[Prevalence and risk factors of obesity in children with Diamond-Blackfan anemia]. / å ˆå¤©æ€§çº¯çº¢ç»†èƒžå†ç”Ÿéšœç¢æ€§è´«è¡€æ‚£å„¿è‚¥èƒ–å‘ç”Ÿæƒ å†µåŠå½±å“å› ç´ åˆ†æž.

OBJECTIVES: To investigate the distribution of body mass index (BMI) and risk factors for obesity in children with Diamond-Blackfan Anemia (DBA). METHODS: The children with DBA who attended National Clinical Research Center for Blood Diseases, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, from January 2003 to December 2020 were enrolled as subjects. The related clinical data and treatment regimens were recorded. The height and weight data measured within 1 week before or after follow-up time points were collected to calculate BMI. The risk factors for obesity were determined by multivariate regression analysis in children with DBA. RESULTS: A total of 129 children with DBA were enrolled, among whom there were 80 boys (62.0%) and 49 girls (38.0%), with a median age of 49 months (range 3-189 months). The prevalence rate of obesity was 14.7% (19/129). The multivariate logistic regression analysis showed that the absence of ribosomal protein gene mutation was closely associated with obesity in children with DBA (adjusted OR=3.63, 95%CI: 1.16-11.38, adjusted P=0.027). In children with glucocorticoid-dependent DBA, obesity was not associated with age of initiation of glucocorticoid therapy, duration of glucocorticoid therapy, and maintenance dose of glucocorticoids (P>0.05). CONCLUSIONS: There is a high prevalence rate of obesity in children with DBA, and the absence of ribosomal protein gene mutation is closely associated with obesity in children with DBA.

Association of ß-cell function and insulin resistance with pediatric type 2 diabetes among Chinese children.

BACKGROUND: In addition to insulin resistance, impaired insulin secretion has recently been identified as a crucial factor in the pathogenesis of type 2 diabetes mellitus (T2DM). Scarce clinical data exist for pediatric T2DM. AIM: To investigate the association of ß-cell function and insulin resistance with pediatric T2DM in the first Chinese multicenter study. METHODS: This multicenter cross-sectional study included 161 newly diagnosed T2DM children and adolescents between January 2017 and October 2019. Children with normal glycemic levels (n = 1935) were included as healthy control subjects. The homeostasis models (HOMAs) were used to assess the ß-cell function (HOMA2-%B) and insulin resistance (HOMA2-IR) levels. The HOMA index was standardized by sex and age. We performed logistic regression analysis to obtain odds ratios (ORs) for T2DM risk using the standardized HOMA index, adjusted for confounding factors including sex, Tanner stage, T2DM family history, body mass index z-score, and lipid profile. RESULTS: The male-female ratio of newly diagnosed T2DM patients was 1.37:1 (OR = 2.20, P = 0.011), and the mean ages of onset for boys and girls were 12.5 ± 1.9 years and 12.3 ± 1.7 years, respectively. The prevalence of related comorbidities including obesity, elevated blood pressure, and dyslipidemia was 58.2%, 53.2%, and 80.0%, respectively. The T2DM group had lower HOMA2-%B levels (P < 0.001) and higher HOMA2-IR levels (P < 0.001) than the control group. Both the decrease in HOMA2-%B z-score (OR = 8.40, 95%CI: 6.40-11.02, P < 0.001) and the increase in HOMA2-IR z-score (OR = 1.79, 95%CI: 1.60-2.02, P < 0.001) were associated with a higher risk of T2DM, and the decrease in HOMA2-%B z-score always had higher ORs than the increase in HOMA2-IR z-score after adjusting for confounding factors. CONCLUSION: Besides insulin resistance, ß-cell function impairment is also strongly associated with Chinese pediatric T2DM. Gender difference in susceptibility and high comorbidities warrant specific T2DM screening and prevention strategies in Chinese children.

Delivery room resuscitation and short-term outcomes of extremely preterm and extremely low birth weight infants: a multicenter survey in North China.

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION: Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.

Effects of rapid growth in early childhood on metabolic and cardiovascular diseases among preschool-aged children.

BACKGROUND AND OBJECTIVES: To investigate whether the tempo of weight gain of children during infancy (from birth up to two years of age) or childhood (between two and five years old) is associated with metabolic and cardiovascular disease. METHODS AND STUDY DESIGN: Cluster sampling was employed to obtain a random sample of preschool children. In total, 1450 children aged five to six years participated in this survey. We obtained data on body weight, height, blood pressure (BP), and serum levels of total cholesterol, triglycerides, glucose, and uric acid, as well as anthropometry at birth and at age 2. RESULTS: The prevalence of obesity at five years old was 14.5%. At five years of age, children with rapid growth (change in body mass index, BMI z-score >0.67) during infancy had a higher odds ratio (OR) of childhood obesity (OR: 2.97 [95% CI: 2.15-4.11]) compared to children with non-rapid growth (change in BMI z-score ≤0.67). Also, children with rapid growth during childhood had a higher OR of childhood obesity (OR: 17.90 [95% CI: 12.31-26.04]), higher systolic BP (OR: 2.38 [95% CI: 1.68-3.39]), higher diastolic BP (OR: 2.42 [95% CI: 1.53-3.83]), and higher triglycerides (OR: 4.09 [95% CI: 1.47-11.33]) or hyperuricemia (OR: 2.23 [95% CI: 1.51-3.29]). CONCLUSIONS: Rapid growth in early childhood is associated with risk factors for both cardiovascular outcomes and metabolic outcomes among preschool children. Developing effective prevention and intervention programs for pre-school children might be important to reduce incidence of long-term metabolic and cardiovascular disease as adults.

Observed and projected trends in paediatric health resources and services in China between 2003 and 2030: a time-series study.

OBJECTIVES: The two-child policy took effect in China on 1 January 2016, thus officially ending the one-child policy. The resultant growth in the population will create a considerable demand for public services such as paediatric healthcare, even while there are limited paediatric resources. We estimated the relationship between paediatric health resources and services and child mortality to determine the degree of the deficiency of such resources in China. Projecting the quantity of paediatric health resource allocation and service supply through 2030 will help provide data reference for future policy decision making. DESIGN: Time-series study. SETTING: The People's Republic of China. PARTICIPANTS: Paediatric patients whose data were recorded between 2003 and 2012 from the National Health and Family Planning Commission of the People's Republic of China. PRIMARY AND SECONDARY OUTCOME MEASURES: Child mortality and paediatric health resources and services data were entered into a cubic polynomial regression model to project paediatric health resources and services to 2030. RESULTS: Child mortality decreased throughout the past decade. Furthermore, the number of paediatric beds, paediatricians and nurses increased between 2003 and 2012, although the proportions increased rather slowly. Both the number and proportion of paediatric outpatients and inpatients increased rapidly. The observed and model-predicted values matched well (adjusted R2=93.8% for paediatric beds; adjusted R2=96.6% for paediatric outpatient visits). Overall, the projection indicated that paediatric beds, paediatricians and nurses will reach 460 148, 233 884 and 184 059 by 2030, respectively. Regarding paediatric services, the number of paediatric outpatient visits and inpatients is expected to reach upwards of 449.95 million and 21.83 million by 2030, respectively. CONCLUSIONS: Despite implementation of the two-child policy, resource allocation in paediatrics has many deficiencies. Proper measures should be taken to actively respond to the demand for paediatric health services.

[Effect of Knockdown of Vascular Cell Adhesion Molecule-1 on the Immunologic Regulation Capacity of Murine Mesenchymal Stem Cells].

OBJECTIVE: To establish the stably lower expression of vascular cell adhesion molecule-1 (VCAM-1) in MSC cell line (C3H10T1/2) by siRNA technology, and explore the effect of knockdown of VCAM-1 on the immunologic regulation capacity of murine MSC. METHODS: The mouse GV118-VCAM-1-RNAi retrovirus vector was constructed by gene recombination technology. The recombinant plasmid was identified by restriction analysis and sequencing, and then the recombinant plasmid GV118-VCAM-1-RNAi was transfected into 293 cells by Lipofectamine, and the supernatant was collected to transfect C3H10T1/2. Moreover, the VCAM-1 lower expression on MSC was evaluated by flow cytometry and fluorescent microscopy. The knockdown VCAM-1 MSC was sorted by flow cytometry. Furthermore, the inhibitory effect of the knockdown VCAM-1 MSC on lymphocyte proliferation was tested by lymphoblast transformation assay (LTT) and mixed lymphocyte reaction assay(MLR). RESULTS: The recombinant retroviral vector of knockdown VCAM-1 (GV118-VCAM-1-RNAi) was successfully constructed and transfected into mouse MSC cell line C3H10T1/2. The knockdown VCAM-1/MSC was obtained by flow cytometric sorting. The LTT and MLR assay showed that the immunosuppressive effect of MSC lower-expressing VCAM-1 dramatically decreased (P<0.05). CONCLUSION: Knockdown VCAM-1 in MSC can significantly down-regulate the inhibitory capability of MSC on the proliferation of T-cells. The data of this study laid an experimental foundation for studying effect of VCAM-1 transfecting into MSC on immune function.

[Effect of Vascular Cell Adhesion Molecule -1 Overexpression on Adipogenic Differentiation of Murine Mesenchymal Stem Cells and Its Mechanism].

OBJECTIVE: To investigate the effect of vascular cell adhesion molecule-1 (VCAM-1) gene overexpression on adipogenic differentiation of mouse mesenchymal stem cells(MSC) and explore its molecular mechanism. METHODS: VCAM-1 overexpression MSC (MIGR1-VCAM-1/MSC) and the empty plasmid transfection MSC (MIGR1/MSC) were induced to adipogenic differentiation, oil-red-O staining and real-time PCR were used to detect the adipogenic differentiation ability and the mRNA expression level of key transcription factors C/EBP α and PPAR γ. The activation of P38, ERK and JNK pathways were analyzed by Western blot. Furthermore, the specific chemical inhibitors of MAPK pathway (SB203580, PD98059 and JNK inhibitor II) were added to the induced culture system and the alteration of the MSC adipogenic differentiation ability were evaluated. RESULTS: no matter in self or induced differentiation groups, the lipid droplets in MIGR1-VCAM-1/MSC became larger, the amount of adipocyte increased than that in MIGR1/MSC (P<0.01), the mRNA expression level of C/EBPα and PPARγ were upregulated, and JNK pathway were down-regulated while the P38 and ERK pathway were significantly up-regulated. The inhibition of JNK pathway of MIGR1-VCAM-1/MSC could lead to increased mRNA expression level of C/EBP α and PPAR γ, the amount of adipocytes increased (P<0.01), however, the inhibition of the P38 and ERK pathway of MIGR1-VCAM-1/MSC could lead to decreased mRNA expression level of C/EBP α and PPAR γ, and the lipid droplets and the number of adipocytes became smaller and less. CONCLUSION: The overexpression of VCAM-1 may promote MSC to differentiate into adipocytes through inhibiting JNK signaling pathway, activating P38 and ERK pathways.

Intercellular adhesion molecule-1 inhibits osteogenic differentiation of mesenchymal stem cells and impairs bio-scaffold-mediated bone regeneration in vivo.

Mesenchymal stem cell (MSC) loaded bio-scaffold transplantation is a promising therapeutic approach for bone regeneration and repair. However, growing evidence shows that pro-inflammatory mediators from injured tissues suppress osteogenic differentiation and impair bone formation. To improve MSC-based bone regeneration, it is important to understand the mechanism of inflammation mediated osteogenic suppression. In the present study, we found that synovial fluid from rheumatoid arthritis patients and pro-inflammatory cytokines including interleukin-1α, interleukin-1ß, and tumor necrosis factor α, stimulated intercellular adhesion molecule-1(ICAM-1) expression and impaired osteogenic differentiation of MSCs. Interestingly, overexpression of ICAM-1 in MSCs using a genetic approach also inhibited osteogenesis. In contrast, ICAM-1 knockdown significantly reversed the osteogenic suppression. In addition, after transplanting a traceable MSC-poly(lactic-co-glycolic acid) construct in rat calvarial defects, we found that ICAM-1 suppressed MSC osteogenic differentiation and matrix mineralization in vivo. Mechanistically, we found that ICAM-1 enhances MSC proliferation but causes stem cell marker loss. Furthermore, overexpression of ICAM-1 stably activated the MAPK and NF-κB pathways but suppressed the PI3K/AKT pathway in MSCs. More importantly, specific inhibition of the ERK/MAPK and NF-κB pathways or activation of the PI3K/AKT pathway partially rescued osteogenic differentiation, while inhibition of the p38/MAPK and PI3K/AKT pathway caused more serious osteogenic suppression. In summary, our findings reveal a novel function of ICAM-1 in osteogenesis and suggest a new molecular target to improve bone regeneration and repair in inflammatory microenvironments.

Association of plasma glucose, insulin, and cardiovascular risk factors in overweight and obese children.

OBJECTIVE: To investigate the association between fasting plasma glucose (FPG), 2-hour post challenge plasma glucose (2hPG), fasting plasma insulin (FINS), 2-hour post challenge plasma insulin (2hINS), and cardiovascular risk factors in obese and overweight children. METHODS: This is a cross-sectional study of 452 obese and overweight children (male: 312, female: 140, aged 6-16 years). This study was conducted in the Department of Pediatrics, General Hospital of Tianjin Medical University, Tianjin, China between June 2008 and November 2012. Anthropometries and blood analysis were carried out. Pearson correlation analysis and multiple stepwise linear regression analysis were used to investigate the association among FPG, 2hPG, FINS, 2hINS and cardiovascular risk factors. RESULTS: Body mass index, waist circumference, waist to hip ratio, systolic blood pressure, diastolic blood pressure, and triglyceride were highly correlated with FINS. Fasting plasma insulin influenced greater variance in most cardiovascular risk factors than 2hPG and 2hINS. CONCLUSION: Fasting plasma insulin was closely associated with most cardiovascular risk factors compared with FPG, 2hPG and 2hINS.

[Effects of ICAM-1 gene transfection on the adipogenic differentiation of MSCs].

OBJECTIVE: To explore the effects of ICAM-1 gene transfection on the differentiation of MSCs to adipocytes. METHODS: The recombinant retroviral expression plasmid MIGR1-ICAM-1 containing full length of mouse ICAM-1 gene was constructed. The constructed plasmid MIGR1-ICAM-1, empty plasmid MIGR1 and packaging plasmid ECOS were transfected into T293 cell lines and then the supernatant generated from T293 cells were used to infect mouse MSCs cell line C3H10T 1/2. The transfective efficiency was determined by inverted fluorescence microscope, real-time PCR and flow cytometry. Furthermore, ICAM-1 overexpressing MSCs (C3H10T 1/2-ICAM-1) and empty vector transfection MSCs (C3H10T 1/2-MIGR1) were cultured in medium with or without induction reagents, Oil-red-O staining was used to detect the lipid accumulation, and the expression of transcriptional factors C/EBPα and PPARγ, which were key factors in the differentiation of MSCs to adipocytes, were tested by real-time-PCR. RESULTS: The recombinant retrovirus vector containing mouse ICAM-1 gene was successful constructed. After transfection into MSCs cell line C3H10T 1/2, the overexpression ICAM-1 MSCs cell line (C3H10T 1/2-ICAM-1) and control cell line (C3H10T 1/2-MIGR1) were obtained. Furthermore, these two cell lines were treated without or with adipocytic induction reagents, C3H10T 1/2-ICAM-1 showed significantly lower mRNA expression level for C/EBPα [(1.2 ± 0.7), (2.9 ± 0.9)] and PPARγ [(1557.6 ± 70.2), (7547.0 ± 442.2)] when compared with C3H10T 1/2-MIGR1 [(5.8 ± 0.5), (23.0 ± 2.3) and (2453.0 ± 215.6), (9856.3 ± 542.2)](P < 0.05). Moreover, little lipid droplet and decreased quantity of adipocytes were detected in C3H10T 1/2-ICAM-1 [(3.2 ± 0.5)/well, (12.2 ± 3.8)/well] than that in C3H10T 1/2-MIGR1 [(11.2 ± 0.4)/well, (51.3 ± 2.8)/well] (P < 0.05). CONCLUSION: Overexpression of ICAM-1 in MSCs can inhibit its adipocytic differentiation.

[Correlation between vaspin concentration and insulin sensitivity in the visceral adipose tissue of young obese rats].

OBJECTIVE: To investigate the correlation between visceral adipose tissue-derived serine protease inhibitor (vaspin) concentration and insulin sensitivity in the visceral adipose tissue of young obese Sprague-Dawley (SD) rats. METHODS: Twenty-four SD rats which had been weaned 3 weeks before were randomly divided into two groups (n=12 each) to receive a high-fat and normal diet. The weight and abdominal circumference (AC) of each rat were measured, the fasting plasma glucose (FPG) and fasting insulin (FINS) in blood from the angular vein were measured after 12 hours of fasting and blood glucose (BG) and insulin (INS) levels in blood from the angular vein were measured at 60 and 120 minutes after intraperitoneal injection of 50% glucose (2 g/kg). The rats were sacrificed, and their liver and visceral adipose tissue were weighed. The vaspin concentration of the visceral adipose tissue in each rat was measured using ELISA. Correlation analysis was performed on the vaspin concentration and other indices. RESULTS: Compared with the normal diet group, the high-fat diet group showed significantly higher weight, AC, weight of visceral adipose tissue, FPG, FINS, 120 minute INS level, vaspin concentration, homeostasis model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment of ß cell function (HOMA-ß) (P<0.05) Insulin sensitivity index (ISI) was significantly lower (P<0.01). Vaspin concentration was positively correlated with visceral adipose tissue and liver weight, AC, 120 minute INS level, FPG, FINS, HOMA-IR and HOMA-ß (P<0.05), and negatively correlated with ISI (P<0.05). CONCLUSIONS: High expression of vaspin is associated with insulin resistance in young obese SD rats. Vaspin is presumably an adipocytokine that can increase insulin sensitivity, promote insulin secretion by islet ß-cells and improve glucose tolerance, and it may be involved in insulin resistance and the disturbance of carbohydrate metabolism.

[Protective and curative effects of prophylactic administration of pulmonary surfactant on neonatal respiratory distress syndrome].

OBJECTIVE: To evaluate the protective and curative effects of prophylactic administration of pulmonary surfactant (PS) on neonatal respiratory distress syndrome (NRDS). METHODS: One hundred neonates aged 0.5 h after birth, with the gestational age < 32 w, birth weight < 1500 g, and number of gastric, stable microbubble < or = 7/mm(2) by gastric stable microbubble test (SMT), but without clinical or radiological manifestations of RDS at the admission, were randomly divided into 2 equal groups: prophylactic group (PG), receiving curosurf, a product of PS, immediately after admission; and non-prophylactic group (N-PG), receiving curosurf only after development of RDS. RESULTS: One hour after the administration of PS, the PaO(2), a/APO(2), pH, and PaO(2) of the PG group were 86.2 mm Hg +/- 8.1 mm Hg, 0.30 +/- 0.04, 7.38 +/- 0.06, and 178 +/- 37, all significantly higher than those of the non-PG group (all P < 0.01), and the PaCO(2) of the PG group was 37.3 mm Hg +/- 9.8 mm Hg, significantly lower than that of the non-PG group (53.6 mm Hg +/- 11.1 mm Hg, P < 0.01). In comparison with the level before the administration of PS (0.75 +/- 0.06), the level of FiO(2) of the 47 pediatric patients receiving mechanical ventilation decreased after the administration of curosurf time-dependently, e.g., was 0.50 +/- 0.09, 0.34 +/- 0.06, and 0.25 +/- 0.07 8, 48, and 96 hours after the administration. In comparison with the level before the administration of curosurf 9.0 +/- 1.0 cm H2O, the level of mean airway pressure (MAP) decreased time-dependently after the administration, e.g., were 7.5 +/- 0.8 and 6.0 +/- 0.3 48 and 96 hours after the administration (all P < 0.01). Compared with that before the administration of curosurf (3.02 +/- 0.2), the X-ray chest score decreased time-dependently after the administration of curosurf, e.g., were 1.89 +/- 0.34, 1.82 +/- 0.33, and 1.17 +/- 0.42 6, 12, and 72 hours after the administration (all P < 0.01). The RDS rate of the PG group was 30%, significantly lower than that of the non-PG group (P < 0.01). The severe case rate of the PG group was 20%, significantly lower than that of the N-PG group (53%, P = 0.01). The mortally of the PG group was 0, significantly lower than that of the non-PG group (P < 0.05). The total times of supplemental oxygen administration, assisted ventilation and hospitalization of the 47 patients with RDS in the PG group were significantly shortened compared with the RDS patients in the N-PG group [(3.6 +/- 1.7) d vs. (5.9 +/- 3.6) d, P < 0.05; (8.6 +/- 5.5 d vs. (14.1 +/- 6.2) d, P < 0.01; and (20.5 +/- 10.0) d vs. (32.8 +/- 17.8) d, P < 0.05). CONCLUSION: Prophylactic administration of PS to the preterm neonates with high risk of RDS effectively decreases the incidence of RDS, development of severe cases and mortality, shorten the disease course, the duration of supplemental oxygen administration and assisted ventilation, thus decreasing the potential morbidity associated with long-term oxygen supplement and assisted ventilation.