The major progress on the study of etiology of the Hirschsprung's disease is the genetic factots and the aherations of microenvironment in primarily embryogenic period.The genetic factors comprise of RETGDNF system.EDNRB.EDN3 system,and many other genes involving in the formulation of the tormer two svstems.such as SOX10,NRG-1, FoxD3,PHOX2B,HOXB5,ZFHXIB,all of which file essencial for the migration and differentiation of neural crest cells(NCC).The alterations of microenvironment in primarily embryogenic period include interstitial ceLls of cajal(ICC),cell adhesion molecules(CAMLl),Ca2+ and so on.Definitely,CAML1 plays as the basis of NCC's migration and differentiation,and the decline of the Ca2+dependent channel's expression brings about the anolnaloug contraction of smooth muscle.

Objective To investigate whether the effect of pioglitazone on TNF-α-induced insulin resistance is associated with altering IRS-1-induced signaling. Methods 3T3-L1 adipocytes were treated with TNF-α for 24 hours with or without being pretreated with 10μM piglitazone for 6 hours or with pioglitazone alone.Insulin-stimulated glucose uptake of 3T3 adipocytes was measured by using 2-deoxy 3H glucose.The Western blot was used to measure IRS-1, PKB, PKC-λ protein and tyrosine phosphorylation on IRS-1, PKB and PKC-λ phosphorylation. Results Both TNF-α and pioglitazone increased glucose uptake of 3T3 adipocytes under basal status.On TNF-α treated cells, insulin-stimulated glucose uptake was decreased by about 50%, accompanied with the reductions of IRS-1 protein level, tyrosine-phosphorylation of IRS-1 and PKB phosphorylation.TNF-α treatment had no effect on PKC-λ phosphorylation. Pioglitazone pretreatment was able to antagonize TNF-α-induced insulin resistance in 3T3 adipocytes partly reverse IRS-1 protein, increase insulin-stimulated tyrosine phosphorylation of IRS-1,and increase phosphorylations of PKB and PKCλ. Conclusion TNF-α-induced insulin resistance in 3T3-L1 adipocytes is related to impaired tyrosine phosphorylation of IRS-1. Pioglitazone antagonizes the above TNF-α induced insulin resistance.

0 05).Conclusion The distribution frequency of bb type of VDR genotypes in Han populations of China was more prevalent,followed by Bb and bb types in turn.In the patients receiving long term glucocorticoid therapy,there is no significant difference in BMD between Bb and BB genotypes.The data suggest that the VDR genotypes may not be a means to identify patients at great risk of glucocorticoid induced osteoporosis,which await to be further confirmed with a large sample size.

MicroRNAs (miRNAs) are small endogenous non-coding RNA molecules.They regulate negatively the expression of target genes at post-transcriptional stages by means of affecting the stability of target mRNA or interfering with the transcriptional process.Recently,there is evidence demonstrating that miRNAs play important roles in the gene expressions of thyrotoxic heart diseases.Elevated levels of thyroid hormones profoundly influence the cardiovascular system through the renin-angiotensin system (RAS).As a principal active component of RAS,angiotensin Ⅱ receptor 1 (AT1 R) interacts with miRNAs in promoting or extenuating the progress of thyrotoxic heart disease.In this article,the roles of AT1R-associated miRNAs,miR-21,miR-155,miR-208a/b,and miR-499 in thyrotoxic heart disease were reviewed.

Objective To explore the right timing of mechanical ventilation in patients with bronchial asthma in emergency room.Methods A total of 67 patients with bronchial asthma undergoing mechanical ventilation were admitted into our Emergency Intensive Care Unit (EICU) from January 2010 to December 2012.According to PaCO2 before intubation,they were divided into 3 groups of low levels of PaCO2 [PaCO2 ≤35 mmHg (1 mmHg =0.133 kPa)] (n =19),normal PaCO2 (35 mmHg ＜ PaCO2 ＜ 45 mmHg) (n =21) and high PaCO2 (PaCO2 ≥ 45 mmHg) (n =27).Their clinical data were retrospectively analyzed.Results The in-hospital mortality of three groups were 5.3％ (1/19),9.5％ (2/21) and 14.8％ (4/27) and the difference was not statistically significant (x2 =1.16,P ＞ 0.05).However the average duration of mechanical ventilation of three groups were (5.6 ± 1.7),(8.3 ± 2.1) and (13.5 ±3.6) days and the difference was statistically significant (F =3.36,P =0.042).The average ICU treatment time was (7.4 ± 2.1),(11.5 ± 3.3) and (16.4 ± 3.5) days and the difference was statistically significant (F =3.23,P =0.047).PaCO2 levels before intubation was positively correlated with the duration of mechanical ventilation and the ICU treatment time (r2 =0.366,0.316,P =0.031,0.029).Conclusion The patients with bronchial asthma undergoing intubation in right time in emergency room will affect the duration of mechanical ventilation and ICU treatment time.

Objective To analysis the prognosis of esophageal carcinoma patients with anemia before radiotherapy. Methods 137 patients with esophageal carcinoma treated with three-dimensional conformal radiation therapy (3D-CRT) in the Second Peopleˊs Hospital of Jiaozuo over the past five years were retrospectively analyzed. There were 40 patients with anemia and 97 cases without anemia before radiotherapy. The prognosis of patients with anemia and the relationship with other clinical factors were evaluated by survival analysis. Results The 3-year and 5-year overall survival (OS) rates in non-anemic group were 43.6 % and 35.7 %, respectively, and 21.0 % and 16.4 % in anemic group. The 3-year and 5-year disease-free survival (DFS) rates in non-anemic group were 38.5 % and 25.3 %, respectively, and 13.1 % and 9.2 %in anemic group. The Kaplan-Meier method showed that both 3-year and 5-year OS and DFS rates in non-anemic group were significantly higher than those in anemic group (P< 0.05). Conclusion Anemia is the independent prognostic factor for patients with esophageal carcinoma in many clinical factors.

AIM: To study the effect of calories restriction on endoplasmic reticulum(ER) chaperone protein 78-kD glucose regulated protein(GRP78) mRNA expression in the liver of high fat diet rats,in order to explore the mechanism of how calories restriction improves insulin resistance.METHODS: Wistar rats(n=24) were randomly divided into 3 groups: normal chow(NC) group,was fed free normal chow(18.94% of calories as fat) for 12 weeks;high fat group(HF) was fed high fat diet(50.55% of calories as fat) for 12 weeks;calories restriction group(CR) was fed high fat diet for 8 weeks at first,then given 50% of diet consumed by the same age NC group.Changes of body weight,height,and food intake were recorded.At the end of experiment,HOMAIR,the rate of visceral fat(including perirenal fat and epididymal fat) vs weight,plasma protein,blood lipid(including total cholesterol and triglyceride),hepatic GRP78 mRNA and hepatic histological changes(including light microscopic studies and electron microscopic studies) were detected.RESULTS:(1) Animals in HF group had an obviously elevation of fasting insulin(27.51?3.51) mU/L vs(15.46?2.25) mU/L,triglyceride(1.35?0.25) mmol/L vs(0.67?0.10) mmol/L,total cholesterol(2.59?0.34) mmol/L vs(1.41?0.28) mmol/L and insulin resistance index HOMAIR(5.85?0.23 vs 2.85?0.60) compared with NC group,and also had obviously lipid accumulations in the liver.(2) After calories restriction,all the abnormal elevated biochemical indicators were decreased to normal levels,the hepatic lipid accumulations were also improved.(3) The changes of liver ultrastructure in HF group showed rough endoplasmic reticulum enlargement,fragmentation,taking off grain,and with glycogen solution.The changes in CR group were nearly the same as those in NC group.(4) High fat diet induced the expression of GRP78 mRNA, calories restriction might reverse it.CONCLUSION: Reasonable food calories restriction is a good method to improve insulin resistance,partly due to improvement of endoplasmic reticulum stress in liver.

Objective:To investigate glucose uptake and IRS-1-associated signaling pathway by stimulated insulin under TNF-? treatment.Methods:3T3-L1 adipocytes were treated with TNF-? within 6 hours and 24 hours respectively. 2-deoxy ~3H glucose was used to measure glucose uptake and western blot was used to measure IRS-1, PKB protein, tyrosine and serine307 phosphorylation on IRS-1, and PKB phosphorylation.Results:On basal status, glucose uptake of 3T3-L1 cells and phospho-tyrosine of IRS-1, PKB phosphorylation, and serine307 phosphorylation on IRS-1 were all low. Insulin stimulation induced glucose uptake and IRS-1 tyrosine phosphorylation, serine307 phosphorylation, PKB phosphorylation rapidly. TNF-? inhibited insulin-induced glucose uptake, tyrosine phosphorylation of IRS-1 and PKB phosphorylation. Rapamycin reversed the effects of TNF-?. Treated with TNF-? within 6 hours increased serine307 phosphorylation but had no effect on IRS-1 protein level. TNF-?-induced serine307 phosphorylation of IRS-1 was not affected by rapamycin. IRS-1 level was decreased under 24 hours TNF-? treatment and rapamycin can reverse the effect.Conclusion:TNF-? induced insulin resistance in 3T3-L1 adipocytes mightbe related to impaired IRS-1 tyrosine phosphorylation, rapamycin could reverse the effects of TNF-?. Treated with TNF-? within 6 hours stimulate phosphrylation of serine307 of IRS-1 and 24 hours treatment decreased IRS-1 protein level. Rapamycin antagonist TNF-?-induced loses of IRS-1.

In order to determine whether the variations in the calpain-10 gene constitutes risk of type 2 diabetes (T2DM) in Chinese, the frequency of UCSNP-43, 44 in 268 adults newly diagnosed with T2DM (according to the 1999 ADA criteria) and 153 non-diabetic control subjects was investigated. For all subjects, the height, weight, waist-to-hip ratio (W/H) and blood pressure, as well as following parameters were measured: (1) 75-g oral glucose tolerance test with insulin, C-peptide, HbA1c and blood lipid profiles; (2) Genomic DNA extracted from peripheral blood lymphocytes was genotyped for UCSNP-43 (calpain-10-g. 4852 G/A) and UCSNP-44 (calpain-10-g. 4841 T/C) by sequencing a polymerase chain reaction (PCR)-amplified fragment. PCR product was selected by single strand conformation polymorphism (SSCP) and then sequenced. The results showed that there was significant difference between T2DM group and normal control group in allele frequencies, haplotype frequencies, or haplotype combinations of UCSNP-43 and -44 either. But in newly diagnosed T2DM group, it was found that the individuals with the genotype UCSNP-44 T/C + C/C had significantly increased fasting and post-challenge insulin levels (Fins and P2hIns), consistent with reduced insulin sensitivity. In the BMI> 25 subgroup, the differences were even more significant. It was demonstrated that the Calpain-10 gene polymorphism UCSNP-44 was associated with insulin sensitivity and Fins and P2hIns in newly diagnosed T2DM, although Calpain-10 doesn't appear as a major diabetes susceptible gene in this population.
Asian Continental Ancestry Group ; Calpain/*genetics ; Diabetes Mellitus, Type 2/*genetics ; Gene Frequency ; Genetic Predisposition to Disease/genetics ; Insulin Resistance/*genetics ; Phenotype ; Point Mutation ; Polymorphism, Genetic/*genetics

The effects of advanced glycation end-products (AGEs) on number and activity of vascular endothelial cells (VEC) from hone marrow stem cells (BMSC) of mice were investigated. 100 μ/ml AGEs markedly inhibited differentiation of BMSC into VEC with decreased vascular endothelial growth factor receptor-2 positive cells, hut 20 μg/ml AGEs had no effect.