Objective:To prevent postoperative myocardial oedema or other causes of acute heart failure in congenital cardiac disease,anticipating delay sternal closure may reduce the number of children requiring cardiopulmonary resuscitation after surgery.The aim of this study was to describe the rate of delay sternal closure after surgery for congenital cardiac disease and to analyse the risk factors that may be associated with it.Methods:We retrospectively reviewed all surgeries with extracorporeal circulation in the cardiothoracic surgery intensive care unit of Shanghai Children's Medical Center in the past five years,from September 2014 to December 2018.The study cohort was divided into the delay sternal closure group (n=418) and the control group (routine chest closure,n=12 188) according to whether a delay sternal closure was applicated.Risk factors associated with delay sternal closure were identified by multivariate Logistic regression analysis.Results:A total of 12 606 cases were eligible,of which 418 (3.32%) were in the delayed sternal closure group.The most common cardiac diagnosis in the delayed sternal group was transposition of the great arteries (26.8%,112/418),whereas the most common cardiac diagnosis in the control group was ventricular septal defect (45.9%,5 599/12 188).All-cause mortality in children in the delayed sternal closure group was 3.3% (14/418) compared with 0.4% (46/12 188) in the control group,with a statistically significant difference ( P<0.05).Multivariate Logistic regression analysis showed that the need for delayed sternal closure were associated with age ( OR 0.164,95% CI 0.079-0.338, P<0.001),positive intropic support before surgery ( OR 0.42,95% CI 0.252-0.699, P=0.001),sex（ OR 0.742，95% CI 0.648-1.098， P<0.05），mean body weight（ OR 1.192，95% CI 1.078-1.318， P<0.001），positive intropic support before surgery（ OR 0.370，95% CI 0.252-0.699， P<0.001），complicated surgery ( OR 0.241,95% CI 0.159-0.367, P<0.001) and extracorporeal circulation diversion time ( OR 6.412,95% CI 4.339-9.475, P<0.001). Conclusion:Delayed sternal closure is an important management strategy for congenital cardiac surgery in infants and children.Delayed sternal closure is associated with age，sex,mean body weight at the time of surgery,positive intropic support before surgery，complicated surgery and extracorporeal circulation diversion time.

Objective·To explore the immune-related characteristics of non-small cell lung cancer(NSCLC),discover potential tumor markers in V-J genes,and lay the foundation for establishing a TCR-antigen recognition prediction model.Methods·A total of 704 NSCLC samples were collected to establish a comprehensive T-cell receptor(TCR)repertoire analysis workflow.The upstream analysis included steps such as raw data processing,quality control,filtering,TCR sequence identification,and extraction.The downstream analysis included repertoire clone distribution,clone typing,V-J gene sharing,CDR3 distribution characteristics,and clone tracking.The sample clone distribution was analyzed by using indices such as Shannon-Weiner index and Chaol index.Clone typing was performed based on the number of clone amplifications to explore differences among different types.The degree of V-J gene segment sharing was analyzed,and the sharing of low-frequency clone types was determined through clone amplification weight analysis of V-J genes by using two samples of papillary thyroid carcinoma.Finally,analysis of the distribution characteristics of V genes and high-frequency clone type CDR3,and clone tracking analysis were conducted to monitor changes in tumor immune clone frequencies before and after analysis,aiming to identify potential tumor markers.Results·① Significant differences were observed in clone distribution and clone typing among different NSCLC tissues,as well as among different ages and genders.② Specific highly-shared V-J genes were identified in the analysis of V-J gene sharing,and non-normal distribution of high-clone V genes and amino acid high-frequency clone types were found in the CDR3 distribution analysis.③ In the analysis of high-frequency clone type clone tracking,highly expressed or newly expressed high-frequency clone types were observed in NSCLC,suggesting that these clone types could serve as potential tumor-associated antigens or bind with CDR3 reference sequences of new antigens.④ It was found that the expression frequency of TRBJ2-5 gene,originally low-expressed,significantly increased,indicating its potential role as a key low-frequency gene in tumor immune response.Conclusion·The TRAV21 and TRBV6.5 genes show high clone amplification in NSCLC and could serve as potential tumor biomarkers.

Objective:To study the evolution of Traditional Chinese Medicine (TCM) syndromes of 171 cases of Kawasaki disease (KD) under the intervention of gamma globulin therapy based on factor analysis.Methods:A cross-sectional study. 171 cases of KD children hospitalized in the Department of Cardiology of Guangzhou Women's and Children's Medical Center from July 2019 to December 2020 were collected. All patients were treated with intravenous gamma globulin (2 g/kg) for 1 week. According to the results of the treatment with C-ball, 171 children with C-ball sensitive KD were selected to collect the four diagnostic data, and the representative syndromes of defensive level, qi level, yin level, and nutritive level were observed. Factor analysis was used to analyze the evolution of syndrome in 171 children with KD c-ball sensitivity.Results:The result of factor analysis showed that the KMO statistics of 171 children with c-ball sensitivity before treatment was 0.792, and Bartley test was significant ( P<0.01). 16 common factors were extracted, and 23 syndromes were screened, mainly including defensive level disorder, qi level disorder,nutritive level disorder,yin level disorder, heat stagnation and blood stasis syndrome. One week after treatment, the statistic of KMO test was 0.787, and Bartley test was significant ( P<0.01). 9 common factors were extracted, and 10 syndromes were screened, mainly including qi deficiency syndrome, yin deficiency syndrome and blood stasis syndrome. Conclusion:Before treatment, the TCM syndromes in KD C-cell sensitive children are mainly nutritive level disorder, defensive level disorder, qi level disorder yin level disorder, and heat stagnation and blood stasis syndrome; after treatment, the main TCM syndromes are mainly qi deficiency syndrome, yin deficiency syndrome and blood stasis syndrome.

Objective:To analyze the risk factors of performing diaphragm plication(DPL) after congenital heart disease(CHD) surgery as well as the timing and clinical efficacy.Methods:Data regarding children underwent open heart surgery at Shanghai Children′s Medical Center from January 2017 to December 2019 were reviewed.According to whether DPL was performed after CHD operation or not, the children were divided into DPL group and non-diaphragm plication(NDPL)group.Clinical data including age, surgery, cardiopulmonary bypass(CPB)temperature and time of two groups were compared, meanwhile the risk factors of DPL surgery were analyzed.Based on the median of 8 days between open heart surgery and DPL, children in DPL group were divided into early surgery group(less than 8 days), and delayed operation group(no less than 8 days). The parameters of comparison included ventilator using time, hospital stay time, hospitalization expenditure, postoperative infection to evaluate the timing of DPL and effect.Results:There were 10 309 children after CHD, including 95 in DPL group and 10 214 in NDPL group.In DPL group, there were 52 males(54.7%) and 43 females(45.3%), with age 147(52, 318) d, weight(5.5±4.1) kg, height(56.8±25.6) cm, CPB time(136.8±93.4) min and aortic occlusion time(62.5±50.2) min.Compared with NDPL group, DPL group had younger age, shorter height, lighter weight, higher incidence of preoperative special treatment, higher proportion of reoperation, lower CPB temperature, longer CPB time and longer aortic occlusion time.There were significant differences between two groups( P<0.05). Multivariate Logistic regression analysis showed that younger operative age( OR=0.998, 95% CI 0.998~0.999, P<0.001), staging operation( OR=72.977, 95% CI 39.096~136.211, P<0.001), long CPB time( OR=1.006, 95% CI 1.002~1.011, P=0.008), and pulmonary venoplasty( OR=4.219, 95% CI 2.132~8.350, P<0.001) were independent risk factors for DPL after CHD.Early surgery group had lower postoperative infection rate(43.59% vs. 88.38%, P=0.007), shorter ventilator duration[168.0(99.5, 280.5) h vs.309.9(166.2, 644.5) h, P=0.029], shorter hospital stay duration[27.00(20.75, 35.00)d vs.37.00(28.00, 53.00)d, P<0.001], and lower hospitalization cost[158.36(128.99, 203.11) thousand yuan vs.232.95(174.54, 316.47) thousand yuan, P<0.001] than delayed operation group. Conclusion:Younger age, staging operation, long CPB time, and pulmonary venoplasty are independent risk factors for DPL due to diaphragmatic paralysis after pediatric CHD surgery.Early surgical intervention is beneficial for the recovery of children.

Objective:To study the changes of cytokines after cardiopulmonary bypass(CPB)in children with congenital heart disease.Methods:A total of 124 children with congenital heart disease underwent CPB surgery at Shanghai Children′s Medical Center from June 2020 to October 2021 with cytokine detection were enrolled.Twelve kinds of cytokines, white blood cell count(WBC)and neutrophil-to-lymphocyte ratio(NLR), C-reactive protein(CRP)and procalcitonin were detected before and 24 hours after operation.All patients were divided into CPB<120 min group ( n=102)and CPB≥120 min group ( n=22)acoording to CPB time, and were divided into systemic inflammatory response syndrome (SIRS) group, compensatory anti-inflammatory response syndrome (CARS) group and control group according to the changes of cytokines.The changes of cytokines, anti-inflammatory factors and pro-inflammatory factors before and after CPB and the correlation with CPB time were analyzed. Results:There were 65 boys and 59 girls with a body weight of(10.69±8.18)kg and a median age of 317(141, 975)d.After CPB, WBC(×10 9/L)(13.47 vs.8.6), NLR(4.93 vs.0.55), and CRP(mg/L)(81.35 vs.0.8) were significantly higher than those before operation( P<0.001). IL-6(pg/mL)(135.69 vs.6.86), IL-8(pg/mL)(33.33 vs.14.95), and IL-10(pg/mL)(6.05 vs.2.44)were significantly higher than those before operation( P<0.001). Compared with CPB<120 min group, IL-6(pg/mL)(211.88 vs.119.47), IL-8(pg/mL)(71.67 vs. 25.39), and IL-10(pg/mL)(7.69 vs. 4.92)in CPB≥120 min group significantly increased( P<0.001). CRP was negatively correlated with CPB time( r=-0.204, P=0.025), while IL-6( r=0.254, P=0.005), IL-8( r=0.358, P=0.001), IL-10( r=0.198, P=0.03) were positively correlated with CPB time.Twelve children(9.7%)had obvious SIRS, and four cases(3.2%)had early CARS.The mortality of CARS group was significantly higher than that of SIRS group and the control group( P=0.011). Conclusion:Il-6 , IL-8, and IL-10 are significantly increased after CPB in children with congenital heart disease.With the increase of CPB time, IL-6 and IL-8 increase significantly, and the correlation between IL-8 and CPB time is the strongest.Although the proportion of children with early postoperative CARS is small, the mortality is high, which indicates clinical surveillance and treatment need to be strengthened for anti-inflammatory response.

Objective:To study the early outcomes of emergency operation employed with one of the prevalent surgical methods in neonates diagnosed as pulmonary atresia with intact ventricle septum(PA/IVS) and critical pulmonary stenosis(CPS), and to analyze the risk factors related to its early results.Methods:A retrospective analysis was conducted to collect the data of neonates suffered from PA/IVS and CPS from January 2016 to January 2020 in cardiothoracic surgery department at Shanghai Children′s Medical Center.According to their Z score, which reflects the development degree of right ventricle, the neonates received one of the relevant popular operations.Early outcomes were summarized and risk factors related to its early stage mortality were analyzed.Results:A total of 65 neonates were enrolled, including 27 CPS cases.They were operated on the basis of their respective Z scores, and also according to these data, the primary surgical procedure was chosen from the following methods: Blalock-Taussig(B-T) shunt, pulmonary valvulotomy and right ventricular outlet enlargement.Totally seven cases died, and mortality was 10.7%.Nine cases received re-operation in several following days because of severe hypoxemia and low cardiac output.All patients had mild improvement in oxygen saturation after operation and relied on large dose of inotropic agent.Multivariate Logistic regression analysis showed that B-T shunt and re-operation in early period were risk factors for death in neonates with PA/IVS and CPS.Conclusion:There is a higher mortality in neonates who received emergency operation for PA/IVS and CPS.Accurate assessment of the right ventricle development degree and selecting the corresponding appropriate surgical method is critical for the optimal result.B-T shunt and early stage re-operation are the risk factors for death in neonates with PA/IVS and CPS who received emergency operation.

Objective:To review the clinical prognosis and causes of death in children with extracorporeal membrane pulmonary(ECMO) assistance after congenital heart disease(CHD) operation in our center, so as to improve the survival rate of ECMO.Methods:All clinical data of 105 children with VA-ECMO assisted after CHD operation who were admitted to the Department of Cardiothoracic Surgery at Shanghai Children′s Medical Center from January 2017 to December 2019 were collected, and the clinical characteristics and causes of death were retrospectively analyzed.Results:The age of 105 children with ECMO was 110(38, 341)days, the weight was 5.30(3.75, 8.45)kg, and the risk adjustment for congenital heart surgery score was 3(2-3)points.There were no statistically significant differences in gender, age, weight, height, risk adjustment for congenital heart surgery score, the number of ECMO installed in the operating room, the number of ECMO installed after cardiopulmonary resuscitation and ECMO duration between the surviving group ( n=51) and the death group ( n=54)( P>0.05). While there was a significant difference in utilization of continuous renal replacement therapy[7.8% (4/51) vs.38.9% (21/54), P<0.001]. The death mainly occurred within one week after evacuating ECMO(83.3%, 45/54). ECMO installation was most in children aged 1 month to 1 year old(52.4%, 55/105), and the survival rate showed a rise over three years(2017 to 2019), increased from 31.6% (6/19) to 65.0% (13/20). Children with 3 to 5 kg were the most affected (39.0%, 41/105) when ECMO was installed, and the survival rate from 2017 to 2019 increased from 28.6%(4/14) to 75.0%(9/12). The main cause of death was heart failure(48.1%, 26/54), followed by bleeding(18.5%, 10/54)and pulmonary hypertension(13.0%, 7/54). Conclusion:With the progress of surgical technology and cardiopulmonary bypass, and the improvement of postoperative management, the mortality of children with CHD in our hospital after ECMO has decreased year by year during the last three years.However, the mortality of children requiring continuous renal replacement therapy assistance during ECMO is higher.Therefore, it is still necessary to strengthen the maintenance of each organ function during ECMO.

Objective:To investigate the sedative effect after congenital heart disease surgery in children under the bi-spectral index monitoring(BIS).Methods:A prospective cohort study was performed, we selected 264 children with congenital heart disease who were admitted to the cardiac intensive care unit at Shanghai Children′s Medical Center from September 2018 to August 2019, 126 cases in the intervention group, and 138 cases in the control group.The control group used Ramsay sedation score to evaluate the sedative effect, meanwhile the intervention group was evaluated by Ramsay sedation score and BIS.The incidence of adverse events related to extubation performed within 8 hours after congenital heart disease surgery, and the length of stay in ICU between two groups were compared.The average mechanical ventilation time of the patients whose mechanical ventilation time was more than 8 hours in two groups was compared.The use of sedative drugs midazolam and morphine in children with mechanical ventilation time for more than 24 hours and liver damage, and the incidence of respiratory depression during ventilator withdrawal were analyzed.Results:In children with early extubation, there were 62 cases in the intervention group and 70 cases in the control group.Compared with the control group, the intervention group had a low incidence of extubation-related adverse events (including unplanned extubation, dysphoria after sputum aspiration, and inhalation inhibition after extubation). The average mechanical ventilation time in the intervention group[(8.18±1.95)h] was less than that in the control group[(9.53±1.37)h, P<0.05] of the patients whose mechanical ventilation time was more than 8 hours but less than 24 hours.In children with mechanical ventilation time more than 24 hours, 28 cases were in the intervention group and 35 cases in the control group.The average doses of midazolam and morphine in the intervention group[(1.82±0.40)μg/(kg·min), (8.64±3.03)μg/(kg·h)] were less than those in the control group[(2.73±0.79) μg/(kg·min), (14.32±5.01)μg/(kg·h), all P<0.05]. Among the 28 children in the intervention group with mechanical ventilation time more than 24 hours, 13 cases had liver damage, and 15 cases of the 35 children in the control group had liver damage.The average doses of midazolam and morphine in the intervention group[(1.42±0.51)μg/(kg·min), (6.88±2.17)μg/(kg·h)] were lower than those in the control group[(2.25±0.62)μg/(kg·min), (11.88±3.56)μg/(kg·h), all P<0.05]. The incidence of inhalation inhibition in the intervention group was lower than that in the control group ( χ2=48.303, P<0.05). Conclusion:The sedation after congenital heart disease surgery in children under the BIS is effective.

Objective:To explore the reliability of estimated transpulmonary gradient(TPG)by comparing the measured TPG with the estimated TPG in echocardiography.Methods:The cardiothoracic surgery database of Shanghai Children′s Medical Center was reviewed.Children with hemodynamic monitoring and ultrasound findings who underwent total cavopulmonary connection between January 2015 and December 2018 were included.TPG was calculated separately according to the formula.Intraclass correlation efficient was used for consistency test.Results:Finally, 27 patients were selected, including 16 males and 11 females with age(4.0±1.6)years old, weight(15.2±3.3)kg and height(99.1±11.2)cm.There were nine cases (33.3%) of right ventricular double outlet and seven cases (25.9%) of pulmonary atresia.For hemodynamic blood monitoring, TPG was 5-16(10.1±3)mmHg, and its echocardiography parameters were estimated as 5.8-20.3(11±3.3)mmHg.The ICC value was 0.117 which was less than 0.4( P=0.277). Conclusion:TPG estimated by total cavopulmonary connection pipe window during perioperative period is inaccurate and higher than actual value, so invasive hemodynamic monitoring is still recommended during perioperative period.

Lung cancer, which is exacerbated by environmental pollution and tobacco use, has become the most common cause of cancer-related deaths worldwide, with a five-year overall survival rate of only 19% (Siegel et al., 2020; Yang et al., 2020; Yu and Li, 2020). Nearly 85% of lung cancers are non-small cell lung cancers, of which lung adenocarcinoma is the most common subtype accounting for 50% of non-small cell lung cancer cases. At present, radiotherapy is the primary therapeutic modality for lung cancer at different stages, with significant prolongation of survival time (Hirsch et al., 2017; Bai et al., 2019; Shi et al., 2020). Irradiation can generate reactive oxygen species (ROS) through the radiolysis reaction of water and oxygen, cause DNA damage and oxidative stress, and subsequently result in cancer cell death (Kim et al., 2019). Nevertheless, radioresistance seriously hinders the success of treatment for lung cancer, owing to local recurrence and distant metastasis (Huang et al., 2021). Compared with small cell lung cancer, non-small cell lung cancer shows more tolerance to radiotherapy. Therefore, it is of great importance to decipher key mechanisms of radioresistance and identify effective molecular radiosensitizers to improve patient survival.