Glucagon-like poptide-1 (GLP-1) is an incretin secreted by the enteroendocrine L cells of the gut. Upon the activation of GLP-1 receptor, adenylyl cyclase is activated and cAMP is generated, leading to the activation of protein kinase A and Epac signal pathway. GLP-1 could also activate calcium/calmodulin pathway as well as mitogen-activated protein kinases and phosphatidyl inositol-3 kinase pathway. GLP-1 not only stimulates the phase 1 and phase 2 insulin secretion, but also increases insulin synthesis. GLP-1 also stimulates proliferation and differentiation of islet β-cells, and protects β-cell from apoptosis and modulates endoplasmic reticulum stress response leading to promotion of β-cell adaptation and survival.

AIM: To study the interrelation between the structure and the function of artificial ribozyme M_1GS. METHODS: Ribozyme M_1GS-T_7, which targeted the mRNA segment of HCMV UL54 gene, was constructed. The secondary structure of M_1GS was simulated under different temperatures (20 ℃, 37 ℃ or 55 ℃, at which the secondary structure of M_1GS was relatively stable) and the interrelation between the secondary structure and the cleavage activity of M_1GS was analyzed under different temperature in vitro. To investigate the interrelation between the structure and the function of ribozyme M_1GS further, mM_1GS-T_7 was designed, in which some mutation sites was added, according to the result of temperature change experiment and the simulated secondary structure, showing that were the same structures at 37 ℃ as that of M_1GS-T_7 at 55 ℃. RESULTS: In temperature change experiment, the cleavage activity of M_1GS-T_7 was highest at 55 ℃. The result of mutant experiment showed that the mutant type was more active than M_1GS-T_7 at 37 ℃. CONCLUSION: The cleavage activity of M_1GS, which has some certain secondary structure, is higher than others. There is some interrelation between the structure and the function of M_1GS.

Objective To report 2 cases of Epstein-Barr virus-associated cutaneous lymphoproliferative disease (LPD) and to evaluate their relationship with chronic active Epstein-Barr virus (CAEBV) infection.Methods The clinical data on, laboratory examination findings in, treatment and therapeutic response of 2cases of LPD were analyzed. Results Both the patients had chronic intermittent fever, lymphadenopathy, recurrent lesions including papules, papulovesicles, necrosis and variola-like scar in light-exposed and unexposed areas. Pathologically, there was a dermal infiltrate of pleomorphic lymphoid cells with the involvement of perivascular area and some subcutaneous tissue. Immunohistochemical staining showed that most of the infiltrating lymphoid cells were positive for CD8, PCR revealed no TCR-γ gene rearrangement, and in situ hybridization for EBV was positive. The copy of EBV DNA was above the normal range in the peripheral blood from both patients. Clinical status was improved after glucocorticoid treatment. Conclusion The biologic behavior of LPD appears to be a chronic and indolent course and is closely associated with CAEBV.

Objective To observe the clinical therapeutic effect of Xuebijing injection on vascular endothelial cell ( VEC) injury,microcirculation disorder and organ dysfunction in patients with sepsis. Methods Seventy?three patients with sepsis were randomly divided into two groups:Xuebijing injection?treated group (40 cases) and control group (33 cases). Routine medicine therapy was applied in both groups. Additionally, the Xuebijing injection?treated group was treated with Xuebijing injection 100 ml and saline 100 ml by intravenous drip every 12 hours for consecutive 5 days. Vascular endothelial injury index, including soluble thrombomodulin( sTM) ,vascular endothelial growth factor 2 ( VEGF?2) ,endothelial specific molecule 1 ( ESM?1),microcirculation index of arterial blood lactic acid (Lac),central venous oxygen saturation (ScvO2),total microvessel density (TVD),the perfusion vascular density (PVD),proportion of perfused vessels (PPV) and microvessel flow index ( MFI) of the two groups before and after therapy were observed and the sequential organ failure score ( SOFA) was recorded before and after treatment. Results Senventy?three patients with sepsis had different degrees of increase in vascular endothelial damage markers,lactate and sequential organ failure scores in arterial blood, while the central venous blood oxygen saturation ( ScvO2 ) , the total vascular density of the sublingual microvasculature ( TVD) ,perfused vessel density ( PVD) ,proportion of perfused vessels ( PPV) and microcirculatory flow index ( MFI) decreased before treatment. After 5?day treatment,the above indicators of all patients were improved,the indexes in the Xuebijing injection group decreased significantly,compared with the control group ,sTM ( (16. 91±4. 55) μg/L,(19. 51±4. 09) μg/L,t=-6. 021,P<0. 05),VEGF?2 (50. 8 (17. 8,127. 7) ng/L vs. 74. 9(22. 7,155. 1) ng/L,t=4. 227,P<0. 05),ESM?1 ( (10. 20 ±2. 43) μg/L vs. (14. 80±3. 52) μg/L,t=-4. 113,P<0. 05),Lac( (2. 1±0. 7) mmol/L vs. (3. 7±1. 1) mmol/L,t=2. 366,P<0. 05) and SOFA ( (5. 9±2. 1) vs. (8. 7±2. 6),t=-7. 990,P<0. 05). ScvO2( (0. 771±0. 153) % vs. (0. 641±0. 113) %,t=5. 061,P<0. 05),PVD ( (16. 8±6. 1) mm/mm2 vs. (12. 1±5. 1) mm/mm2,t=4. 002, P<0. 05),PPV ( (66. 2±21. 3) % vs. (50. 4±19. 3) %,t=-2. 550,P<0. 05) and MFI (6. 2 ±2. 4) vs. (3. 8 ±2. 2),t=-5. 001,P<0. 05) were significantly higher than those in the control group in the same period. sTM and PPV had a significant negative correlation (r=-0. 755,P=0. 000),PVD,PPV,ESM?1 and MFI were negatively correlated (r=-0. 665,P=0. 000; r=-0. 600,P=0. 000; r=-0. 469,P=0. 000),PPV,MFI and SOFA were negatively correlated ( r=-0. 798,P=0. 000;r=-0. 995,P=0. 000);sTM,ESM?1 and SOFA were significantly positively correlated ( r = 0. 883, P = 0. 000;r = 0. 881, P = 0. 000 ) . Conclusion Vascular endothelial cell dysfunction probably plays an important role in the pathophysiology of sepsis and Xuebijing injection has therapeutic effect on sepsis by protecting vascular endothelial cell function.

Objective To study the association of glucagon like peptide 1 receptor (GLP1R) gene polymorphism with type 2 diabetes in Han population in Shanghai. Methods In the study, 360 type 2 diabetic patients and 313 normal control subjects were enrolled. Diabetic patients were further subdivided into insulin treated non obese patients (BMI28, 192 subjects). A single nucleotide polymorphism (SNP) rs 2268657 was genotyped in all the subjects enrolled in the study using allele specific real time PCR and its association with type 2 diabetes was examined. Results The frequencies of AA,AG, GG genotype incontrol group were0.086,0.447, 0.466 respectively, 0.155, 0.375, 0.470 in non obese diabetic patient group respectively, and 0.109, 0.500, 0.391 in obese diabetic patient group respectively. There was significant difference of the frequency of genotype AA between control group and non obese diabetic patient group (OR=1.939, P

Objective To observe the clinical effect of traditional Chinese medicine inflammatory mixture on vascular endothelial cell injury, mcrocirculation disorder and organ dysfunction in sepsis. Methods 73 patients with sepsis were randomly divided into two groups: Anti-inflammatory mixture-treated group (40 cases) and control group (33 cases). Routine medicine therapy was given in both groups.Additionally, in the Anti-inflammatory mixture-treated group, 100 ml Anti-inflammatory mixture was given By oral or nasal feeding, every 12 hours for consecutive 7 days. Vascular endothelial injury index (Soluble thrombomodulin,Vascular endothelial growth factor-2, endothelial specific molecule-1), mcrocirculation disorder index (arterial blood lactate, central venous oxygen saturation, total vessel density, perfused vessel density, proportion of perfused vessels, microcirculatory flow index) of two group patients before and after therapy were observed and the sequential organ failure score (SOFA) was recorded before and after treatment. Results After treatment, the indexes of vascular endothelial injury sTM (12.37 ± 5.08 μg/L vs. 18.77 ± 6.88 μg/L, t=3.448), VEGF-2 [45.6 ng/L (14.3, 112.5) vs. 52.4 ng/L (17.2, 123.6), Z=4.009], ESM-1 (15.54 ± 4.09 ng/ml vs. 17.64 ± 6.79 ng/ml, t=-1.551), Lac (2.6 ± 1.2 mmol/L vs. 3.7 ± 1.8 mmol/L, t=4.115) and SOFA (4.1 ± 1.7 vs. 6.1 ± 3.2, t=-2.118) in anti-inflammatory mixture group decreased significantly than those in the control group. but the ScvO2(0.719 ± 0.243 vs. 0.603 ± 0.201, t=-2.773), PVD (14.8 ± 5.8 mm/mm2 vs. 13.1±5.1 mm/mm2, t=-5.114), PPV (59.1% ± 22.5% vs. 53.9% ± 20.6%, t=1.779), MFI (9.4 ± 4.6 vs. 7.2 ± 2.2, t=4.339) in the anti-inflammatory mixture group were significantly higher than those in the control group. Correlation analysis showed that the sTM and PPV were significantly negatively correlated (r=-0.875, P＜0.01), ESM-1 was significantly negatively correlated with PVD, PPV and MFI (r=-0.877, P＜0.01; r=-0.799, P＜0.01; r=-0.821, P＜0.01) and ESM-1 and SOFA were significantly positively correlated (r=0.840, P＜0.01). Conclusions Anti-inflammatory mixture of Chinese medicine has a certain therapeutic effect on sepsis by protecting vascular endothelial cell function.

Objective To investigate the difference of niacin skin flush response between patients with major depressive disorder (MDD) and healthy controls (HCs), and its sensitivity and specificity for the diagnosis of MDD. Methods Twenty-one untreated patients with MDD and 28 age- and gender-matched HCs were enrolled in this study. The severity of depressive symptoms was assessed mainly by using the 17-item Hamilton Depression Rating Scale (HDRS-17). Methyl Nicotinate (MN) solution at 8 different concentrations (10-5 mol/L, 10-4 mol/L, 10-3.5 mol/L, 10-3 mol/L, 10-2.5 mol/L, 10-2 mol/L, 10-1.5 mol/L, 10-1 mol/L) were applied on subjects' forearms. Signals of blood flow were collected using the Doppler Laser Flowmetry to detect the skin flushing of the test. Results Under the concentrations of 10-2.5 mol/L, 10-2 mol/L, 10-1.5 mol/L and 10-1 mol/L MN solution, the blood flow was significantly higher in depressive patients than in HCs (P<0.01). The MN sensitivity (logEC50) was inversely correlated to the severity of depressive symptoms (r=-0.57, P<0.05). ROC curve analysis implied that the maximum blood flow (MBF) caused by the niacin skin flush response, could efficiently discriminate MDD from HCs (AUC=0.90, P<0.01). Conclusion The presence of enhanced niacin skin flush response may be helpful in the diagnosis of MDD.