were significantly increased in agonist-CD137 group,while the effects could be blocked by adding specific P38 inhibitor SB203580((1.99±0.07) king unit/gprot vs. (2.40±0.25) king unit/gprot, (3.74±0.20) mmol/gprot vs. (5.51±0.33) mmol/gprot, both P<0.05).The ALP activity and calcium concentration was similar between single anti-P38 group and the control group((1.60±0.25) king unit/gprot vs. (1.40±0.21)king unit/gprot, (2.66±0.28) mmol/gprot vs. (3.15±0.31) mmol/gprot, both P>0.05). (5) Compared with the control group,the calcification of VSMCs in the agonist-CD137 group was significantly increased,while the calcification in the anti-P38 group was significantly reduced.Compared with the agonist-CD137 group,the level of calcification in the anti-CD137 group was obviously increased,and the calcification in the agonist-P38 group was significantly higher than that in the anti-CD137 group and the control group. Conclusion These findings suggest that CD137-CD137L signaling may regulate VSMCs calcification via modulating P38 pathway.