Quantification of the iduronate-2-sulfatase activity in prenatal diagnosis of mucopolysaccharidosis type Ⅱ / 中华实用儿科临床杂志

Objective:To evaluate the activity of iduronate-2-sulfatase (IDS) in fetal villi and peripheral blood plasma of pregnant women at high risk of mucopolysaccharidosis type Ⅱ (MPS Ⅱ), and to discuss the application of gene analysis in prenatal diagnosis of MPS Ⅱ.Methods:The enzymatic testing and gene analysis results of 23 pregnant women at high risk of MPS Ⅱ, who underwent prenatal diagnosis in Guangzhou Women and Children′s Medical Center from February 2013 to December 2020, were analyzed retrospectively.The IDS activity in fetal villi (30 cases) and plasma (28 cases) was detected by artificial substrate fluorescence.The IDS activity in fetal villi (28 cases) and plasma (34 cases) of normal pregnant women was taken as control.Meanwhile, the fetal villi of both pregnant women at high risk of MPS Ⅱ and normal pregnant women were also analyzed by gene testing and for fetal sex identification.Data were compared between groups by the independent samples t test. Results:The normal reference values of the IDS activity in fetal villi and plasma of normal pregnant women were(71.2±23.4) nmol/(mg·4 h) and (611.1±114.5) nmol/(mL·4 h), respectively.Among the 30 cases of high-risk fetal villi, the IDS activity in fetal villi of 8 affected male fetuses was (1.7±0.3) nmol/(mg·4 h), which was significantly lower than that of 11 unaffected male fetuses (83.2±6.3) nmol/(mg·4 h) and that of 9 non-carrier female fetuses (80.0±7.5) nmol/(mg·4 h) ( t=10.8, 8.8; all P<0.01). Meanwhile, the IDS activity was measured in the maternal peripheral plasma of 28 pregnant women at high risk of MPS Ⅱ.Among them, the IDS activity in 8 affected male fetuses was(225.4±20.5) nmol/(mL·4 h), which was significantly lower than that in non-affected male fetuses[(451.0±15.1) nmol/(mL·4 h)] and that in non-carrier female fetuses[(467.7±45.3)nmol/(mL·4 h)]. Eight known pathogenic mutations were found in 30 cases at high risk of MPS Ⅱ of fetal villi, and the mutation types were c. 1048A>C, c.212G>A, c.514C>T, c.257C>T, c.425C>T, and c. 998C>T.Of the 8 cases, 6 affected male fetuses had significantly reduced IDS activities, and the other 2 female carriers had normal IDS enzyme activities. Conclusions:The IDS activity in fetal villi and peripheral plasma of pregnant woman is consistent with the gene analysis results.The IDS activity has an important reference value for the prenatal diagnosis of MPS Ⅱ in the first trimester.When no genetic mutations are found in the probands or the pathogenicity of the new mutation remains unclear, the IDS activity in fetal villi can be detected separately for the prenatal diagnosis of MPS Ⅱ.

Predictive value of bioelectrical impedance analysis-measured body fat to abnormal lipid profiles in children and adolescents: the optimal cut-off values of body fat / 中华实用儿科临床杂志

Objective:To assess the predictive values of bioelectrical impedance analysis(BIA)-measured body fat indices to abnormal lipid profiles, and to preliminary propose optimal cut-off values of body fat in children and adolescents.Methods:Children and adolescents, aged 6-16 years, were selected from 30 schools (8 primary schools, 21 middle schools and one 12-year education school) in Dongcheng, Tongzhou, Fangshan and Miyun districts of Beijing by adopting a stratified cluster sampling method from November 2017 to January 2018.Questionnaire survey, body mass index(BMI), body fat mass index (FMI), fat mass percentage (FMP) and four lipid profiles were conducted.Results:A total of 14 309 participants, aged (11.0±3.3) years, were enrolled in the analysis, with 49.9% boys.In boys and girls, the percentile values ( P60- P95) fitted by FMI and FMP with K-median-coefficient of variation(LMS) method were taken as the cutting points, and P75 values were selected as the cut-off points of excessive body fat for their better sensitivity, specificity, predictive value and area under curve (AUC) for identification of abnormal lipid profiles.Boys with FMI above P75 accounted for 28% of the total population, and controlling boys with FMI below P75 could prevent dyslipidemia of 8%-57%.FMI in girl population occupied about 26% of the above, and controlling FMI in girl population below this cut-off point may prevent dyslipidemia from 8%-42%.FMP observed similar results to FMI.Assessed by FMI or FMP with P75 cut-off values, adiposity performed better than BMI for recognizing abnormal lipid profiles in boys (AUC: 52.4%-69.6% vs.50.2%-67.1%, P<0.05) rather than in girls ( P>0.05). In addition, when FMI or FMP beyond P90, the specificity of each abnormal lipid profiles was around 90%. Conclusions:The recommend cut-off points for body fat may be to assess children′s adiposity, and can be applied in preventive activities.

Design of ultrahigh-affinity and dual-specificity peptide antagonists of MDM2 and MDMX for P53 activation and tumor suppression

Peptide inhibition of the interactions of the tumor suppressor protein P53 with its negative regulators MDM2 and MDMX activates P53

A comparative study on diagnostic cut points of dyslipidemia in children and adolescents in China / 中华流行病学杂志

Objective@#To compare the power of dyslipidemia diagnosis by different sets of cut points in the prediction of cardiovascular metabolic risk factors and identify the appropriate cut points for the diagnosis of dyslipidemia in children and adolescents in China.@*Methods@#Data were obtained from the baseline survey of 'School-based Cardiovascular and Bone Health Promotion Program’ in Beijing in 2017. Dyslipidemia was diagnosed by using two set of cut points. Receiver operating characteristic curve analysis was conducted to assess the power of dyslipidemia diagnosis by the two set of cut points to predict the prevalence of hypertension, obesity, high fat mass percentage and impaired fasting glucose.@*Results@#A total of 14 390 children and adolescents were in included in the study. The prevalence rates of high TC, high LDL-C, low HDL-C, and high TG in the participants were 2.7%, 2.7%, 14.4%, and 3.7% according to 'Chinese Reference Standard’, and 5.0%, 3.7%, 13.3%, and 3.5% according to 'China Expert Consensus’. Low HDL-C and high TG defined by the 'Chinese Reference Standard’ had better performance for the prediction of high fat mass percentage and obesity in boys, but worse performance in girls (P<0.001).@*Conclusions@#Using 'China Reference Standard’ can increase the true positive rate in the prediction of obesity or high fat mass percentage in boys, and reduce the false positive rate in girls. The cut points for the diagnosis of dyslipidemia in Chinese children and adolescents need to be further validated by using national representative sample and in longitudinal study.

White matter hyperintensities rather than the overall burden of cerebral small vessel disease is correlated with the outcomes in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the correlation between white matter hypertensities (WMHs) and the overall burden of cerebral small vessel disease (CSVD) and clinical outcome of patients with acute ischemic stroke.Methods:From November 2018 to June 2019, patients with acute ischemic stroke hospitalized in the Department of Neurology, the Affiliated Jiangning Hospital of Nanjing Medical University were enrolled prospectively. Their demographic and clinical data were collected. The National Institutes of Health Stroke Scale (NIHSS) was used to evaluate the baseline severity of stroke. The total burden of CSVD was evaluated according to the head MRI findings. The severity of WMHs was assessed based on Fazekas scale. The modified Rankin Scale (mRS) was used to evaluate the outcomes at 90 d after onset. The mRS score 0-1 was defined as good outcome, and ≥2 was defined as poor outcome. Multivariate logistic regression analysis was used to determine independent risk factors for poor outcomes. Results:A total of 153 consecutive patients with acute ischemic stroke were enrolled, of which 126 (82.35%) had a good outcome and 27 (17.65%) had a poor outcome. There were significant differences in age, baseline NIHSS score, lipoprotein-associated phospholipase A 2, total Fazekas score, periventricular WMHs score, and deep WMHs score between the two groups, while there was no significant difference in the total burden of CSVD. Multivariate logistic regression analysis revealed that the baseline NIHSS score (odds ratio 1.245, 95% confidence interval 1.023-1.515; P=0.028) and the total Fazekas score (odds ratio 1.635, 95% confidence interval 1.049-2.549; P=0.030) were the independent risk factors for poor outcomes at 90 d after the onset in patients acute ischemic stroke. Conclusions:The overall burden of CSVD is not associated with the short-term outcomes in patients with acute ischemic stroke. WMHs and baseline NIHSS score are the independent risk factors for poor short-term outcomes in patients with acute ischemic stroke.

The evaluation of dietary salt and potassium intake assessed by two 24-hour urine specimens among 284 primary and secondary school students / 中华预防医学杂志

Objective@#To estimate the dietary salt and potassium intake by two 24 hour urine salt and potassium excretion in primary and secondary school students.@*Methods@#The boarders from Grade 5 to 6 in a rural primary school and Grade 1 to 3 in a rural middle school in Changde City, Hunan Province were recruited from October to December in 2017. Subjects who had 2 and more urinary incontinence episodes or a history of kidney disease or diarrhea and girls in menstruation were excluded. The final analysis included 284 subjects. Questionnaires on basic demographic information were collected, and height and weight were examined. Two inconsecutive 24-hour urine specimens were collected in weekdays. The differences and consistency between two 24-hour urine were tested and dietary salt and potassium intake were assessed by the average of two 24-hour urine collections.@*Results@#A Total of 284 participants was (12.1±1.5) years old, of which 148 (52.1%) were boys and 36 (12.7%) were overweight. In the first 24-hour urine, the volume [P50 (P25, P75)=670 (513, 868) ml], potassium concentration [P50 (P25, P75)=29 (21, 39) mmol/L] and potassium excretion [P50 (P25, P75)=0.7 (0.6, 1.0) g] were similar to those in the second 24-hour urine [P50 (P25, P75) values were 660 (490, 916) ml, 30 (21,40) mmol/L, and 0.8 (0.6, 1.0) g, respectively]. But the sodium and creatinine concentrations, salt excretion in the first 24-hour urine [P50 (P25, P75) values were 175 (123, 219) mmol/L, 7.20 (5.15, 10.86) mmol/L and 6.6 (5.0, 8.7) g, respectively] were lower than those in the second 24-hour urine [P50 (P25, P75) values were 188 (133, 248) mmol/L, 8.66 (5.99, 12.47) mmol/L and 7.3 (5.2, 9.2) g, respectively] (all P values<0.05). The intraclass correlation coefficients between salt and potassium excretions in the two 24-hour urine were 0.534 (95%CI: 0.412-0.631) and 0.478 (95%CI: 0.341-0.587) (P<0.001), respectively. The mean±SD of salt consumed was (7.3±2.5) g (range: 2.3 to 18.8 g) per day by all participants. Overweight children consumed more salt [(8.2±2.6) g/d] than those non-overweight [(7.2±2.4) g/d] (P<0.05). The mean±SD of potassium consumed was (1.1±0.3) g (range: 0.4 to 2.3 g) per day. Boys consumed more potassium [(1.1±0.3) g/d] than girls [(1.0±0.3) g/d] (P<0.05), and overweight children had higher potassium intake [(1.2±0.3) g/d] than those non-overweight [(1.0±0.3) g/d] (P<0.05). A total of 212 participants (74.6%) consumed more salt than the recommended level and all participants had inadequate potassium intake.@*Conclusion@#The problem of excessive salt intake and insufficient potassium intake of rural primary and middle school students was serious.

The baseline characteristics of School-based Cardiovascular and Bone Health Promotion Program in Beijing / 中华预防医学杂志

Objective@#To describe the baseline characteristics of School-based Cardiovascular and Bone Health Promotion Program(SCVBH) in Beijing.@*Methods@#Children and adolescents were selected in 30 schools (8 primary schools, 21 middle schools and one 12-year education school) from Dongcheng, Tongzhou, Fangshan and Miyun districts of Beijing by using a stratified cluster sampling method. 15 391 students in grade 1 to 4 from primary schools, grade 1 from junior and senior high schools were enrolled in the investigation with an exclusion of students who were not able to participate due to trauma or other uncomfortable physical conditions. The baseline survey including a questionnaire survey, physical examination and blood biochemical test was conducted from September 2017 to January 2018. Obesity, blood pressure, fasting blood glucose, lipid, bone density and grip were evaluated.@*Results@#The prevalence of obesity, hypertension, hyperglycemia (impaired fasting glucose and diabetes), dyslipidemia, lower bone density were 22.3%(3 394), 14.8%(2 248), 10.4%(1 490), 20.3%(2 919) and 2.1%(316) in total respectively, and 27.2%(2 081), 16.3%(1 244), 12.8%(922), 22.2%(1 595) and 1.2%(94) for boys, 17.3%(1 313), 13.3% (1 004), 7.9%(568), 18.4%(1 324) and 2.9%(229) for girls. Boys had higher prevalence of obesity, hypertension, hyperglycemia, and dyslipidemia and lower prevalence of low bone density than girls (all P values <0.05) The mean of body mass index, systolic blood pressure, fasting plasma glucose and grip of boys were significantly higher than that of girls (all P values <0.05).The mean of body mass index, systolic blood pressure, fasting plasma glucose and grip of boys were significantly higher than that of girls (all P values <0.05), the mean of fat mass percentage, total cholesterol, triglyceride, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol of boys were significantly lower than those of girls (all P values <0.05).@*Conclusion@#The prevalence of risk factors of chronic cardiovascular disease was high and the low bone density was appearing in children and adolescents in this study. The promotion of cardiovascular and bone health should be implemented in children and adolescents.

Influence of change in blood pressure status from childhood to adulthood on renal dysfunction: a cohort study / 中华预防医学杂志

Objective@#To investigate the influence of change in blood pressure status from childhood to adulthood on renal damage.@*Methods@#Data were obtained from Beijing Blood Pressure Cohort initiated from 1987. 3 198 children and adolescents aged 6-18 years from 6 primary and 6 middle schools in Chaoyang, Xicheng and Haidian Districts of Beijing were enrolled at baseline by using a cluster random sampling method, and 1 222 participants were followed up during 2010-2012. The measurements included weight, height, and blood pressure at baseline and microalbumin, serum creatinine, cystatin C and blood pressure at follow-up. Based on blood pressure status in childhood and adulthood, the participants were divided into four groups: participants with normal blood pressure in both childhood and adulthood, participants with elevated blood pressure in childhood but normal blood pressure in adulthood, participants with normal blood pressure in childhood but elevated blood pressure in adulthood, and participants with elevated blood pressure in both childhood and adulthood. Multivariate linear regression model was used to investigate the association of change in blood pressure from childhood to adulthood on renal dysfunction.@*Results@#The prevalence of elevated blood pressure in childhood and adulthood was 17.9% and 39.9%, respectively. The P50 (P25-P75) of microalbumin was 5.7(3.0-12.0) mg/L, and the concentration of eGFR and cystatin C were (118.0±19.8)% and (0.734±0.184)mg/L, respectively. With adjustment for sex, baseline age and follow-up years, compared with participants with persistently normal blood pressure from childhood to adulthood, participants with normal blood pressure in childhood but elevated blood pressure in adulthood had significantly higher levels of microalbumin (β=0.502, 95%CI: 0.320-0.684) and cystatin C (β=0.049, 95%CI: 0.025-0.073). After adjustment for sex, baseline age, follow-up duration, and adult BMI, smoking and drinking, participants with normal blood pressure in childhood and elevated blood pressure in adulthood had higher levels of adult urine microalbumin (β=0.322, 95%CI: 0.128-0.516) and cystatin C (β=0.032, 95%CI:0.007-0.057).@*Conclusion@#An increase in blood pressure during childhood and adulthood has an adverse impact on renal functional damage in adulthood. These findings underscore the importance of maintaining normal blood pressure during life course to prevent the development of chronic kidney disease.

Correlation analysis of child and adolescent Korotkoff phase Ⅳ and Ⅴ sound with subclinical cardiovascular diseases in adulthood / 中华实用儿科临床杂志

Objective To examine the value of child and adolescent Korotkoff phase Ⅳ(K4)and Korotkoff phaseⅤ(K5)diastolic blood pressures for predicting subclinical cardiovascular disease(CVD)in adulthood.Methods The data was obtained from the Beijing Children Blood Pressure Study.A total of 3 198(1 700 males,53.2%)healthy children aged 6-18 years from 6 districts in Beijing in 1987 were selected.The physical examination process included measuring height,weight,and blood pressure.From a follow-up survey in 2010-2012,1 252 subjects were analyzed by the same measurements (height,weight and blood pressure)and also by using subclinical markers for vascular damage,including carotid intima-media thickness (cIMT)and carotid-femoral pulse wave velocity (cfPWV).Childhood hypertension at baseline and adulthood hypertension were diagnosed according to the China Guideline for Hypertension Prevention and Control issued in 2010.High cfPWV and high cIMT were defined in adults as having higher than age and gender-specific 75th percentile of cfPWV and cIMT.Pearson correlation coefficients were calculated to describe the association of K4 and K5 in childhood with systolic blood pressure(SBP),diastolic blood pressure(DBP),cfPWV, and cIMT in adulthood.Logistic regression was used to analyze the values of K4 and K5 to predict subclinical CVD in adulthood.Results The baseline mean value of K4 DBP was (66.4 ± 9.1)mmHg (1 mmHg＝0.133 kPa)and K5 DBP was (54.1 ± 11.1)mmHg.The prevalence rates of high-normal blood pressure were 9.4% with DBP measured by using K4,and 6.9% with DBP measured by using K5,respectively. The prevalence rates of hypertension were 11. 3% with DBP measured by using K4,and 8.4%with DBP measured by using K5.After adjustment for age and follow-up age,Pearson correlation analyses showed K4 DBP and K5 DBP in childhood were all significantly associated with adult SBP,DBP,cIMT,cfPWV in males and in females (all P＜0.05).K4 in childhood was better correlated with SBP,DBP,cIMT and cfPWV in adulthood than K5.With multi-factor logistic regression analysis,K4 was better than K5 in predicting CVD in adulthood after controlling gender and age.Further K4 was more effective in predicting cfPWV than cIMT.Conclusions There was a significant difference between K4 and K5 in Chinese children and adolescents. K4 in childhood was better correlated with CVD in adults than K5,and K4 is superior to K5 when using auscultator technique to measure DBP.

High risk screening and disease spectrum for 24 kinds of lysosomal storage diseases / 中华实用儿科临床杂志

Objective To evaluate the sensitivity and specificity of enzyme assays,and to provide disease spectrum of lysosomal storage diseases (LSDs).Methods Three thousand three hundred and sixty-four high risk individuals were screened for 24 LSDs at Guangzhou Women and Children's Medical Center between January 2009 and December 2016.Twenty-two kinds of enzyme activities from peripheral blood leucocytes or plasma were measured by using the fluorometry or colorimetry of corresponding artificial substrates,screening for 24 LSDs diseases.Measurement data were represented by (x) ± s,and count data were expressed as a percentage or composition ratio.Results A total of 283 subjects were diagnosed with 18 different kinds of LSDs,and the positive rate of high-risk screening was 8.4％.Among the identified patients,172 cases (60.8％) were mucopolysaccharidosis (MPS),79 cases (27.9％) were sphingolipidoses,18 cases (6.4％) were Pompe diseases,10 cases (3.5％) were affected with mucolipidoses,3 cases (1.1％) were glycoprotein storage diseases,and 1 case(0.4％) was Wolman disease.Of the MPS cases,there were 75 cases of MPS Ⅱ (43.6％),45 cases of MP5 ⅣA (26.2％),24 cases of MPS Ⅵ (14.0％) and 20 cases of MPS Ⅰ (11.6％).Gaucher disease (23/79 cases,29.1％) and metachromatic leukodystrophy (MLD) (21/79 cases,26.6％) were common in sphingolipidoses group.Both the sensitivity and specificity of enzyme assays on peripheral blood leucocytes for LSDs were 100％.Conclusions The most common kinds of LSDs are MPS Ⅱ,MPS Ⅳ A,MPS Ⅵ,Gaucher disease,MLD and Pompe disease.Leukocyte enzymology analysis of high-risk screening LSDs has high sensitivity and specificity.

Effect of genetic polymorphisms on change in body mass index and obesity status during childhood / 中华预防医学杂志

Objective@#The present study aimed to prospectively validate whether the single nucleotide polymorphisms (SNPs) in obesity-related genes were associated with change in body mass index (BMI) and obesity status during childhood.@*Methods@#Based on the Beijing Child and Adolescent Metabolic Syndrome study (BCAMS), which was initiated between April and October in 2004, we conducted a follow-up study among 1 624 children aged 6 to 11 years old with genetic data in December 2010. A total of 777 children (246 obese and 531 non-obese) were reassessed for BMI. Z-score of BMI was used to standardize for age and sex. The changes in BMI Z-score during follow up were calcnlated SNPs were genotyped by quantitative Real-time PCR (rs9939609, rs6499640, rs7138803, rs1805081, rs17782313, rs6265, rs10938397, rs6235, rs29941, rs2844479, rs10913469 and rs4788102). Overweight and obesity were diagnosed by the age-and sex-specific BMI cutoffs recommended by the International Obesity Task Force. A multilocus genetic risk score for BMI was calculated as the simple sum of alleles of all the SNPs associated with BMI. Linear regression models and logistic regression models were performed to assess the associations of change in BMI Z-score and obese status with genotypes (assuming an additive model), respectively.@*Results@#During 6 years of follow-up, 158 previously obese children remained obese as they aged into adolescence, and 88 transiently obese children were not obese during the second survey, 58 children were newly identified obese, and the other 473 children remained their non-obese state. BMI Z-score increased from 1.41±0.05 at baseline to 1.57±0.06 at follow up.The genotypes of the SNPs except rs6499640(P=0.033) and rs6265(P=0.041) were in Hardy-Weinberg equilibrium in each group (P>0.05). Each additional copy of the rs9939609 A allele was significantly associated with an increase in BMI Z-score (β=0.205, P=0.014) during follow up. Per C allele of rs17782313 was associated with an increase in BMI Z-score at baseline (β=0.268, P=0.003). As the non-obese reference, a significantly relative risk of obesity at follow up was observed for children carrying rs9939609 A-allele versus the T-allele carriers (OR=2.37, 95%CI: 1.45-3.88, P=0.001). Rs17782313 C-allele was significantly increase the risk of obesity only at baseline (OR=1.79, 95%CI: 1.24-2.60, P=0.002). Rs1805081 A-allele was significantly associated with durative of obesity (OR=1.45, 95%CI: 1.04-2.03, P=0.028). Each unit higher genetic risk score was associated with increases risk of 0.18 times (OR=1.18, 95%CI: 1.05-1.33) in childhood transient obesity, and 0.22 times (OR=1.22, 95% CI: 1.06-1.42) in incident obesity at follow-up. But it was not significantly associated with persisted obesity during 6 years of follow-up (OR=1.09, 95% CI: 0.99-1.20).@*Conclusion@#We confirmed that the change of BMI and obesity status in children was affected by different genetic factors. Individual who carries more risk alleles in obesity-related genes may increase the susceptibility to obesity.

Current situation in studies on precision medicine and its visualization analysis / 中华医学图书情报杂志

The development trend, countries, institutions, co-authors, and subjects in MEDLINE-covered papers were analyzed by Excel, Ucinet and SciMAT respectively in order to understand the current situation in studies on precision medicine, which showed that precision medicine is in a rapid development stage, the impact power of pa-pers on precision medicine published in United States of America is high, the source journals published in United States of America are the core journals in precision medicine, the academic level of papers on precision medicine published in United States of America is high. Co-authors analysis showed that the co-authors network is of the small world effect. Subject evolution analysis revealed that the subjects involved in studies on precision medicine are increasingly rich with genomics, drug treatment and oncology accounted a large proportion. Analysis of the evo-lution in genomics, drug treatment and oncology displayed that the subjects involved in studies on precision medi-cine have experienced macro-stage, micro-stage, and combined macro- and micro-stage.

Change in the prevalence of obesity phenotypes and cardiometabolic disorders among children aged 6- 17 in Beijing during 2004- 2013 / 中华预防医学杂志

<p><b>OBJECTIVE</b>To examine the prevalence of obesity phenotypes and cardiometablic disorders (CDs) among children aged 6- 17 in Beijing from 2004 to 2013.</p><p><b>METHODS</b>Data were obtained from two cross-section surveys, which were conducted in 2004 and 2013. In 2004, by using stratified cluster sampling design, 20 primary or middle schools were selected from 7 districts (Xicheng, Dongcheng, Chaoyang, Haidian, Daxing, Pinggu, and Yanqing) in Beijing, and 20 554 school children aged 6-17 were recruited, with weight, height, waist circumference and blood pressure measured. Fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were measured in 962 subjects from one school. In 2013, by using the same sampling design, 7 211 students from two districts (Haidian and Dongcheng) were surveyed with weight, height, waist circumference and blood pressure measured, and fasting plasma glucose and lipid profile (TC, TG, HDL-C, LDL-C) were measured for 1 344 subjects in the same school measured in 2004. Student's-t test was used to analyze the difference in body mass index(BMI), WC, and waist to height ratio (WHtR) among children between 2004 and 2010. Chi-square test was used to analyze the difference of hypertension, impaired fasting glucose(IFG), dyslipidemia, and metabolic disorders clustering between 2004 and 2010, and among different types of obesity; logistic regression model was used to analyze the association between three types of obesity and risks of cardiovascular metabolic disorders.</p><p><b>RESULTS</b>In boys, BMI ((20.3 ± 4.4) vs (19.4 ± 4.2) kg/m(2), t=11.18, P<0.001), WC ((70.6 ± 12.8) vs (66.7 ± 11.8) cm, t=17.20, P<0.001) and WHtR (0.451 ± 0.064 vs 0.437 ± 0.059, t=11.64, P<0.001) were significantly higher in 2013 than those in 2004. Similarly in girls, BMI ((18.9 ± 3.6) vs (18.7 ± 3.7) kg/m(2), t=12.21, P<0.001), WC ((64.5 ± 9.6) vs (63.0 ± 9.3) cm, t=8.15, P<0.001) and WHtR (0.430 ± 0.047 vs 0.423 ± 0.047, t=14.13, P<0.001) were also significantly higher in 2013 than those in 2004. The prevalence of combined obesity rose from 8.27% (1 697/20 526) in 2004 to 10.74% (774/7 209) in 2013, and central obesity from 3.08% (632/20 526) to 4.44% (320/7 209). The prevalence of hypertension (10.78%(313/1 344) vs 4.29% (42/962), χ(2)=36.76, P<0.001), IFG(49.54%(664/1 344) vs 6.45%(63/962), χ(2)=506.61, P<0.001), high TC(11.53%(155/1 344) vs 5.03%(49/962), χ(2)=28.31, P< 0.001), high TG(7.51%(101/1 344) vs 3.59%(35/962), χ(2)=29.59, P<0.001) were significantly higher in 2013 than those in 2004. Subjects with combined obesity had higher risks of hypertension (OR=5.88, 95% CI: 4.42-7.82), high TG (OR=7.12, 95%CI: 4.35-11.64), low HDL-C (OR=3.04, 95%CI: 1.55-5.95), high LDL-C (OR=2.27, 95% CI: 1.22-4.02), CDs≥2 (OR=3.07, 95% CI: 2.09-4.50), comparing to children without obesity.</p><p><b>CONCLUSION</b>The prevalence of types of obesity and obesity-related metabolic disorders, except for low HDL-C and high HDL-C, were significantly higher in 2013 than those 2004 among chlildren aged 6-17 year in Beijing. Children with combined obesity had higher prevalence of metabolic disorders.</p>

Effect of childhood adiposity on long-term risks of carotid atherosclerosis and arterial stiffness in adulthood / 中华预防医学杂志

<p><b>OBJECTIVE</b>To observe the effect of childhood excessive adiposity on long-term risk of adult carotid atherosclerosis and arterial stiffness.</p><p><b>METHODS</b>At baseline, in 1987, by using stratified cluster sampling design, 3 198 healthy children aged 6-18 were recruited from six primary schools and six middle schools from three districts (Chaoyang, Xicheng, and Haidian) in Beijing, with blood pressure, weight, height and left scapular skinfold thickness (LSSF) measured. From April 2010 to July 2012, 1 225 subjects were followed from childhood to adulthood. Questionnaire, biochemistry parameters, carotid-femoral pulse wave velocity (cfPWV), and carotid intima media thickness (cIMT) were measured at follow-up. Based on weight statuses in childhood and adulthood, subjects were classified into four groups (persistent non-overweight from childhood to adulthood, overweight in childhood but non-overweight in adulthood, non-overweight in childhood but overweight in adulthood, persistent overweight from childhood to adulthood). Multiple logistic regression model was used to analyze the association between weight statuses changing from childhood to adulthood and adult high cfPWV and high cIMT.</p><p><b>RESULTS</b>The prevalence of overweight (including obesity) at adulthood was 52.2% (639). Males had higher prevalence of smoking (62.5%(422/675) vs 29.4%(160/550), χ(2)=133.21, P<0.001), drinking (52.1%(353/675) vs 26.1%(140/550), χ(2)=87.13, P<0.001), overweight (including obesity) (69.3% (468/675) vs 31.1% (171/550), χ(2)=182.18, P< 0.001) than females. With adjusting for gender, age, and length of follow-up, the risk of high cfPWV and high cIMT increased by 26% and 58% for 1 units increase in BMI, and by 30% and 36% for 1 units increase in LSSF. Compared to subjects with persistent non-overweight from childhood to adulthood, subjects with overweight in childhood but non-overweight in adulthood had similar risks of high cfPWV (OR=1.59, 95%CI: 0.77-3.30)and high cIMT (OR=1.47, 95%CI:0.65-3.31). The risks of high cfPWV and high cIMT increased among subjects with non-overweight in childhood but overweight in adulthood (OR=1.92, 95%CI:1.37-2.68; OR=3.69, 95% CI:2.61- 5.23) and among subjects with persistent overweight from childhood to adulthood (OR=2.53, 95%CI:1.70-3.76; OR=5.37, 95%CI:3.62-7.97).</p><p><b>CONCLUSIONS</b>We concluded that a overweight children changed to a healthy weight adult, the risks of adult subclinical atherosclerosis and arterial stiffness would not be increased.</p>

Association of childhood and adolescents obesity with adult diabetes / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the correlation between obesity in children and diabetes in adults from a cohort study, and further more to explore the necessity of preventing diabetes by controlling obesity in children.</p><p><b>METHODS</b>In 1987, 3 198 children and adolescents aged 6-18 were recruited from 6 elementary schools and 6 high schools located in 3 districts (Chaoyang, Haidian, and Xicheng) of Beijing using stratified cluster sampling design. The physical examination process included physical development test, blood pressure measurement, and questionnaire investigation. All children were invited to participate in the study, except for those who had history of congenital heart disease, chronic kidney disease, and limb disability. A total of 1,225 adults were enrolled in a prospective follow-up study from March 2010 to July 2012, anthropometric measures and blood sample were obtained. The obesity was defined by the following criteria: for children aged 6, the age-and the gender-specific 95th percentile of BMI from the US Centre for Disease Control and Prevention Growth charts 2000 as the baseline; for children age 7-18, recommendation from Working Group on Obesity in China (WGOC) as the standard; for adults, BMI≥28 kg/m(2) as the diagnosis standard. Diabetes was defined based on fasting plasma glucose(FPG) ≥7.0 mmol/L or 2 hours postprandial blood glucose (2 h PG) ≥11.1 mmol/L or glycosylated hemoglobin (HbA1c) ≥6.5% or current using blood glucose-lowering agents or current using insulin. Logistic regression was used to analyze the association obesity in children with diabetes in adults.</p><p><b>RESULTS</b>The prevalence of diabetes diagnosed by FPG and 2 h PG in adults who were obese children (16.2%, 18/111) was higher than those who were non-obese children (5.6%, 62/1,114)(χ(2)=18.76, P<0.001). The prevalence of diabetes diagnosed by HbA1c in adults who were obese children(18.1%,20/111) was higher than those who were non-obese children (6.9%, 77/1,114) (χ(2)=16.66, P<0.001). With multi-factor logistic regression analysis, we found that after controlling follow-up age, genders and lifestyle (smoking, alcohol consuming, dietary, and sleeping), in comparison with those non-obese from childhood to adulthood, those obese only in childhood or only in adulthood did not predict any risk of diabetes diagnosed by blood glucose in adults (OR(95%CI) were 1.90 (0.86-4.19), 1.71(0.50-5.79), respectively). Those obese both in childhood and in adulthood increased the risk of diabetes diagnosed by blood glucose in adults (OR(95%CI) was 4.50(2.22-9.14)). With multi-factor logistic regression analysis, we found that after controlling age, sex and lifestyle (smoking, alcohol consuming, dietary, and sleeping) in comparison with those non-obese from childhood to adulthood, those obese only in childhood or only in adulthood did not increase the risk of diabetes diagnosed by HbA1c in adults (OR(95%CI) were 1.42(0.71-2.86), 3.13(0.83-11.75), respectively). Those obese both in childhood and in adulthood increased the risk of diabetes diagnosed by HbA1c in adults (OR(95%CI) was 5.93(3.06- 11.49)).</p><p><b>CONCLUSION</b>Obesity in children even sustained to adulthood was a risk factor for diabetes in adulthood. It is necessary to control obesity in children to prevent diabetes in adults.</p>

Joint effect of birth weight and obesity measures on abnormal glucose metabolism at adulthood / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the joint effect of birth weight and each of obesity measures (body mass index (BMI) and waist circumference (WC)) on abnormal glucose metabolism (including diabetes) at adulthood.</p><p><b>METHODS</b>Using the historical cohort study design and the convenience sampling method, 1 921 infants who were born in Beijing Union Medical College Hospital from June 1948 to December 1954 were selected to do the follow-up in 1995 and 2001 respectively. Through Beijing Household Registration and Management System, they were invited to participate in this study. A total of 972 subjects (627 were followed up in 1995 and 345 were followed up in 2001) with complete information on genders, age, birth weight, family history of diabetes, BMI, WC, fasting plasma glucose (FPG) and 2-hour plasma glucose (2 h PG) met the study inclusion criteria at the follow-up visits. In the data analysis, they were divided into low, normal, and high birth weight, respectively. The ANOVA and Chi-squared tests were used to compare the differences in their characteristics by birth weight group. In addition, multiple binary Logistic regression model was used to investigate the single effect of birth weight, BMI, and waist circumference on abnormal glucose metabolism at adulthood. Stratification analysis was used to investigate the joint effect of birth weight and each of obesity measures (BMI and WC) on abnormal glucose metabolism.</p><p><b>RESULTS</b>There were 972 subjects (males: 50.7%, mean age: (46.0±2.2) years) included in the final data analysis. The 2 h PG in low birth weight group was (7.6±3.2) mmol/L , which was higher than that in normal birth weight group (6.9±2.1) mmol/L and high birth weight group (6.4±1.3) mmol/L (F=3.88, P=0.021). After adjustment for genders, age, body length, gestation age, family history of diabetes, physical activity, smoking and alcohol consumption, and duration of follow-up, subjects with overweight and obesity at adulthood had 2.73 (95% confidence interval (CI) =2.06- 3.62) times risk to develop abnormal glucose metabolism when compared with norm weight ones. Likewise, subjects with central obesity were more likely to develop abnormal glucose metabolism than ones with normal waist (odds ratio (OR)=3.35, 95%CI=2.49-4.50). In addition, compared to subjects with normal birth weight and normal BMI at adulthood, ones with normal birth weight and overweight (including obesity) at adulthood were more likely to have abnormal glucose metabolism (OR= 2.60, 95%CI=1.94-3.49); subjects with low birth weight and overweight (including obesity) at adulthood had the highest risk for abnormal glucose metabolism (OR=4.70, 95% CI=1.84- 11.99). The attributable proportion of interaction between low birth weight and overweight (including obesity) at adulthood was 48.5%. In addition, compared to subjects with normal birth weight and normal WC at adulthood, one with normal birth weight and central obesity at adulthood were more likely to have abnormal glucose metabolism (OR=3.18, 95% CI=2.33- 4.32); subjects with low birth weight and central obesity at adulthood had the highest risk for abnormal glucose metabolism (OR=4.78, 95% CI=2.01- 11.38); subjects with high birth weight and central at adulthood also had high risk for abnormal glucose metabolism (OR=4.35, 95%CI=1.38- 13.65). We found that the attributable proportion of interaction between low birth weight and central obesity at adulthood was 38.5% , and was 28.3% for interaction between high weight and central obesity.</p><p><b>CONCLUSION</b>There was strong interaction effect between birth weight and overweight (especially central obesity) at adulthood on abnormal glucose metabolism at adulthood. Effective measures should be adopted to prevent and control adult obesity in order to offset the adverse effect of birth weight on long-term health risk.</p>

IL-27 Alleviates the Bleomycin-induced Pulmonary Fibrosis through Regulating TGF-β/Smad Signaling Pathway / 昆明医科大学学报

Objective To explore whether IL-27 inhibited the pulmonary fibrosis through regulating the expression of TGF-β/Smad signaling pathway in the bleomycin-induced pulmonary fibrosis model. Methods Forty male C57/BL6 mice were randomly divided into normal control group(group A),bleomycin-induced pulmonary fibrosis group(group B),bleomycin+IL-27 group(group C)and bleomycin+IL-27 antibody group(group D) with 10 in each. Five mice in each group were sacrificed on days 7 and 28 after with intratracheal bleomycin. TGF-βR1,Smad1 and Smad3 in right lung tissue were measured by Western Blot. Results 1. In the bleomycin-induced pulmonary fibrosis model,the expression of TGF-βR1 was higher on days 7 and 28,which was inhibited by IL-27. 2. The expressions of p-Smad1 and p-Smad3 were highest in group D on days 7 and 28, but were lower in group C on day 7 than those in group B. Conclusion Exogenous IL-27 might alleviate pulmonary fibrosis through inhibiting the related protein phosphorylation in TGF-β/Smad signaling pathway.

The association between uric acid levels and cardiovascular metabolic disorders and non - alcohol fatty liver disease among obese children / 中华实用儿科临床杂志

Objective To observe the prevalence of hyperuricemia(HUA)among obese children,and to ex-plore the association between uric acid(UA)levels and cardiometabolic risk factors,acanthosis nigricans and non - al-cohol fatty liver disease(NAFLD). Methods By using representative sampling method,1 753 obese children aged 6 -17 years old from 18 schools in 3 districts of Beijing(Xicheng,Haidian,Miyun)were selected to participate in the clini-cal examinations,including anthropometric measurements(height,weight)and blood pressure. Serum biochemical pa-rameters were assessed,including fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG),high - densi-ty lipoprotein cholesterol(HDL - C),low - density lipoprotein cholesterol(LDL - C)and UA. Acanthosis nigricans and B - model ultrasonography of the liver were conducted. Results The prevalence of hypertension,impaired fasting glu-cose,dyslipidemia,acanthosis nigricans,and NAFLD among these 1 753 obese children was 33. 6%(589 cases), 66. 5%(1 156 cases),54. 3%(943 cases),23. 3%(408 cases),and 17. 0%(298 cases),respectively. The preva-lence of HUA was 40. 70%(714 / 1 753 cases),with 50. 17%(581 / 1 158 cases)in boys and 22. 34%(133 / 595 ca-ses)in girls. There was a significant increase in body mass index,systolic blood pressure,diastolic blood pressure, FPG,TG and LDL - C with the increase of UA,but there was a decrease in HLD - C with the increase of UA(all P ﹤0. 05). In boys,the adjusted odds ratios( OR)and 95% CI of the highest quartile of UA for hypertension,impaired fasting glucose,dyslipidemia,acanthosis nigricans,and NAFLD were 1. 16(0. 77 - 1. 74),1. 34(0. 90 - 1. 99),1. 29 (0. 89 - 1. 87),1. 89(1. 17 - 3. 04),and 1. 71(1. 03 - 2. 84),respectively;in girls,the adjusted OR and 95% CI of the highest quartile of UA for hypertension,impaired fas-ting glucose,dyslipidemia,acanthosis nigricans,and NAFLD was 0. 70(0. 40 - 1. 24),0. 60(0. 40 - 1. 00),1. 69(1. 04 - 2. 70),1. 67(0. 80 - 3. 49),and 1. 33(0. 48 - 3. 66),re-spectively. Conclusions The prevalence of HUA is relatively high in obese children and there is a strong association between UA and some car-diovascular metabolic disorders,acanthosis nigricans and NAFLD.

Clinical and molecular characteristics of a child with juvenile Sandhoff disease / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the clinical features and molecular mutation of HEXB gene in a case with juvenile Sandhoff disease.</p><p><b>METHOD</b>We retrospectively reviewed the clinical, neuroimaging and biochemical findings in this Chinese child with juvenile Sandhoff disease. Hexosaminidase A and hexosaminidase A & B activities were measured in blood leukocytes by fluorometric assay. HEXB gene molecular analysis was performed by PCR and direct sequencing.</p><p><b>RESULT</b>The 9-year-old boy was admitted for psychomotor regression. He presented slowly progressive gait disorder and dysarthria during the last three years. Cranial MRI revealed a marked cerebellar atrophy with normal intensity in the thalamus and basal ganglia. Brain MRS showed normal in the thalamus and basal ganglia. Hexosaminidase A was 69.5 (mg·h) [normal controls 150-360 nmol/(mg·h)], hexosaminidase A & B activity was 119 nmol/(mg·h)[normal controls 600-3 500 nmol/(mg·h)], confirming the diagnosis of Sandhoff disease. The patient was a compound heterozygote for a novel deletion mutation c.1404delT (p. P468P fsX62) and a reported mutation c.1509-26G>A.</p><p><b>CONCLUSION</b>The clinical features of juvenile Sandhoff disease include ataxia, dysarthria and cerebellar atrophy. The enzyme assay and molecular analysis of HEXB gene can confirm the diagnosis of Sandhoff disease. The novel mutation c.1404delT(p. P468P fsX62) is a disease-related mutation.</p>

Maturity-onset diabetes of the young 2 with a novel mutation of glucokinase gene in a Chinese boy and the clinical follow-up / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the clinical and gene mutation characteristics of a child with maturity-onset diabetes of the young 2 (MODY2).</p><p><b>METHOD</b>The clinical and follow-up data of 1 patient with MODY2 were reviewed. GCK mutational analysis was performed by PCR and direct sequencing in the proband and his family members.</p><p><b>RESULT</b>The 9 years and 6 months old boy was referred to our department for short stature and mild hyperglycemia. His fasting blood glucose was elevated to 7.4-7.8 mmol/L, hemoglobin A1C 6.7%. His height was 122 cm (-2 s), weight 25 kg (-1 s), body mass index (BMI) 16.8 kg/m(2). His physical exam was unremarkable without dysmorphic features or acanthosis nigricans. The oral glucose tolerance test (OGTT) showed fasting glucose 8.17 mmol/L, insulin <2.0 mU/L, 2 h glucose 8.69 mmol/L, insulin 5.06 mU /L. The boy was treated with insulin injection for half a year. His fasting blood glucose was stable at 5.6-8.5 mmol/L, hemoglobin A1C 6.7%-6.8%. His mother's fasting blood glucose was 6.86 mmol/L, OGTT 2 h blood glucose 10.36 mmol/L, hemoglobin A1C 6.8%. GCK sequence revealed a novel GCK mutation c.34_44+15del26 in the proband and his mother, which was co-segregated with diabetes. The boy's treatment was shifted from insulin injection to diet and exercise after the diagnosis of MODY2 was confirmed. Being followed up for 2 and a half years, his fasting blood glucose was stable at 4.6-8.0 mmol/L and hemoglobin A1C 6.8%-7.1%.</p><p><b>CONCLUSION</b>The clinical features of MODY2 are persistent and stable fasting hyperglycemia over a period of months or years and small blood glucose increment (less than 3 mmol/L) after an OGTT (2 h glucose-fasting glucose). We identified a novel c.34_44+15del26 mutation in GCK which co-segregated with diabetes phenotype in this family.</p>