Jinghao Zheng

Meta Analysis of the Association between MTHFR C677T Polymorphism and the Risk of Congenital Heart Defects

Methylenetetrahydrofolate reductase (MTHFR) polymorphism C667T has been associated with congenital malformation; this common missense mutation in the MTHFR gene may reduce enzymatic action, and may be involved in the etiology of congenital heart defects (CHD). The aim of this study was to investigate the relationship of the MTHFR C677T polymorphism with the risk of CHD in children with CHD and their parents by meta‐analysis. Studies were identified by searching electronic literature for papers before 2011, focusing on MTHFR C667T and the risk of CHD. All data were analyzed using the fixed effects model in Cochrane Review Manager 5.1.1. Twenty eligible case‐control and family‐based studies were included. Overall analysis yielded pooled odds ratios (OR) of 1.55 (95%CI 1.25–1.93), 1.84 (95%CI 1.23–2.74) and 1.20 (95%CI 0.94–1.54) for fetal, paternal and maternal MTHFR TT genotypes in case‐control studies, respectively, but yielded a summarized OR of 0.9 (95%CI 0.97–1.12) in family‐based studies. Our results suggested that the fetal and paternal MTHFR C667T gene may be associated with an increased occurrence of CHD. Further larger studies should be performed to investigate the interaction between maternal genetic polymorphism, folic acid intake and hyperhomocysteinemia, and the development of CHD.

Electrospun gelatin/polycaprolactone nanofibrous membranes combined with a coculture of bone marrow stromal cells and chondrocytes for cartilage engineering.

Electrospinning has recently received considerable attention, showing notable potential as a novel method of scaffold fabrication for cartilage engineering. The aim of this study was to use a coculture strategy of chondrocytes combined with electrospun gelatin/polycaprolactone (GT/PCL) membranes, instead of pure chondrocytes, to evaluate the formation of cartilaginous tissue. We prepared the GT/PCL membranes, seeded bone marrow stromal cell (BMSC)/chondrocyte cocultures (75% BMSCs and 25% chondrocytes) in a sandwich model in vitro, and then implanted the constructs subcutaneously into nude mice for 12 weeks. Gross observation, histological and immunohistological evaluation, glycosaminoglycan analyses, Young’s modulus measurement, and immunofluorescence staining were performed postimplantation. We found that the coculture group formed mature cartilage-like tissue, with no statistically significant difference from the chondrocyte group, and labeled BMSCs could differentiate into chondrocyte-like cells under the chondrogenic niche of chondrocytes. This entire strategy indicates that GT/PCL membranes are also a suitable scaffold for stem cell-based cartilage engineering and may provide a potentially clinically feasible approach for cartilage repairs.

Involvement of a novel GATA4 mutation in atrial septal defects

Atrial septal defect (ASD) is one of the most common types of congenital heart disease and is associated with a significant increase in the morbidity and mortality of affected individuals. Accumulating evidence indicates that genetic defects play important roles in the pathogenesis of congenital ASD. However, ASD is genetically heterogeneous and the genetic determinants for ASD in the majority of the patients remain to be identified. In this study, the entire coding region of GATA4, a gene encoding a zinc-finger transcription factor crucial to embryogenesis, was initially sequenced in 120 unrelated patients with ASD. The available relatives of patients carrying the identified mutation and 200 ethnicity-matched unrelated control individuals were genotyped. The functional characteristics of the GATA4 mutant were compared to its wild-type counterpart using a luciferase reporter assay system. A novel heterozygous missense GATA4 mutation, p.G21V, was identified in 2 unrelated families with ASD, which was not detected in the control population nor reported in the human gene mutation database. Alignment of multiple GATA4 proteins displayed that the affected amino acid residue was highly conserved across species. Functional analysis showed that the p.G21V GATA4 mutation was associated with a decreased transcriptional activity. The findings underscore the pathogenic link between compromised GATA4 function and congenital ASD, providing new insight into the molecular mechanism involved in this common form of congenital cardiovascular anomalies.

Total Anomalous Pulmonary Venous Connection: The Current Management Strategies in A Pediatric Cohort of 768 Patients

Background: Total anomalous pulmonary venous connection (TAPVC) is a rare form of congenital heart disease. This study describes current surgical treatment strategies and experiences in a cohort of patients from 2 congenital cardiac centers in Shanghai and Guangdong in China. Methods: This retrospective study included 768 patients operated on between 2005 and 2014. Although most patients (n=690) underwent conventional repair, a sutureless technique was used in 10% (n=78) of cases. A multilevel mixed-effects parametric survival model and a competing-risk analysis were used to analyze associated risk factors for death and recurrent pulmonary venous obstruction (PVO), respectively. Kaplan-Meier analysis was used to analyze the overall survival. The Nelson-Aalen cumulative risk curve was used to compare distributions of time with recurrent PVO. Results: The mean surgical age and weight were 214.9±39.2 days and 5.4±3.6 kg, respectively. Obstructed TAPVC (PVO) was documented in 192 (25%) of the 768 patients. There were 38 intraoperative deaths and 13 late deaths. A younger age at the time of repair (P=0.001), mixed (P=0.004) and infracardiac (P=0.035) TAPVC, preoperative PVO (P=0.027), prolonged cardiopulmonary bypass time (P<0.001), and longer duration of ventilation (P=0.028) were associated with mortality. The median follow-up was 23.2 months (range; 1–112 months). Among the 717 survivors, recurrent PVO was observed in 111 patients (15%). Associated risk factors for recurrent PVO included preoperative PVO (P<0.001), infracardiac TAPVC (P<0.001), mixed TAPVC (P=0.013), and prolonged cardiopulmonary bypass time (P<0.001). Sutureless technique was associated with a lower restenosis rate compared with conventional repair in patients with preoperative PVO (P=0.038), except in newborn patients (P=0.443). Reintervention for restenosis was performed in 24 patients. The function of most survivors (91%) was classified according to the New York Heart Association as functional class I or II. Conclusions: Surgical correction in patients with TAPVC with a biventricular anatomy can achieve an acceptable outcome. Risk factors such as a younger age at the time of repair, infracardiac and mixed TAPVC, and preoperative PVO were associated with a poorer prognosis.

Electrospun collagen–poly(L-lactic acid-co-ε-caprolactone) membranes for cartilage tissue engineering

AIMnTo study the feasibility of electrospun collagen-poly(L-lactic acid-co-ε-caprolactone) (collagen-PLCL) membranes for cartilage tissue engineering.nnnMATERIALS & METHODSnCharacteristics and mechanical properties of collagen-PLCL membranes were analyzed. The cell affinity of collagen-PLCL membranes with chondrocytes was also assessed. Then, the cell-scaffold constructs were engineered with collagen-PLCL membranes seeded chondrocytes by a sandwich model. After culture for 1 week in vitro, the constructs were implanted subcutaneously into nude mice for 4, 8 and 12 weeks, followed by evaluation of the quality of neocartilage.nnnRESULTSnCollagen-PLCL membranes exhibited excellent balanced properties without cytotoxicity. With the extension of implantation time in vivo, the constructs revealed more cartilage-like tissue especially at 8 and 12 weeks. The Youngs modulus of the constructs also significantly increased and neared that of native cartilage at 12 weeks postimplantation.nnnCONCLUSIONnWe suggest that collagen-PLCL membranes facilitate the formation of cartilage and thus may represent a promising scaffold for cartilage tissue engineering.

Novel NKX2-5 Mutations in Patients With Familial Atrial Septal Defects

Atrial septal defect (ASD) is a common cardiovascular malformation and an important contributor to substantial morbidity and mortality. Increasing evidence demonstrates that mutated NKX2-5, a gene encoding a homeobox transcription factor crucial to cardiogenesis, is a significant genetic determinant for congenital ASD. Nevertheless, the genetic basis for ASD in a majority of ASD patients remains largely unknown. In the current study, the entire coding region of NKX2-5 was sequenced initially for 58 unrelated probands with familial ASD. The relatives of the probands harboring identified mutations and 200 unrelated control individuals were subsequently genotyped. Three novel heterozygous NKX2-5 mutations (p.P43GfsX59, p.C46xa0W, and p.S179F) were identified respectively in three families with autosomal dominantly inherited ASD. These mutations, absent in 200 control individuals, cosegregated with ASD in the families that had complete penetrance. The findings expand the spectrum of mutations in NKX2-5 linked to ASD and contribute to genetic counseling, clinical interventions, and prenatal prevention of ASD for individuals with genetic susceptibility.

Evaluation of Early Macrophage Activation and NF-κB Activity in Pulmonary Injury Caused by Deep Hypothermia Circulatory Arrest: An Experimental Study

This study aimed to analyze changes in nuclear factor-kappa B (NF-κB), inflammation factors, and macrophages in pulmonary tissue under deep hypothermia circulatory arrest (DHCA) at different time points, which can be used to infer the role of early macrophage activation and NF-κB activity in pulmonary injury. The possible pathogenic mechanisms of DHCA-induced pulmonary injury were investigated in this study to provide an experimental basis for clinical lung protective strategies. Piglets (nxa0=xa012) were randomly divided into 2 groups, with 6 piglets in each group. The control group had ambient temperature cardiopulmonary bypass (CPB), and the experimental group had DHCA. Both groups had conventional CPB with 30xa0min of parallel circulation. Changes in NF-κB and inflammatory factors were examined in each group at 6 different time points. At 0.5xa0h after ischemia–reperfusion, NF-κB expression in the nucleus of pulmonary tissue reached its peak, and brown-stained nuclei were mainly polymorphonuclear antibodies. At 1xa0h after ischemia–reperfusion, plasma tumor-necrosis factor (TNF)-α in the experimental group was significantly increased compared with that before reperfusion (Pxa0<xa00.05). The plasma levels of interleukin (IL)-8 and IL-6 in the experimental group were significantly increased at 1.5xa0h after ischemia–reperfusion compared with the levels before reperfusion (Pxa0<xa00.05). Early activation of NF-κB under DHCA might play an important role in DHCA-induced pulmonary injury.

Tissue-engineered trachea from a 3D-printed scaffold enhances whole-segment tracheal repair

Long segmental repair of trachea stenosis is an intractable condition in the clinic. The reconstruction of an artificial substitute by tissue engineering is a promising approach to solve this unmet clinical need. 3D printing technology provides an infinite possibility for engineering a trachea. Here, we 3D printed a biodegradable reticular polycaprolactone (PCL) scaffold with similar morphology to the whole segment of rabbits’ native trachea. The 3D-printed scaffold was suspended in culture with chondrocytes for 2 (Group I) or 4 (Group II) weeks, respectively. This in vitro suspension produced a more successful reconstruction of a tissue-engineered trachea (TET), which enhanced the overall support function of the replaced tracheal segment. After implantation of the chondrocyte-treated scaffold into the subcutaneous tissue of nude mice, the TET presented properties of mature cartilage tissue. To further evaluate the feasibility of repairing whole segment tracheal defects, replacement surgery of rabbits’ native trachea by TET was performed. Following postoperative care, mean survival time in Group I was 14.38u2009±u20095.42 days, and in Group II was 22.58u2009±u200916.10 days, with the longest survival time being 10 weeks in Group II. In conclusion, we demonstrate the feasibility of repairing whole segment tracheal defects with 3D printed TET.

Cell sources for trachea tissue engineering: past, present and future.

Trachea tissue engineering has been one of the most promising approaches to providing a potential clinical application for the treatment of long-segment tracheal stenosis. The sources of the cells are particularly important as the primary factor for tissue engineering. The use of appropriate cells seeded onto scaffolds holds huge promise as a means of engineering the trachea. Furthermore, appropriate cells would accelerate the regeneration of the tissue even without scaffolds. Besides autologous mature cells, various stem cells, including bone marrow-derived mesenchymal stem cells, adipose tissue-derived stem cells, umbilical cord blood-derived mesenchymal stem cells, amniotic fluid stem cells, embryonic stem cells and induced pluripotent stem cells, have received extensive attention in the field of trachea tissue engineering. Therefore, this article reviews the progress on different cell sources for engineering tracheal cartilage and epithelium, which can lead to a better selection and strategy for engineering the trachea.

Arterial Switch Operation with Coronary Arteries from a Single Sinus in Infants

Abstractu2002 Background: The implantation of a coronary artery (CA) is critical for the arterial switch operation (ASO) done to treat complete transposition of the great arteries (TGA). Coronary artery abnormalities are risk factors for both early and late mortality after surgery. In this study, the methodology and effects of ASO surgery with coronary arteries from a single sinus were evaluated. Methods and Results: From March 1999 to June 2006, 31 patients were treated with ASO with coronary arteries from a single sinus in our hospital. They aged 11 hours ˜ 16 months (2.8 ± 3.9 months) and weighted 2.3 ˜7.8Kg (3.1 ± 2.5Kg). 27 cases had TGA and a ventricular septal defect (VSD), and 4 had TGA and an intact ventricular septum (IVS). During surgery, a CA button was implanted in the new proximal aorta with “trapdoor” technique or by inverting 90 degrees dorsally; pericardium or arterial augmentation was implanted at the base of the new major artery. The mortality rate after surgery was 25.8%. After 2‐5 years of follow‐up, 2 cases with residual shunting recovered spontaneously, 2 cases had residual pulmonary artery obstruction (30‐56 mmHg), and none of the patients had any significant changes in myocardial ischemia. Conclusion: The implantation of an abnormal coronary artery is practical and feasible; it can reduce both the occurrence of twisting and deforming in the coronary artery after implantation, as well as myocardial ischemia after surgery. Thus, this could improve the surgical success and cure rates.