Schistosoma japonicum infection associated with membranous nephropathy: a case report.

BACKGROUND: Schistosomiasis is one of the most contagious parasitic diseases affecting humans; however, glomerular injury is a rare complication mainly described with Schistosoma mansoni infection. We report a case of membranous nephropathy associated with Schistosoma japonicum infection in a Chinese man. CASE PRESENTATION: A 51-year-old Chinese male with a long history of S. japonicum infection presented to the hospital with a slowly progressing severe lower limb edema and foaming urine for over 5 months. Serum S. japonicumantigen test was positive and immunohistochemistry showed that the glomeruli were positive for the antigens. The renal pathologic diagnosis was stage III membranous nephropathy. The patient was treated with glucocorticoid, praziquantel, and an angiotensin-converting enzyme inhibitor. The edema in both lower limbs disappeared within 2 weeks, but his renal function declined progressively and proteinuria persisted after 5 months of therapy. CONCLUSIONS: Different classes of schistosomal glomerulopathy have completely different clinical manifestation and prognosis. Therefore, efforts should focus on alleviating symptoms, prevention, and early detection. S. japonicumassociated with membranous nephropathy may show a good curative effect and prognosis. However, it is necessary to monitor the renal function in such patients.

Comparison of Clinical Efficacy and Safety of Metformin Sustained-Release Tablet (II) (Dulening) and Metformin Tablet (Glucophage) in Treatment of Type 2 Diabetes Mellitus.

Objectives: This study investigated the clinical efficacy and safety of metformin hydrochloride sustained-release (SR) tablet (II) produced by Dulening and the original metformin hydrochloride tablet produced by Glucophage in the treatment of type 2 diabetes mellitus (T2DM). Methods: This randomized, open and parallel controlled clinical trial consecutively recruited a total of 886 patients with T2DM in 40 clinical centers between May 2016 and December 2018. These patients were randomly assigned to the Dulening group (n=446), in which patients were treated with Dulening metformin SR tablets, and the Glucophage group (n=440), in which patients were treated with Glucophage metformin tablets, for 16 weeks. The changes in the levels of glycated hemoglobin (HbAc1) and fasting blood glucose (FBG) as well as weight loss were compared between these two groups. Also, the overall incidence of adverse drug reactions (ADRs) and the incidence of ADR of the gastrointestinal system observed in patients of these two groups were also compared. Results: There were no significant differences in demographic and basal clinical characteristics between these two groups. The Dulening and Glucophage groups showed comparable levels of decrease in HbA1c levels, FBG and weight loss after 12-week treatment (all p>0.05). The Dulening group had a significantly lower overall incidence of ADRs as well as gastrointestinal ADR than the Glucophage group. Conclusions: Metformin SR tablets (II) and the original metformin tablets exhibit similar therapeutic efficacy in the treatment of T2DM, but metformin SR tablets (II) has the significantly lower incidence of ADRs than the original metformin tablets.

Krüppel-like factor 3 inhibition by mutated lncRNA Reg1cp results in human high bone mass syndrome.

High bone mass (HBM) is usually caused by gene mutations, and its mechanism remains unclear. In the present study, we identified a novel mutation in the long noncoding RNA Reg1cp that is associated with HBM. Subsequent analysis in 1,465 Chinese subjects revealed that heterozygous Reg1cp individuals had higher bone density compared with subjects with WT Reg1cp Mutant Reg1cp increased the formation of the CD31hiEmcnhi endothelium in the bone marrow, which stimulated angiogenesis during osteogenesis. Mechanistically, mutant Reg1cp directly binds to Krüppel-like factor 3 (KLF3) to inhibit its activity. Mice depleted of Klf3 in endothelial cells showed a high abundance of CD31hiEmcnhi vessels and increased bone mass. Notably, we identified a natural compound, Ophiopogonin D, which functions as a KLF3 inhibitor. Administration of Ophiopogonin D increased the abundance of CD31hiEmcnhi vessels and bone formation. Our findings revealed a specific mutation in lncRNA Reg1cp that is involved in the pathogenesis of HBM and provides a new target to treat osteoporosis.

MiR-497∼195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch and HIF-1α activity.

A specific bone vessel subtype, strongly positive for CD31 and endomucin (CD31hiEmcnhi), is identified as coupling angiogenesis and osteogenesis. The abundance of type CD31hiEmcnhi vessels decrease during ageing. Here we show that expression of the miR-497∼195 cluster is high in CD31hiEmcnhi endothelium but gradually decreases during ageing. Mice with depletion of miR-497∼195 in endothelial cells show fewer CD31hiEmcnhi vessels and lower bone mass. Conversely, transgenic overexpression of miR-497∼195 in murine endothelium alleviates age-related reduction of type CD31hiEmcnhi vessels and bone loss. miR-497∼195 cluster maintains the endothelial Notch activity and HIF-1α stability via targeting F-box and WD-40 domain protein (Fbxw7) and Prolyl 4-hydroxylase possessing a transmembrane domain (P4HTM) respectively. Notably, endothelialium-specific activation of miR-195 by intravenous injection of aptamer-agomiR-195 stimulates CD31hiEmcnhi vessel and bone formation in aged mice. Together, our study indicates that miR-497∼195 regulates angiogenesis coupled with osteogenesis and may represent a potential therapeutic target for age-related osteoporosis.

[The design and baseline characteristics of a phase III study to evaluate the efficacy and safety of alogliptin versus placebo in type 2 diabetes mellitus in Mainland China].

OBJECTIVE: To assess the design and the Mainland China subgroup baseline characteristics of the study to evaluate the efficacy and safety of alogliptin versus placebo in subjects with type 2 diabetes (T2DM) as monotherapy, add-on to metformin or add-on to pioglitazone. METHODS: This was a multi-center, randomized, double-blind, placebo-controlled, 16-week study comparing alogliptin (ALO, 25 mg, 1/d) versus placebo (PLA) as monotherapy (A), add-on to metformin (B) or add-on to pioglitazone ± metformin (C). The T2DM subjects with glycosylated hemoglobin A1c(HbA1c) between 7% and 10% and aged between 18 years and 75 years were enrolled and randomized to the alogliptin group and the placebo group in 1: 1 ratio with 16 weeks treatment. All patients were followed up every 4 weeks. The safety endpoints consisted of the incidence of hypoglycemia and other adverse events. RESULTS: A total of 491 patients were enrolled in the Mainland China subgroup of the study (181 in group A, 186 in group B and 124 in group C). In each treatment group, the baseline characteristics including age, gender, body mass index, diabetes duration, HbA1c, fasting plasma glucose, body weight, daily dosage of metformin and daily dosage of pioglitazone were all well balanced. CONCLUSION: The demographic data, medical history, glycemic profile and treatment regimen at baseline in Mainland China subgroup are well balanced. The result of this study will provide the clinical evidence for the use of alogliptin in Chinese T2DM patients.

KCNQ1 gene polymorphisms are associated with the therapeutic efficacy of repaglinide in Chinese type 2 diabetic patients.

The present study evaluated the effects of KCNQ1 rs2237892 and rs2237895 polymorphisms on repaglinide efficacy in Chinese patients with type 2 diabetes mellitus (T2DM). In all, 367 T2DM patients and 214 controls were genotyped. Forty of the T2DM patients were randomly selected to undergo 8 weeks repaglinide treatment. The frequency of the rs2237892 allele was lower in the T2DM patients than in the control group (P < 0.05). The frequency of the rs2237895 C allele was higher in T2DM patients than in healthy control subjects (P < 0.05). Diabetic patients with the rs2237892 risk C allele had lower fasting insulin levels (P < 0.01) and homeostasis model assessment of insulin resistance (HOMA-IR; P < 0.01) values than carriers of the T allele. Diabetic patients with the rs2237895 risk C allele had higher fasting plasma glucose (P < 0.01), postprandial plasma glucose (PPG) levels (P < 0.01) and HOMA-IR values (P < 0.01) than those with the A allele. Following repaglinide treatment, those T2DM patients with the rs2237892 T allele and rs2237895 C allele were more likely to have a positive response to repaglinide in terms of PPG levels (P < 0.05) than T2DM patients with the rs2237892 CC and rs2237895 AA genotypes. In conclusion, KCNQ1 rs2237892 and rs2237895 polymorphisms were found to be associated with the therapeutic efficacy of repaglinide in Chinese T2DM patients.

[Association of adiponectin gene polymorphism with obesity in children].

OBJECTIVE: To study the distribution characteristics of adiponectin gene +45 single nucleotide polymorphisms (SNP) in Chinese children, and to determine the role of adiponectin gene +45 polymorphisms in the pathogenesis of childhood obesity. METHODS: A total of 147 Chinese obese and 118 healthy children were randomly selected and enrolled to identify adiponectin gene SNP+45 polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Plasma adiponectin levels were determined using ELISA. Waist circumference (WC), waist to hip ratio (WHR), percentage of body fat (%BF), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), serum triglycerides (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), plasma fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR) were measured. RESULTS: The allelic frequency of adiponectin gene SNP+45 in children with obesity and healthy controls were 40.5% and 25.4%, respectively. There were significant differences in the distribution of genotypes and the allelic frequency between the two groups (P<0.05). The plasma adiponectin levels were significantly higher, in contrast, %BF, HOMA-IR, TC and LDL-C levels were significantly lower in obese children with TT genotype than those in obese children with TG or GG genotype. CONCLUSIONS: The adiponectin gene SNP+45 polymorphism may be associated with pathogenesis of obesity in children. T→G variance may be associated an increased risk of childhood obesity and result in a decreased level of adiponectin.

Effect of repaglinide and gliclazide on glycaemic control, early-phase insulin secretion and lipid profiles in.

BACKGROUND: Both repaglinide and gliclazide are insulin secretagogues widely used in the treatment of type 2 diabetes. They stimulate insulin secretion through distinct mechanisms and may benefit patients from different aspects. The present study was to evaluate the effects of repaglinide or gliclazide on glycaemic control, insulin secretion, and lipid profiles in type 2 diabetes patients. METHODS: A total of 47 newly diagnosed type 2 diabetes patients were randomized 1:1 to receive a 4-week treatment with repaglinide or gliclazide. The standard mixed meal tolerance test was performed before and after the treatment. Plasma glucose (PG), insulin concentration, and lipid profiles were measured. The area under insulin concentration curve (AUC(ins)) and the early-phase insulin secretion index (ΔI(30)/ΔG(30)) were calculated. RESULTS: After the trial, fasting and postprandial PG and postprandial insulin improved significantly in both groups (P < 0.05). The maximum insulin concentration occurred earlier in the repaglinide group than that in the gliclazide group. AUC(ins) increased in both groups (P < 0.05), but no significant difference was found between groups. ΔI(30)/ΔG(30) increased in both groups (P < 0.05), especially in the repaglinide group (P < 0.05). Triglyceride and total cholesterol decreased significantly in the repaglinide group in some time points, while no significant change was observed in the gliclazide group. CONCLUSIONS: Repaglinide and gliclazide had similar effects on glycaemic control and total insulin secretion, while repaglinide had more effects on improvements in ß-cell function and lipid metabolism.

[Expression of imprinted genes during the course of differentiation from mouse embryonic stem cells to islet-like cells in vitro].

OBJECTIVE: To study the effects of in vitro inducement on the expression of SF1-G imprinted genes, Kcnq1 and Cdkn1c during the course of differentiation from mouse embryonic stem (ES) cells to islet-like cells. METHODS: Mouse ES cells were induced to differentiate into islet-like cells in vitro. The expression of islet specific markers was tested by RT-PCR or immunofluorescence. RT-PCR/RFLP was used to test the imprinted genes parental expression in cells at different stages. RESULTS: Islet specific genes, such as Insulin, Glucagon, Somatostatin, IAPP and Glut2, were expressed in differentiated cells. The proteins of insulin, C-peptide and Somastatin were expressed in the final stage cells. Imprinted gene Kcnq1 and Cdkn1c were biallelicly expressed in islet-like cells. CONCLUSIONS: Mouse ES cells can be successfully induced into islet-like cells in vitro. Gene imprinting status of Kcnq1 and Cdkn1c may be changed in differentiated cells (causing loss of imprinting) during the in vitro inducement.

[Serum leptin level and its association with bone mineral density in obese children].

OBJECTIVE: To investigate serum leptin level and its relationship with bone mineral density in obese children from Changsha City. METHODS: One hundred and nineteen obese children and 103 normal children aged 7 to 12 years from five primary schools of Changsha City were enrolled. Obesity was assessed based on the body mass index (BMI). Dual energy X-ray absorptiometry (DEXA) was used to determine bone mineral density (BMD) and body composition. Serum leptin level was measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: The obesity group had higher height, weight, BMI, waist circumference and waist to hip ratio (WHR) compared with the normal group (p<0.01). BMD, bone mineral content (BMC), lean mass (LM), fat mass (FM), percentage of body fat (%BF) and leptin concentration in the obesity group were significantly higher than those in the normal group (p<0.01). Serum leptin level was positively correlated with BMD, BMC, LM and FM (r=0.528-0.903, p<0.01). Multiple stepwise regression analysis indicated that BMI and %BF were independent influencing factors for serum leptin level. CONCLUSIONS: Obese children have higher serum leptin level. Serum leptin concentration is significantly correlated with BMD and body composition. BMI and %BF are independent influencing factors for serum leptin level in children.

Rosiglitazone inhibits high glucose-induced apoptosis in human umbilical vein endothelial cells through the PI3K/Akt/eNOS pathway.

Previous studies have shown that the phosphatidylinositol 3-kinase / Akt / endothelial nitric oxide synthase / NO (PI3K/Akt/eNOS/NO) pathway is involved in high glucose-induced endothelial cell apoptosis and rosiglitazone has a protective effect on endothelium. In the present study, we investigated the antiapoptotic effect of rosiglitazone on human umbilical vein endothelial cells (HUVECs) exposed to high glucose and explored its possible mechanism. Treatment of high glucose (33 mmol/L) for 48 h significantly induced the apoptosis of HUVECs, concomitantly with increased caspase-3 activity. High glucose treatment also decreased Akt and eNOS phosphorylation levels with subsequent NO production. All these alterations induced by high glucose were attenuated by rosiglitazone (1 micromol/L). Interestingly, the antiapoptotic effect of rosiglitazone was inhibited by PI3K inhibitor (LY294002, wortmannin) or eNOS inhibitor NG-l-nitro-arginine methyl ester (l-NAME). The reverse effects of rosiglitazone on phosphorylation of Akt and eNOS with subsequent NO production were also inhibited by LY294002, wortmannin or l-NAME, respectively. These findings suggest that rosiglitazone inhibits high glucose-induced apoptosis in HUVECs through the PI3K/Akt/eNOS pathway.

[Hyperlipidemia induced by high fat diet ingestion activates TGF-beta/Smad signaling pathway in the kidney of diabetic rats].

OBJECTIVE: To investigate the effect of diet-induced hyperlipidemia on TGF-beta/Smad signaling pathway in the kidney of diabetic rats, and to explore the mechanism by which hyperlipidemia leads to renal injury in diabetes. METHODS: Diabetic rats and non-diabetic rats were fed with normal fat diet and high fat diet for 16 weeks, respectively. The expressions of TGF-beta1, TbetaRII, and Col-IV mRNA in the renal cortex were examined by reverse transcriptase-PCR,TbetaRII and p-Smad staining in glomerular cells were detected by immunohistochemical staining, and the expression of TGF-beta1 and Col-IV protein was determined by Western blot. RESULTS: Diet-induced hyperlipidemia up-regulated the levels of TGF-beta1, TbetaRII, p-Smad, and Col-IV protein and mRNA in the renal cortex of diabetic rats compared with those of non-diabetic rats. However, feeding high fat diet to non-diabetic rats had no influence on the expression of TGF-beta1, TbetaRII, p-Smad2, and Col-IV in the renal cortex. CONCLUSION: Hyperlipidemia induced by high fat diet ingestion leads to renal injury in diabetic rats through activating TGF-beta1 /Smad signaling pathway.

[Effect of rosiglitazone on NO and eNOS via PI3K/PKB signal pathways in cultured human umbilical vein endothelial cells].

OBJECTIVE: To observe the effect of rosiglitazone on the production of nitric oxide (NO) and the expression of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) /the endothelial nitric oxide synthase (eNOS) in cultured human umbilical vein endothelial cells(HUVECs), and to investigate the mechanism of signal transduction of rosiglitazone in improving the endothelial function. METHODS: HUVECs were treated with various concentrations of rosiglitazone. The NO level was measured using Griess Reaction in cell culture supernatants; the expressions of PI3K-, PKB- and eNOS mRNA were measured using RT-PCR; and the expressions of PKB, eNOS, and phosphorylation of PKB-Ser473, eNOS-Ser1177 were measured using Western Blot. RESULTS: Rosiglitazone increased the endothelial NO production in a dose- and time-dependent manner in cultured HUVECs, and also increased the expression of PI3K mRNA and the phosphorylation of PKB-Ser473 and eNOS-Ser1177 in a concentration-dependent manner, with no alteration in the expression of PKB and eNOS in cultured HUVECs. N(w)-nitro-L- arginine methyl ester (L-NAME, eNOS synthase inhibitor) blocked the rosiglitazone-induced NO formation; LY294002 (a PI3K inhibitor) prevented the NO production; and the phosphorylation of eNOS and PKB was induced by rosiglitazone. CONCLUSION: Treatment with rosiglitazone can increase the NO production and improve the endothelial function through up-regulating the PI3K/PKB/eNOS signal pathways in cultured HUVECs.

[Changes of endothelium-dependent vasodilation in patients with impaired glucose tolerance and type 2 diabetes].

OBJECTIVE: To investigate the changes of endothelium-dependent flow-mediated dilation (FMD) in patients with impaired glucose tolerance (IGT) and Type 2 diabetes (T2DM) and its influencing factors. METHODS: The patients with IGT and T2DM were divided into IGT group (n=36), T2DM without vascular complication group (DM1;n=57), and T2DM with vascular complication group (DM2;n=31). And 25 normal subjects served as controls (NC group). The FMD was measured by high resolution ultrasound.The serum levels of tumor necrosis factor-alpha (TNF-alpha) and high sensitive C-reactive protein (hs-CRP) were detected with ELISA, and nitric oxide (NO) with Griess Reaction. The serum glucose, lipids, and other indexes were also detected. RESULTS: Compared with the NC group, the serum levels of triglyceride (TG) total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), hs-CRP, and TNF-alpha significantly increased (P<0.05), but the serum levels of high density lipoprotein-cholesterol (HDL-C), the NO, and FMD significantly decreased (P<0.05) in the IGT, DM1, and DM2 group. With the progress of diabetes, FMD level descended. Pearson correlation analysis showed a negative correlation between FMD and glycosylated hemoglobin (HbA1c), insulin resistant index (HOMA-IR),TG,TC,hs-CRP, and TNF-alpha (P<0.01), but a positive correlation between FMD and NO,HDL-C (P<0.01) in IGT and T2DM patients. In multiple linear stepwise regression with FMD as dependent variable, NO,HbA(1)c,HDL-C,HOMA-IR, TNF-alpha, and hs-CRP showed a significant association with FMD (P<0.01). CONCLUSION: Endothelium-dependent vasodilation is impaired in patients with IGT and T2DM,which is associated with hyperglycaemia, insulin-resistance, hyperlipemia, and inflammation.

[Aortic endothelium-dependent vasodilation function and PI3K-, PKB-, eNOS mRNA expressions in insulin-resistant and type 2 diabetic rats].

OBJECTIVE: To observe the changes of aortic endothelium-dependent vasodilation function (EDVR) and expressions of endothelial nitric oxide synthase (eNOS), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (PKB) in insulin-resistance (IR) and type 2 diabetic rats. METHODS: IR rat model was established by feeding 4-6 week-old male SD rats with high glucose and cholesterol diet for 6 weeks and type 2 diabetes (DM) were induced by intraperitoneal injection with low dose streptozotocin (STZ) to IR rats. Glucose infusion rate (GIR) was determined by euglycemic hyperinsulinemic clamp technique, EDVR by acetylcholine (Ach)-induced vasodilation response in isolated aortic rings, aortic NO concentration by Griess Reaction, activation of eNOS detected by immunohistochemical SP method, mRNA expressions of eNOS-, PI3K- and PKB of aorta were assayed by RT-PCR, aorta ultrastructure observed by electron microscopy. Body weight, fast plasma glucose (FPG), insulin (FINS), triglyceride (TG), cholesterol (TC) were determined and the insulin sensitivity index (ISI) was calculated. RESULTS: (1) Body weight, FINS, TG and TC levels were significantly higher while ISI and GIR significantly lower in IR and DM rats than that in normal control rats (P < 0.05). (2) Aorta EDVR decreased significantly in IR and DM group compared with that in control group (P < 0.05) and EDVR was also significantly reduced in DM rats than that in IR rats (P < 0.05). The maximum Ach-induced vasodilation response (EDVR(max), P < 0.01) was positively correlated with ISI and negatively correlated with FPG, TG, TC and FINS (P < 0.01). (3) Aortic NO concentration, the mRNA expressions of eNOS-, PI3K-, and PKB and eNOS immunohistochemical expression in aorta were significantly lower in IR and DM rats compared with normal control rats and the decrease was more pronounced in DM rats (P < 0.05 vs. IR). (4) Pathologic aortic ultrastructure changes were also visualized in IR and DM rats. CONCLUSION: Our results suggest that reduced NO concentration and expression as well as reduced PI3K-, PKB-, and eNOS mRNA expressions might contributed to the reduced EDVR function and related pathological ultrastructure changes in IR and DM rats.

[Effects of rosiglitazone on endothelium-dependent vasodilation in patients with Type 2 diabetes].

OBJECTIVE: To investigate the effects of rosiglitazone on endothelium-dependent vasodilation in patients with Type 2 diabetes. METHODS: Eighty-three newly diagnosed patients with Type 2 diabetes were divided into metformin group (metformin 750 mg/d), therapeutic alliance group (rosiglitazone 4 mg/d and metformin 750 mg/d), and rosiglitazone group (rosiglitazone 4 mg/d), and 25 normal subjects were as the control group. All patients were treated for 12 weeks. The height, weight, blood pressure, fasting plasma glucose (FPG), fasting serum insulin (FINS), glycosylated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and serum nitric oxide (NO) were measured before and after the therapy. The body mass index (BMI) and homeostasis model assessment-insulin resistant index (HOMA-IR) were calculated. The flow-mediated dilatation (FMD) and endothelium independent dilatation (EID) were measured by high-resolution ultrasound. RESULTS: The BMI, TG, TC, LDL-C, FPG, HBA1c, HOMA-IR were higher (P<0.01), but HDL-C, NO, FMD were lower (P<0.01) in all diabetic groups than those in the control group before the treatment. After the 12-week treatment, TG, FPG, HBA1c, HOMA-IR decreased significantly in all the diabetic groups (P<0.01); FINS decreased, but HDL-C, NO, FMD and EID increased (P<0.01) in therapeutic alliance group and rosiglitazone groups, while HDL-C, FINS, NO, FMD had no change in metformin group compared with those before the treatment. CONCLUSION: Endothelium-dependent vasodilation function is impaired in patients with Type 2 diabetes. The therapy with rosiglitazone can increase the serum NO level, and improve endothelium-dependent vasodilation,but metformin has no influence on the above-mentioned indexes.

[Effects of rosiglitazone on the IMTc and serum MMP-9 levels in newly diagnosed type 2 diabetic patients].

OBJECTIVE: To investigate the change of carotid intima-media thickness (IMTc) and serum matrix metalloproteinases-9 (MMP-9) levels in newly diagnosed Type 2 diabetic patients, and to analyze the relationship between MMP-9 and IMTc; at the same time, to assess the effect of rosiglitazone on IMTc and MMP-9 levels. METHODS: Fifty-eight patients with Type 2 diabetes mellitus were selected in our study, and 25 healthy adults served as normal controls. Diabetic patients were divided into 2 groups: Group A (31 subjects) were treated with rosiglitazone (4 mg/d), and Group B (27 subjects) were treated with metformin alone (500 approximately 1,500 mg/d). They all received the treatment for 3 months. The IMTc was measured by high resolution ultrasonography, and the serum MMP-9 was determined by enzyme linked immunosorbent assay (ELISA) to assess the relationship between IMTc and MMP-9. RESULTS: The mean level of serum IMTc and MMP-9 in Type 2 diabetic patients was significantly higher than that in healthy adults (P < 0.05). After treatment with rosiglitazone and metformin, IMTc and serum MMP-9 levels decreased significantly (P < 0.05). There was no obvious change in IMTc and serum MMP-9 levels in group B before and after the treatment (P = 0. 071, P = 0.065). Using multiple linear stepwise regression analysis, the significant correlation between IMTc and HbA1C, BMI, WHR, HDL-C, MMP-9 were discovered. CONCLUSION: IMTc and MMP-9 levels increase in newly diagnosed Type 2 diabetic patients, suggesting that there is closely relationship between serume MMP-9 levels and early diabetic macrovascular disease. IMTc and MMP-9 can be reduced significantly in the newly diagnosed diabetic patients after being treated with rosiglitazone, which may be one of the protective mechanisms of vascular vessels.

[Effect of plasma glucose on the vascular endothelial function and analysis of relevant factors].

OBJECTIVE: To compare the flow-mediated dilatation (FMD) among the newly diagnosed impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), and the normal controls (NC) and to analyze relevant factors under different glucose levels. METHODS: The study included IGT (n=34), DM1 (n=52), DM2 (n=33) and NC (n=25). Levels of fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG), fasting insulin (FINS), 2-hour postprandial insulin (PINS), triglyceride (TG), total cholesterol (TC), and hemoglobin A1C (HbA1C) were determined in all participants. High resolution ultrasound examining FMD was performed to measure vascular endothelial function subsequently. RESULTS: There was statistically significant difference between IGT, DM, HG and NC group in FMD (P=0.008). Partial correlation analysis found that a significant negative correlation existed between FMD and homeostasis model assessment-index (HOMA-IRI), difference of plasma glucose (DPG), FPG and PPG (P<0.01), and a negative correlation between FMD and HbA1C (P<0.05). Setting FMD as dependent variable to conduct multiple linear stepwise regression, in IGT group it was the waist/hip ratio (WHR) and HOMA-IRI that entered the regression equation; in DM1 group it was HOMA-IRI, PPG and DPG that entered the regression equation; in DM2 group it was FPG and HOMA-beta that entered the regression equation. CONCLUSION: There exists a flow-mediated vasodilatation dysfunction in patients of newly diagnosed IGT and T2DM. Effect of relevant factors on FMD differs with different glucose levels.

[Isolation, induction and differentiation of human blood-derived endothelia progenitor cells].

OBJECTIVE: To determine the biological traits and optimal condition for the induction and differentiation of endothelial progenitor cells from peripheral blood in healthy adults. METHODS: Mononuclear cells isolated from peripheral blood of healthy adults were cultured in M199 medium supplemented with VEGF, bFGF, IGF-1, and EGF. The appearing time of cell clusters or spindle-shaped cells was recorded respectively. Attached spindle-shaped cells were detached and labeled with a series of antibodies against blood vessel endothelial-specific markers. RESULTS: Attached spindle-like cells appeared 4 days after the culture, cell clusters were observed at 5 to 8 days, and cord-like structure was formed by 10th day. These cells expressed endothelial-specific markers. CONCLUSION: Endothelial progenitors cells were derived from mononuclear cells of peripheral blood, which can be induced into endothelial cells at specific conditions.

[Effects of simvastatin on TGF-beta system of diabetic rat kidneys].

OBJECTIVE: To investigate the effects and mechanism of renal benefit of simvastatin on diabetic rat kidneys. METHODS: Twenty STZ-induced SD rats and 10 normal rats were assigned to diabetic rat (DM) group, simvastatin [ 4 mg/( kg x d) ] treatment (S) group and normal control (C) group. Immunohistochemistry, RT-PCR and western-blot were employed to examine the changes of the mRNA and protein expression of TGF-beta1 and Tbeta II R in the kidneys of the rats. RESULTS: Compared with the normal control group, both the mRNA and protein expression of TGF-beta1 and Tbeta II R in the diabetic rat group and treatment group were significantly increased (P < 0.05). Compared with the diabetic rat group, simvastatin could markedly decrease the mRNA and protein expression of TGF-beta1 and Tbeta II R (P < 0.05). CONCLUSION: Simvastatim may play a protective role in the diabetic kidneys by down-regulating TGF-beta1 and Tbeta II R and inhibiting the TGF-beta signal pathway.