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OBJECTIVE To analyze the patents of new target oral drugs for type 2 diabetes mellitus （T2DM）， and to provide references for the research and development direction and patent layout of new domestic diabetes drugs. METHODS Based on global patent data in the HimmPat database， from multiple perspectives such as the number of patent applications and authorization， development trend， regional distribution and main applicants， statistics and analysis were performed for the patents related to 3 types of new target oral drugs for T2DM， such as glucokinase activator （GKA）， protein tyrosine phosphatase 1B inhibitor （PTP-1B-IN）， and 11β-hydroxysteroid dehydrogenase 1 inhibitor （11β-HSD1-IN）. RESULTS & CONCLUSIONS A total of 1 649 patents of GKA， 709 patents of PTP-1B-IN， 592 patents of 11β-HSD1-IN were obtained， the main applicants were well-known pharmaceutical companies， which possessed the core patents of pharmaceutical compounds. The research on GKA drugs was more mature， with a larger number of patent applications and a more comprehensive enterprise layout. Domestic enterprises， universities and research institutions had advantages in the field of PTP-1B-IN. Domestic enterprises and research institutions can leverage the advantages of traditional Chinese medicine and resources to enhance their research capabilities and improve technological competitiveness through core technology exploration， the exploration of process route， patent layout， industry- university-research cooperation and the establishment of patent pool.
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Objective To explore the effect of Linc00460 on the aerobic glycolysis of breast cancer (BC) cells through sponge adsorption of miR-320a. Methods The qRT-PCR method was used to detect Linc00460 and miR-320a expression levels in normal breast epithelial cell line MCF-10A and five BC cell lines. The effect of interfering Linc00460 on miR-320a expression was detected by qRT-PCR. The double luciferase reporter gene experiment was used to analyze the targeting relationship between miR-320a and Linc00460. In addition, the si-Linc00460 and miR-320a inhibitor were co-transfected into MDA-MB-231 cells, and the expression level of miR-320a in the cells was detected by qRT-PCR; cell proliferation ability was measured by the MTT method; glucose uptake rate was detected by 2-NBDG method; the content of lactic acid in the cell supernatant was detected by colorimetric method; the key enzymes of glycolysis was detected by the enzyme activity kit; and the expression levels of the key proteins in the glycolysis pathway were detected by Western blot. Results Linc00460 was highly expressed in five BC cell lines, while miR-320a was lowly expressed as compared with MCF-10A cells. The expression of miR-320a in MDA-MB-231 cells significantly increased after interfering with Linc00460. The double luciferase reporter gene experiment confirmed that miR-320a and Linc00460 could target binding. Interfering with the expression of Linc00460 could inhibit MDA-MB-231 cells proliferation (all P=0.000), reduce the rate of cellular glucose uptake and the content of lactic acid in the cell supernatant (all P=0.000), inhibit the activities of PFK, PK, and LDH enzymes (all P=0.000), and downregulate the protein expression levels of PFKM, GLUT1, and LDHA (all P=0.000). Meanwhile, inhibition of miR-320a could reverse the inhibitory effect of si-Linc00460 on the proliferation and glycolysis of MDA-MB-231 cells (all P=0.000 or 0.001). Conclusion Linc00460 might adsorb miR-320a, consequently leading to upregulation of PFKM expression, thereby promoting aerobic glycolysis in BC cells.
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Objective To detect the nucleation-promoting potency of retinol binding protein (RBP) in the simulated bile system,and observe the process of cholesterol nucleation and crystallization.Methods Small and synthetic bile systems were synthesized.RBP (RBP group),α1-acid glycoprotein (AAG,AAG group) and albumin ( Alb,Alb group) were added into the Small bile respectively.The derived indices of nucleation time,crystal growth rate and final concentration of crystal were studied by Busch method.Alb ( control group) and RBP (experimental group) were added into the Small and synthetic bile systems respectively.The nucleation time was detected by polarizing microscopy according to the Holan method and the nucleation-promoting potency was calculated according to the Holzbach method. The morphological dynamics of cholesterol nucleation and crystallization were observed under a light microscope.All data were analyzed by using the analysis of variance or the t test.Results The derived indices of nucleation time,crystal growth rate and final concentration of crystal were 0.66,1.29 and 1.01 in the AAG group,and 0.73,1.02,0.95 in the RBP group,respectively.In the Small bile system,the average nucleation time of cholesterol monohydrate crrystals were ( 12.2 ± 1.2 )days in the control group and (8.2 ± 1.5)days in the experimental group,respectively,with a significant difference between the 2 groups (t =2.97,P ＜ 0.05 ).The nucleation activity of RBP was 0.67 in the Small bile system.In the synthetic bile system,the average nucleation time of cholesterol monohydrate crystals were (9.5 ± 1.1 ) days in the control group and (7.5 ± 1.1 )days in the experimental group,respectively,with a significant difference between the 2 groups ( t =2.35,P ＜ 0.05 ).The nucleation activity of RBP was 0.79 in the synthetic bile system.The process of cholesterol nucleation and crystallization was divided into 4 stages,and the split phenomenon appeared in the bile system at day 21.Conclusion RBP is a pro-nucleation factor in simulated bile system.
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Objective To study the correlation of the number and ratio of involved lymph nodes and the prognosis of gastric carcinoma .Methods 174 patients with positive gastric lymph nodes were included,they were treated by radical gastrectomy and lymph nodes dissection (D2 or D3)in our department. The number and ratio of metastastic gastric lymph nodes were calculated. Their influence and their interrelation with pathogenic parameters were analyzed. Results The overall 5 year survival rate was 29.59%, and the five year survival rates of patients with 1 20 per cent and more than 20% positive lymph nodes were 70.58%,11.86% respectively, one to five positive lymph nodes and five more were 46.47%,17.35% respectively, the five year survival rate was decreased as the ratio and number of involved lymph nodes increased. Studies also indicated that with the increase of depth of cancer invasion ,the number and ratio of involved lymph node elevated.Conclusions The results shows that the number and ratio of involved lymph nodes correlated to tumour progression and the five survival rate.Perigastric lymph node status can be considered as a simple and effective prognosis factor.
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Objective:To study the correlation of the ratio and number of involved lymph nodes and the prognosis of gastric carcinoma.Methods: 174 patients of positive gastric lymph nodes were included.They were treated by radical gastrectomy and lymph nodes dissection(D 2 or D 3)in our department.The ratio and number of metastastic gastric lymph nodes were calculated.Their influence and their interrelation with pathogenic parameters were analyzed.Results: The overall 5-year survival rate was 29.6%,and the five-year survival rate of 1～20 per cent and more than 20% were 70.6%,12.0% respectively.One to five positive lymph nodes and five more were 46.6%,17.4% respectively.The five-year survival rate was decreased as the ratio and number of involved lymph nodes increased.Studies also indicated that with the increase of depth of cancer invasion,the ratio and number of involved lymph node elevated.Conclusion: The results shows that the ratio and number of involved lymph nodes correlated to tumour progression and the five survival rate.Perigastric lymph node status can be considered as a simple and effective prognosis factor.
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Objective To investigate the relationship between the expression of VCAM-1 and oncogenesis, tumor angiogenesis and metastasis in breast carcinoma. Methods Using semi-RT-PCR and immunohistochemistry technique, specimens from 63 patients of breast cancer,20 of fibroadenoma were detected for expression of VCAM-1.Microvessel density(MVD) was counted by endothelial cells immunostained using monoclonal antibody CD34.Circulating sVCAM-1 concentrations were measured by enzyme linked immunosorbent assay. Results Of 63 breast cancer tumor tissues VCAM-1 mRNA was detected in 37 cases. The rate of VCAM-1 mRNA in the primary breast cancer tissues were significantly higher than that in the adjacent non-cancerous tissues and benign fibroadenoma tissues (?2=43,P