The direetion of radical treatment ( complete remission ) for type 1A diabetes is to correct immune disorder and to full repair damaged pancreatic islet cells.It includes the application of immune modulators and islet β-cell replacement therapy.Autologous hematopoietic stem cell transplantation (AHSCT) is a new promising approach for the treatment of type 1A diabetes by reconstitution of immunotolerance and promoting β-cell regeneration.The candidates for AHSCT are limited to the people with early-onset diabetes and keeping obvious residual islet β-cell function.Because of the potential mechanisms underlying the action of AHSCT is still not very clear,careful balancing of the pros and coins of A HSCT is still needed by further trials and intensive studies.

Objective To evaluate the difference of carotid intimal medial thickness (IMT) among different glucose tolerance status and to investigate the association of IMT with different glucose levels of 4 time points during oral glucose tolerance test (OGTT) and the lipid metabolic indices in non-diabetic subjects. Methods Eleven normal control subjects, 69 subjects with impaired glucose regulation (IGR) newly diagnosed by OGTT (including 28 patients with non-elevated OGTT 30 min and 60 min glucose values (

Objective To investigate the factors which may affect the secretions of human leptin and free fatty acids (FFA) by measuring plasma glucose, serum insulin, leptin and FFA levels during reduced sample number intravenous glucose tolerance tests (IVGTT) in the subjects with different status of insulin resistance and ? cell function. Methods According to oral glucose tolerance test, 7 normal, 10 overweight/obese individuals, 12 subjects with impaired glucose tolerance (IGT) and 11 with type 2 diabetes mellitus (DM) were recruited. During IVGTT, serum insulin, leptin and FFA levels at 12 time points were simultaneously measured. Results Compared to the stable secretion of leptin, during 180 min in the IVGTT, the FFA secretion showed a "U" shape profile. The correlation analysis showed that the average serum leptin and FFA levels in 3 h were independent to fasting plasma glucose concentration. The partial correlation coefficient of leptin and insulin decreased after being adjusted for FFA (before r=0.77, P0.05). Conclusion The changes of serum FFA levels in IVGTT are more significant than those of leptin after glucose loading. Fasting plasma glucose levels do not significantly affect the average serum levels of leptin and FFA. On the contrary, insulin manifests such action but does not affect the secretion profile of these parameters.

Objective To investigate the clinical and genetic characteristics in a male patient with 21hydroxylase deficiency combined with adrenal and testicular tumors.Methods Clinical features and laboratory data were collected from the patient.Testicular biopsy was performed.The CYP21 gene was sequenced for mutations.Results The patient presented left adrenal and testicular enlargements.The laboratory examinations showed that plasma ACTH,androstenedione,testosterone,progesterone,and 17-hydroxyprogesterone were markedly elevated.CT scan revealed that the right adrenal gland being resected and the left adrenal with nodular enlargement.Furthermore,testicular biopsy showed a prominent peritubular fibrosis with increased number of peritubular fibroblasts,tubular hyalinisation,and calcification.Sequencing analysis showed a A>G homozygous mutation at intron 2.Conclusion Patients with untreated 21-hydroxylage deficiency may.have adrenal adenomas and(or)testicular adrenal rest tumor simultaneously.

The clinical and genetic characteristics in a patient with 46,XY complete gonadal dysgenesis was investigated. Clinical features and laboratory data were collected from the patient and the family. The exon of SRY gene was amplified by PCR and sequenced. The patient presented with primary amenorrhea, nonambiguous female external genitalia, slight breast development, and no axillary hair or pubic hair. The female internal reproductive organs consisted of uterus and streaks of ovarian tissue. Howerver, the chromosome karyotype was 46,XY. A missense mutation of A66T in SRY gene was identified, which was not previously reported. The novel SRY mutation caused the sex reversal in this 46,XY female patient.

Objective Measurement of ankle brachial index (ABI) is a simple method of assessing lower limb arterial blood supply,while measurement of toe brachial index (TBI)has only been advocated as an alternative.The aim of this study was to obtain information about whether TBI should be taken in type 2 diabetes,even when ABI is normal,and to evaluate the relationship between TBI and atherosclerosis.Methods In a crosssection study,ABI,TBI,and carotid intimal-medial thickness (IMT) were measured on 979 outpatients with type 2 diabetes in Ruijin Hospital.Those with normal ABI (0.9 ≤ABI ＜ 1.3,n = 945) were divided into two groupsnormal TBI group(TBI≥0.6,n=893) and low TBI group(TBI＜0.6,n=52),and then the clinical and laboratory data were compared between these two groups.Furthermore,the relationship between TBI and atherosclerosis was investigated.Atherosclerosis was defined as the maximum IMT ≥ 1.1 mm.Results Low ABI and low TBI were detected in 1.3% and 6.6% of the patients,respectively.Comparison of the clinical and laboratory data between the two groups showed that age and HbA1C values were significantly higher in the low TBI group.Furthermore,TBI was inversely associated with IMT(β=-0.217,P＜0.01),an indicator for atherosclerosis of the carotid artery.Multiple logistic regression analysis revealed that decline of TBI was an independent risk factor of atherosclerosis (OR=1.30,95% CI 1.01-1.69,P＜0.05).Conclusion In type 2 diabetes,the decline of TBI is associated with atherosclerosis,indicating the necessity for diabetic patients to detect TBI,even when ABI is within normal range,in order to detect peripheral artery disease in early stage,and reduce the risk for atherosclerosis.

Objectlve To explore the mechanism of the protection in high expression of HO-1 induced by CoPP on murine islet xenografts. Method An islet transplantation of a SD rat-to-C57 BL/6 mouse model was established.Mice were randomized into five groups i.e.control,CoPP-induction in vivo,CoPP+ZnPP in vivo.CoPP-induction in vitro and CoPP+ZnPP in vitro and the islet xenografts were transplanted into the subrenal capsule.Normoglycemia time was recorded and insulin-releasing test was performed.IL-10、TNF-α、IL-1β and INF-γ in serum and their cytokine mRNA and HO-1 in xenografts were measured by RT-PCR and Western-blotting.The pathological examination was done to observe the lymphocyte infiltration. Results There Was significant difference in the normoglycemia time between CoPP-induction in vivo and in vitro and other three groups.The results of insulin-releasing stimulated by low level glucose were identical among groups,but that of insulin-releasing stimulated by high-glucose in in vivo group were the hiishest as in CoPP-induction in vivo and in vitro and control group were 187.68 ±19.93、137.22±11.73,91.25±12.64 μIU·ml~(-1)·10islets~(-1)·45 min~(-1),(P<0.05).The IL-10 in serum in CoPP-induction in vivo and in vitro(in vivo:72.97±9.74 pg/ml;in vitro:70.84±3.56 pg/ml)was significantly hisher than other three groups(control:30.57±3.93 pg/ml;CoPP+ZnPP in vivo:39.78±3.00 pg/ml;CoPP+ZnPP in vitro:35.42±4.30 pg/ml).The expression tendency of IL-10 mRNA was similar to that of insulin secretion.There was no significant difieFence in TNF-α、IL-1β and INF-γ.The expression of HO-1 by PCR and Western-blot analysis in CoPP-induction in vivo and vitro was higher than other three groups.The pathological examination showed that fewer lymphocytes infiltrated into the islet xenografts from CoPP-treated in comparison with xenografts from other three groups. Conclusion HO-1 could improve the survival of islet xenograft:the induetion of HO-1 expression in vivo was much mole efficient than in vitro.The CoPP-induction could be related to immune modulation of IL-10.

Objective To investigate the effect of diltiazem, one of calcium antagonists, on the function of rat beta cells and the re- lease of insulin induced by D860. Methods Intravenous glucose tolerance test (IVGTY) was conducted to assess beta-cell function of rats among control, dihiazem, D860, and dihiazem plus D860 groups, followed by treatment with dihiazem and D860 for 4 weeks respectively. Another IVGTT was carded out at the end of the study. Results The data showed that diltiazem could inhibit insulin released from normal SD rats. Moreover, it reduced the hypoglycemic effect promoted by D860. However, in long term, the rise of blood sugar in rats treated with D860 respectively was not found. Conclusion Diltiazem did not impair beta cells function and interfere the hypoglycemic effect of D860 in rats in long time.

Objective To analyze the dose-effect relationship between cobalt protoporphyrin (CoPP) and heme oxygenase-1 (HO-1) expression in islets and to investigate the protective effect of strongly expression of HO-1 in islet xenotransplantation. Methods Donor islets isolated and purified from SD rats were randomly divided into 5 groups and incubated with different doses of CoPP for 24 h.Group A: 0 mmol/L; Group B: 5 mmol/L; Group C: 25 mmol/L; Group D: 50 mmol/L; Group E:75 mmol/L. The expression of HO-1 mRNA and protein in islets was detected by RT-PCR and Western blot respectively. Glucose of low and high concentrations was added to islets in vitro to test insulin-releasing function. The optimal dose of CoPP which could induce the strongest HO-1 expression was chosen according to the results. Recipients were randomly divided into 2 groups. Control group received untreated xeno-islets, and the experimental group received islets incubated with optimal CoPP close in vitro. Glycemia and rejection were observed after transplantation daily. Results The expression of HO-1 mRNA and protein in xeno-islets of group D was significantly higher than in other groups (P＜0.05). After stimulation of glucose, the insulin concentration in group D was significantly higher than in other groups (P＜0.05). The optimal dose of CoPP which could induce the strongest HO-1 expression was 50 mmol/L. The time for normoglyeemia in experimental group was (14.63±1.19) days, significantly longer than that in control group (9.88±2.17)days (P＜0.01). Conclusion The strongest expression of HO-1 induced by CoPP in vitro promotes the glucose-stimulated insulin secretion of islets and prolonged the survival of xeno-islet grafts by protecting them from rejection.

Objective To investigate the effects of peritoneal injection of cobaltic protoporphyrin Ⅸ chloride(CoPP)to induce heme oxygenase-1(Ho-1)upregulation in rat islet cells.Mthods Forty rats were divided into 5 groups by management 24 h before islets isolation:group A received inlzaporitoneal injection with 2.5 ms/ks CoPP,group B with 5 ms/ks CoPP,group C with 7.5 ms/kg CoPP,and group D with 10 mg/kg CoPP.In control group NS was used instead.A modified Goth approach was used for islet isolation.the yield and purity of the islets were assessed.The expression of Ho-1 mRNA and protein were detected by real time-PCR and Western blotting respectively.Islet function was tested by glucose stimulation test.Result Severe damage was found in tlle rats in group C and D.There was no difference in islet yield and purity for group A、B、C and control(P＞0.05).Group B had the highest Ho-1 mRNA and protein expression among the 4 groups.Though there was no difference in insulin secretion by low glucose challenge for group A、B and control's islets(P＞0.05),when challenged by hish level of glucose,significant deviation was observed.The imulin secretion level was(172.37±16.4)、(187.68±19.93)and(91.25±Conclusion Peritoneal iajection of 5 mg/kg CoPP can significantly enhance the expression of Ho-1 mRNA and protein in tat islet safely and enhance the function of islet when challenged by hish concentration of glucose.