Design, synthesis, and evaluation of 2,2'-bipyridyl derivatives as bifunctional agents against Alzheimer's disease.

Alzheimer's disease (AD) is a complex multifactorial neurodegenerative disease. Metal ion dyshomeostasis and Aß aggregation have been proposed to contribute to AD progression. Metal ions can bind to Aß and promote Aß aggregation, and ultimately lead to neuronal death. Bifunctional (metal chelation and Aß interaction) compounds are showing promise against AD. In this work, eleven new 3,3'-diamino-2,2'-bipyridine derivatives 4a-4k were synthesized, and evaluated as bifunctional agents for AD treatment. In vitro Aß aggregation inhibition assay confirmed that most of the synthesized compounds exhibited significant self-induced Aß1-42 aggregation inhibition. Among them, compound 4d displayed the best inhibitory potency of self-induced Aß1-42 aggregation with IC50 value of 9.4 µM, and it could selectively chelate with Cu2+ and exhibited 66.2% inhibition of Cu2+-induced Aß1-42 aggregation. Meanwhile, compound 4d showed strong neuroprotective activity against Aß1-42 and Cu2+-treated Aß1-42 induced cell damage. Moreover, compound 4d in high dose significantly reversed Aß-induced memory impairment in mice.

PLOD3 regulates the expression of YAP1 to affect the progression of non-small cell lung cancer via the PKCδ/CDK1/LIMD1 signaling pathway.

Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD3) is a crucial oncogene in human lung cancer, whereas protein kinase C δ (PKCδ) acts as a tumor suppressor. In this study, we aimed to explore the regulation by PLOD3 on the expression of YAP1 to affect the progression of non-small cell lung cancer (NSCLC) via the PKCδ/CDK1/LIMD1 signaling pathway. We found that PLOD3, CDK1, and YAP1 were highly expressed, while LIMD1 was poorly expressed in NSCLC tissues. Mechanistic investigation demonstrated that silencing PLOD3 promoted the cleavage of PKCδ in a caspase-dependent manner to generate a catalytically active fragment cleaved PKCδ, enhanced phosphorylation levels of CDK1, and LIMD1 but suppressed nuclear translocation of YAP1. Furthermore, functional experimental results suggested that loss of PLOD3 led to increased phosphorylation levels of CDK1 and LIMD1 and downregulated YAP1, thereby suppressing the proliferation, colony formation, cell cycle entry, and resistance to apoptosis of NSCLC cells in vitro and inhibiting tumor growth in vivo. Taken together, these results show that PLOD3 silencing activates the PKCδ/CDK1/LIMD1 signaling pathway to prevent the progression of NSCLC, thus providing novel insight into molecular targets for treating NSCLC.

Heat stress inhibits TLR4-NF-κB and TLR4-TBK1 signaling pathways in broilers infected with Salmonella Typhimurium.

With the global warming, the harm of heat stress (HS) to the breeding industry has become more common, which causes the decline of animal production performance and low immunity. This study aimed to analyze the effect of HS on the intestinal immune function of Salmonella-infected chickens. Fourteen-day-old broilers were divided into the following four groups of eight replicates: control (Control), heat stress (HS), Salmonella Typhimurium (ST), and heat stress + Salmonella Typhimurium (HS+ST). The broilers were subjected to a heat stress of 35 °C from 15 to 28 days of age. Salmonella Typhimurium (ST, 14028, 109 cfu/mL) was inoculated, via oral administration at 29 days of age, into ST and HS+ST group birds. On the 4th day after Salmonella Typhimurium administration, an increase in jejunum IgA levels was observed in chickens infected with Salmonella Typhimurium. Mechanistic regulation of TLR4-NFκB-NLRP3 and TLR4-TBK1 signaling by heat stress was evaluated in Salmonella Typhimurium-infected broilers. Heat stress markedly inhibited the expression of cytokines including TNF-α, IL-6, IL-1ß, NLRP3, caspase-1, NF-κB-p65, and p-NF-κB-p65, and the TLR4-TBK1 cytokines IFN-α, IFN-γ, p-IRF3, and p-TBK1 in jejunum of broilers infected with Salmonella Typhimurium. Collectively, our results demonstrate that heat stress can inhibit intestinal immune response by downregulating the expression of TLR4-NFκB-NLRP3 and TLR4-TBK1 signaling pathways in broilers infected with Salmonella Typhimurium.

Heat stress inhibits expression of the cytokines, and NF-κB-NLRP3 signaling pathway in broiler chickens infected with salmonella typhimurium.

High ambient temperature has potential influence on oxidative stress, or systemic inflammation affecting poultry production and immune status of chickens. Heat stress (HS) induces intestinal inflammation and increases susceptibility of harmful pathogens, such as Salmonella and Escherichia coli. Intestinal inflammation is a common result of body immune dysfunction. Therefore, we designed an experiment to analyze the effects of 35 ± 2 °C HS on salmonella infection in chickens through regulation of the immune responses. 40 broiler chickens were randomly divided into 4 groups: control group, heat stress (HS) group, salmonella typhimurium (ST) group and model group (heat stress + salmonella typhimurium, HS + ST). Birds in HS and model group were treated with 35 ± 2 °C heat stress 6 h a day and for 14 continuous days. Then, ST and model group birds were orally administrated with 1 mL ST inoculum (109 cfu/mL). Chickens were sacrificed at the 4th day after ST administration and ileum tissues were measured. We observed that heat stress decreased ileum TNF-α and IL-1ß protein expressions. Concomitantly heat stress decreased NLRP3 and Caspase-1 protein levels. The protein expressions of p-NF-κB-p65 and p-IκB-α in ileum. Heat stress also inhibited IFN-α, p-IRF3 and p-TBK1, showing a deficiency in the HS + ST group birds. Together, the present data suggested that heat stress suppressed intestinal immune activity in chickens infected by salmonella typhimurium, as observed by the decrease of immune cytokines levels, which regulated by NF-κB-NLRP3 signaling pathway.

Deletion of Dcf1 Reduces Amyloid-ß Aggregation and Mitigates Memory Deficits.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease. One of the pathologies of AD is the accumulation of amyloid-ß (Aß) to form senile plaques, leading to a decline in cognitive ability and a lack of learning and memory. However, the cause leading to Aß aggregation is not well understood. Dendritic cell factor 1 (Dcf1) shows a high expression in the entorhinal cortex neurons and neurofibrillary tangles in AD patients. OBJECTIVE: Our goal is to investigate the effect of Dcf1 on Aß aggregation and memory deficits in AD development. METHODS: The mouse and Drosophila AD model were used to test the expression and aggregation of Aß, senile plaque formation, and pathological changes in cognitive behavior during dcf1 knockout and expression. We finally explored possible drug target effects through intracerebroventricular delivery of Dcf1 antibodies. RESULTS: Deletion of Dcf1 resulted in decreased Aß42 level and deposition, and rescued AMPA Receptor (GluA2) levels in the hippocampus of APP-PS1-AD mice. In Aß42 AD Drosophila, the expression of Dcf1 in Aß42 AD flies aggravated the formation and accumulation of senile plaques, significantly reduced its climbing ability and learning-memory. Data analysis from all 20 donors with and without AD patients aged between 80 and 90 indicated a high-level expression of Dcf1 in the temporal neocortex. Dcf1 contributed to Aß aggregation by UV spectroscopy assay. Intracerebroventricular delivery of Dcf1 antibodies in the hippocampus reduced the area of senile plaques and reversed learning and memory deficits in APP-PS1-AD mice. CONCLUSION: Dcf1 causes Aß-plaque accumulation, inhibiting dcf1 expression could potentially offer therapeutic avenues.

Heat stress aggravates intestinal inflammation through TLR4-NF-κB signaling pathway in Ma chickens infected with Escherichia coli O157:H7.

Heat stress can decrease poultry performance indices, immune function, and intestinal development, which can reduce birds' innate protective mechanisms and may be more susceptible for pathogens. Ma chickens heat-stressed with 41°C for 12 h and recovered for 7 d had extremely low immunity. In this study, a susceptible chicken model induced by heat stress and then infected with Escherichia coli O157:H7 was established to explore the mechanisms of birds' intestinal immune function changes. Ma chickens in heat stress + E. coli (HS + E. coli) group were stressed at 41°C for 12 h and recovered for 7 d, then chickens in E. coli group and HS + E. coli group were orally administered with 1 mL E. coli O157:H7 (1 × 109 cfu/mL). Chickens were sacrificed at the fourth day after E. coli administration. Results showed that the HS + E. coli group had increased intestinal length and weight, had higher E. coli counts in cecum contents than the E. coli group. Heat stress also enhanced serum diamine oxidase and decreased IgA level in chickens infected by E. coli. Heat stress had protective effects in small intestinal morphology except for duodenum by using hematoxylin and eosin staining. Compared with the E. coli group birds, IL-1ß, TNF-α, and caspase-1 protein levels in the duodenum and ileum were significantly increased. Heat stress also can significantly enhance the gene and protein expression of Hsp70, TLR4, and NF-κB in the duodenum and ileum, respectively. The gene expression of Hsp70, TLR4, and NF-κB in the jejunum was not influenced, but the protein expression of Hsp70 and NF-κB was inhibited by heat stress. The results indicated heat stress can amplify the effect of E. coli on intestinal inflammatory injury of Ma chickens through increasing TLR4-NF-κB signaling pathway.

Diverse Enzymes With Industrial Applications in Four Thraustochytrid Genera.

Thraustochytrids are heterotrophic fungus-like protists that can dissolve organic matters with enzymes. Four strains, AP45, ASP1, ASP2, and ASP4, were isolated from the coastal water of Taiwan, and respectively identified as Aurantiochytrium sp., Schizochytrium sp., Parietichytrium sp., and Botryochytrium sp. based on 18S rRNA sequences. Transcriptome datasets of these four strains at days 3-5 were generated using Next Generation Sequencing technology, and screened for enzymes with potential industrial applications. Functional annotations based on KEGG database suggest that many unigenes of all four strains were related to the pathways of industrial enzymes. Most of all four strains contained homologous genes for 15 out of the 17 targeted enzymes, and had extra- and/or intra-cellular enzymatic activities, including urease, asparaginase, lipase, glucosidase, alkaline phosphatase and protease. Complete amino sequences of the first-time identified L-asparaginase and phytase in thraustochytrids were retrieved, and respectively categorized to the Type I and BPPhy families based on phylogenetic relationships, protein structural modeling and active sites. Milligram quantities of highly purified, soluble protein of urease and L-asparaginase were successfully harvested and analyzed for recombinant enzymatic activities. These analytical results highlight the diverse enzymes for wide-range applications in thraustochytrids.

Author Correction: Distribution pattern of leftventricular myocardial strain analyzed by a cine MRI based deformation registration algorithm in healthy Chinese volunteers.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Left ventricular function recovery in peripartum cardiomyopathy: a cardiovascular magnetic resonance study by myocardial T1 and T2 mapping.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is rare and potentially life-threatening; its etiology remains unclear. Imaging characteristics on cardiovascular magnetic resonance (CMR) and their prognostic significance have rarely been studied. We sought to determine CMR's prognostic value in PPCM by using T1 and T2 mapping techniques. METHODS: Data from 21 PPCM patients from our CMR registry database were analyzed. The control group comprised 20 healthy age-matched females. All subjects underwent comprehensive contrast-enhanced CMR. T1 and T2 mapping using modified Look-Locker inversion recovery and T2 prep balanced steady-state free precession sequences, respectively. Ventricular size and function, late gadolinium enhancement (LGE), myocardial T1 value, extracellular volume (ECV), and T2 value were analyzed. Transthoracic echocardiography was performed at baseline and during follow-up. The recovered left ventricular ejection fraction (LVEF) was defined as LVEF ≥50% on echocardiography follow-up after at least 6 months of the diagnosis. RESULTS: CMR imaging showed that the PPCM patients had severely impaired LVEF and right ventricular ejection fraction (LVEF: 26.8 ± 10.6%; RVEF: 33.9 ± 14.6%). LGE was seen in eight (38.1%) cases. PPCM patients had significantly higher native T1 and ECV (1345 ± 79 vs. 1212 ± 32 ms, P < 0.001; 33.9 ± 5.2% vs. 27.1 ± 3.1%, P < 0.001; respectively) and higher myocardial T2 value (42.3 ± 3.7 vs. 36.8 ± 2.3 ms, P < 0.001) than did the normal controls. After a median 2.5-year follow-up (range: 8 months-5 years), six patients required readmission for heart failure, two died, and 10 showed left ventricular function recovery. The LVEF-recovered group showed significantly lower ECV (30.7 ± 2.1% vs. 36.8 ± 5.6%, P = 0.005) and T2 (40.6 ± 3.0 vs. 43.9 ± 3.7 ms, P = 0.040) than the unrecovered group. Multivariable logistic regression analysis showed ECV (OR = 0.58 for per 1% increase, P = 0.032) was independently associated with left ventricular recovery in PPCM. CONCLUSIONS: Compared to normal controls, PPCM patients showed significantly higher native T1, ECV, and T2. Native T1, ECV, and T2 were associated with LVEF recovery in PPCM. Furthermore, ECV could independently predict left ventricular function recovery in PPCM.

Role of the overexpression of TRAF4 in predicting the prognosis of intrahepatic cholangiocarcinoma.

The incidence of intrahepatic cholangiocarcinoma (ICC) is progressively increasing worldwide, and its prognosis remains poor. Accumulating evidence has demonstrated that tumor necrosis factor receptor-associated factor 4 (TRAF4), an adaptor protein, is involved in the carcinogenesis and progression of several tumor types. However, the function of TRAF4 in predicting prognosis, and mediating migration and invasion of ICC remains to be elucidated. In the present study, immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to determine that the expression of TRAF4 at the mRNA and protein levels in ICC tissues was significantly higher compared with that in non­tumor tissues. The overexpression of TRAF4 was positively correlated with poor differentiation, regional lymphatic metastasis, and high tumor­node-metastasis staging. Inhibiting the expression of TRAF4 using small interfering RNA decreased the migration and invasion of ICC cells in vitro. In addition, the AKT inhibitor perifosine eliminated the effect of TRAF4 on the invasion and migration of ICC cells in vitro. Clinically, the overexpression of TRAF4 was correlated with shorter overall survival rate and elevated recurrence rate in patients with ICC. Furthermore, patients with ICC with a high expression of TRAF4 and lymphatic metastasis were closely associated with a poorer prognosis compared with the other groups. Multivariate analysis indicated that the overexpression of TRAF4 was an independent prognostic indicator for patients with ICC. It was identified that a high level of TRAF4 facilitated the invasiveness of ICC cells via the activation of AKT signaling. The overexpression of TRAF4 may be a prognostic biomarker and candidate therapeutic target for patients with ICC.

Down-regulation of miR-30a-3p/5p promotes esophageal squamous cell carcinoma cell proliferation by activating the Wnt signaling pathway.

AIM: To investigate the potential role of microRNA-30a (miR-30a) in esophageal squamous cell carcinoma (ESCC). METHODS: Expression of miR-30a-3p/5p was analyzed using microarray data and fresh ESCC tissue samples. Both in vitro and in vivo assays were used to investigate the effects of miR-30a-3p/5p on ESCC cell proliferation. Furthermore, Kyoto Encyclopedia of Genes and Genomes analysis was performed to explore underlying mechanisms involved in ESCC, and then, assays were carried out to verify the potential molecular mechanism of miR-30a in ESCC. RESULTS: Low expression of miR-30a-3p/5p was closely associated with advanced ESCC progression and poor prognosis of patients with ESCC. Knock-down of miR-30a-3p/5p promoted ESCC cell proliferation. Increased miR-30a-3p/5p expression inhibited the Wnt signaling pathway by targeting Wnt2 and Fzd2. CONCLUSION: Down-regulation of miR-30a-3p/5p promotes ESCC cell proliferation by activating the Wnt signaling pathway through inhibition of Wnt2 and Fzd2.

Distribution pattern of left-ventricular myocardial strain analyzed by a cine MRI based deformation registration algorithm in healthy Chinese volunteers.

The cine magnetic resonance imaging based technique feature tracking-cardiac magnetic resonance (FT-CMR) is emerging as a novel, simple and robust method to evaluate myocardial strain. We investigated the distribution characteristics of left-ventricular myocardial strain using a novel cine MRI based deformation registration algorithm (DRA) in a cohort of healthy Chinese subjects. A total of 130 healthy Chinese subjects were enrolled. Three components of orthogonal strain (radial, circumferential, longitudinal) of the left ventricle were analyzed using DRA on steady-state free precession cine sequence images. A distinct transmural circumferential strain gradient was observed in the left ventricle that showed universal increment from the epicardial to endocardial myocardial wall (epiwall: -15.4 ± 1.9%; midwall: -18.8 ± 2.0%; endowall: -22.3 ± 2.3%, P < 0.001). Longitudinal strain showed a similar trend from epicardial to endocardial layers (epiwall: -16.0 ± 2.9%; midwall: -15.6 ± 2.7%; endowall: -14.8 ± 2.4%, P < 0.001), but radial strain had a very heterogeneous distribution and variation. In the longitudinal direction from the base to the apex of the left ventricle, there was a trend of decreasing peak systolic longitudinal strain (basal: -23.3 ± 4.6%; mid: -13.7 ± 7.3%; apical: -13.2 ± 5.5%; P < 0.001). In conclusion, there are distinct distribution patterns of circumferential and longitudinal strain within the left ventricle in healthy Chinese subjects. These distribution patterns of strain may provide unique profiles for further study in different types of myocardial disease.

Effect of low-dose X-ray irradiation and Ti particles on the osseointegration of prosthetic.

Low-dose irradiation (LDI) exhibits a positive effect on osteoblasts and inhibitory effect of inflammation. Here, we test the hypothesis that LDI can promote osseointegration and inhibit the inflammatory membrane formation in the presence of titanium (Ti) particles. Endotoxin-free titanium particles were injected into rabbit, prior to the insertion of a Ti6-Al-4-V sticks pre-coated with hydroxyapatite. Two days after operation, both distal femurs of the animal were exposed to 0.5 Gy X-ray irradiation. All ani-mals were euthanized 8 weeks after the operation. The PINP concentration was determined at day 0, 2, 4, and 8 weeks after operation. Trabecular morphology around the implants 8 weeks after operation was assessed using micro-CT, then the maximum push out force of simples was assessed using biomechanics test. Five samples in each group were chosen for bone histomorphology study without decalcification 8 weeks after operation. The results confirmed that the LDI can significantly improve ingrowth of bone into the prosthetic interface and stability of the prosthesis when there was no wear particles. Although promotion effects for bone formation induced by LDI can be counteracted by wear particles, LDI can significantly inhibit the interface membrane formation around the implant induced by wear particles. Based on these results, we conclude that LDI may be useful for enhancing the stability of prosthesis when there are no wear particles and for inhibiting the interface membrane formation during the early stage of aseptic loosening in the presence of wear particles. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1688-1696, 2016.

[Reference Values for Left Ventricular Myocardial Strains Measured by Feature-tracking Magnetic Resonance Imaging in Chinese Han Population].

OBJECTIVES: To establish reference values for left ventricular (LV) myocardial strains in a cohort of healthy Chinese volunteers with feature tracking cardiac magnetic resonance imaging. METHODS: A total of 60 healthy volunteers were recruited, receiving a cardiac magnetic resonance imaging (CMR) examination at 3.0T scanner (Tim Trio, Magnetum, Siemens, Germany). A new feature tracking CMR software (Trufisp-strain, Siemens) was used to analyze left ventricular myocardial strain parameters, including radial, circumferential, longitudinal strain, systolic strain rate, and early diastolic strain rate. RESULTS: The image quality was sufficient to perform strain analysis.The reference values of global strain, global strain rate and segmental strains were obtained. A good inter- and intra-observer agreement was achieved in global strain analysis (except circumferential straininter-observer in apical level), with (37.7±9.6)% for LV global mean radial strain, (-18.4±3.3)% for circumferential strain and (-15.2±2.3%) for longitudinal strain, respectively.Age was positively correlated with global mean radial strain ( r=0.416, P<0.001) and negatively correlated with early diastolic strain rate (circumferential or longitudinal) and circumferential strain( r=-0.436, P<0.001; r=-0.326, P=0.011; r=-0.273, P=0.035, respectively). Women showed higher circumferential and longituinal strain values and lower systolic circumferential strain rate than men. The strain parameters were correlated with left ventricular ejection fraction (LVEF) ( P<0.05). CONCLUSIONS: FT-CMR (Trufisp-strain software) is a fast, convenient and highly reproducible method for analyzing left ventricular myocardial strains, which can sensitively detect gender and age differences. The reference values of LV myocardial strains can support further studies in the future.

Chromium level and intake from Chinese made tea.

Tea is a popular drink around the world. It is also one of the sources of metal intake. The objectives of this study were to assess chromium (Cr) intake from popular green, oolong, black and Pu-erh tea. In total, 128 Chinese made teas were analysed and concentration differences among four types of tea were explored. Black tea contained highest total Cr, which varied between 0.63 and 17.60 mg/kg. The lowest content was found in the green tea samples, between 0.26 and 1.30 mg/kg. Cr(III) and Cr(VI) in black tea were higher than in other types of tea. Cr(III), Cr(VI) and total Cr concentration in different tea infusions were also analysed. The results suggest that drinking tea is an effective way for Cr intake and the risk of adults and children being chronically intoxicated by tea infusions is low.

Benefits and risks from the national strategy for improvement of iodine nutrition: a community-based epidemiologic survey in Chinese schoolchildren.

OBJECTIVE: Mild to severe iodine deficiency has been documented in China since 1960. To eliminate this persisting iodine deficiency, legislation on universal salt iodization was introduced in 1995 as a long-term public health intervention strategy. We examined the urinary iodine excretion and the iodine content of drinking water and salt samples to assess the benefits and risks of this national strategy. METHODS: We examined the urinary iodine excretion of 1594 schoolchildren 8 to 10 y old from the 16 counties of China. The iodine content of 1097 drinking water and 4501 table salt samples also was assessed in these counties. The study was conducted from April 2009 through October 2010. Urinary iodine excretion and iodine levels in drinking water and table salt samples were measured based on the Sandell-Kolthoff reaction. Data were interpreted according to World Health Organization criteria. RESULTS: The median urinary iodine levels of the schoolchildren were 198.2, 277.2, 336.2, and 494.8 µg/L in areas with iodine levels lower than 10, 10 to 150, 150 to 300, and higher than 300 µg/L in the drinking water, respectively. The mean iodine level in the table salt specimens was 30.4 mg/kg, the coverage rate was 98.6%, and the qualified rate was 96.7%. The goiter prevalence was 8.0% in the areas with an iodine level higher than 150 µg/L in the drinking water. CONCLUSION: In each area, the median urinary iodine of schoolchildren was nearly or above 200 µg/L, which confirmed the effectiveness of the iodization strategy. However, in areas with an iodine content higher than 150 µg/L in the drinking water, the schoolchildren had more than adequate or excessive iodine intake, which was associated with the prevalence of goiter. Therefore, it is important to adjust the strategy of universal salt iodization control in China.

Bruns-Cushing nystagmus due to hypertensive unilateral paramedian pontine base infarction.

Bruns-Cushing nystagmus is unusually rare and is known to be related with cerebellopontine angle tumor. A 32-year-old male patient came to our emergency department 3 times because of dizziness, right upper limb ataxia, hypertension, and Bruns-Cushing nystagmus. Magnetic resonance imaging demonstrated left paramedian pontine infarction. In conclusion, Bruns-Cushing nystagmus not only indicates a cerebellopontine angle tumor but may also be associated with pontine infarction.

One stage surgical correction of congenital cardiac disease and congenital tracheal stenosis in infants and children.

OBJECTIVE: We describe our experience with patients undergoing one stage surgical correction of congenital cardiac disease and congenital tracheal stenosis. METHODS: Between February 2001 and June 2007, eight patients underwent one stage repair of congenital cardiac disease and congenital tracheal stenosis. Their ages ranged from 30 days to 3 years (mean 16.25 +/- 11.67 months) and weights from 4.2 to 10.5 kg (mean 8.24 +/- 2.16 kg). The congenital cardiac disease was treated during cardiopulmonary bypass, and the tracheal stenosis was corrected simultaneously. RESULTS: There was no operative mortality. One 4-month-old female who underwent polytetrafluroethylene patch tracheoplasty developed granulation tissue and died 3 months postoperatively of bronchial obstruction. The medium-term result of the remaining seven patients, after a mean follow-up of 50.4 months (range 9 to 76 months), was a stabile and complication-free clinical outcome. CONCLUSION: We advocate one stage surgical correction of congenital cardiac disease and congenital tracheal stenosis for the treatment of these conditions.