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.

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 compare gene expression profile of human hepatocellular carcinoma (HCC) cell lines with different metastatic potentials, so as to screen for metastasis-related genes.

METHODSGene expression profile of MHCC97-L and HCCLM3, two HCC cell lines with similar genetic background but different in spontaneous metastatic potentials, were studied by cDNA microarray.

RESULTSFrom 1,626 screened genes, 25 differentially expressed genes were found, 18 showed decreased expression including the decreased expression of cell cycle control genes Rb2, mismatch repair gene hMSH2, and signal transduction gene protein kinase C beta 2 and 7 increased expression including signal transduction gene MAP kinase kinase 6, cell proliferation gene E25, immunity related gene SP40, 40, etc in HCCLM3.

CONCLUSIONThe genes, being closely associated with cancer metastasis, could be considered as potential markers to predict metastasis and targets for anti-metastasis intervention.

Blotting, Northern ; Carcinoma, Hepatocellular ; genetics ; pathology ; Gene Expression ; Gene Expression Profiling ; Humans ; Liver Neoplasms ; genetics ; pathology ; Neoplasm Metastasis ; genetics ; Oligonucleotide Array Sequence Analysis ; RNA, Neoplasm ; analysis ; Tumor Cells, Cultured

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

OBJECTIVETo examine the prevalence of obesity phenotypes and cardiometablic disorders (CDs) among children aged 6- 17 in Beijing from 2004 to 2013.

METHODSData 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.

RESULTSIn 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.

CONCLUSIONThe 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.

Adolescent ; Beijing ; Blood Glucose ; analysis ; Blood Pressure ; Body Mass Index ; Body Weight ; Cardiovascular Diseases ; epidemiology ; Child ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Cross-Sectional Studies ; Dyslipidemias ; epidemiology ; Female ; Humans ; Hypertension ; epidemiology ; Lipids ; blood ; Logistic Models ; Male ; Obesity, Abdominal ; epidemiology ; Pediatric Obesity ; epidemiology ; Phenotype ; Prevalence ; Triglycerides ; blood ; Waist Circumference

OBJECTIVETo observe the effect of childhood excessive adiposity on long-term risk of adult carotid atherosclerosis and arterial stiffness.

METHODSAt 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.

RESULTSThe 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).

CONCLUSIONSWe concluded that a overweight children changed to a healthy weight adult, the risks of adult subclinical atherosclerosis and arterial stiffness would not be increased.

Adiposity ; Adolescent ; Adult ; Atherosclerosis ; epidemiology ; Beijing ; Blood Pressure ; Body Mass Index ; Carotid Artery Diseases ; epidemiology ; Carotid Intima-Media Thickness ; Child ; Female ; Humans ; Male ; Overweight ; epidemiology ; Pediatric Obesity ; epidemiology ; Pulse Wave Analysis ; Risk Factors ; Vascular Stiffness