Targeting a cardiac abundant and fibroblasts-specific piRNA (CFRPi) to attenuate and reverse cardiac fibrosis in pressure-overloaded heart failure.

Cardiac fibrosis under chronic pressure overload is an end-stage adverse remodeling of heart. However, current heart failure treatments barely focus on anti-fibrosis and the effects are limited. We aimed to seek for a cardiac abundant and cardiac fibrosis specific piRNA, exploring its underlying mechanism and therapeutic potential. Whole transcriptome sequencing and the following verification experiments identified a highly upregulated piRNA (piRNA-000691) in transverse aortic constriction (TAC) mice, TAC pig, and heart failure human samples, which was abundant in heart and specifically expressed in cardiac fibroblasts. CFRPi was gradually increased along with the progression of heart failure, which was illustrated to promote cardiac fibrosis by gain- and loss-of-function experiments in vitro and in vivo. Knockdown of CFRPi in mice alleviated cardiac fibrosis, reversed decline of systolic and diastolic functions from TAC 6 weeks to 8 weeks. Mechanistically, CFRPi inhibited APLN, a protective peptide that increased in early response and became exhausted at late stage. Knockdown of APLN in vitro notably aggravated cardiac fibroblasts activation and proliferation. In vitro and in vivo evidence both indicated Pi3k-AKT-mTOR as the downstream effector pathway of CFRPi-APLN interaction. Collectively, we here identified CFPPi as a heart abundant and cardiac fibrosis specific piRNA. Targeting CFRPi resulted in a sustainable increase of APLN and showed promising therapeutical prospect to alleviate fibrosis, rescue late-stage cardiac dysfunction, and prevent heart failure.

LncRNA CFRL aggravates cardiac fibrosis by modulating both miR-3113-5p/CTGF and miR-3473d/FN1 axis.

Cardiac fibrosis is a major type of adverse remodeling, predisposing the disease progression to ultimate heart failure. However, the complexity of pathogenesis has hampered the development of therapies. One of the key mechanisms of cardiac diseases has recently been identified as long non-coding RNA (lncRNA) dysregulation. Through in vitro and in vivo studies, we identified an lncRNA NONMMUT067673.2, which is named as a cardiac fibrosis related lncRNA (CFRL). CFRL was significantly increased in both mouse model and cell model of cardiac fibrosis. In vitro, CFRL was proved to promote the proliferation and migration of cardiac fibroblasts by competitively binding miR-3113-5p and miR-3473d and indirectly up-regulating both CTGF and FN1. In vivo, silencing CFRL significantly mitigated cardiac fibrosis and improved left ventricular function. In short, CFRL may exert an essential role in cardiac fibrosis and interfering with CFRL might be considered as a multitarget strategy for cardiac fibrosis and heart failure.

Targeting gut microbiota-derived kynurenine to predict and protect the remodeling of the pressure-overloaded young heart.

Pressure-overloaded left ventricular remodeling in young population is progressive and readily degenerate into heart failure. The aims of this study were to identify a plasma metabolite that predicts and is mechanistically linked to the disease. Untargeted metabolomics determined elevated plasma kynurenine (Kyn) in both the patient cohorts and the mice model, which was correlated with remodeling parameters. In vitro and in vivo evidence, combined with single-nucleus RNA sequencing (snRNA-seq), demonstrated that Kyn affected both cardiomyocytes and cardiac fibroblasts by activating aryl hydrocarbon receptors (AHR) to up-regulate hypertrophy- and fibrosis-related genes. Shotgun metagenomics and fecal microbiota transplantation revealed the existence of the altered gut microbiota-Kyn relationship. Supplementation of selected microbes reconstructed the gut microbiota, reduced plasma Kyn, and alleviated ventricular remodeling. Our data collectively discovered a gut microbiota-derived metabolite to activate AHR and its gene targets in remodeling young heart, a process that could be prevented by specific gut microbiota modulation.

Analysis of clinical features of neonates with congenital heart disease who develop necrotizing enterocolitis: a retrospective case-control study.

Background: Infants with congenital heart disease (CHD) are known to have higher rates of necrotizing enterocolitis (NEC). Although the etiology is recognized as distinct from the premature neonatal population, there is not a universal consensus regarding etiology or specific risk factors. To analyze the clinical features of neonates with CHD who develop NEC. Methods: A retrospective study of neonates with CHD in the cardiac intensive care unit (ICU) between 2015 and 2018 was performed, and modified Bell's criteria were used to diagnose NEC. Patients were divided into 2 groups according to ductal-dependent (DD) lesions, and were further stratified by Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) score and Aristotle score, to compare the differences. Results: Among 412 patients with CHD, 69 (16%) developed NEC. The incidence of NEC was notably higher among DD patients than among non-DD (nDD) patients (18.7% vs. 11.1%; P=0.04). Patients with RACHS-1 >2 also had a higher rate of NEC than did those with RACHS-1 ≤2 (19.49% vs. 9.29%; P=0.01). nDD patients who developed NEC were younger, had a lower gestational age (36.25±1.88 vs. 38.10±1.28 weeks; P=0.00), a lower weight (2.86±0.85 vs. 3.33±0.55 kg; P=0.01), and a lower birth weight (2.79±0.79 vs. 3.26±0.55; P=0.01) compared to the DD group. All nDD patients developed NEC after congenital heart surgery, while only 38 cases (76%), NEC occurred after heart surgery in the DD group. Four patients needed surgery for NEC in the DD group and RACHS-1 >2 group. Presence of NEC was not associated with an increased risk of mortality in any group. Conclusions: NEC is a common complication in neonates with CHD and can occur both before and after CHD operations. Likely there are varying mechanism for NEC in different forms of CHD. While NEC is more common in patients with DD CHD and those with more complex forms of CHD, there was no significant difference observed in weight-for-age Z-score (WAZ) between the DD group during follow-up.

Subepicardial lipoma of the posterior atrioventricular sulcus in children: a case report and review of the literature.

Cardiac lipoma is rarely reported in the pediatric population. We reported a case of subepicardial lipoma of the posterior atrioventricular sulcus in a child. The tumor was resected successfully and the patient recovered well after the operation.

Exosomes from 3T3-J2 promote expansion of tracheal basal cells to facilitate rapid epithelization of 3D-printed double-layer tissue engineered trachea.

Functional epithelization plays a pivotal role in maintaining long-term lumen patency of tissue-engineered trachea (TET). Due to the slow migration of autologous epithelium, spontaneous epithelization process of transplanted TET is always tardive. Seeding tracheal basal cells (TBCs) on TET before transplantation might be favorable for accelerating epithelization, but rapid expansion of TBCs in vitro is still relatively intractable. In this study, we proposed a promising expansion strategy which enables the TBCs to proliferate rapidly in vitro. TBCs were isolated from the autologous tracheal mucosae of rabbit, and co-cultured with exosomes derived from 3T3-J2 cells. After co-culture with exosomal component, TBCs could vigorously proliferate in vitro and retained their multi-potency. It was in stark contrast to that the single-cultured TBCs could only be expand to passage 2 in about 30 days, moreover, the most majority of single-cultured cells entered late apoptotic stage. On the other hand, a bionic tubular double-layer scaffold with good mechanical property and bio-compatibility was designed and fabricated by 3D printing technology. Then TET with bi-lineage cell-type was constructed in vitro by implanting autologous chondrocytes on the outer-layer of scaffold, and TBCs on the inner-layer, respectively. And then TET was pre-vascularized in vivo, and pedicled transplanted to restore long-segmental defect in recipient rabbits. It was found that the chondrocytes and TBCs seeded on double-layer scaffolds developed well as expected. And almost complete coverage with ciliated epitheliums was observed on the lumen surface of TET 2-week after operation, in comparison with that the epithelization of TET without pre-seeding of TBCs accomplished nearly 2-month after operation. In conclusion, the promising expansion strategy of TBCs together with 3D-printed double-layer scaffolds facilitate the rapid epithelization process of transplanted TET, which might be of vital significance for clinical and translational medicine.

Preoperative Morphological Prediction of Early Reoperation Risk After Primary Repair in Tetralogy of Fallot: A Contemporary Analysis of 83 Cases.

This study was conducted to investigate the pulmonary artery (PA) variations in tetralogy of Fallot (TOF) and preoperative morphological predictors for early reoperation. Eighty-three TOF patients and 20 children with normal PA were included. The TOF group was divided into two subsets according to whether or not reoperation was performed within 3 years postoperatively. Clinical information was obtained, along with computed tomography (CT)-based three-dimensional geometry of the PA. Morphological measurements of the length of the main PA branches, the angles between them, and the cross-sectional area of each segment of the PAs were acquired using computer software. Logistic regression and receiver operating characteristic curves were applied to analysis. The TOF group showed a significantly smaller PA size and irregular PA shape, with lower Nakata and McGoon indices, than the control group. The median bifurcation angle (angle-γ) was greater than 100° in the TOF group, as compared to 66.70° in the control group (P < 0.000). Residual obstruction of the infundibulum or PAs was the main reason for early reoperation in this series. The development of the main PA and left PA was poorer in the reoperation subset than in the non-reoperation subset (P ≤ 0.01). The preoperative angle-γ in the reoperation subset was larger than that in the non-reoperation subset (median, 117.8° vs. 112.0°, P = 0.026). Higher weight (OR = 0.372) and McGoon index (OR = 0.122) were protective factors, while larger angle-γ (> 114.8°, OR = 5.040) and angle-γ normalized by body surface area (BSA) (γ/BSA > 297.9, OR = 18.860) were risk factors. This study provides an intuitive perspective of PA anatomical variations in TOF. Larger preoperative PA bifurcation angle and γ/BSA were morphological risk predictors of postoperative reoperation in patients with TOF.

Elevated Arterial-Central Venous Carbon Dioxide Partial Pressure Difference Indicates Poor Prognosis in the Early Postoperative Period of Open Heart Surgery in Infants with Congenital Heart Disease.

BACKGROUND: Elevated arterial-central venous carbon dioxide partial pressure difference (AVCO2) may be an important marker to predict tissue and organ hypoperfusion in adults. We analyzed the hemodynamic data of infants with congenital heart disease who underwent corrective repair with cardiopulmonary bypass (CPB) to identify whether AVCO2 has clinical significance in early postoperative tissue hypoperfusion, occurrence of complications, and clinical outcomes. METHODS: Infants with clinical conditions of hypoperfusion, without volume responsiveness and with ineffective initial treatment, within 3 h of cardiac surgery were enrolled in this study. A pulse contour cardiac output catheter was used to monitor the cardiac index (CI). Eight measurements of arterial blood gas and central venous blood gas were taken within 42 h after surgery. Clinical data of all patients were recorded. RESULTS: A total of 69 children were enrolled in this study. Arteriovenous oxygen difference, AVCO2, lactic acid level, and vasoactive inotropic score in the hypoperfusion group (oxygen supply/oxygen consumption ratio [DO2/VO2] of ≤ 2) were significantly higher than those in the non-hypoperfusion group (DO2/VO2 > 2), while the CI in the hypoperfusion group was significantly lower than that in the non-hypoperfusion group. The cutoff value of AVCO2 to predict DO2/VO2 ≤ 2 was 12.3 within 42 h of surgery with area under the curve of 0.84. High AVCO2 is more likely to be associated with some complications and prolonged mechanical ventilation and length of stay in the intensive care unit. CONCLUSION: Elevated AVCO2 within 42 h of CPB in infants is associated with tissue and organ hypoperfusion and incidence of complications. Persistent or repeated increase in AVCO2 indicates poor prognosis.

Congenitally Corrected Transposition of the Great Arteries: Mid-term Outcomes of Different Surgical Strategies.

BACKGROUND: Optimal management for congenitally corrected transposition of the great arteries (ccTGA) is controversial. We applied different surgical strategies based on individual variations in our single-centered practice over 10 years, aming to describe the mid-term results. METHODS: From January 2008 to June 2021, 90 patients with ccTGA were reviewed and grouped by three different surgical strategies: 41 cases with biventricular correction as biventricular group, 11 cases with 1.5 ventricular correction as 1.5 ventricular group, and 38 cases with Fontan palliation as univentricular group. The mean age at primary surgery was 41.4 ± 22.7 months. Patients were followed for mortality, complications, reoperation, cardiac function, and valve status. RESULTS: The median follow-up period was 5.1 years (range, 1.5-12.5 years). The overall 10-year survival and freedom from reoperation rate was 86.7 and 82.4%, respectively. There were 3 early deaths and 3 mid-term deaths in the biventricular group, while 2 early deaths and 1 mid-term deaths were reported in the univentricular group. Although 1.5 ventricular group presented no death and the fewest complications, we still found similar mortality (p = 0.340) and morbidity (p = 0.670) among the three groups. The bypass time, aortic-clamp time, and ICU stay length were the longest in the biventricular group, followed by the 1.5 ventricular group (p < 0.001). However, in mid-term follow-up, biventricular and 1.5 ventricular groups both showed excellent cardiac function and obvious improvement of tricuspid regurgitation (p = 0.008 and p = 0.051, respectively). Fontan palliation provided acceptable mid-term outcomes as well, despite a lower ejection fraction. CONCLUSION: Satisfactory mid-term outcomes could be achieved for highly selected ccTGA patients using the whole spectrum of surgical techniques. Moreover, 1.5 ventricular correction, as a new emerging technique in recent years, might hold great promise in future practice.

Impact of 3D Printing on Short-Term Outcomes of Biventricular Conversion From Single Ventricular Palliation for the Complex Congenital Heart Defects.

Background: Although Fontan palliation seems to be inevitable for many patients with complex congenital heart defects (CHDs), candidates with appropriate conditions could be selected for biventricular conversion. We aimed to summarize our single-center experience in patient selection, surgical strategies, and early outcomes in biventricular conversion for the complex CHD. Methods: From April 2017 to June 2021, we reviewed 23 cases with complex CHD who underwent biventricular conversion. Patients were divided into two groups according to the development of the ventricles: balanced ventricular group (15 cases) and imbalanced ventricular group (8 cases). Early and short-term outcomes during the 30.2 months (range, 4.2-49.8 months) follow-up period were compared. Results: The overall mortality rate was 4.3% with one death case. In the balanced ventricular group, 6 cases received 3D printing for pre-operational evaluation. One case died because of heart failure in the early postoperative period. One case received reoperation due to the obstruction of the superior vena cava. In the imbalanced ventricular group, the mean left ventricular end-diastolic volume was (33.6 ± 2.1) ml/m2, the mean left ventricular end-diastolic pressure was 9.1 ± 1.9 mmHg, and 4 cases received 3D printing. No death occurred while one case implanted a pacemaker due to a third-degree atrioventricular block. The pre-operational evaluation and surgery simulation with a 3D printing model helped to reduce bypass time in the balanced group (p < 0.05), and reduced both bypass and aorta clamp time in the imbalanced group (p < 0.05). All patients presented great cardiac function in the follow-up period. Conclusion: Comprehensive evaluation, especially 3D printing technique, was conducive to finding the appropriate cases for biventricular conversion and significantly reduced surgery time. Biventricular conversion in selected patients led to promising clinical outcomes, albeit unverified long-term results.

Pulmonary Hypoplasia Resulting from Pulmonary Artery Banding in Infancy: A Neonatal Rat Model Study.

The aim of this study was to establish a neonatal rat model of decreased pulmonary blood flow (PBF) for studying pulmonary pathophysiological changes in newborn lung development with reduced PBF. Horizontal thoracotomy surgery with banding of the main pulmonary artery (PA) was performed on 30 rats in the PA banding (PAB) group and without banding on another 30 rats in the sham group within 6 h after birth. The body growth and mortality were recorded. Constriction of PA was checked by echocardiography on postnatal day 7 (P7). Lung morphology was assessed with computed tomography scanning and three-dimensional reconstruction. Histological differences of two groups were evaluated using hematoxylin and eosin (H&E) staining, Masson's trichrome staining, TdT-mediated dUTP nick-end labeling assay, and CD31 labeling with microscopic examination. PA ultrasound confirmed the establishment of constriction on P7. Relative to the sham group, the neonates' physical growth, survival fraction, and lung geometry volume were decreased in the PAB group over time (p < 0.05). Histologic appearance with reduced PBF characterized a markedly simplified alveolarization with noted lower radial alveolar count and alveolar septal thickness in the PAB group (p < 0.0001), pulmonary arteries with thinner/uneven membranous layers and smaller lumina. The deficient alveolar capillary bed, enhanced pulmonary collagen deposition, and increased apoptotic alveolar epithelium were significant in the PAB group compared to the sham group (p < 0.0001). A neonatal rat PAB model demonstrated that PBF reduction during early infancy impairs alveolarization and pulmonary microvasculature.

Neonatal Rabbit Model for Pressure-Overloaded Heart Failure and Preliminary Exploration of Mechanism.

BACKGROUND: This study aimed to establish a model of pediatric heart failure (PHF) with concomitant left ventricle pressure overload by transverse aortic constriction (TAC) and study the PHF mechanism primarily at the gene transcription level. METHODS: Twenty-four neonatal rabbits within 7 days after birth were randomly divided into sham (n = 8), moderate TAC (50% constriction, n = 8) and severe TAC (sTAC; 75% constriction, n = 8) groups. After the procedure transthoracic echocardiography was performed at 2, 4, and 6 weeks to measure left ventricle structure and function. Histologic staining and gene sequencing of left ventricle myocardial tissue were performed at 6 weeks. RESULTS: Six weeks after procedure transthoracic echocardiography showed that the pressure at the ligation of the aorta was 12.13 ± 0.95 mm Hg in the sTAC group, which was 26 times more than that of the sham group (P < .05), and left ventricular dilatation began to appear in the sTAC group. Gene sequencing showed significantly different microRNA expression between the sTAC and sham groups. Bioinformatics analysis among the 3 groups showed that the expression of ocu-miR-411-5p, ocu-miR-214-3p, and ocu-miR-432-5p was decreased in the sTAC group compared with the sham group (P < .05) and that the focal adhesion, insulin, and PI3K-Akt signaling pathways were also affected. CONCLUSIONS: Aortic constriction of 75% was optimal for the establishment of the PHF model. The expression of ocu-miR-411-5p, ocu-miR-214-3p, and ocu-miR-432-5p was significantly decreased, and the focal adhesion, insulin, and PI3K/AKT pathways may play significant roles in PHF progression.

One patient with an anomalous origin of the left pulmonary artery directly from the right ventricle: a case report.

BACKGROUND: The anomalous origin of one pulmonary artery is a rare malformation, which so far has mainly been found as an anomalous origin from a different site of the aorta, accounting for 0.12% of all congenital heart diseases. This case report introduced a very rare case of the anomalous origin of one pulmonary artery which had never reported in the clinic. CASE SUMMARY: A 2-year-old boy with a 6-month history of shortness of breath and recurrent respiratory infection, was diagnosed left pulmonary artery (LPA) directly arising from the right ventricle by transthoracic echocardiography and multidetector computed tomography without a deletion in the region of 22q11. Eventually, the LPA was further conformed that arised from the right ventricle during the operation, and was corrected with a well clinical outcome. DISCUSSION: The surgical technique for repair of this anomalous LPA was not difficult in our case. However, the embryonic development of the present case still could not be completely explained by the current embryologic postulates since it was a new malformation that never reported. Due to its rarity, there is still much to learn about the origin and development of the pulmonary arteries that possibly develop prenatally.

miR-381-abundant small extracellular vesicles derived from kartogenin-preconditioned mesenchymal stem cells promote chondrogenesis of MSCs by targeting TAOK1.

Small extracellular vesicles (sEVs) derived from mesenchymal stem cells have been shown to possess potent regenerative potential. In this study, we evaluated the chondrogenic effect of sEVs derived from kartogenin-preconditioned human umbilical cord mesenchymal stem cells (hUCMSCs). sEVs were isolated from the supernatants of KGN-preconditioned hUCMSCs (KGN-sEV) by gradient ultra-centrifugation, and internalized by native hUCMSCs, thereby inducing the chondrogenic differentiation. The underlying mechanism of KGN-sEV-induced chondrogenesis was explored by high-throughput sequencing and verified by transfection with the corresponding mimic and inhibitor. Sequencing identified the unique enrichment of a set of miRNAs in KGN-sEV compared with sEVs derived from unpreconditioned cells (un-sEV). Overexpression/inhibition in vitro and in vivo demonstrated that this chondrogenesis-inducing potential was primarily attributed to miR-381-3p, one of the most abundant miRNAs in KGN-sEV. Dual-luciferase reporter assays showed that miR-381-3p promoted chondrogenesis through direct suppression of TAOK1 by targeting its 3' untranslated region, thereby suppressing the Hippo signaling pathway. Collectively, our results highlight the regenerative potential of KGN-sEV to induce chondrogenic differentiation of MSCs, which is mainly achieved by delivering sEV-miR-381-3p, which targets TAOK1.

Chinese expert consensus on surgical treatment of congenital heart disease (4): pulmonary atresia with intact ventricular septum / 中国胸心血管外科临床杂志

@#Pulmonary atresia with intact ventricular septum (PA/IVS) is a rare congenital heart disease with high mortality. Due to the complexity and diversity of pathological anatomy, there is no uniform standard for the optimal surgical scheme of PA/IVS. In order to further standardize the surgical treatment strategy of PA/IVS, this expert consensus will focus on the evaluation of right ventricular anatomy and function, operation timing, operation mode and prognosis of PA/IVS. Through the synthesis of many domestic treatment experience, the Chinese expert consensus on PA/IVS surgical treatment has been finally formed.

Effect of off-pump pulmonary valvotomy as the initial surgery for pulmonary atresia with intact ventricular septum: A single-center clinical analysis / 中国胸心血管外科临床杂志

@#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.

Anatomic correction for congenitally corrected transposition of the great arteries and 10-year follow-up: A retrospective cohort study / 中国胸心血管外科临床杂志

@#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.

Integrated model for the prenatal diagnosis and postnatal surgical treatment of total anomalous pulmonary venous connection: A multidisciplinary collaborative experience and preliminary results.

BACKGROUND: This study aimed to evaluate an integrated model for the prenatal diagnosis and postnatal treatment of total anomalous pulmonary venous connection (TAPVC). METHODS: From January 2014 to December 2018, 11 patients were considered as a prenatally diagnosed group, who would accept the integrated model for prenatal diagnosis and postnatal treatment of TAPVC. Besides, 25 patients as postnatally diagnosed group underwent emergency surgery during the corresponding period at the same age. The perioperative status, survival and risk factors for death were compared between the two groups. RESULTS: In a prenatally diagnosed group, three pregnant women chose termination; eight patients followed the integrated model, and their newborns were rapidly transported to a children's hospital within 24 hours after birth. Other than one patient who was prenatally diagnosed with infracardiac type was later confirmed as a mixed type of TAPVC, the prenatal and postnatal diagnoses of the other seven patients were consistent. The 30-day, 1-year, and 5-year survival rates in the prenatally diagnosed group were 100%, 100%, and 100%, while those in the postnatally diagnosed group were 92%, 87.8%, and 87.8%, without significant difference (P > .05). Although Fisher's exact test indicated that an oxygen saturation <70% at admission might be an independent predictor of mortality (P < .01), none of the risk factors for death were significantly different by multivariate Cox regression analysis. CONCLUSION: The integrated model of prenatal diagnosis and postnatal treatment by multidisciplinary collaboration could lead to satisfactory outcomes, and prenatal diagnosis combined with postnatal oxygen saturation evaluation would facilitate early intervention for TAPVC.

Long-segmental tracheal reconstruction in rabbits with pedicled Tissue-engineered trachea based on a 3D-printed scaffold.

Long-segmental tracheal defects constitute an intractable clinical problem, due to the lack of satisfactory tracheal substitutes for surgical reconstruction. Tissue engineered artificial substitutes could represent a promising approach to tackle this challenge. In our current study, tissue-engineered trachea, based on a 3D-printed poly (l-lactic acid) (PLLA) scaffold with similar morphology to the native trachea of rabbits, was used for segmental tracheal reconstruction. The 3D-printed scaffolds were seeded with chondrocytes obtained from autologous auricula, dynamically pre-cultured in vitro for 2 weeks, and pre-vascularized in vivo for another 2 weeks to generate an integrated segmental trachea organoid unit. Then, segmental tracheal defects in rabbits were restored by transplanting the engineered tracheal substitute with pedicled muscular flaps. We found that the combination of in vitro pre-culture and in vivo pre-vascularization successfully generated a segmental tracheal substitute with bionic structure and mechanical properties similar to the native trachea of rabbits. Moreover, the stable blood supply provided by the pedicled muscular flaps facilitated the survival of chondrocytes and accelerated epithelialization, thereby improving the survival rate. The segmental trachea substitute engineered by a 3D-printed scaffold, in vitro pre-culture, and in vivo pre-vascularization enhanced survival in an early stage post-operation, presenting a promising approach for surgical reconstruction of long segmental tracheal defects. STATEMENT OF SIGNIFICANCE: We found that the combination of in vitro pre-culture and in vivo pre-vascularization successfully generated a segmental tracheal substitute with bionic structure and mechanical properties similar to the native trachea of rabbits. Moreover, the stable blood supply provided by the pedicled muscular flaps facilitated the survival of chondrocytes and accelerated epithelialization, thereby improving the survival rate of the rabbits. The segmental trachea substitute engineered by a 3D-printed scaffold, in vitro pre-culture, and in vivo pre-vascularization enhanced survival in an early stage post-operation, presenting a promising approach for surgical reconstruction of long segmental tracheal defects.

Rare Copy Number Variations Might Not be Involved in the Molecular Pathogenesis of PA-IVS in an Unselected Chinese Cohort.

Congenital heart defect (CHD) is one of the most common birth defects in China, while pulmonary atresia with intact ventricular septum (PA-IVS) is the life-threatening form of CHD. Numerous previous studies revealed that rare copy number variants (CNVs) play important roles in CHD, but little is known about the prevalence and role of rare CNVs in PA-IVS. In this study, we conducted a genome-wide scanning of rare CNVs in an unselected cohort consisted of 54 Chinese patients with PA-IVS and 20 patients with pulmonary atresia with ventricular septal defect (PA-VSD). CNVs were identified in 6/20 PA-VSD patients (30%), and three of these CNVs (15%) were considered potentially pathogenic. Two pathogenic CNVs occurred at a known CHD locus (22q11.2) and one likely pathogenic deletion located at 13q12.12. However, no rare CNVs were detected in patients with PA-IVS. Potentially pathogenic CNVs were more enriched in PA-VSD patients than in PA-IVS patients (p = 0.018). No rare CNVs were detected in patients with PA-IVS in our study. PA/IVS might be different from PA/VSD in terms of genetics as well as anatomy.