[Mechanism of Notoginseng Radix et Rhizoma in regulating PI3K/Akt/mTORC1-mitochondrial energy metabolism to treat chronic renal failure in rats with blood stasis syndrome].

This study observed the effects of Notoginseng Radix et Rhizoma on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin complex 1(mTORC1) signaling pathway and mitochondrial energy metabolism in the rat model of adriamycin-induced renal fibrosis with blood stasis syndrome to explore the mechanism of Notoginseng Radix et Rhizoma in protecting the kidney. Thirty male rats with adriamycin-induced renal fibrosis were randomized into model, low-, medium-, and high-dose Notoginseng Radix et Rhizoma, and positive control groups(n=6). Six clean SD male rats were selected into the normal group. The normal group and model group were administrated with normal saline, and other groups with corresponding drugs. After 8 weeks of treatment, the renal function, renal pathology, adenosine triphosphate(ATP) levels, Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities, and the protein levels of ATP5B, mTORC1, 70 kDa ribosomal protein S6 kinase(P70S6K), P85, Akt, p-Akt, and SH2-containing inositol phosphatase(SHIP2) in the renal tissue were determined. Compared with the normal group, the model group showed elevated levels of blood urea nitrogen(BUN) and serum creatinine(SCr)(P<0.01). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control lowered the levels of BUN and SCr, which were significant in the medium-and high-dose Noto-ginseng Radix et Rhizoma groups and the positive control group(P<0.05). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control alleviated the pathological changes in the renal tissue, such as vacuolar and fibroid changes, glomerulus atrophy, cystic expansion of renal tubules, and massive infiltration of inflammatory cells. Compared with the normal group, the model group showed decreased mitochondrial ATP content and Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities in the renal tissue(P<0.05), and medium-and high-dose Notoginseng Radix et Rhizoma and positive control mitigated such decreases(P<0.05). Compared with the model group, medium-and high-dose Notoginseng Radix et Rhizoma and the positive control up-regulated the protein levels of ATP5B and SHIP2 and down-regulated the protein levels of mTORC1, P70S6K, P85, Akt, and p-Akt(P<0.05 or P<0.01 or P<0.001). Notoginseng Radix et Rhizoma may exert an anti-fibrosis effect by inhibiting the activation of the PI3K/Akt/mTORC1 pathway to restore mitochondrial energy metabolism, thus protecting the kidney.

Effects of Persimmon Tannin-Aloe vera Composite on Cytotoxic Activities, and Radioprotection Against X-rays Irradiated in Human Hepatoma and Hepatic Cells.

A persimmon tannin-Aloe vera composite powder (PT-A) was investigated for its capacity to protect against ionizing radiation. Human hepatic cells (L02 cells) and human hepatoma cells (HepG2 cells) were pretreated with different concentrations of PT-A or the single compounds (PT or Aloe vera) and radiated with X-rays. After radiation and post-incubation for 12 h or 24 h, the cell viability, apoptosis, and reactive oxygen species (ROS) production were analyzed by Cell Counting Kit 8 (CCK-8), 2',7'-dichlorfluorescein diacetate (DCFH-DA) staining, and Hoechst 33258 staining/flow cytometry, respectively. CCK-8 results illustrated that the optimal radiation dose L02 cells was 8 Gy for L02 cells, and the cell activity was 71.72% (IC50 = 412.1 µg/mL) after post-radiation incubation of 12 h. For HepG2 cells, the optimal radiation dose was 8 Gy, and the cell activity was 62.37% (IC50 = 213.0 µg/mL). The cell apoptotic rate was the lowest at a PT-A concentration of 200 µg/mL in L02 cells (4.32%, P < 0.05), and at 100 µg/mL in HepG2 cells (9.80%, P < 0.05). ROS production induced by radiation could be effectively inhibited by 200 µg/mL of PT-A in L02 cells, and by 100 µg/mL of PT-A in HepG2 cells. The PT-A composite has good radioprotective effects on cell vitality and apoptosis of X-rays radiation exposure towards L02 cells and HepG2 cells compared to the persimmon tannin or Aloe vera. Therefore, PT-A composite might be useful as a natural, harmless anti-ionizing radiation agent, and has various clinical application prospects in future.

Ant Colony Evacuation Planner: An Ant Colony System With Incremental Flow Assignment for Multipath Crowd Evacuation.

Evacuation path optimization (EPO) is a crucial problem in crowd and disaster management. With the consideration of dynamic evacuee velocity, the EPO problem becomes nondeterministic polynomial-time hard (NP-Hard). Furthermore, since not only one single evacuation path but multiple mutually restricted paths should be found, the crowd evacuation problem becomes even challenging in both solution spatial encoding and optimal solution searching. To address the above challenges, this article puts forward an ant colony evacuation planner (ACEP) with a novel solution construction strategy and an incremental flow assignment (IFA) method. First, different from the traditional ant algorithms, where each ant builds a complete solution independently, ACEP uses the entire colony of ants to simulate the behavior of the crowd during evacuation. In this way, the colony of ants works cooperatively to find a set of evacuation paths simultaneously and thus multiple evacuation paths can be found effectively. Second, in order to reduce the execution time of ACEP, an IFA method is introduced, in which fractions of evacuees are assigned step by step, to imitate the group-based evacuation process in the real world so that the efficiency of ACEP can be further improved. Numerical experiments are conducted on a set of networks with different sizes. The experimental results demonstrate that ACEP is promising.

[Comparison of transabdominal-hiatal approach and standard thoracoabdominal approach in radical gastrectomy for advanced proximal gastric cancer].

OBJECTIVE: To investigate the safety and efficacy of the transabdominal-hiatal approach of radical gastrectomy for the advanced proximal gastric cancer. METHODS: The clinical data of 40 advanced proximal gastric cancer patients with involvement of distal esophagus admitted in Tongcheng People's Hospital from June 2003 to September 2006 were analyzed retrospectively. Patients included 27 men and 13 women with a mean age of 56.1 years (range: 37 to 76 years). The data were compared with those of 40 proximal gastric cancer patients undergoing standard thoracoabdominal approach (control group) during the same period. RESULTS: As compared with the control group, the transabdominal-hiatal approach showed less blood loss [(181.3 ± 63.7) ml vs.(248.8 ± 79.7) ml], shorter operating time [(4.1 ± 0.6) h vs. (5.3 ± 0.7) h], shorter ICU stay [(6.5 ± 5.7) d vs. (19.4 ± 18.0) d] and shorter postoperative hospital stay [(14.0 ± 2.3) d vs.(18.7 ± 3.0) d] (all P<0.05). The complication rates of transabdominal-hiatal approach group and thoracoabdominal approach group were 7.5% (3/40) and 10.0% (4/40), and the 5-year survival rates were 51.3% and 60.0%, respectively (both P>0.05). CONCLUSION: The transabdominal-hiatal approach of radical gastrectomy for proximal gastric cancer is safe and effective, which may substitute the standard thoracoabdominal technique.

KRAS mutation in patients with lung cancer: a predictor for poor prognosis but not for EGFR-TKIs or chemotherapy.

BACKGROUND: The prognostic and predictive value of KRAS mutations in patients with lung cancer is controversial. Biases in disease stage, treatment regimen, small-scale patient studies, and biomarker status have led to inconsistent results in previous reports. METHODS: The KRAS and EGFR genes were examined in 1935 consecutive patients with non-small cell lung cancer. All patients were divided into KRAS mutation (KRAS group), EGFR mutation (EGFR group), and KRAS/EGFR wild type (WT group) groups. Randomly selected cases were paired with patients with the KRAS mutation, the EGFR mutation, and KRAS/EGFR wild type patients according to tumor, node, metastasis stage, time of first visit within 1 year, and pathology. Progression-free survival (PFS) and overall survival were evaluated by Kaplan-Meier and Cox models. RESULTS: The KRAS mutation rate for lung adenocarcinoma was 5.90 %. The overall survival was 14.47, 20.57, and 42.73 months for the KRAS group, WT group, and EGFR group, respectively (P < 0.001). Multivariate analysis indicated that KRAS mutation status was an independent prognostic factor (hazard ratio 2.69, 95 % confidence interval 1.91-3.80, P < 0.001). No difference was found in PFS and tumor responsiveness between patients with a KRAS mutation and those with wild type KRAS/EGFR for chemotherapy and EGFR tyrosine kinase inhibitors (TKI). PFS did not significantly differ for chemotherapy among the three groups (P = 0.270). CONCLUSIONS: KRAS mutation is a poor prognosis factor, but it is not an independent predictor of response to EGFR-TKI or chemotherapy in patients with lung cancer.

How calcium inhibits the magnesium-dependent kinase gsk3ß: a molecular simulation study.

Glycogen synthase kinase 3ß (GSK3ß) is a ubiquitous serine/threonine kinase that plays a pivotal role in many biological processes. GSK3ß catalyzes the transfer of γ-phosphate of ATP to the unique substrate Ser/Thr residues with the assistance of two natural activating cofactors Mg(2+). Interestingly, the biological observation reveals that a non-native Ca(2+) ion can inhibit the GSK3ß catalytic activity. Here, the inhibitory mechanism of GSK3ß by the displacement of native Mg(2+) at site 1 by Ca(2+) was investigated by means of 80 ns comparative molecular dynamics (MD) simulations of the GSK3ß···Mg(2+)-2/ATP/Mg(2+) -1 and GSK3ß···Mg(2+)-2/ATP/Ca(2+)-1 systems. MD simulation results revealed that using the AMBER point charge model force field for Mg(2+) was more appropriate in the reproduction of the active site architectural characteristics of GSK3ß than using the magnesium-cationic dummy atom model force field. Compared with the native Mg(2+) bound system, the misalignment of the critical triphosphate moiety of ATP, the erroneous coordination environments around the Mg(2+) ion at site 2, and the rupture of the key hydrogen bond between the invariant Lys85 and the ATP O(ß2) atom in the Ca(2+) substituted system were observed in the MD simulation due to the Ca(2+) ion in active site in order to achieve its preferred sevenfold coordination geometry, which adequately abolish the enzymatic activity. The obtained results are valuable in understanding the possible mechanism by why Ca(2+) inhibits the GSK3ß activity and also provide insights into the mechanism of Ca(2+) inhibition in other structurally related protein kinases.

A novel inhibitor of human La protein with anti-HBV activity discovered by structure-based virtual screening and in vitro evaluation.

BACKGROUND: Over 350 million people worldwide are infected with hepatitis B virus (HBV), a major cause of liver failure and hepatocellular carcinoma. Current therapeutic agents are highly effective, but are also associated with development of viral resistance. Therefore, strategies for identifying other anti-HBV agents with specific, but distinctive mechanisms of action are needed. The human La (hLa) protein, which forms a stabilizing complex with HBV RNA ribonucleoprotein to promote HBV replication, is a promising target of molecular therapy. AIMS: This study aimed to discover novel inhibitors of hLa that could inhibit HBV replication and expression. METHODS: A multistage molecular docking approach was used to screen a Specs database and an in-house library against hLa binding sites. Sequential in vitro evaluations were performed to detect potential compounds with high scores in HepG2.2.15 cells. RESULTS: Of the 26 potential compounds with high scores chosen for experimental verification, 12 had HBV DNA inhibition ratios of less than 50% with P<0.05. Six had significant inhibition of HBV e antigen (HBeAg) levels, and 13 had significant inhibition of HBV surface antigen (HBsAg) levels by in vitro assays. Compounds HBSC-11, HBSC-15 and HBSC-34 (HBSC is system prefix for active compounds screened by the library) were selected for evaluation. HBSC-11 was found to have an obvious inhibitory effect on hLa transcription and expression. CONCLUSIONS: Our findings suggest that anti-HBV activity of HBSC-11 may be mediated by a reduction in hLa levels. In addition, our data suggest the potential clinical use of hLa inhibitors, such as HBSC-11, for treating HBV infection.

[Study on the pathogenesis of stress myocardial injury].

OBJECTIVE: To investigate the pathogenesis of stress myocardial injury. METHODS: Thirty Wistar rats were randomly divided into three groups, with 10 rats in each group: normal control group, movement restriction and ice swimming stress group (rat movement was restricted 6 hours per day; beginning from 13th day rats were allowed to swim in ice water for 5 minutes, ice stress group), and endotoxin stress group [intraperitoneal injection of lipopolysaccharide (LPS) 10 mg/kg, LPS group]. The myocardial tissue was harvested, the pathological changes in myocardial was observed with light microscopy, and the changes in myocardial ultrastructure were observed with electron microscope. The levels of serum cardiac troponin I (cTnI) was determined by enzyme-linked immunosorbent assay (ELISA), apoptosis of myocardial cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and the apoptotic index was calculated.The caspase-8 and caspase-3 expression in myocardial tissue were assessed by immunohistochemistry. The correlation between caspase and apoptotic index was analyzed. RESULTS: Compared with normal control group, in ice stress group and LPS group, myocardial tissue was found to be injured seriously in different degrees under light microscopy and electron microscopy; the content of cTnI (µg/L) in serum was significantly increased (0.63 ± 0.12, 0.74 ± 0.08 vs. 0.53 ± 0.03, P < 0.05 and P < 0.01); apoptosis index of myocardial tissue was significantly increased in different degrees [(7.91 ± 1.71)%, (12.94 ± 2.00)% vs. 0]; caspase-8 and caspase-3 expressions in the myocardium were increased (caspase-8 gray scale: 126.65 ± 3.13, 114.82 ± 8.67 vs. 156.99 ± 9.66; caspase-3 gray scale: 130.20 ± 2.96, 108.58 ± 5.72 vs. 160.51 ± 5.25, all P < 0.01). However, the above indexes in LPS group were significantly higher than those in ice stress group (P < 0.05 or P < 0.01). The correlation analysis showed that in ice stress group, positive correlation was found between caspase-8, caspase-3 and apoptotic index [r(1) = 0.914, P(1) = 0.002; r(2) = 0.929, P(2) = 0.001]; in LPS group, the positive correlation also exist between caspase-8, caspase-3 and apoptotic index [r(1) = 0.956, P(1) = 0.000; r(2) = 0.916, P(2) = 0.001]. CONCLUSION: Severe stress may produce stress injury of myocardium via increasing expression of caspase-8 and caspase-3 protein.

[The changes of insulin secretion in type A insulin resistance syndrome: a 7-year follow up].

OBJECTIVE: A previously reported female diagnosed with type A insulin resistance syndrome bearing a heterozygous missense mutation of R1174W in the insulin receptor gene was followed for 7 years since the age of 16 years. METHODS: Five-hour oral glucose tolerance tests (OGTT) were done on baseline, the 3(rd), 6(th) and 7(th) year respectively, with serum insulin and C-peptide measured at the same time points. Areas under of curve (AUC) of glucose, insulin and C-peptide were compared between the years. Acute insulin response (AIR) was determined at baseline and the 7(th) year. The dose response were insulin secretion rates at each time point during OGTT being plotted over the corresponding glucose levels, and the slopes of which quantified the insulin secretion responding to glucose. RESULTS: The follow up data showed that the glucose metabolism of the subject did not deteriorate over time with yearly glycosylated hemoglobin A1c (HbA1c) being normal (4.6% - 5.5%), and hyperinsulinemic hypoglycemia was a persistent phenomenon observed at 4 - 5 hours post-load. The fasting and AUCs of serum insulin and C-peptide tended to decline without simultaneously increase of those of plasma glucose. The AIR decreased by 56% as compared to baseline. The dose response curves shifted downward as years went by. CONCLUSIONS: It supports that with the alleviation of physiological insulin resistance after puberty, the gross hyperinsulinemia tends to ameliorate, and ß-cell secretion does not deteriorate over time as glucose homeostasis maintains.

A novel mutation (D631del) of the RET gene was associated with MEN2A in a Chinese pedigree.

Germline mutations in the RET proto-oncogene (RET gene) are well documented as the genetic causes of multiple endocrine neoplasia type 2A (MEN2A). We performed genetic analysis by direct RET gene mutation analysis in a Chinese MEN2A family and compared these results with biochemical screening tests and pathological examinations. Twenty-one exons and flanking introns of the RET gene were amplified using polymerase chain reaction (PCR). The PCR products were subjected to sequencing directly, or cloned into pGEM-T plasmids and sequenced. Restriction fragment length polymorphism (RFLP) was employed to confirm the mutation on the RET sequence. A novel heterozygous mutation of a 3-bp (GAC) deletion at codon 631 (D631del) of exon 11, resulting in the deletion of an aspartic acid at the locus, was identified in four MEN2A patients and one phenotypically normal family member. The average clinical onset-age of four MEN2A patients was 33.7 years, no cervical lymph node metastasis was found in MEN2A patients with medullary thyroid carcinoma in the family. The study indicated that the novel heterozygous deletion mutation at D631 of RET gene was co-segregated with MEN2A phenotype and promoted the development of MEN2A. This report is the first description of the D631del mutation in the family with MEN2A.

[DelD631: a novel mutation of the RET proto-oncogene in multiple endocrine neoplasia type 2A (MEN2A)].

OBJECTIVE: To detect RET mutations in a rare Chinese big family with Multiple endocrine neoplasia type 2A (MEN2A). METHODS: One MEN2A family, including the proband, have 22 members of two generations, it is a rare big family in modern Chinese families. The DNAs of the 22 members from the family including 4 patients were extracted from blood leukocytes, PCR and gene sequencing of PCR products by an automated DNA sequencer were applied to scan the exon10 and 11 of RET proto-oncogene. Sequencing results were compared with the Pubmed's. Clone sequencing was adopt to further confirm the results, then verifying the novel mutation through the human gene mutation database at the institute of medical genetics in cardiff. Invitrogen biotechnology company (Shanghai) provided the technology of clone sequencing. RESULTS: A novel deletion mutation of D631 (GAC) (del D631) was detected in exon11 of the RET proto-oncogene in 4 MEN2A patients of the family, this rare deletion mutation of D631 (GAC) lead base sequence of TGC(angle)GACGAGCTG change to TGCGAGCTG. Besides 4 MEN2A patients, the son of II6 (the first class relative) was found to be a carrier of delD631 mutation. CONCLUSION: A novel deletion mutation (del D631) of RET proto-oncogene was detected in the family with MEN2A and it has never been reported before in the world. DelD631 may be related to the late onset of MEN2A compared to the cysteine mutations and pheochromocytoma might be the first manifestation prior to the development of MTC.

[Characteristics and correlative factors of posterior corneal surface changes after laser in situ keratomileusis].

OBJECTIVE: To assess the changes of the posterior corneal surface and the factors influencing these changes after laser in situ keratomileusis (LASIK). These factors included the preoperative refraction, preoperative intraocular pressure (IOP), preoperative corneal thickness, spherical equivalent correction and one-week postoperative corneal thickness. METHODS: The posterior corneal radius of curvature for the posterior best fit sphere (PBFS), irregularity of posterior surface, and anterior chamber depth (ACD) were obtained with the scanning slit topography system before and 1 week, 1 month and 3 months after LASIK in 64 eyes of 34 patients with myopic refractive errors of -2.25 to -12.5 diopters. Multiple regression analysis was used to assess the factors that affecting these changes of posterior corneal surface. The difference of radius PBFS and posterior elevation difference (PED) was used as an indicator for the forward shift of posterior corneal surface. RESULTS: The ACD before the surgery and 1 week, 1 month and 3 months after the surgery was (3.2448 +/- 0.2806), (3.2770 +/- 0.2810), (3.2579 +/- 0.2932) and (3.2651 +/- 0.2875) mm, respectively. The PBFS at that time was (6.5095 +/- 0.2177), (6.3731 +/- 0.2127), (6.4257 +/- 0.2358) and (6.4354 +/- 0.2266) mm, respectively. The posterior corneal irregularity at 5 diameters zone was 0.622 +/- 0.142, 0.978 +/- 0.244, 0.884 +/- 0.207 and 0.881 +/- 0.174, respectively The preoperative posterior corneal radius of curvature for PBFS, the irregularity of the posterior surface and the ACD were significantly different from that of postoperative data at each time point (P < 0.01). There was no significant difference in these indexes between 1 month and 3 months postoperatively. Multiple regression analysis showed that factors relevant to the changes of posterior corneal surface were the corrected preoperative refraction (regression coefficient r = 0.0173, P = 0.005) and 1 week postoperative corneal thickness (mm) (regression coefficient r = -1.495, P = 0.001). CONCLUSIONS: The posterior corneal surface after LASIK become steeper and more irregular and remains stable in three months after the surgery. Eyes with thinner corneas and higher myopia requiring more ablation are more predisposed to the changes of posterior corneal surface. The results of the present study should not be used in extremely high degree myopia. A study using a larger group of patients with a longer observation period is required.

[Influencing factors for the curative effects of short-term continuous subcutaneous insulin infusion on newly diagnosed type 2 diabetes].

OBJECTIVE: To investigate the effects of short-term continuous subcutaneous insulin infusion (CSII) on newly diagnosed type 2 diabetes and to identify the influencing factors for the curative effects of CSII. METHODS: 138 newly diagnosed type 2 diabetic patients with fasting plasma glucose > 11.1 mmol/L were treated with CSII for 2 weeks. Intravenous glucose tolerance test (IVGTT) was performed before and after CSII. The target of glycemic control were fasting blood glucose < 6.1 mmol/L and postprandial blood glucose (PBG) < 8.0 mmol/L. The age, body mass index (BMI), fasting and postprandial plasma glucose, hemoglobin A(1C) (GHbA(1C)), Homa beta, Homa IR, area under the curve of insulin (AUC) during IVGTT were compared between the good glycemic control group and the inadequate glycemic control group. RESULTS: After 2 weeks' CSII treatment, good glycemic control was achieved in 126 patients (group A) but not in the remaining 12 patients (group B). There were no differences in age, BMI, postprandial plasma glucose, GHbA(1C), and Homa IR between the two groups before and after CSII treatment. But the fasting plasma glucose was higher and Homa B was lower in group B than in group A before CSII treatment. The DeltaAUC (AUC after CSII subtracted from that before CSII) representing the recovery of beta-cell function was much greater in group A than in group B. The insulin dose of group B was significantly higher than that of the good glycemic control group. CONCLUSION: More severe hyperglycemia and relative beta-cell function deficiency may be the main reasons responsible for not achieving good glycemic control in newly diagnosed type 2 diabetic patients with short-term intensive CSII treatment.

[Anterior corneal topographic changes after scleral buckling surgery].

OBJECTIVE: To investigate corneal refractive changes after scleral buckling surgery. METHODS: In a prospective self-controlled clinical study, we investigated the changes of refractive power, astigmatic power, astigmatic axis, and irregular astigmatic power of anterior corneal surface following scleral buckling surgery for retinal detachment in 30 patients (30 eyes). The corneal shapes were detected by Orbscan II topography at 1 day before surgery, and 1 week, 1 month, and 3 months after surgery. The effects of some surgical factors on the anterior corneal refractive changes were analyzed. RESULTS: After surgery, refractive power on corneal anterior surface decreased significantly in peripheral zone at 1 week (P < 0.01). Astigmatic power increased obviously in central zone. The direction of astigmatic axis matched the direction of the buckle, and changed obviously in central zone after 1 week (P < 0.05). Irregular astigmatic power did not change significantly. There was a significant correlation between the encircling length/the buckle width and the refractive changes of corneal anterior surface. CONCLUSION: Refractive changes of corneal anterior surface following scleral buckling surgery was mainly temporary. Changes in the shape of corneal should be minimized to ensure a favorable postoperative visual acuity.

[Common variants in beta 3-adrenergic-receptor and uncoupling protein-2 genes are associated with type 2 diabetes and obesity].

OBJECTIVE: 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. METHODS: 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. RESULTS: (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 P > 0.05). 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). CONCLUSION: 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.