ObjectiveTo investigate whether neuronal intermediate filament protein(NF-66) could be used as a molecular marker for the determination of malignancy of insulinoma.MethodsThe expression of NF-66 protein was detected in insulinoma and pana - cancerous tissues and 3 insulinoma cell lines by immunohistochemistry staining. The relationship between the expression of NF-66 protein and the clinicopathological characteristics,survival was analyzed by univariate and multivariate statistical analysis.ResultsExpression of NF-66 was found in 102(77％ ) out of 132 insulinomas and none of 98 paired control (P =4.86 × 10-31 ).NF-66 was highly expressed in 3 insulinoma cell lines.The expression of NF-66 was found in 96 (81％) out of 118 benign tumors (P =0.003),while out of 14 malignant insulinomas,6(43％ ) were found to express NF-66 ( P =0.003 ).The expression of NF-66 was significantly associated with tumor size (3 cm as the cut-off point),distant metastasis (38％ vs 81％,P =0.013) and distant plus lymph node metastasis (46％ vs 81％,P =0.009),respectively.The expression of NF-66 was not correlated with age,gender,recurrence and overall survival.ConclusionsDown-regulation of NF-66 was significantly associated with tumor malignancy,suggesting that NF-66 could be a potentially novel molecular bionarker to distinguish malignancy from benign insulinoma.

Objective To investigate the relationship between gene polymorphism of transcripion factor 7-like 2 (TCF7L2) at positions rs290487, rs11196205, rs11196218 and gestational diabetes mellitus (GDM) in Chinese women.Methods In 1140 unrelated pregnant Northern Chinese women (335 women with GDM, 158 gestational cases with impaired glucose tolerance and 647 pregnant non-diabetic controls) ,three single nucleotide polymorphisms (rs290487, rs11196205, and rs11196218) in the TCF7L2 gene were genotyped using ligase detection reaction (LDR).In the present study, cases with GDM and impaired glucose tolerance (IGT) were indistinguishable clinically and biochemically, and were combined into case group.Results The frequency of C allele of rs290487 was 41.6% in case group, being significantly higher than that in control group (36.3%, P=0.012).There was significant difference in the frequency of CC genotype between case group and control group (18.7% vs 14.0%, P=0.033).Compared with T allele carriers, CC genotype carriers had a 1.418-fold increased risk of GDM (95% CI 1.028-1.955).After adjusting for age, body mass index, family history of diabetes,systolic blood pressure,and diastolic blood pressure, pregnant women with CC genotype carriers of rs290487 were more prone to hyperglycemia compared with the T allele carriers (OR 1.518, 95% CI 1.064-2.166).Conclusions The TCF7L2 rs290487 variant may contribute to the genetic predisposition to GDM.CC genotype is likely to be associated with an increased risk of GDM in the pregnant Chinese women.

ObjectiveTo study the expression of p27 and its relationship with CpG island methylation phenotype (CIMP) in insulinoma.MethodsExpression of p27 was tested in 27 insulinoma tissues and 11 paired control tissues by immunohistochemistry staining.CpG island methylation of p16,MLH1,RAR-β,MGMT,THBS1 (CIMP) was detected in 27 insulinoma tissues and 11 paired cantrol tissues by methylation specific PCR (MSP).The data of p27 and CIMP expression were correlated with the clinicopathological characteristics.ResultsThe positive expression rate of p27 in insulinoma tissues was significantly lower than that in paired control tissues (48％ vs 91％,P =0.008).High rate of CIMP occurrence in insulinoma tissues was 33％ (9/27),while it was 18％ (2/11) in paired control tissues,and difference between the two groups was not statistically significant ( P =0.350 ).The methylation of MGMT was reversely associated with p16 methylation ( P =0.004).p27 expression in insulinoma tissues was reversely associated high rate of CIMP occurrence but it was not statistically significant ( P =0.420).Neither the expression of p27 nor the occurrence of CIMP was associated with the clinicopathological features.ConclusionsDown-regulation of p27 and high rate of CIMP occurred in insulinomas,suggesting that the inactivation of p27 and epigenetic alterations of several genes might contribute to the carcinogenesis of insulinoma.

Objective To explore the relationship between CA repeats polymorphism in the promoter region of IGF-1 gene and MS in the Han nationality.Methods 1047 subjects were recruited from general population of Dongcheng District in Beijing.MS was diagnosed based on the criteria for MS in 2005 by IDF.Genomic DNA was extracted by standard methods.PCR,Genescan,Genotyper and direct sequencing were conducted to screen CA repeats polymorphism in the promoter region of the human IGF-1 gene.Levels of plasma glucose,lipids,serum insulin and IGF-1 were determined.BMI and ISI were calculated.Results The prevalence of MS in (CA) 19 homozygote was lower than that in (CA) 19 heterozygote (9.1% vs 18.3%,x2 = 8.55,P ＜ 0.01) and without (CA) 19 (9.1% vs 24.0%,x2 = 18.05,P ＜ 0.01).The level of serum IGF-1 had differences among the three groups [ (114.0 ± 52.6) μg/L vs (136.6 ± 80.5) μg/L vs (129.2±49.1) μg/L,F =3.16,P ＜0.05],(CA)19 homozygote had lower serum IGF-1 than (CA)19heterozygote and without (CA) 19.BMI,WC,TG,FIns,2hIns and ISI had difference among the three groups (P ＜0.05).Conclusions (CA)19 repeats polymorphism in the promoter region of IGF-1 gene was significantly associated with MS in Han nationality.

Objective To study the plasma and intratumoral levels of ghrelin, leptin and their relationship and clinical significance in patients with pancreatic endocrine tumor.Methods Preoperative plasma levels of ghrelin and leptin were detected by ELISA in 11 patients with pancreatic endocrine tumors and 28 normal controls.Expressions of ghrelin and its receptor GHS-R 1A were tested in 11 tumors and 27 paired control tissues by immunohistochemistry staining, and they were correlated with the clinicopathological characteristics.Results The plasma levels of ghrelin was ( 16.0 ± 5.0) pg/ml, which was significantly lower than that in normal controls [ (21.0 ± 2.0) pg/ml, P = 0.047 ].The plasma levels of leptin was (0.34 ±0.03 ) ng/ml, which was not significantly different with that in normal controls [ 0.38 ± 0.04) ng/ml ].There was positive association between plasma levels of leptin and ghrelin (P =0.015 ), but was not associated with clinicopathological parameters.The plasma levels of leptin in control group was positively associated with BMI (P = 0.002), but they were not associated in patients with tumor.The expression rate of ghrelin in tumor tissue was significantly lower than that in control group (64% vs 100%, P = 0.004 ).But the expression rate of GHS-R I A was not significantly different between the two groups.The expression of ghrelin and GHS-R1A in tumor was not significantly associated with clinicopathological parameters.Conclusions The ghrelin and its receptor GHS-R 1A were extensively expressed in pancreatic endocrine tumors, and the serum levels of ghrelin and leptin was changed.

Objective To evaluate the values of continuous subcutaneous insulin/rapid insulin analoguc infusion in desensitization for allergy to recombinant human insulin. Methods Two patients allergic to recombinant human insulin received desensitization therapy by continuous subcutaneous insulin lispro infusion. The diluted insulin lispro solution was pumped with initial basal rate of O. O1 U/h, and the basal rate and insulin lispro concentration increased gradually until the insulin dosage for clinical treatment was reached. After that, continuous subcutaneous insulin lispro infusion was replaced by regimen of insulin lispro subcutaneous injection plus oral hypoglycemic agents. Results Local wheals were not observed in both two patients during continuous subcutaneous insulin lispro infusion or during bolus subcutaneous injection of insulin lispro after desensitization. Conclusion The desensitization therapy by continuous subcutaneous insulin/rapid insulin analogue infusion can be applied for allergy to recombinant human insulin.

To examine the relationship between genetic variants in the interleukin-6 receptor gene and obesity. The result showed that the carriers of Asp358 homozygotes had higher risk in developing obesity when compared with Ala358 homozygotes (OR = 1.32,95% CI 1.07-1.68, P = 0. 041). Interleukin-6 receptor gene pulymorphism was significantly associated with obesity.

Objective To evaluate the underlying causes of death of the in - patients with type 2 diabetes in Peking Union Medical College Hospital. Methods A cohort of 247 known dead in - patients with type 2 diabetes(132 men and 115 women) was identified from 1991 ～ 2003 in Peking Union Medical College Hospital. Underlying causes of death were obtained from death certificates and were coded according to the International Classifecation of Diseases (ninth revision). Results In our study, carduvascular disease was the most com-mon underlying cause of death and 110 death cases were attributable to it, and 64 to neoplasms,36 to respiratory disease, 14 to digestive disease, 10 to diabetes - related diseases, 1 to traffic accident cause, 13 to other natural causes. Conclusion This study confirms the im-portance of carduvascular disease as the major cause of death in people with type 2 diabetes. The evidence of an early effect on mortality suggests that prevention , early diagnosis, and treatment should be improved.

Objective To investigate the role of hMSH2 in the pathogenesis of sporadic insulinomas and to determine whether the expression of hMSH2 could be used to differentiate benign sporadic insulinomas from malignant ones. Methods Fifty-five sporadic insulinomas (40 benign and 15 malignant tumors) resected from 50 patients were obtained. Expression of hMSH2 was detected by immunohistochemistry staining. DNA was obtained from micradissected tissue. Loss of heterozygnsity (LOH) of hMSH2 gene was detected by PCR-LOH. 6 microsatellite markers were selected on 3 chromosomes, and microsatellite instability (MSI) status of tumor tissue were detected by PCR. The findings were analyzed in relation to the clinicopathological characteristics. Results Down-regulation of hMSH2 expression was found in 13% of 55 sporadic insulinomas. LOH of the hMSH2 gene was not present in 55 insulinomas. High frequency MSI (MSI-H, MSI occurred in at least 2 out of 6 sites) was present in 36% (20/55) of all the insulinomas. Down-regulation of hMSH2 expression was found in 33% of the 15 malignant tumors, while it was 5% in benign tumors (P < 0. 05). Conclusions Down-regulation of mismatch repair gene hMSH2 may be correlated with the degree of tumor malignancy. The expression of hMSH2 could be used as a potential marker for distinguishing benign insulinoma from malignant ones.

Objective To evaluate the features of insulin sensitivity and ?-cell function in a Chinese population with normal fasting glucose.Methods 2,388 subjects aged≥20 years were divided into 5 groups based on the results of oral 75-g glucose tolerance test(OGTT):low-NFG,mid-NFG,high-NFG,IFG,T2DM.We compared insulin secretion and insulin sensitivity using several indexes derived from OGTT.Results There was a progressive decline in indexes of ?-cell function and insulin sensitivity when moving from NFG to type 2 diabetes.Compared with subjects with mid-NFG(FPG 4.9～5.6mmol/l),subjects with high-NFG(FPG5.6～6.1mmol/l)were more resistant to insulin,and had reduced insulin secretion,higher plasma triglyceride level and reduced HDL cholesterol concentrations(P