[Phenotypic and genotypic analysis of a girl carrying a 2q22.3 microduplication encompassing the MBD5 gene].

OBJECTIVE: To carry out single nucleotide polymorphism (SNP)-based chromosome microarray analysis (CMA) for a boy featuring global developmental delay. METHODS: The SNP array was conducted for the child, and real-time PCR was used to validate its result and identify the origin of pathological copy number variants. RESULTS: SNP array revealed that the patient has carried a de novo 2.5 Mb duplication at 2q22.3q23.3, which encompassed ACVR2A, KIF5C, MBD5, EPC2, LYPD6, LYPD6, MMADHC and ORC4 genes. Literature review suggested that the MBD5 gene from the duplicated region may have predisposed to the global developmental delay shown by the girl. CONCLUSION: The patient's clinical phenotype was consistent to that of 2q23 duplication, for which the MBD5 gene may play a key role. CMA has provided an important tool for the diagnosis of patients with global developmental delay.

Rho/ROCK Pathway Regulates Migration and Invasion of Esophageal Squamous Cell Carcinoma by Regulating Caveolin-1.

BACKGROUND Esophageal squamous cell carcinoma (ESCC) is a common cancer with poor prognosis. Caveolin-1 (Cav1) and Rho/ROCK pathway play important roles in tumor metastasis, separately. However, less research was focused on the relationship between Cav1 and Rho/ROCK in ECSS metastasis. Therefore, we investigated the relationship between Cav1 and Rho/ROCK pathway in ESCC metastasis. MATERIAL AND METHODS Cav1 and phosphorylated Cav1 (PY14Cav1) were examined in ESCC and in adjacent and non-tumorous tissues from ESCC patients by immunohistochemistry (IHC). Small interfering RNA (siRNA) targeting Cav1 or Rho/ROCK inhibitor was used to treat EC109, Eca109, TE1, and TE13 cells. Western blotting (WB) was used to detect Cav1 and PY14Cav1 expression. The wound healing scratch test and transwell assays were used to assess migration and invasion. RESULTS Cav1 and PY14Cav1 were gradually expressed at higher levels in ECSS than in adjacent and non-tumor tissues as ESCC stage and lymphatic metastasis increased, and this difference was significant (P<0.05). Cav1 was expressed at higher levels in TE1 and TE13 than in EC109 and Eca109, while PY14Cav1 was enhanced in TE1 and TE13 cells but not in EC109 and Eca109, and the difference was significant (P<0.05). TE1 and TE13 had significantly (P<0.05) stronger motility, migratory, and invasion abilities than EC109 and Eca109 cells. Silencing Cav1 decreased PY14Cav1 expression in TE1 and TE13 cells, as well as suppressing the migration and invasion of all ECSS cells, and these differences were significant (P<0.05). Suppressing the Rho/ROCK pathway obviously inhibited Cav1 and PY14Cav1 expressions, as well as significantly (P<0.05) decreasing migration and invasion of ESCC cells. CONCLUSIONS Cav1 and PY14Cav1 were positively correlated with ESCC lymphatic metastasis and cancer stages. Rho/ROCK pathway activation promoted ESCC metastasis by regulating Cav1.

Analysis of Prescription Compliance and Influencing Factors in Cardiac Rehabilitation after Surgery in Children with Congenital Heart Disease Based on Generalized Trust Theory.

AIMS: To understand the compliance, influencing factors, and action path of family cardiac rehabilitation exercise prescriptions for children after congenital heart disease surgery. METHODS AND RESULTS: A random sampling method was used to select 200 pediatric patients and their parents from a pediatric hospital in Shanghai. Among them, 57 cases (28.5%) of children's families followed the cardiac rehabilitation exercise prescription. Path analysis showed that peak oxygen uptake exerted a negative impact on the compliance of family cardiac-rehabilitation prescriptions for patients after congenital heart disease surgery through doctor-patient trust, with a standardized path coefficient of -0.246 (P = 0.001). Disease-related knowledge exerted a positive effect on the compliance of family cardiac-rehabilitation prescriptions for children after congenital heart surgery through doctor-patient trust, with a standardized path coefficient of 0.353 (P < 0.001). The dimension of friend support in social support had a direct positive effect on the compliance of family cardiac-rehabilitation prescriptions for children after cardiac surgery, with a standardized path coefficient of 0.641 (P = 0.006). CONCLUSION: The compliance of cardiac rehabilitation exercise prescription in children with congenital heart disease is not good and is affected by many factors, and there is a complex path relationship between various factors; the kilogram oxygen consumption of the child, the disease-related knowledge of the caregiver, and social support all play important roles in the compliance of the child's family's health prescription. REGISTRATION: SCMCIRB-K2021002-1.

Improving long-term care and outcomes of congenital heart disease: fulfilling the promise of a healthy life.

Advances in the prevention, diagnosis, and treatment for congenital heart disease (CHD), the most common birth defect in China, have drastically improved survival for individuals with the disease. However, China's current health system is not well prepared to manage the growing population of people with CHD and their complex medical needs, which range from early detection of the condition and intervention for physical, neurodevelopmental, and psychosocial impairment, to long-term management of major complications and chronic health problems. Health disparities caused by long-standing regional differences in access to care pose challenges when major complications such as pulmonary hypertension arise, and when individuals with complex CHD become pregnant and give birth. Currently, no data sources track neonates, children, adolescents, and adults with CHD in China and delineate their clinical characteristics and use of health resources. This scarcity of data should warrant attention from the Chinese Government and relevant specialists in the field. In the third paper of the Series on CHD in China, we summarise key literature and current data to identify knowledge gaps and call for concerted efforts by the government, hospitals, clinicians, industries, and charitable organisations to develop an actionable, lifelong framework of congenital cardiac care that is accessible and affordable for all individuals with CHD. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Pharmacokinetics of treprostinil in children with functional single-ventricle pulmonary arterial hypertension: a randomized controlled trial.

BACKGROUND: Application of Treprostinil (TRE) in the patients with single ventricle (SV) physiology is very limited, and the optimal dose for children has not been determined. In this study, we aimed to analyze plasma samples to assess the attainment of clinically therapeutic concentrations of TRE and its efficacy and safety in the treatment of pediatric functional SV pulmonary arterial hypertension (FSV-PAH).. METHODS: Pediatric patients with FSV-PAH were recruited in this study. IV TRE at an initial rate of 5 ng/kg/min was administered through the femoral vein with an increase in rate to 10 ng/kg/min every 30 minuntil the aiming dose of 80 ng/kg/min had been reached. The drug was gradually discontinued after 12 h of treatment at a stable dose. The mean postoperative pulmonary artery pressure (mPAP), pulmonary-to-systemic arterial pressure ratio (Pp/Ps), and the ratio between arterial oxygen partial pressure and inhaled oxygen concentration (PaO2/FiO2) were used to evaluate the efficacy of TRE treatment. A multiple linear regression model was used to explore the relevant factors associated with TRE blood concentration. RESULTS: A total of eight patients were enrolled in the investigation, with an age range of 2.5-9.9 years. The median stable dose of TRE was 70 ng/kg/min with a range of 55-75 ng/kg/min. The median subliminal dose was 55 ng/kg/min with a range of 25-75 ng/kg/min. A linear relationship was established between the TRE dose and the plasma concentration. TRE blood concentrations were associated with dose and patient height. After TRE treatment, mPAP, Pp/Ps, and PaO2/FiO2 were significantly improved (P<0.05). CONCLUSIONS: A linear relationship was found between the blood concentration of TRE and its dose. IV TRE was an effective therapy without serious side effects in pediatric patients with FSV-PAH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02865733.

[Effect of prone or spine position on mechanically ventilated neonates after cardiac surgery with acute lung injury].

OBJECTIVE: To compare the efficacy and safety ventilated with pressure support ventilation (PSV) or neurally adjusted ventilatory assist (NAVA) in neonates undergoing open-heart surgery with acute lung injury (ALI) in spine and prone positions. METHODS: Fifteen neonates with a mean age of (15 +/- 9) days and a mean weight of (3.5 +/- 0.6) kg underwent open-heart surgery with ALI from July to December in 2009 were enrolled in this study. After hemodynamic stabilization ventilated with pressure regulated volume control (PRVC-base), all cases were ventilated with PSV and NAVA both in spine (SP) and prone (PP) positions for 60 minutes in a randomized crossover trial respectively. The hemodynamics, blood gas analysis, airway pressure, electrical activity of diaphragm (EAdi) and asynchrony index (AI) during every mode were recorded. RESULTS: The heart rate, systolic blood pressure and central venous pressure were stable in every mode. The peak inspiratory pressure and mean airway pressure in every mode had no significant difference but were significantly lower than in PRVC-base either in spine or prone position. The respiratory rate in PSV and NAVA with prone position was more rapid than in spine position and in PRVC-base (P < 0.05). But there was no significant difference in minute ventilation (MV) for each mode. The oxygenation index was higher in NAVA or PSV in both positions versus PRVC-base [(200 +/- 60) mm Hg in PRVC-base, (272 +/- 76) mm Hg in PSV-SP, (308 +/- 90) mm Hg in PSV-PP, (347 +/- 84) mm Hg in NAVA-SP and (365 +/- 87) mm Hg in NAVA-PP respectively, P < 0.01]. The oxygenation index was significantly higher in NAVA-PP than in PSV-SP (P < 0.05) while PaCO(2) was in normal range and had no significant difference for any mode. The minimal EAdi in NAVA-PP was significant lower than that in PSV-SP [(0.2 +/- 0.1) microV vs (0.5 +/- 0.2) microV, P < 0.05]. The AI of NAVA either in spine or in prone position was 0. It was significantly lower than that in PSV-SP [(21.5 +/- 4.8)%, P < 0.01] and PSV-PP [(22.4 +/- 3.4)%, P < 0.01]. CONCLUSION: Especially in a prone position, NAVA demonstrates a better synchrony in ALI neonates after cardiac surgery. It helps to provide a better oxygenation for the patients.

Hypoxia-induced cytosolic calcium decrease is mediated primarily by the forward mode of Na(+)/Ca(2+) exchanger in smooth muscle cells of fetal ductus arteriosus.

Closure of the ductus arteriosus (DA) after birth, essential for postnatal adaptation, is initiated by the transition from hypoxia to normoxia. The current study investigated how hypoxia affects the level of cytosolic calcium ([Ca(2+)](i)) in fetal lamb DA smooth muscle cells (DASMCs) and the role of calcium pumps in this process. The [Ca(2+)](i) variation in response to acute hypoxia was determined spectrofluorometrically with fura-3-AM in cultured fetal DASMCs. Interventions using chemicals or solutions including thapsigargin, vanadate, KB-R7943, alkaline PH9.0 solution, or Na(+)-free medium were administered when samples were exposed to acute hypoxia. The results show that [Ca(2+)](i) decreased dramatically under acute hypoxia. This decrease was not attenuated completely by an inhibitor of sarcoplasmic/endoplasmic reticulum Ca(2+) adenosine triphosphatase (ATPase) (SERCA), a blocker of plasma membrane Ca(2+) ATPase (PMCA), or an inhibitor and activator of the reserve mode of the Na(+)/Ca(2+) exchanger (NCX). In contrast, KT-R9743, an inhibitor of the forward mode of NCX at a high concentration (30 microm), greatly diminished the hypoxia-induced [Ca(2+)](i) decrease in fetal DASMCs. These results suggest that a hypoxia-induced Ca(2+) decrease in fetal DASMCs results from cytosolic Ca(2+) efflux mediated primarily by the forward mode of NCX.

[Outcome of oral bosentan in children with congenital heart disease associated pulmonary arterial hypertension].

OBJECTIVE: To investigate the outcome of dual endothelin receptor antagonist bosentan in children with congenital heart disease (CHD) associated pulmonary arterial hypertension (PAH). METHODS: A total of 32 children were recruited into this prospective and observational study. Among them, there were 18 cases with left-to-right shunt and 14 cases with elevated pulmonary vascular resistance (PVR) in functional single ventricle (FSV). All the cases were treated with oral bosentan, initiated from 90 days before or 8 years after operation, and were followed up periodically to analyze the clinical outcome and monitor its side effects. RESULTS: In the left-to-right shunt group, pulmonary arterial pressure (PAP) was measured at (57 +/- 26), (52 +/- 31) and (46 +/- 22) mm Hg after oral bosentan therapy at 1, 2 and 3 months respectively. The measurements significantly decreased as compared with the pre-dosing level of (74 +/- 15) mm Hg (P < 0.05). After a 3-months therapy of bosentan, World Health Organization functional class (WHO FC) improved significantly (P < 0.01). In the elder cases, the 6-minute walking distance after a 3-month bosentan therapy significantly increased as compared with the pre-dosing level, i. e. (497 +/- 56) vs (424 +/- 31) m (P < 0.05). In the FSV group, as compared with the pre-dosing level, the transcutaneous oxygen saturation increased significantly in the last follow-up during bosentan exposure, i. e. (86 +/- 5)% vs (78 +/- 6)% (P < 0.01). WHO FC improved significantly (P < 0.01) and the incidence of facial edema and pleural effusion was significant lower (P < 0.05) in the last follow-up for the treatment group. Patients tolerated bosentan well and no significant rise in hepatic transaminases was observed. CONCLUSIONS: Bosentan is safe in treating CHD associated PAH in children. In left-to-right shunt cases, oral bosentan can reduce PAP and improve both WHO FC and exercise capacity. And it can also improve WHO FC and transcutaneous oxygen saturation in FSV and reduces the occurrence of elevated PVR-related complications.

Effect of flow rate, negative pressure, and duration of modified ultrafiltration on hemodynamics and inflammatory mediators.

The objective of this study was to evaluate the effect of flow rate, negative pressure, and duration on modified ultrafiltration (MUF). Eighty children weighing less than 10 kg with congenital heart disease were randomly divided into four groups: group C (conventional MUF); group H (high flow rate MUF); group P (high negative pressure MUF); and group L (long duration, high flow rate MUF). The changes in body weight, hematocrit, and hemodynamics were recorded. Tumor necrosis factor and interleukin-6 were measured before bypass, bypass stop, and MUF cessation. The durations of MUF in groups H and P were significantly shorter than in the other two groups; the volume filtered in group L was much greater than in the other three groups. The changes of bodyweight, heart rate, blood pressure, and hematocrit were similar in all groups. The increased extent of inflammatory mediators was a little lower in group L. Modified ultrafiltration can reverse hemodilution and improve cardiac function even with high flow rate or negative pressure. Prolonging the duration of MUF can filter out more inflammatory mediators, but the increased trend cannot be reversed in 15 minutes.