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In this study, a simple and sensitive LC-MS/MS method was developed and validated for simultaneous determination of icotinib and its four circulating metabolites in human plasma. The analytes were extracted with acetonitrile and separated on a C18 column using 2 mm ammonium acetate containing 0.2% formic acid and acetonitrile as mobile phase. The analytes were introduced into the mass spectrometer via an electrospray ionization source operated in positive ion mode. Precursor-to-product transitions were optimized to be m/z 392.2 → 304.1 for icotinib, m/z 424.1 → 278.2 for M1 and M2, m/z 408.2 → 320.1 for M3, m/z 410.2 → 322.1 for M4 and m/z 394.4 → 278.1 for IS. The assay showed good linearity over the concentration ranges of 0.1-600 ng/mL for icotinib and 0.1-200 ng/mL for metabolites, with correlation coefficients >0.994 (r > 0.994). The LLOQ was 0.1 ng/mL for each analyte. The intra- and inter-day precisions (RSD) were ≤12.98% while the accuracy (RE) ranged from -8.76 to 12.01%. No significant matrix effect was observed. The validated method was successfully applied for the pharmacokinetic study of icotinib and its four circulating metabolites in human plasma after oral administration of icotinib at a single dose of 125 mg.

A novel method of direct aniline multi-interfacial polymerization on paper substrate is introduced in this paper. Cellulose base papers with and without PAE reinforced were discussed. The PANI-paper composites after more than 3 polymerizations had much lower surface resistivity. Their mechanical strength and thermal stability were analyzed by tensile test and GTA. FTIR results explained that there was strong interaction between NH groups in aniline monomers and OH groups in fibers. Conductive composites made with PAE treated paper had both good thermal stability and good mechanical strength with high conductivity.

Polyaniline-paper composite is prepared on a paper template by interfacial polymerization. Using SEM and FESEM, the morphology of PANI on fiber and pores between fibers are inspected based on different polymerization. The flake shape of PANI is formed on fiber surface at the beginning due to electrostatic attraction, while the granular is growing on the pores freely. This flake shape on fiber is changed with 3rd polymerization into granular. When the resistivity is below 100cm/S, linear PANI in pores is growing to the fiber nearby, and PANI network formed. The morphology also confirmed that PANI on fiber only remains on the upside not fully covered surface of fiber. Very few PANI is found inside paper substrate by cross section SEM. The method is discussed also with polyaniline-fiber composite polymerization and in-site paper polymerization.

Switchgrass contains high content of cellulose which is suitable to enzymetically hydrolyze to glucose, and is a good potential biomass for biofuel production. The paper studied a kind (Alamo, CA993,CA992,Kanlow) switchgrass ball milled lignin structure using 13C NMR and 31P NMR. Both NMR lignin spectrums showed little difference of this switchgrass. Its extractive-free compositional components were also analyzed like acid insoluble lignin, acid soluble lignin, ash and carbohydrates separately. Its acid insoluble and soluble lignin contents were close to each other in the range of 21% and 2.5% respectively. Their carbohydrates are made mainly up of glucose and xylose, which fractions are around 52% to 40% based on the whole carbohydrates.

A fatty acid-starch complex was prepared to apply in the linerboard surface treatment (sizing). Compared with the raw corn starch and commercial size press cationic starch, the fatty acid-starch complex displayed better water resistance, higher tensile strength and higher bending stiffness of treated samples. Two different fatty acids of C16 like palmitic acid and C18 like stearic acid were compared. Both C16 and C18 fatty acids showed similar results. Small amount of clay addition to the complex could increase the tensile strength and bending stiffness of sized samples, while keeping the good water resistance. PCC also could increase the tensile strength with the small amount of addition to the fatty acid-starch complex as surface sizing agent in our study. The SEM pictures of surface treated samples using the complex with and without clay and PCC were taken and the bonding characteristics and surface film formation were investigated.

In numerical manifold schemes for direct solution of steady Navier-Stokes equations, mixed cover for velocity and pressure was adopted in finite element cover system. The patch test of numerical schemes was investigated, mixed cover manifold element has been proved to meet the stability conditions, and can be applied to directly solve Navier-Stokes equations coupled velocity and pressure. As an application, the numerical manifold schemes were used to simulate the steady flow past a step. Numerical solutions illustrate the stability of numerical manifold schemes, and it indicates that manifold method is an effective numerical method for steady Navier-Stokes equations.

Tumor necrosis factor (TNF ) locus has been a long-standing type 2 diabetes (T2D) candidate gene. Few studies have been conducted on TNF SNP (single nucleotide polymorphism) as rs1799964 (T-1031C), rs1800630 (A-863C) and rs1799724 (C-857T) in T2D. The purpose of this study is to examine the association of TNF SNP and T2D in a case control study and further explore whether these SNPs influence the clinical efficacy of insulin therapy.A total of 109 newly diagnosed type 2 diabetics and 168 healthy individuals were recruited. Three tag SNPs (rs1799964 (T-1031C), rs1800630 (A-863C), rs1799724 (C-857T)) were selected across the TNF locus and polymerase chain reaction (PCR) directed sequencing was performed. The patients received Lispro 25 twice daily to achieve glycemic control and they were followed up for 1 year. Plasma glucose level, lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR) and homeostatic model assessment for beta-cell function (HOMA-β) were compared among groups with different haplotypes of SNPs.Haplotype of TNF-1031C-863C-857C increased the risk of T2D (OR = 2.7, P0.05) . Comparing with homozygote of TNF-1031T-863C-857C diabetics (TCC), those carrying CCC allele had higher fasting serum insulin (16.1(12.0-20.3) mU/L) and HOMA-IR (lnHOMA-IR 1.8 ± 0.4) levels (TCC group: 10.6(8.1-14.3) mU/L and 1.42 ± 0.54 respectively, P0.05)). One-year insulin treatment decreased HbA1c effectively in both TCC and CCC groups (P0.05). However, higher HOMA-IR was still observed in CCC group than that of TCC after normoglycemia (lnHOMA-IR: 2.5(0.9-3.9) vs 1.1(0.8-1.8) respectively, P0.05) . Moreover HOMA-β showed no significant improvement in CCC group as it was in TCC group by the endpoint of follow-up.TNF-1031C-863C-857C is a risk haplotype for T2D. CCC carrying patients failed to achieve HOMA-β improvement. And it might be due to increased endogenous HbOMA-IR level comparing with TCC homozygote.

To explore the role and mechanism of SIRT1 (Sirtuin1) in the differentiation of adipocyte.SIRT1(-/-) mice with C57BL/6J gene background were generated and litter-mate wild-type (WT) mice were used as controls. Body weight and fat content were detected and their epididymal fat pads were collected at 28 weeks old of age. The tip part of epididymal fat tissue was incubated in phosphate buffered saline (PBS) containing both BODIPY 558/568 (5 µmol/L in PBS) for adipocytes and isolectin Alexa Fluor 488 (40 µg/ml in PBS) for endothelial cells overnight. The stained cells were then visualized under confocal microscope.Reconstruction of 3D data sets was accomplished with image processing software Imaris.Immunohistochemistry was used to detect the protein level of endothelial cell marker CD31.Hematoxylin and eosin staining was performed for fixed epididymal fat tissue. Mouse embryonic fibroblast (MEF) cells were prepared from 13-14 days embryos of SIRT1(-/-) or WT mice and differentiated into adipocytes. Then oil-red O staining was performed.Compared with wild-type controls, both body weight (WT 42.1 g ± 1.6 g vs SIRT1(-/-) 25.4 g ± 1.0 g, P0.05) and epididymal fat mass (WT 13.4 g ± 1.0 g vs SIRT1(-/-) 7.8 g ± 0.5 g, P0.05) were much smaller in the SIRT1(-/-) mice. HE staining of fat tissue exhibited a significant reduction in adipocyte size and extracellular matrix in SIRT1(-/-) mice.However, the adipogenesis ability of MEF cells was significantly enhanced in vitro in SIRT1(-/-) MEF cells.Further study found that the density of vascular network decreased by 50% in the tip portion of epididymal fat pads of SIRT1(-/-) mice (capillary density:WT 2.92% ± 0.03% vs SIRT1(-/-) 1.34% ± 0.02%, P0.05). CD31, a cellular marker of decreased angiogenesis, decreased significantly in epididymal fat pads of SIRT1(-/-) mice.SIRT1 knockout impairs adipocyte differentiation in SIRT1(-/-) mice with C57BL/6J gene background through reduced angiogenesis but not adipogenesis.

A reconfigurable multiwavelength erbium-doped fiber laser, using two multimode fiber Bragg gratings (MFBGs), is presented. Two MFBGs in L-band are cascaded to form two overlapping resonant cavities. Various configurations of four-, three-, or two-wavelength lasing are demonstrated experimentally by appropriately controlling the two polarization controllers inside the cavities. © 2007 Wiley Periodicals, Inc. Microwave Opt Technol Lett 49: 1509–1511, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.22493

We present the optimization and fabrication of the stitched long-period fiber gratings (SLPGs) for gain flattening of an ultrawide-band erbium-doped fiber amplifier (EDFA). With an improved genetic algorithm, the gain spectrum of a practical EDFA with bandwidth of 80 nm is flattened within /spl plusmn/0.69 dB by an optimized SLPG. Furthermore, the SLPG is designed specially for a point-by-point grating writing technique. A superior control of the fabrication procedure of the designed SLPG has been demonstrated in the experiment.

We report the fabrication and characterization of a highly sensitive refractive-index sensor based on a long-period grating (LPG) pair with a fiber-taper section in between. Two LPGs with /spl sim/3-dB transmissivity form an in-fiber Mach-Zehnder interferometer. A fiber taper is made between the two LPGs to improve and tailor the sensitivity of the sensor. Enhanced sensitivity, which is about five times higher than that of a normal LPG pair, is achieved in the experiment.

To determine the current prevalence and risk factors of metabolic syndrome (MS) among adult residents in Chinese developed areas.The clinical data of 6614 adult residents, including 4051 women, from Guangdong and Jiangsu provinces from China Diabetes and Metabolic Disorders Study (2007-2008) were analyzed. Age and sex standardized prevalences of MS were calculated according to the criteria of Chinese Diabetes Society (CDS), US National Cholesterol Education Program Adult Treatment Panel III (ATP III), International Diabetes Federation (IDF) and Joint Interim Statement (JIS), respectively. Logistic regression analysis was performed to identify the risk factors of MS.Age and sex standardized prevalences of MS were 17.88% (CDS), 28.50% (ATPIII), 21.99% (IDF) and 31.50% (JIS), respectively. The prevalences of residents with at least one metabolic abnormality were 67.86% (CDS) 79.56% (ATPIII), 79.62% (IDF) and 80.74% (JIS), respectively. MS was more common in female than in male by the ATPIII and IDF criterion (ATPIII: 30.63% vs 26.45%, P0.01; IDF: 26.04% vs 17.91%, P0.01), while the prevalence was higher in male by CDS criteria (15.94% vs 19.87%, P0.01). There was no significant difference in the MS prevalence between the rural and the urban residents. Kappa test showed ATPIII and JIS criteria were most homogenous (κ = 0.95, P0.01). The risk factors for MS by the logistic regression model were male, older age, lower degree of education, family history of hypertension and obesity, drinker as well as uncontrolled diet.The prevalence of MS is high in the adult residents of Chinese developed areas (Guangdong and Jiangsu provinces), whatever diagnostic criterion was used .Effective measures should be taken to control the modifiable MS risk factors.

To determine the incidence and the predictors of diabetes ketoacidosis (DKA) in Chinese type 1 diabetics so as to lay a foundation for better prevention and treatment.For this cross-sectional study, a total of 611 patients with established type 1 diabetes between August 6, 2010 and March 31, 2012 were recruited from 16 hospitals in Guangdong Province. And 491 of them were over 18 years old. A data entry form was used to collect the patient information on demographics, medical history, acute/chronic complications, smoking/drinking status, diet, exercise, physical examination and treatment, etc. Hemoglobin A1c (HbA1c) and stimulated C peptide levels were centrally measured. The incidence rate of diabetic ketoacidosis (DKA) was calculated at events per 100 patient-years. To determine the predictors of DKA, Poisson's regression model was used for analysis. And backward stepwise logistic regression analysis was performed to identify the predictors of DKA recurrence. The protocol and informed consent form were approved by Ethics Committee of Third Affiliated Hospital, Sun Yat-sen University. Written informed consent was obtained from patients (age18 years) or their legal guardians (age18 years).Among them, 53.7% were females. The mean age was 27.8 years (range: 19.5 - 37.3). The age of onset was 22.7 (14.0 - 31.4) years old and disease duration 4.3 (1.7 - 7.9) years. Overweight and obese patients accounted for 10.8% and 1.0% respectively. Among them, the self-monitoring frequency of blood glucose was 0.4 (0.1 - 1.4) times per day. Overall, 26.4% patients reached the target of age-specific HbA1c values. The overall incidence of DKA was 26.4 per 100 patient-years. Significant predictors of DKA in the Poisson regression model were females (RR = 2.12), medical insurance claiming percentage below 50% (RR = 1.84), uncontrolled diet (never controlled diet vs. usually controlled diet, RR = 1.76), smoking (RR = 2.18) as well as worse glycemic control (HbA1c per 1.0% increment, RR = 1.15). Totally, 34.4% of DKA episodes occurred in 3.8% of type 1 diabetics with recurrent events (no less than 2 episodes). The recurrence of DKA was associated with females (RR = 10.56), smoking (RR = 6.99), worse beta cell function (stimulated C peptide per 100 pmol/L decrement, RR = 4.88) and worse glycemic control (HbA1c per 1.0% increment, RR = 1.16).There is a high incidence of DKA in Chinese type 1 diabetics. And it is recurrent in high-risk patients. Comprehensive management should be offered to control modifiable risk factors in these patients.

Traditional cell-tracking methods fail to meet the needs of preclinical or clinical research. Thus, the aim of the present study was to establish a new method of double labeling bone marrow mesenchymal stem cells (BMSCs) from type 1 diabetic (T1D) minipigs with super-paramagnetic iron oxide (SPIO) and enhanced green fluorescent protein (eGFP) and tracing them using MRI in vitro.Isolated BMSCs from T1D minipigs were labeled with eGFP and different concentrations of SPIO. The effects of lentivirus (LV)-eGFP transfection and SPIO on the viability and growth curves of BMSCs were determined by Trypan blue exclusion, the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry. Cellular ultrastructure was evaluated by transmission electron microscopy. Magnetic resonance imaging was used to evaluate BMSCs labeled with SPIO-eGFP complexes 6 weeks after labeling.Expression of eGFP in BMSCs peaked 96 h after transfection with LV-eGFP. Prussian blue staining revealed scattered blue granules in the cytoplasm of SPIO-labeled cells. Transmission electron microscopy revealed that the dense granules aggregated mainly in secondary lysosomes. On MRI, T2* -weighted imaging was far more sensitive for SPIO-labeled BMSCs than other image sequences 3 and 6 weeks after the cells had been labeled with SPIO-eGFP.We have developed a relatively simple and safe method for double labeling of BMSCs from T1D minipigs using SPIO and LV-eGFP and tracing them in vitro by MRI for 6 weeks.

To explore the renoprotective effect of Compound Xueshuantong Capsule (XST) on diabetic rat model with nephropathy.Twenty-eight male Sprague Dawley diabetic rats were induced to hyperglycaemia (3 days later, fasting blood glucose16.7 mmol/L) by peritoneal injection with streptozotocin (STZ, 50 mg/kg). And they were divided into four groups: diabetic nephropathy (vehicle treatment), irbesartan (20 mg×kg(-1)×d(-1)), low-dosage XST (900 mg×kg(-1)×d(-1)) and high-dosage XST (1800 mg×kg(-1)×d(-1)). Seven normal rats were used as control. After a 12-week intervention, urine protein was examined. Pathological morphology was observed by hematoxylin-eosin (HE), Masson and (periodic acid Schiff) PAS stains. Blood nitric oxide (NO), malondialdehyde (MDA) and blood superoxide dismutase (SOD) and urine SOD were detected. And the expression of (matrix metalloproteinase-2) MMP-2 was detected by Western blot in each group.The model rats presented with hyperglycemia, polydipsia, hyperphagia, polyuria and hyper microalbuminuria. The intervention groups showed decreased microalbuminuria and there was no effect on blood glucose or body weight. Glomerular sclerosis and extracellular matrix (ECM) increased in model group and improved in irbesartan and XST groups as judged by HE, Masson and PAS stains. Three intervention groups had no effect on the elevated expression of MMP-2 in diabetic rats. Compared with the model group, the irbesartan, low-dosage and high-dosage XST groups had significantly decreased blood levels of NO ((104.9 ± 11.0) µmol/L vs (41.9 ± 9.6) µmol/L and (14.7 ± 1.9) µmol/L, P0.05) and MDA ((19.6 ± 1.6) nmol/L vs (6.6 ± 0.9) mol/L and (4.5 ± 1.2) nmol/L, P0.05), increased blood and urine activities of SOD (blood: (222 ± 20)×10(3) vs (231 ± 18)×10(3) and (237 ± 24)×10(3) U/L,P0.05), urine: (11.8 ± 1.1)×10(3) vs (23.3 ± 2.0)×10(3) and (25.7 ± 1.8)×10(3) U/L).Compound Xueshuantong Capsule may decrease proteinuria through its suppression of oxidative stress and not its improvement of ECM metabolism.

To decipher the characteristics of real-life glucose profiles in normal glucose tolerance (NGT) persons by continuous glucose monitoring system (CGMS).Forty NGT subjects confirmed by oral glucose tolerance test (OGTT) completed a 3-day period of glucose monitoring via CGMS.The values of 24 h mean blood glucose (MBG), standard deviation of MBG (SDBG), mean amplitude of glycemic excursions (MAGE), largest amplitude of glycemic excursions (LAGE) and means of daily differences (MODD) were 6.0 ± 0.7, 0.9 ± 0.1, 1.9 ± 0.8, 2.9 ± 1.4 and 1.1 ± 0.1 mmol/L respectively. Two of them experienced asymptomatic hypoglycemia defined as glucose concentration2.8 mmol/L. And 72.5% (29/40) subjects reached glucose concentrations7.8 mmol/L for 5.2 ± 4.6 hours. In addition to higher glucose concentration (FPG: 5.0 ± 0.4 vs 4.8 ± 0.3 mmol/L, MBG: 6.4 ± 0.7 vs 5.7 ± 0.5 mmol/L), the subjects with glucose concentrations7.8 mmol/L showed more dramatic glucose excursion represented by higher SDBG (1.1 ± 0.3 vs 0.6 ± 0.2 mmol/L), MAGE (2.3 ± 1.1 vs 1.1 ± 0.3 mmol/L), LAGE (3.3 ± 1.2 vs 2.0 ± 1.0 mmol/L) and MODD (1.2 ± 0.4 vs 0.9 ± 0.3 mmol/L) versus those with glucose concentrations within 7.8 mmol/L.CGMS provides more detailed information of real-life glucose profiles in NGT subjects. And 72.5% NGT subjects in the present study spent a considerable amount of time at pre-diabetic or even diabetic glucose levels characterized by more predominant glucose excursion.

The clinical manifestation of chronic mountain sickness (CMS) is polycythemia, pulmonary hypertension and mionectic blood. However, the pathogenesis of it is not identified now. So it is necessary to investigate the effects of the angiogenic growth factors on the pathophysiologic development of CMS.The serum levels of basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) in 13 healthy Tibetan natives (Native), 17 healthy people in Xining (control group) and 35 CMS patients were determined by quantitative sandwich enzyme immunoassay. Meanwhile, the levels of Hb, Hct and SaO2 were determined.The serum levels of bFGF (107.26 +/- 7.86) ng/L, PDGF (630.18 +/- 9.89) ng/L and VEGF (543.74 +/- 6.76) ng/L in CMS were significantly higher than those in Natives (37.01 +/- 9.16; 292.16 +/- 6.88; 125.51 +/- 7.26) ng/L, and in control group (40.58 +/- 5.34; 287.68 +/- 8.33; 76.26 +/- 4.60) ng/L, respectively (P0.01). There was no difference between the natives and the control group in bFGF and PDGF (P0.05), while there was predominant difference between the Natives and the control group in VEGF (P0.01). There was a predominant positive correlation between the serum levels of bFGF, PDGF or VEGF and hemoglobin concentrations in CMS respectively (P0.01). And there were positive relations between angiogenic growth factors each other.The serum levels of bFGF, PDGF and VEGF in patients with CMS significantly increase, these angiogenic growth factors may play important role on the pathophysiologic development of CMS; the VEGF level likely contributes to the adaptation to plateau hypoxia in healthy Tibetan natives; the elevated bFGF, PDGF and VEGF levels are likely associated with excessive erythropoiesis in CMS.

To identify the related gene for a typical maturity onset diabetes of the young 2 (MODY2) pedigree.The genomic DNA of all the members of the pedigree was extracted and then PCR amplification on 5', 3' untranslated region and exon 1 - 10 of glucokinase (GCK) gene was carried out. Sequencing in both directions was performed to identify mutation on GCK gene.A novel GCK-E339K mutation which was cosegregated with diabetes/impaired glucose tolerance was identified.The novel GCK-E339K mutation might be linked to this MODY2 pedigree.

To analyse the clinical characteristics of intracranial germinoma.Retrospective analysis was applied to study the clinical characteristics of 26 intracranial germ cell tumor patients admitted to our hospital during 1991-2003. The clinical, biochemical and imaging profiles including human chorionic gonadotropin-beta, alphafetoprotein, MRI and CT as well as treatments were analysed.26 intracranial germ cell tumor patients were admitted to our hospital during 1991-2003, accounting for 0.9% of all intracranial tumors (3020 cases) at the same time. Among these patients 19 cases (73.1%) were primary intracranial germinoma, 9 patients (47.4%) were female and 10 patients (52.6%) were male. 13 patients (68.4%) were younger than 20 years. 14 patients (73.7%) had headache, vomiting and nausea, 8 patients (42.1%) had diabetes insipidus, 5 patients (26.3%) had hypopituitarism. 9 patients' tumors (47.3%) were in pine region, 7 patients' tumors (38.8%) were in sellar region. 14 patients (73.7%) were treated wit radiotherapy and all of them were discharged with good condition. 10 patients were treated with operation (7 patients accepted radiotherapy after operation) and 2 of them died after operation.Intracranial germinoma mainly affects female children and adolescents, pine and suprasellar regions are the commonly involved regions, the most common manifestations of intracranial germinoma are headache, vomiting, nausea, diabetes insipidus and hypopituitarism. Radiotherapy has good efficacy in the treatment of intracranial germinoma.

The benefits of using multi-granularity switching to reduce the number of ports, including both electronic and optical ports, have been investigated. A multi-layer ring architecture with multiple switches is suggested and two equations to count the number of ports are derived. Comparisons are made among multi-layer multi-granularity switching (MM-XC), multi-switching (M-XC), and single switching (S-XC).

We present the design and fabrication of a broadband all-fiber wavelength-division multiplexing (WDM) filter based on the long-period grating (LPG) technology. By utilizing the improved LPGs, i.e. the LPG with step-changed index modulation, an LPG with a 3-dB flat-bottom stop-band was designed with transfer matrix method. The fabrications of the designed LPG and the broadband WDM filter are also realized by using the point-by-point grating writing technique in the experiments.

We present a novel scheme for simultaneous measurement of the external RI and temperature by using the sandwiched long-period gratings (SLPGs). An LPG pair coupling between the guided mode and the low-order cladding mode acts a temperature reference element, and another LPG in-between coupling with the higher-order cladding mode performances an RI sensor. The period and length of the paired LPG (with a center to center distance 47.5mm) are 643 μm and 22.5mm, respectively, and those of LPG in-between are chosen to be 428 μm and 23mm, respectively. The experimental results show that the RI sensitivities of a paired LPG coupling with the third order cladding mode is -6.71 nm/R.I.U (refractive index unit), and the sensitivity of the LPG in between coupling with the ninth order cladding mode is -27.77 nm/R.I.U. The temperature sensitivities of these LPGs are -0.315nm/°C; and -0.337nm/°C;, respectively.

To investigate the additive effects of uncoupling protein 2 (UCP2) gene Ala55Val variation and ADR beta(3) gene Trp64Arg variation on the obesity in Chinese Han population.The UCP2 gene Ala55Val variation and ADR beta(3) gene Trp64Arg variation were examined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) in 119 obese subject with mean BMI (27.9+/-2.98)kg/m(2) and in 177 control subjects with mean BMI(21.9+/-1.9)kg/m(2). The additive effects of the two gene mutations were analyzed.(1) The frequency of ADR beta(3) gene Trp64Arg variation in obese subjects was not significantly different from that in control subjects. In control subjects, the Trp64Arg variation carriers had higher fasting glucose level and 2-hour-post-prandial glucose level than did non-carriers. (2) The frequency of homozygote of UCP2 gene Ala55Val variation in obese subjects was higher than that in the control subjects (OR=3.71, P=0.001). In control subjects the Ala55Val variation carriers had higher BMI. (3) When there was only UCP2 gene or ADR beta(3) gene mutation, the frequency of gene mutation in obese subjects was not significantly different from that in control subjects (P0.05). But when there were simultaneously two gene mutations, the frequency of gene mutations was higher in obese subjects than in control subjects (OR=2.57, P=0.009). (4) The genotype carriers with Val/Val+ Trp/Arg were the greatest relation to obese obesity (OR=8.58, P=0.002).The homozygote of UCP2 gene Ala55Val mutation increases the risk of obesity. Though the UCP2 gene mutation alone or the ADR beta(3) gene mutation alone is not associated with obesity, the possible additive effects of the two micro-genes increase the occurring of obesity.

To investigate the effects of uncoupling protein-2 (UCP2) gene Ala55Val variation and beta(3)-adrenergic-receptor (beta(3)-AR) gene Trp64Arg variation on type 2 diabetes and obesity, as well as the combined effects between the two variations.The peripheral blood samples of 173 type 2 diabetics, 119 obese persons, and 177 control subjects were collected. PCR-RFLP was used to detect the UCP2 gene Ala55Val variation and beta(3)-AR gene Trp64Arg variation. The haplotype and allele frequency distributions among the three groups were analyzed. The combined effect of the two gene mutations was analyzed too.(1) The frequencies of homozygote of UCP2 gene Ala55Val variation in the diabetes and obesity patients were both significantly higher than that in the control subjects (OR = 4.62, P = 0.001; OR = 3.71, P = 0.001). The Ala55Val variation carriers had higher BMI in the control subjects. (2) The gene frequency of homozygote of beta(3)-AR gene Trp64Arg variation was significantly higher in the diabetes patients than in the control subjects. The Trp64Arg variation carriers had higher fasting and 2-hour postgrandual glucose levels than the non-carriers in the control subjects. (3) When there was only UCP2 gene mutation or beta(3)-AR gene mutation, their frequencies in diabetes and obesity patients were not significantly different from that in the control subjects (both P0.05). However, the frequencies of the combined mutations of these two genes in either the diabetes patients or in the obesity patients were both significantly higher than in the control subjects (OR = 3.69, P = 0.000; OR = 2.57, P = 0.009). (4) The Val/Val + Trp/Arg carriers had the greatest relation with diabetes (OR = 10.43, P = 0.000) and obesity (OR = 8.58, P = 0.002).The homozygote of UCP2 gene Ala55Val mutation significantly enhances the risks of diabetes and obesity. The homozygote of beta(3)-AR gene Trp64Arg mutation is related with diabetes. The accumulation of the effects of two micro-genes creates obvious phenotypic effects.