OBJECTIVES:The aims of our study were: (1) to determine the prevalence of asymptomatic hepatic steatosis and presumed nonalcoholic steatohepatitis, in our local population of obese Chinese children referred for medical assessment; and (2) to assess the correlation between severity of ultrasonographic hepatic steatosis and degree of obesity, insulin resistance and serum biochemical abnormalities. DESIGN: Cross-sectional study. METHODS: In total, 84 obese children, 25 girls and 59 boys with median age and body mass index (BMI) of 12.0 years (interquartile range (IR): 9.5-14.0) and 30.3 kg/m 2 (IR: 27.1-33.4), respectively, referred for medical assessment were studied. All subjects underwent physical examination, anthropometric and dual energy X-ray absorptiometry (DEXA) scan measurements and real-time ultrasonographic (US) examination of the liver. Fasting blood samples were collected for the measurement of liver function, hepatitis status, levels of serum glucose and insulin and lipid profile. Degree of fatty infiltration of the liver was graded according to ultrasonic appearance of liver echotexture, liver-diaphragm differentiation in echo amplitude, hepatic echo penetration and clarity of hepatic blood vessels. RESULTS: All recruited subjects had no history of alcohol abuse and tests for Hepatitis B or C virus were negative. Thorough examination showed all of them to be in general good health without signs of chronic liver disease. Hepatic steatosis identified by defined ultrasonic appearances was diagnosed in 65 subjects (77%); 17 girls and 48 boys. The severity of fatty liver was positively related to anthropometric measurements including BMI, waist and hip circumference, subscapular skinfold thickness; insulin resistance markers [QUICKI and homeostasis model assessment (HOMA)], and hypertriglyceridaemia. Multvariate ordinal regression analysis showed that BMI and raised alanine aminotransferase (ALT) were positively associated with fatty liver. Combination of hepatic steatosis with raised ALT (presumptive NASH) was found in 19 subjects (24%). This group of patients had significantly higher waist hip ratio and conicity index compared to those with isolated hepatic steatosis. Boys with presumed NASH were also found to have significantly higher insulin resistance. CONCLUSION: Nonalcoholic fatty liver disease (NAFLD) was common among our cohort of obese children referred for medical assessment. The prevalence of simple steatosis and presumed NASH was 77 and 24%, respectively. The severity of US steatosis was positively correlated with BMI, raised ALT, insulin resistance and hypertryglyceridaemia. Ultrasonography being noninvasive and readily available could be used for the monitoring of the progression of hepatic steatosis. Further longitudinal studies are required to determine the natural disease progression and the role of insulin resistance and other factors in the pathophysiology of NAFLD.

The aim of the current study was to review the aetiology of non-cystic fibrosis (CF) bronchiectasis from two tertiary paediatric respiratory units in order to determine how often making a specific aetiological diagnosis leads to a change in management, and to assess the contribution of computed tomography (CT) in determining the underlying diagnosis.The case records of all patients who were diagnosed as having bronchiectasis by CT, currently being seen at the Royal Brompton Hospital and Great Ormond Street Hospital for Children (London, UK), were reviewed. All patients had undergone extensive investigations, and the underlying aetiology and the area of pulmonary involvement (as seen on CT) were recorded. A total of 136 patients were identified; there were 65 young males and the group median (range) age was 12.1 yrs (3.1-18.1). Immunodeficiency, aspiration and primary ciliary dyskinesia accounted for 67% of the cases. In 77 (56%) children, the identification of a cause led to a specific change in management. There was no association between aetiology and the distribution of CT abnormalities.In conclusion, immunodeficiency and other intrinsic abnormalities account for the majority of cases of non-cystic fibrosis bronchiectasis seen in the current authors' units. Computed tomography scans do not contribute towards identifying the aetiology and, most importantly, a specific aetiological diagnosis frequently leads to a change in management.

Aims: (1) To determine the predominant pulmonary function abnormality in our population of obese children; and (2) to assess the correlation between the severity of lung function impairment and the degree of obesity as assessed by dual energy x ray absorptiometry (DEXA). Methods: Sixty four obese patients underwent physical examination, standardised pulmonary function tests (spirometry, lung volumes, and single breath diffusion capacity for carbon monoxide), and DEXA scan measurements. The trunk and subtotal (total − head) body fat mass were used as surrogate index of body adiposity. Results: Sixteen girls and 48 boys with median age and body mass index (BMI) of 12 years (interquartile range (IQR): 10-14) and 30.1 kg/m 2 (IQR: 27.2-32.8) respectively were studied. None of the patients had clinical evidence of cardiopulmonary disease. Reduction in functional residual capacity (median FRC 93% predicted, IQR: 68.5-116.5%) and impairment of diffusion capacity (median DLco 83.5% predicted, IQR: 70.0-100.7%) were the most common abnormalities in our cohort, being observed in 30 (46%) and 21 (33%) patients respectively. Obstructive ventilatory impairment was found in three patients. There was significant negative correlation between the degree of reduction of FRC but not DLco with DEXA scan measurements, but such a relation was not found when BMI was used as the indicator of obesity. Conclusion: Reduction in FRC and diffusion impairment were the commonest abnormalities found in our cohort of obese patients. Reduction in static lung volume was correlated with the degree of obesity.

Background: Unlike the adult sleep related disordered breathing (SDB) patients who are typically obese, the relation between obesity and childhood SDB is not clear. Aims: To investigate whether obese children are more at risk of obstructive SDB when compared to normal population, and whether this risk is potentiated by the presence of pharyngeal lymphoid tissue. Methods: Forty six obese children (age 10.8 (SD 2.3) years; BMI 27.4 (SD 5.1)), and 44 sex and age matched normal weight children (age 11.7 (SD 2.1) years; BMI 18 (SD 1.8)) were studied. All children underwent a set of physical examinations (including the upper airways) and sleep studies. Results: The obese children were different from the normal weight children in terms of type (predominantly obstructive), frequency, and severity of respiratory disturbances. Depending on the criteria used, 26% or 32.6% of obese children had SDB; 2.3% of normal controls had OAI >1 and 4.5% had RDI >5. Presence of SDB was related to presence of tonsils (size .2; range 0-4) (OR 12.67, 95% CI 2.14 to 75.17) and BMI (OR 1.20, 95% CI 1.08 to 1.33). Conclusions: Results suggest that obese children are at increased risk of obstructive SDB; the presence of any pharyngeal lymphoid tissue enlargement in obese children should therefore be aggressively managed.

Background:MiR-646 has been reported to be aberrantly expressed in human cancers. However, the underlying molecular mechanisms of action of miR-646 in gastric cancer (GC) have not yet been investigated.Methods:In vitro function of miR-646 in GC was evaluated using EdU assay, plate colony formation assay, and matrigel invasion assay. Real-time PCR or western blotting was performed to detect miR-646 and FOXK1 expressions. In vivo tumour growth and metastasis were conducted in nude mice.Results:MiR-646 expression was downregulated in GC tissues compared with adjacent normal tissues. Low miR-646 expression is associated with malignant progression. Transient transfection of GC cells with miR-646 inhibited their growth and migration. Moreover, miR-646 influenced the expression of epithelial–mesenchymal transition (EMT)-associated proteins. TGF-β1 treatment significantly suppressed the expression of miR-646 and overexpression of this microRNA counteracted the influence of the TGF-β1-induced EMT phenotype. In terms of the underlying mechanism, miR-646 directly targeted FOXK1. In vivo, it inhibited the FOXK1-mediated proliferation and EMT-induced metastasis. Consistently, inverse correlations were also observed between the expression of miR-646 and FOXK1 in human GC tissue samples. Furthermore, miR-646 regulated Akt/mTOR signalling after FOXK1.Conclusions:miR-646 inhibited GC cell proliferation and the EMT progression in GC cells by targeting FOXK1.

Aims: (1) To determine the pattern of respiratory impairment in children with thalassaemia major (TM); (2) to assess the relation between the degree of respiratory impairment and total body iron content. Methods: Twenty nine TM patients were recruited. All underwent physical examination, standardised pulmonary function tests (spirometry, lung volume, and single breath diffusion capacity for carbon monoxide), and magnetic resonance imaging measurements of the liver. Serum ferritin was measured. The signal intensity ratio of liver to that of paraspinal muscle (T1 weighted sequence) and serum ferritin were used as surrogate index of body iron content. Results: Sixteen boys and 13 girls (median age 14.2 years) were studied. None had clinical evidence of congestive heart failure. Sixteen had normal lung function. Impairment of diffusion capacity (median DL co 83.5% predicted) was the most common abnormality, being observed in 34% of patients. Pure restrictive and obstructive ventilatory impairment was found in one and two patients respectively. Five patients had a combination of ventilation and diffusion defects. There was no correlation between the degree of impairment of each respiratory abnormality and body iron content. Conclusion: Diffusion impairment was the commonest abnormality found in our cohort of paediatric TM patients. Our data did not support the notion that respiratory function impairment was correlated with body iron content.

Background: A study was undertaken to assess the correlation between cough frequency in asthmatic children with lung function and two non-invasive markers of airway inflammation. Methods: Thirty two children of median age 12.0 years (interquartile range (IQR) 9.5-13.4) with stable asthma were recruited. They underwent spirometric testing, exhaled nitric oxide (eNO) measurement, sputum induction for differential cell count, and ambulatory cough monitoring over 17 hours and 40 minutes. Coughing episodes were counted both as individual spikes and as clusters. Results: Complete cough frequency data were available in 29 children (90%) and their median forced expiratory volume in 1 second (FEV 1 ) and eNO were 88.5% (IQR 79.5-98) and 23.9 ppb (IQR 11.4-41.5), respectively. The median number of cough episodes was 14 (IQR 7.0-24.0) which was significantly higher than that of normal children (6.7 (IQR 4.1-10.5), p,0.001). Sputum induction was successful in 61% of the subjects; the median induced sputum eosinophil count was 0.05% (IQR 0-9.0). Cough frequency was found to have a significant positive correlation with eNO (Spearman's r = 0.781, p,0.001) but not with FEV 1 or sputum eosinophil count (r = 20.270, p = 0.157; r = 0.173, p = 0.508, respectively). Conclusions: Children with stable asthma have increased cough frequency compared with normal controls and cough frequency was greater during the day than at night. Cough may be a more sensitive marker of airway inflammation than simple spirometry.

Our results provide further evidence of the need for developing ethnic-specific WC charts and for recommending that a WHtR cutoff of 0.5 may not be appropriate to predict cardiometabolic risk in children of different ethnic groups.