HIF1α Elevations at Tissue and Serum Levels and Their Association With Metabolic Disorders in Children With Obesity.

OBJECTIVE: We aimed to examine the expression profile and circulating level of hypoxia-inducible factor 1 alpha (HIF1α) in children and the relationships with metabolic disorders. METHODS: A total of 519 children were recruited, with paired subcutaneous and omental adipose tissues collected from 17 children and serum samples from the remaining children. All children underwent anthropometric and biochemical analyses. The mRNA, protein, and serum levels of HIF1α were determined by real-time PCR, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. RESULTS: Both HIF1α mRNA and protein levels, especially in omental adipose tissue, were increased in overweight or obese (OV/OB) children (P < .05). Likewise, serum HIF1α level was remarkably higher in OV/OB children than in normal-weight children (P < .05). Serum HIF1α level was positively correlated with BMI z-score, fat mass percentage, waist to height ratio, systolic blood pressure, alanine aminotransferase, total triglycerides, uric acid, and homeostasis model assessment of insulin resistance (IR). Furthermore, a binary logistic regression analysis of serum HIF1α level indicated that the risks for IR, nonalcoholic fatty liver disease (NAFLD), and metabolic syndrome remained significant in the presence of all potential confounding variables. Finally, the area under the receiver operating characteristic curves for serum HIF1α level in children who were diagnosed with IR, NAFLD, and metabolic syndrome were 0.698 (95% CI, 0.646-0.750; P < .001), 0.679 (95% CI, 0.628-0.731; P < .001), and 0.900 (95% CI, 0.856-0.945; P < .001). CONCLUSION: HIF1α expression is higher in the adipose tissue, especially omental, of children with obesity than in children with normal weight. Elevated serum HIF1α level is associated with adiposity and metabolic disorder, which may predict a higher risk of obesity complications.

hKLK alleviates myocardial fibrosis in mice with viral myocarditis.

Myocardial fibrosis is the most serious complication of viral myocarditis (VMC). This study aimed to investigate the therapeutic benefits and underlying mechanisms of lentivirus-mediated human tissue kallikrein gene transfer in myocardial fibrosis in VMC mice. We established VMC mouse model via intraperitoneal injection with Coxsackie B3 virus. The effect was then assessed after treatment with vehicle, the empty lentiviral vectors (EZ.null), and the vectors expressing hKLK1 (EZ.hKLK1) via tail vein injection for 30 days, respectively. The results showed that administering EZ.hKLK1 successfully induced hKLK1 overexpression in mouse heart. Compared with EZ.null treatment, EZ.hKLK1 administration significantly reduced the heart/weight ratio, improved cardiac function, and ameliorated myocardial inflammation in VMC mice, suggesting that hKLK1 overexpression alleviates VMC in mice. EZ.hKLK1 administration also significantly abrogated the increased myocardial collagen content, type I/III collagen ratio, TGF-ß1 mRNA and protein expression in VMC mice, suggesting that hKLK1 overexpression reduces collagen accumulation and blunts TGF-ß1 signaling in the hearts of VMC mice. In conclusion, our results suggest that hKLK1 alleviates myocardial fibrosis in VMC mice, possibly by downregulating TGF-ß1 expression.

Clinical characteristics and risk factors of nonalcoholic fatty liver disease in children with obesity.

BACKGROUND: With the increasing number of children with obesity worldwide, nonalcoholic fatty liver disease (NAFLD) has become the most common liver disease among children. It is necessary to recognize the risk factors of NAFLD for prevention in childhood since NAFLD is asymptomatic in the early stage. OBJECTIVES: The objective of this study was to investigate possible risk factors of NAFLD in children with obesity, providing evidence for monitoring and prevention strategies at an early stage for obese children with NAFLD. METHODS: Data were collected from 428 children and adolescents aged 6-16 years recruited from the Children's Hospital at Nanjing Medical University from September 2015 to April 2018 and analyzed. Based on a combination of ultrasound results and alanine transaminase levels, subjects were divided into three groups: simple obesity (SOB), simple steatosis (SS), and nonalcoholic fatty hepatitis (NASH). Blood biochemical examination included glucose, insulin, uric acid, lipid profile and liver enzymes. RESULTS: Among 428 children with obesity, 235 (54.9%) had SS and 45 (10.5%) had NASH. Body mass index, body mass index standard deviation score (BMI-SDS), waist circumference, body fat, liver enzymes, uric acid and HOMA-IR level were significantly higher in the NASH group than in the SS and SOB groups (p < 0.001). 53.3% of the SS group and 49.8% of the NASH group had metabolic syndrome, significantly more than in the SOB group (19.6%, p < 0.001). After adjustment for confounding factors, logistic regression models revealed that NASH was associated with BMI-SDS ≥ 3, gender, hyperuricemia and insulin resistance. CONCLUSIONS: The prevalence of NASH in children with obesity is closely related to high BMI-SDS, gender, insulin resistance and hyperuricemia. These findings provide evidence that monitoring risk factors of childhood obesity can assist in developing prevention strategies for liver disease at an early stage.

Nutritional risk screening and its clinical significance in hospitalized children.

BACKGROUND & AIMS: To analyse nutritional risk in hospitalized children and its relationship with clinical outcomes to provide evidence for improved nutritional management. METHODS: The investigation involved 1325 consecutively enrolled hospitalized children from Nanjing Children's Hospital. The nutritional risks in the hospitalized children were evaluated using the STRONGkids tool. During hospitalization, the incidence of infectious complications, length of hospital stay, weight loss, hospital expenses and nutritional support were recorded. RESULTS: The percentages of children with high, moderate and low nutritional risk were 9.1% (121), 43.3% (574) and 47.6% (630), respectively. Children with cardiac, respiratory or oncologic disease were most likely to have high nutritional risk. STRONGkids scores were correlated with clinical outcome. Higher complication rates, longer stay lengths, greater weight loss and greater hospital expenses were observed in children with high nutritional risk compared to those with moderate or low risk (p < 0.001). Nutritional support during hospitalization was given to 62.8% (76) of children with high nutritional risk, 18.6% (107) of children with moderate nutritional risk and 8.9% (56) of children with low nutritional risk. CONCLUSIONS: Hospitalized children exposed to high or moderate nutritional risks have poor clinical outcomes. Nutritional support is not yet performed appropriately. Evidence-based guidelines should be created to improve this situation.

[Nutritional risk screening and its clinical significance in 706 children hospitalized in the surgical department].

OBJECTIVE: To investigate nutritional risk and its relationship with clinical outcome in children hospitalized in the surgical department, and to provide a scientific basis for clinical nutrition management. METHODS: Nutritional risk screening was performed on 706 children hospitalized in the surgical department using the Screening Tool for Risk on Nutritional Status and Growth. The data on nutritional support during hospitalization, incidence of infectious complications, length of hospital stay, post operative length of hospital stay and total hospital expenses were recorded. RESULTS: Of the 706 cases, 11.5% had high nutritional risk, 46.0% had moderate nutritional risk, and 42.5% had low nutritional risk. Congenital hypertrophic pyloric stenosis, intestinal obstruction and congenital heart disease were the three most common types of high nutritional risk. The incidence of high nutritional risk was significantly higher in infants than in other age groups (P<0.01). Fifty-two (64.2%) of the eighty-one children with high nutritional risk received parenteral nutrition. Children with high nutritional risk were significantly more likely to have weight loss than children with low nutritional risk (P<0.05). Children with high nutritional risk had significantly increased incidence of infectious complications, length of hospital stay, post operative length of hospital stay and total hospital expenses compared with those with moderate or low nutritional risk (P<0.01). CONCLUSIONS: Moderate or high nutritional risk is seen in children hospitalized in the surgical department. Nutritional risk score is correlated with clinical outcome. Nutritional support for these children is not yet properly provided. Nutritional risk screening and standard nutritional support should be widely applied among hospitalized children.