[Clinical characteristics and prognosis of infantile-onset glycogen storage disease type II in 16 Chinese patients].

OBJECTIVE: To explore the clinical characteristics and prognosis of infantile-onset glycogen storage disease type II (GSDII) in Chinese patients. METHODS: Sixteen children diagnosed as infantile-onset GSDII in Shanghai Children's Medical Center during Jan 2005 to Dec 2012 were recruited. Their disease history, presenting symptom, physical signs, biochemical tests and examinations of electrocardiogram and echocardiography were analyzed retrospectively. Follow-up data on motor development and survival were also collected and analyzed retrospectively. RESULTS: 16 cases were diagnosed as infantile-onset GSDII (10 males, 6 females), in which the peripheral blood levels of acidic α-glucosidase were remarkably low or completely absent. All of them were complicated with cardiac hypertrophy and left ventricular mass index was 161-616 g/m(2). Severe muscular weakness, hypotonia and development lag were found in all during the follow-up. Creatine kinase was detected in 15 patients and its level became significantly elevated in 14 of them. Alanine aminotransferase and aspartate aminotransferase were detected in 15 patients and their levels became significantly elevated in all of them. The median age was 3.6 (2.0-6.8) months at symptom onset and 6.5 (3.8-9.3) months at diagnosis. And 14 of them died during the follow-up and the median age at death was 9.0 (4.7-18.7) months. CONCLUSIONS: As a fatal disease, infantile-onset GSDIIhas the prominent clinical manifestations of progressive cardiac hypertrophy and muscular weakness or hypotonia. The clinical features and nature history of Chinese patients are similar as those reported in other countries. Detection of acidic α-glucosidase activity in peripheral blood is an effective way of screening for infantile-onset GSDII.

[Efficacy of percutaneous balloon aortic valvuloplasty for severe aortic valve stenosis in four infants under three months of age].

OBJECTIVE: To evaluate the outcome of percutaneous balloon aortic valvuloplasty (PBAV) for severe aortic valve stenosis in infants younger than 3 months of age. METHODS: Four infants under the age of 3 months (ranged from 34 to 87 days) underwent PBAV for severe aortic stenosis between June 2010 and March 2011 were included in this study. The weight of infants ranged from 2.8 to 4.8 kg. The peak systolic valve gradient, left ventricular ejection fraction (LVEF) and aortic regurgitation were measured in all patients just before and immediately after balloon dilation respectively. Patients were followed-up up to 1 month after PBAV. RESULTS: The aortic annulus diameter ranged from 7.0 to 8.8 mm. The ratio of balloon to aortic annulus diameter ranged from 0.86 to 1.00. PBAV was successful in all cases. The peak systolic valve gradient measured by Doppler echocardiography was (60.6 ± 15.2) mm Hg (1 mm Hg = 0.133 kPa) and LVEF was (47.6 ± 7.5)% before PBAV. Immediately after PBAV, the peak systolic valve gradient decreased to (29.5 ± 8.0) mm Hg (P < 0.01) and LVEF increased to (52.2 ± 18.9)% (P > 0.05). Two patients experienced significant bradycardia during PBAV and restored normal cardiac rhythm after cardiopulmonary resuscitation. At 1 month after PBAV, the peak systolic valve gradient measured by Doppler echocardiography was (36.5 ± 11.0) mm Hg (P < 0.05 vs. pre-PBAV) and LVEF was (81.0 ± 1.1)% (P < 0.01 vs. pre-PBAV). Only trivial to mild aortic regurgitation was detected post PBAV in the 4 patients. CONCLUSION: PBAV is a feasible palliative procedure for infants with isolated aortic valve stenosis without annular or ventricular hypoplasia.

[Efficacy of the transcatheter closure of perimembranous and muscular ventricular septal defects with the Amplatzer duct occluder II].

OBJECTIVES: To evaluate the feasibility and efficacy of transcatheter closure of perimembranous ventricular septal defects (pmVSD) with aneurysmatic formation and muscular ventricular septal defects (mVSD) with Amplatzer duct occluder II. METHODS: This retrospective analysis included 48 cases received transcatheter closure of pmVSD aneurysmatic formation or mVSD from February 2011 to March 2012 in our hospital (42 pmVSD with aneurysmatic formation and 6 mVSD). Median age was 5.2 years (range: 1.8 - 15 years), and median weight was 20.2 kg (range: 12 - 44 kg). Amplatzer duct occluder II was selected depending on the condition of ventricular septal defect. The device was implanted by antegrade or retrograde approach. Complications such as residual shunt, valvular regurgitation and arrhythmia were evaluated by echocardiography or angiography. Median follow-up was 9.5 months (range: 1 - 13 months). RESULTS: The mean ratio of pulmonary (Qp) to systemic (Qs) blood flow was 1.35 ± 0.15 before transcatheter closure. The diameter of exit hole of ventricular septal defects was (2.46 ± 0.53) mm measured by transthoracic echocardiography, and (2.35 ± 0.40) mm by angiography. Successful implantation of the device was achieved in 46 patients (96%) and unsuccessful in two cases due to acute aortic insufficiency. Forty-two (92%) patients were closed successfully, and trivial residual leak was evidenced in four patients and remained unchanged during follow-up. One patient with mVSD still had trivial residual shunt at 6 months post procedure. New trivial tricuspid insufficiency was observed in 1 patient (2.1%) during follow-up. Two patients developed procedural related left anterior fascicular block and remained unchanged during follow-up. CONCLUSIONS: pmVSD with aneurysm and mVSD could be successfully treated with Amplatzer duct occluder II. However, the long waist and large disc of the device could interfere with tricuspid valve function and cause tricuspid insufficiency.

Detecting 22q11.2 deletion in Chinese children with conotruncal heart defects and single nucleotide polymorphisms in the haploid TBX1 locus.

BACKGROUND: Conotruncal heart defects (CTDs) are present in 75-85% of patients suffering from the 22q11.2 deletion syndrome. To date, no consistent phenotype has been consistently correlated with the 22q11.2 deletions. Genetic studies have implicated TBX1 as a critical gene in the pathogenesis of the syndrome. The aim of study was to determine the incidence of the 22q11.2 deletion in Chinese patients with CTDs and the possible mechanism for pathogenesis of CTDs. METHODS: We enrolled 212 patients with CTDs and 139 unrelated healthy controls. Both karyotypic analysis and multiplex ligation-dependent probe amplification were performed for all CTDs patients. Fluorescence in situ hybridization was performed for the patients with genetic deletions and their relatives. The TBX1 gene was sequenced for all patients and healthy controls. The χ2 and Fisher's exact test were used in the statistical analysis. RESULTS: Thirteen of the 212 patients with CTDs (6.13%) were found to have the 22q11.2 deletion syndrome. Of the 13 cases, 11 presented with a hemizygous interstitial microdeletion from CLTCL1 to LZTR1; one presented with a regional deletion from CLTCL1 to DRCR8; and one presented with a regional deletion from CDC45L to LZTR1. There were eight sequence variants in the haploid TBX1 genes of the del22q11 CTDs patients. The frequency of one single nucleotide polymorphism (SNP) in the del22q11 patients was different from that of the non-del patients (P < 0.05), and the frequencies of two other SNPs were different between the non-del CTDs patients and controls (P < 0.05). CONCLUSIONS: CTDs, especially pulmonary atresia with ventricular septal defect and tetralogy of Fallot, are the most common disorders associated with the 22q11.2 deletion syndrome. Those patients with both CTDs and 22q11.2 deletion generally have a typical or atypical deletion region within the TBX1 gene. Our results indicate that TBX1 genetic variants may be associated with CTDs.

Green economic efficiency and its influencing factors in China from 2008 to 2017: Based on the super-SBM model with undesirable outputs and spatial Dubin model.

Due to the pressure of global ecological degradation, the coordination of economic increase and ecological protection has drawn attention from policymakers and practitioners. Green economic efficiency (GEE) is a comprehensive index to measure economic, social, and environmental development. As China is the second-biggest economy in the world with high-energy consumption, it is necessary to investigate its green economy efficiency. In this paper, we innovatively adopt a super-SBM (slacks-based measure) model with undesirable outputs to calculate the GEE in 30 provinces of China between 2008 and 2017, and then comprehensively apply a spatial Dubin model (SDM) to investigated its influencing factors. The results showed that the overall GEE in China during the study period was at a low level with significant regional differences. The inter-regional GEE generally showed a gradient decreasing pattern of "East-Middle-West", which demonstrates a gradual decline from the East to the West in China. The trend of the national GEE initially dropped and then gradually stabilized over the study period. Foreign trade dependence and direct investment had significant positive effects on the GEE, while the secondary industry and urbanization level had a significant negative effect.

[Frequency of 22q11 deletions in children with isolated conotruncal defects].

OBJECTIVE: The frequency of the 22q11.2 deletion syndrome is increasing worldwide. The cardiovascular anomalies are one of the most frequent clinical manifestations in this syndrome. This study was designed to determine the frequency of 22q11.2 deletions in a prospectively ascertained sample from children with isolated conotruncal defects in China. METHODS: Twenty-four children with isolated conotruncal defects were prospectively enrolled and screened for the presence of 22q11.2 deletions using fluoresence in situ hybridization. The 24 patients consisted of two cases of persistent truncus arteriosus (PTA), five cases of pulmonary atresia/ventricular septal defect (PA/VSD), thirteen cases of tetralogy of Fallot (TOF), and four cases of double outlet right ventricle (DORV). RESULTS: Only 1 of the 24 patients had 22 q11.2 deletions. The frequency of 22q11.2 deletions (4.2%) was lower than that reported by other authors. CONCLUSIONS: Although 22q11.2 deletion is common in syndromic conotruncal anomalies, it is rare in isolated conotruncal anomalies.

[Effects of chronic hypoxia on the expression of calmodulin and calcicum/calmodulin-dependent protein kinase II and the calcium activity in myocardial cells in young rats].

OBJECTIVE: Calcium plays an important role in the impairment of heart function and arrhythmia under the condition of acute hypoxia, but the mechanism is different from that of chronic hypoxia. This study aimed to evaluate the effect of chronic hypoxia on the expression of calmodulin (CaM) and calcicum/calmodulin-dependent protein kinase II (CaMKII) and the calcium activity in myocardial cells through an animal model of chronic hypoxia in order to get a deeper sight into the mechanism. METHODS: A chronic hypoxia model of the rat was prepared by hypoxia exposure (FiO2=10%). The expression of mRNA and protein of CaM and CaMKIIgamma and CaMKIIdelta in myocardial cells were measured by RT-PCR and Western Blot in normal rats and hypoxia rats 1 and the 3 weeks after exposure. The cardiac cells of the rats from the control group and the 3-week hypoxia group were cultured. Then the intracellular calcium activity was detected using laser confocal equipment. The effect of CaMKII on the calcium activity in myocardial cells was evaluated by the application of KN-62 (CaMKII specific inhibitor). RESULTS: The expression of CaM, CaMKIIgamma and CaMKIIdelta mRNA in myocardial tissues increased in hypoxia rats compared with that in normal controls (P<0.01). The CaM and CaMKIIdelta mRNA expression was different between the 1-week and the 3-week hypoxia groups (P<0.01). The laser confocal demonstrated that the amplitude of calcium wave in hypoxic myocardial cells was not different from that in normal controls, but the duration of calcium wave in hypoxic myocardial cells was longer than that in normal controls (P<0.01). After KN-62 use, the amplitude of calcium wave decreased and the duration of calcium wave prolonged significantly. CONCLUSIONS: The contents of CaM and CaMKII in myocardial cells increased under condition of chronic hypoxia as a compensation to keep calcium homeostasis in a certain time. With more prolonged hypoxia time, abnormal electric activities of heart occurred and the heart function may be impaired.

Paris Saponins enhance radiosensitivity in a gefitinib-resistant lung adenocarcinoma cell line by inducing apoptosis and G2/M cell cycle phase arrest.

Acquired resistance to epidermal growth factor inhibitors has been reported to be associated with cross­resistance to radiation. Paris Saponins (PSs) exert a wide range of pharmacological activities, including cell apoptosis induction, multidrug resistance inhibition, angiogenesis inhibition and tumor cell migration by modulating various signaling pathways. The present study aimed to investigate the radiosensitization effects of PSII, PSVI and PSVII in a gefitinib­resistant PC­9­ZD lung adenocarcinoma cell line, and the possible mechanism underlying their function. A clonogenic assay was performed to determine the effects of PS radiosensitization on the PC­9­ZD cell line. The cell cycle was analyzed by flow cytometry, and cell apoptosis was analyzed with Annexin V/propidium iodide and Hoechst staining. Protein expression levels were detected by western blotting. The results of the present study revealed a significant increase in PC­9­ZD cell line radiosensitivity following treatment with PSs. PSs induced G2/M cell cycle phase arrest and apoptosis of the irradiated PC­9­ZD cells. Notably, the expression levels of B cell lymphoma 2 (Bcl­2) were downregulated, and those of caspase­3, Bcl­2­associated X protein (Bax) and p21/Waf1/Cip1 were upregulated following treatment with PSs. The present results demonstrated that PSs induced radiosensitivity in gefitinib­resistant cells by inducing G2/M phase arrest and by enhancing the apoptotic response via the modulation of caspase­3, Bax, Bcl­2 and p21/Waf1/Cip1 expression.

[Hearing screening for high-risk newborns].

OBJECTIVE: To investigate the morbidity of congenital hearing impairment among high-risk newborns and the relevant pathogenic factors. METHODS: Initial screening of hearing by otoacoustic emission (OAE) was conducted among 208 high-risk newborns, 130 males and 78 females after they were born and the second screening was conducted by OAE was conducted 42 days after those with positive results were examined by auditary brainstem response (ABR). RESULTS: All of the 208 newborns received the initial screening with a screening rate of 100%, and 130 newborns received the second screening with a screening rate of 62.5%. The positive rates in the initial screening and second screening were 34.61% and 7.14% respectively. Six newborns were examined by ABR and 2 of them were diagnoses as with hearing impairment with a prevalence rate of 1.78%. The factors, such as sex, age, and Apgar score affected the initial screening results. CONCLUSION: The most proper time for initial hearing screening is around the 42nd day after birth. High-risk newborns should receive regular test even though they pass the initial screening. A special follow-up system should be constructed for the high-risk newborns.

Paris saponin I induces apoptosis via increasing the Bax/Bcl-2 ratio and caspase-3 expression in gefitinib-resistant non-small cell lung cancer in vitro and in vivo.

Polyphyllins, a major component of Rhizoma paridis, have been extensively used in non-small cell lung cancer (NSCLC). The aim of the present study was to evaluate the effects of Paris saponin I (PSI) on a panel of gefitinib-resistant NSCLC cell lines and its inhibition of tumor growth in a nude mouse model. The MTT assay was used to assess growth inhibition. The cell cycle was analyzed using flow cytometry and apoptosis was assessed using Annexin V/propidium iodide staining. The morphology of the apoptotic cells was determined by transmission electron microscopy. The protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-3 were detected using western blot analysis. In addition, the glucose metabolism in tumor-bearing mice was evaluated using 18F-fludeoxyglucose (FDG) micro-positron emission tomography imaging. The PSI-induced growth inhibition rate was observed to significantly increase in a time- and dose-dependent manner. Furthermore, PSI induced significant G2/M-phase arrest and apoptosis. The expression levels of Bcl-2 decreased, while those of Bax and caspase-3 increased following PSI treatment. 18F-FDG-uptake in the PSI treatment groups was significantly decreased compared with that in the control group in vivo. In conclusion, PSI is a potent antitumor agent that acts by inhibiting the proliferation of gefitinib-resistant cells, and has potential as a candidate for a natural drug for gefitinib-resistant therapy. PSI-induced apoptosis, which occurred via multiple pathways, including G2/M-phase arrest and upregulation of the Bax/Bcl-2 ratio and caspase-3 expression, ultimately led to cell death and tumor inhibition.

[Transcatheter closure of patent ductus arteriosus with the new Amplatzer Duct OccluderII].

OBJECTIVE: To evaluate the indications, methodology and results of the transcatheter closure of patent ductus arteriosus (PDA) with the new Amplatzer Duct Occluder II (ADO-II). METHOD: Totally 51 patients underwent transcatheter closure of PDA with the new ADO-II. The devices were delivered by 4F or 5F sheath through arterial or venous side respectively. The descending aorta angiography and transthoracic echocardiography was performed to evaluate the device position, residual shunt and complications caused by the device during and after implantation. RESULT: Forty-nine patients had successful transcatheter closure of the PDA without significant residual shunts and artery obstruction during the short-term follow-up. One patient received the ADO-II dislodgment and first generation ADO re-implantation for the obvious descending aortal obstruction caused by ADO-II. Another patient had the ADO-II dislodgment and left pulmonary artery shaping surgery, because the ADO-II implantation led to obstruction of the left pulmonary artery. Both the obstructions in these two patients were ameliorated afterwards. CONCLUSION: The transcatheter closure using the ADO-II is safe and effective for the non-window type PDA with a small size.

[Clinical presentation and therapeutic outcomes of carnitine deficiency-induced cardiomyopathy].

OBJECTIVE: Carnitine deficiency has been associated with progressive cardiomyopathy due to compromised energy metabolism. The objective of this study was to investigate clinical features of carnitine deficiency-induced cardiomyopathy and the therapeutic efficacy of L-carnitine administration. METHOD: Between January 2010 and December 2011, filter-paper blood spots were collected from 75 children with cardiomyopathy. Free carnitine and acylcarnitine profiles were measured for each individual by tandem mass spectrometry (MS/MS). For those in whom carnitine deficiency was demonstrated, treatment was begun with L-carnitine at a dose of 150 - 250 mg/(kg·d). Clinical evaluation, including physical examination, electrocardiography, chest x-ray, echocardiography and tandem mass spectrometry, was performed before therapy and during follow-up. RESULT: Of 75 cardiomyopathy patients, the diagnosis of carnitine deficiency was confirmed in 6 patients, which included 1 boy and 5 girls. Their age ranged from 0.75 to 6 years. Free carnitine content was (1.55 ± 0.61) µmol/L (reference range 10 - 60 µmol/L). Left ventricular end-diastolic diameter (LVDd) was (5.04 ± 0.66) cm and left ventricular ejection fraction (LVEF) was (38.5 ± 10.5)%. After 10 - 30 d therapy of L-carnitine, free carnitine content rose to (30.59 ± 15.02) µmol/L (t = 4.79, P < 0.01). LVDd decreased to (4.42 ± 0.67) cm (t = 4.28, P < 0.01) and LVEF increased to (49.1 ± 7.6)% (t = 6.59, P < 0.01). All patients received follow-up evaluations beyond 6 months of treatment. Clinical improvement was dramatic. LVEF returned to normal completely in all the 6 patients. LVDd decreased further in all the 6 patients and returned to normal levels in 3 patients. No clinical signs or symptoms were present in any of the 6 patients. The only complications of therapy had been intermittent diarrhea in 1 patient. CONCLUSION: Tandem mass spectrometry is helpful to diagnose carnitine deficiency and should be performed in all children with cardiomyopathy. L-carnitine has a good therapeutic effect on carnitine deficiency-induced cardiomyopathy.

[Adenosine for pulmonary vasodilator testing in children with idiopathic pulmonary arterial hypertension].

OBJECTIVE: The assessment of pulmonary vascular reactivity plays an important role in the management of idiopathic pulmonary arterial hypertension (IPAH). The aim of this study was to explore the indications and methodology of pulmonary vasodilator testing in children with IPAH. METHODS: From October 2009 to June 2011, a cohort of pediatric patients with IPAH in WHO functional classes II to III were enrolled in the study. Right heart catheterization was performed in all patients. After baseline hemodynamics were obtained, adenosine infusions were started at a dose of 50 µg/(kg·min), increased by 25 µg/(kg·min) at 2 min intervals to a maximum of 250 µg/(kg·min) or until a positive acute response. RESULTS: A total of 15 patients with IPAH were enrolled in the study. The mean age of the patients was 6.3 yrs. Mean pulmonary artery pressure (mPAP) was (67.1 ± 15.9) mm Hg. Pulmonary capillary wedge pressure (PCWP) was (9.7 ± 2.9) mm Hg. Pulmonary vascular resistance index (PVRI) was (17.9 ± 7.5) Wood U·m(2). Three patients were responders, defined as a fall in mPAP of at least 10 mm Hg to a pressure level of 40 mm Hg or lower. Twelve patients were nonresponders according to the same criteria. Five out of the 15 patients experienced adverse effects, including chest discomfort (n = 1), systemic hypotension (n = 3) and bradycardia (n = 1). All side effects abated within 30-60 s of the discontinuation of the adenosine infusion. CONCLUSION: Adenosine is an effective vasodilator in children with IPAH and can be used for safe and rapid assessment of vasodilator reserve in these patients.

[The parents' opinions on screening program regarding newborn hearing].

OBJECTIVE: To investigate opinions on screening of newborn hearing from parent's and its influence to parents and their families. METHODS: Parents were divided into two groups and were given the same questionnaire. Those parents whose babies had passed the first test were in the first group, and those parents whose babies failed the test were in the second group. RESULTS: Most of the parents showed their ignorance to hearing screening with about 97.5% of parents admitted they had little knowledge of hearing screening. 93.06% of the parents showed positive attitude to the screening after being informed of the test. 59.73% of the parents thought the test results were reliable. 73.12% of the parents whose babies showed negative result at the first-test, thought the results were accurate. There were only 38.19% of the parents whose babies failed the first test held the same opinion. We also found that there were some disagreement among 78% of the parents who believed that the positive screening results might cause additional psychological stress on them and therefore affecting their normal family life. CONCLUSIONS: Being informed of the screening, parents showed awareness of the test and were willing to cooperate. They believed the test was beneficial to their babies. Some parents whose babies did not pass the first screening test were often doubtful to the results and refused to be followed up. Therefore, we should improve our diagnostic technology to reduce the negative effects of the test. The results of our investigation suggested that the newborn hearing screening was applicable in our country.