Acute liver failure and end-stage liver diseases are llfe-threatening.So far,orthotopic liver transplantation is the unique treatment available for these late-stage liver diseases,which,however,is limited by the lack of donor liver.While hepatocyte transplantation,bioartificial liver and tissue engineered liver are potential alternative treatments,the limited availability of functional hepatoeytes is the major hurdle.Due to their extensive capacity for self-renewal and pluripotency to differentiate into cells,embryonic stem cells represent a potential unlimited cell source for therapy.The clinical application of embryonic stem cells in liver diseases requires well-defined and efficient protocols for differentiation,characterization and purification in vitro.Hepatic differentiation of embryonic stem cells in different culttire systelns and the problems remained are reviewed in this article.

Objective To analyze the dynamic trends of physical development,constitutional fitness,and prevalence of obesity among Han children and adolescents in Ningxia aged 7-18 years from 1985 to 2010.Methods Data were collected from the National Survey on Students Constitution and Health in 1985,1991,1995,2000,2005 and 2010,respectively.Height,weight and chest circumference were used to evaluate physical development,vital capacity,50-meter running and vital capacity versus weight ratio for the evaluation of constitutional fitness.Results 1.Weight and chest circumference increased faster than height.The average annual increase of weight among the urban girls was significantly faster than those in rural areas.2.The tempo per year of vital capacity in both boys and girls decreased during 25 years,especially after 2005.The rural students had a faster tempo than those in the urban students,and the rate in boys was higher than those in girls.Vital capacity to weight ratio in boys decreased from 2005 much more than before,and had a decreasing trend in each age group except for a few groups in girls.There was a decrease in the mean time of 50-meter running in both boys and girls from 1985 to 2005,whereas the decrease became slow during 1995-2005.The prolonged trend in 50-meter-run time existed during 2005-2010.The average prolonged speeds per decade in boys and urban students was higher than that in girls and rural areas.3.From 1985 to 2010 year,the increasing prevalence of overweight and obesity among boys and girls was 15.0％,25.0％ and 28.1％,12.4％,respectively.The average increasing rate was much higher in the obese than in the over-weighted children,and there were more in boys than in girls.There was a similar positive trend of increasing prevalence of overweight and obesity with the increased gross domestic product.Conclusions The physical growth and development among students in Ningxia increased rapidly,along with the descending trend of average annual rate of physical fitness as well as the rising trend of prevalence obesity.Some measures should be taken by the government to tackle with the situation,and the healthy intervention should be applied to the high risk population.

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.

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.

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.

Objective To understand the current status of physical activity among urban school-aged children and its association with obesity.Methods 295 pupils,aged 9 to 13 years were selected,using the method of convenience sampling.Data on anthropometric measurements was collected,including weight and height.Questionnaire survey,clinic examination,dietary investigation of school lunch and surveillance on 7-day physical activity by pedometers,were done and Multi-linear regression was used to analyze the relationship between waist to height ratio (WHtR),fat mass percentage (FMP),body mass index (BMI) and physical activity.Single-variable and multiple non-conditional logistic regression modeling were applied to analyze data collected from obesity and physical activities.Results 15.5％ of boys and 13.1％ of girls reached 60 minutes per day of ‘ moderate-vigorous physical activities’.Compared with normal children,overweight/obesity children showed an increase of sedentary activity time,total energy expenditure,and energy expenditure of physical activity.With the increase of 1 hours daily on going to school by private car,WHtR and FMP increased by 0.01 and 2.06 units,respectively.FMP increased 0.89 units among with the increase of sedentary activity time,1 hour daily.BMI and the intake of leafy vegetables (eg.spinach,cabbage)showed a negative correlation.As the frequency of leafy vegetables consumption increased once weekly,BMI fell 0.10 units.After adjustment for sex and age,the risk of overweight/obesity was 3.82-fold (95％CI:1.17-12.47) among children who had sedentary activity time more than 120 min/ d,than those having less than 120 min/d.Conclusion Our data showed that children' s daily physical activity was not enough and measures should be taken to decrease the time of sedentary behavior and increase the energy expenditure through physical activities.

Objective To assess the cardiovascular structure and function in children with confirmed primary hypertension,and to explore the impact of hypertension and related risk factors on cardiovascular structure and function of children.Methods Parameters related to cardiac structure,vascular structure and function were measured in 213 hypertensive children,who were confirmed upon repeated measurements on separate occasions.A total of 197 healthy children were recruited as controls.Results 1) In hypertensive children,left ventricular end-diastolic diameter (LVEDd),left ventricular end-systolic diameter (LVESd),left ventricular mass (LVM),left ventricular mass index (LVMI),left ventricular posterior wall thickness (LVPT) and interventricular septal thickness (IVST) were all significantly higher than their counterparts (P＜0.05).No statistical differences were found in carotid intima-media thickness (cIMT),relative wall thickness (RWT) and brachial ankle pulse wave velocity (ba-PWV).2) Compared with controls,LVEDd,LVESd,LVM,LVMI were all significantly higher in hypertensive children (P＜0.05),regardless of age group or weight-status.No statistical differences were found in ccIMT and RWT,while ba-PWV was statistically higher in controls among children aged 6-12 years.3) Data from multiple linear regression analysis noticed that LVMI was associated with age,sex,BMI and hypertension while RWT was associated with age and BMI.Conclusion In children with primary hypertension,changes of vascular structure and function were not shown but left ventricular remodeling and early changes of function had been developed in children under 12 years old.

Objective To evaluate the prevalence of metabolic syndrome (MS) in Chinese children and adolescents to provide scientific basis for early prevention of MS in the related populations.Methods Studies on CNKI,Wanfangdata,VIP and PubMed databases on related prevalence of metabolic syndrome in Chinese children and adolescents between 2004-2014 were searched.Quality of literatures was evaluated according to the cross-sectional study standard in Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement.Stata 12.0 software was used to estimate the prevalence of MS,as well as on gender,weight and other factors to make subgroup analysis.According to funnel plot and Egger assess publication bias,sensitivity analysis performed by excluding the impact of any article was generated by the combined effect of the value of literature.Results This study included 19 papers from the literature (5 in English,14 in Chinese).According to International Diabetes Federation (IDF),National Cholesterol Education Program Ⅲ (NCEP Ⅲ) and The definition and prevention recommends of metabolic syndrome in Chinese children and adolescents (CHN2012),the prevalence rates of MS in Chinese children were seen as 1.8％,2.6％ and 2.0％.According to IDF,the prevalence rates of MS appeared 2.9％ in boys and 1.8％ in girls,0.2％ in children with normal weight,4.7％ in overweight and 17.3％ in obesity.Both the results from NCEP Ⅲ and CHN2012 showed that the prevalence rates of MS as boys＞girls,obesity＞overweight＞normal weight.Conclusion Prevalence of MS in Chinese children and adolescents showed a general trend.Data under different standards showed different prevalence rates.Obesity appeared an important risk factor of MS,suggesting that in order to control obesity in children,attention should be paid to identifying and carrying out effective interventions on children under overweight or obesity.

To evaluate the reagent 2-methoxy-4,5-dihydro-1H-imidazole used for isotopic labeling in quantitative proteomics, we synthesized 2-methoxy-4,5-dihydro-1H-imidazole and its tetradeuterated analog in three steps. Prior to tryptic cleavage, bovine serum albumin (BSA) was reduced and alkylated. Tryptic peptides were derivatized with an equal volume of either DO or D4 and D4-derivatized peptides were mixed with at variable ratio (from 10:1 to 1:5) prior to MS and MS/MS analysis. We used matrix assisted laser desorption/ionization-mass spectrometry (MALDI-MS) and Electro spray ionization-mass spectrometry (ESI-MS) to evaluate the quantitative capability of labeling. The specificity of the reagent is excellent: only lysine side chains were modified among tryptic peptides. MALDI and ESI ionization modes not only could achieve the quantification of differentially expressed proteins but also facilitate the de novo sequencing. This side-chain modification can be used for quantitative analysis with proteomic strategies involving liquid chromatography. Reverse phase liquid chromatography (RPLC) kept a good resolution, and the introduction of D atoms did not introduce a variation of retention time between heavy and light peptides in RPLC.
Imidazoles ; chemistry ; Isotope Labeling ; methods ; Lysine ; chemistry ; Peptides ; analysis ; chemistry ; Proteomics ; methods ; Serum Albumin, Bovine ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; methods

OBJECTIVETo determine whether urinary type IV collagen can serve as an indicator specific for diabetic nephropathy.

METHODSUsing a novel sandwich ABC-ELISA to measure type IV collagen directly, the 24-hour urinary type IV collagen excretion rate was determined in 120 diabetic patients and some groups of controls. Urinary albumin determinations were made with a RIA kit at the same time. A total of 13 diabetic patients with microalbuminuria underwent percutaneous renal biopsy for definitive diagnosis of diabetic nephropathy. Type IV collagen and TGF-beta 1 immunoreactivities were detected with ABC methods in renal biopsies.

RESULTSUrinary type IV collagen excretion was significantly increased in diabetic patients with microalbuminuria, especially those with albumin excretion above 200 mg/24 h. By comparison, collagen excretion was equivalent to that in healthy controls when measured in diabetics with normalbuminuria and in patients with primary glomerular disease, primary hypertension, or coronary heart disease. Urinary type IV collagen excretion in diabetics was negatively correlated with creatinine clearance. In renal biopsies from subjects with elevated collagen excretion, the glomeruli showed pathological changes typical of diabetic nephropathy. Also, excessive type IV collagen and TGF-beta 1 immunoreactivity were detected in the glomeruli, Bowman's capsule and interstitium.

CONCLUSIONSExcretion of type IV collagen, possibly reflecting increased production or decreased degradation of this protein, may be a clinically useful indicator of incipient diabetic nephropathy.

Albuminuria ; urine ; Biomarkers ; urine ; Collagen Type IV ; urine ; Diabetes Mellitus, Type 2 ; urine ; Diabetic Nephropathies ; diagnosis ; Humans ; Transforming Growth Factor beta ; analysis