Interferon-stimulating gene 15(ISG15),an ubiquitin-like molecule belonging to the superfamily of ubiquitin-like proteins,is highly expressed in various malignant tumors and induced by type Ⅰ interferon.How-ever,its specific regulatory mechanism remains unclear.Numerous studies have demonstrated its close association with tumorigenesis and development.In this study,we provide a comprehensive review on the role of ISG15 protein in hepatocellular carcinoma,esophageal carcinoma,gastric carcinoma,colorectal carcinoma,and other cancers.Our aim is to identify new therapeutic targets for gastrointestinal malignancies and improve prognostic assessment.

Interferon-stimulating gene 15(ISG15),an ubiquitin-like molecule belonging to the superfamily of ubiquitin-like proteins,is highly expressed in various malignant tumors and induced by type Ⅰ interferon.How-ever,its specific regulatory mechanism remains unclear.Numerous studies have demonstrated its close association with tumorigenesis and development.In this study,we provide a comprehensive review on the role of ISG15 protein in hepatocellular carcinoma,esophageal carcinoma,gastric carcinoma,colorectal carcinoma,and other cancers.Our aim is to identify new therapeutic targets for gastrointestinal malignancies and improve prognostic assessment.

Aim To examine the influence of tetramethylpyrazine on learning and memory function of hypoxic hypoxia rats, and the expression of gamma aminobutyric acid(GABA) receptor and forkhead box P2(FOXP2) in hippocampus of rats.Methods A total of 120 Sprague Dawley rats were randomly divided into low hypoxic hypoxia and high hypoxic hypoxia groups, then according to different time points every group was divided into 1 d, 3 d, 7 d 15 d, 30 d group, with 12 rats per each group.Experiment group and the control group were treated with tetramethylpyrazine and 0.9% normal saline, respectively.The hypoxic hypoxia environment was achieved by putting the rats in a hypobaric chamber at a simulated altitude of 5 500 meters for different days.The capabilities of learning and memory of rats were detected by Morris water maze test.The expression of GABA receptor and FOXP2 protein in hippocampus of rat was determined by Western blot.Results ① Morris water maze test showed that the total distance of rats in the simulated hypobaric hypoxia control group was longer than that in the tetramethylpyrazine group(P<0.01) and the number of crossing the bestride platform increased compared with that in the hypobaric hypoxia control group(P<0.01) from the third day;② Western blot results showed that the expression of GABAAα1 receptor have no statistical significance(P>0.05);however,GABAB1 receptor and FOXP2 protein rose from the third day(P<0.05).The expression of GABAAα1 receptor and FOXP2 protein expression were correlated to total distance of Morris water maze in the control group(r=-0.738, P<0.05;r=-0.693, P<0.05), and the expression of GABAB1 receptor was correlated with FOXP2 protein level(r=0.834, P<0.05).Conclusion The simulated high-altitude hypobaric hypoxia can decrease the learning and memory abilities of rats, which may be ameliorated by tetramethylpyrazine intervention, and this effect might be related to the increase of GABAB1R receptor and FOXP2 expression in hippocampus of rats.

Objective To explore the relationship between the fibroblast growth factor 2 (FGFR2) gene polymorphism (rs 2981582 ,rs 1219648 ,rs 2420946) and the breast cancer risk in Tibetan population ,Qinghai province .Methods This is a case con‐trol study .Peripheral blood samples from 210 breast cancer patients and 230 healthy women in Qinghai area were collected .DNA samples were extracted from peripheral blood cells .FGFR2 gene polymorphism (rs 2981582 ,rs 1219648 ,rs 2420946) were typed by Taqman‐MGB probe based on PCR and DNA sequencing ,then analyzed its correlation with breast cancer in Tibetan population , Qinghai province .Results The genotype frequencies of rs 2981582 CC ,CT and TT were 40 .48% ,39 .05% and 20 .47% among the breast cancer patients while 36 .09% ,48 .69% and 15 .22% among the controls .The genotype frequencies of rs 1219648 GG ,AG and AA were 24 .76% ,26 .19 % and 49 .05% among the patients while 23 .91% ,47 .39% and 28 .70% among the controls .The genotype frequencies of rs 2420946 CC ,CT and TT were 29 .05% ,45 .24% and 25 .71% among the patients while 30 .87% , 51 .74% and 17 .39% among the controls .The genotype frequencies of all genetic loci had no significant difference between rs 2981582 and rs 2420946 (P>0 .05) .But the genotype frequencies of rs 1219648 AA have statistical sense (P< 0 .05) ,compared with GG ,the incidence of breast cancer was remarkably increased with AA [OR=1 .65 ,95% CI= (1 .01 ,2 .69)] .Conclusion This study shows that FGFR2 rs1219648 AA is related to breast cancer risk among Tibetan population .

Objective To investigate the mechanism of gastric bypass surgery in the treatment of type 2 diabetes mellitus in a rat model. Methods Seventy-two 8-week-old GK rats were randomly divided into operation group, sham operation group, diet control group and control group (18 rats in each group) according to the random number table. Rats in the operation group and the sham operation group received gastric bypass surgery and transection and reanastomosis of the gastrointestinal tract, respectively. The food intake was set as 15 g/d for each rat in the diet control group, while rats in the control group were fed ad libitum. The levels of fasting blood glucose ( FBG), postprandial blood glucose (PPBG) and glucagon-like peptide-1 (GLP-1) were detected before operation and at postoperative week 2, 4 and 8. The levels of PPBG and GLP-1 were detected at postoperative week 2, 4 and 8, then 6 rats of each group were sacrificed to detect the apoptosis of islet B cells using the TUNEL method. All data were analyzed using the t test. Results In the operation group, the preoperative levels of FBG and PPBG were (16.2±0.8)mmol/L and (31.1 ± 1. L)mmol/L, respectively, which were significantly higher than (9.2± 0.6) mmol/L and (13.1 ±0.7) mmol/L at 4 weeks after the operation, and (9. 7 ± 0. 7) mmol/L and (12. 3 ± 0.7) mmol/L at 8 weeks after the operation (t = 20. 7, 49. 7; 18. 8, 39. 0, P < 0.05 ). The levels of FBG and PPBG before the operation and at 4 and 8 weeks after the operation in the operation group were significantly lower than those in the sham operation group, diet control group and control group at corresponding time points (t = 27.7, -57.8; 11.3, -59.9; -27.4, -48.2; -13.2, -52.7; -7.0, -24.9; -18.2, -56.4, P<0.05). In the operation group, the levels of fasting GLP-1 and postprandial GLP-1 were ( 10. 7 ± 1. 0) pmol/L and (42.5 ±1.2)pmol/L, respectively, which were significantly lower than (26. 1 ±0.9)pmol/L and (90.7 ± 1.7)pmol/L at4 weeks after the operation, and (25.3 ± 1.2)pmol/L and (90.4 ±2.0)pmol/L at 8 weeks after the operation (t=42.1, -92.4; -29.1, -72.7, P <0.05). The levels of fasting GLP-1 and postprandial GLP-1 before the operation and at 4 and 8 weeks after the peration in the operation group were significantly higher than those in the sham operation group, diet control group and control group at corresponding time points (t = 48.0, 61.9; 38.0, 62.2; 50.9, 65.2; 37.0, 48. 1; 27.5, 51.6; 17.5, 52.9, P<0.05). The number of the apoptotic islet β cells in the operation group was decreased with time. The apoptosis rates in the operation group, sham operation group, diet control group and control group were 5.9%±0.7% , 47.2%± 1.0% , 21. 1%± 1. 2% , 46.5%±1.4% at 4 weeks after the operation, and 6.3%±1. 1% , 47.2%±1.0% , 21.2%±1.2% and 46.0% ± 1.4% at 8 weeks after the operation. The apoptosis rates in the operation group were significantly lower than those in the sham operation group, diet control group and control group at corresponding time points (t = -82. 2, - 67. 0; - 27. 1, - 22. 4; - 55. 2, - 54. 6, P < 0.05). Conclusion After gastric bypass surgery, the level of blood glucose reduces and the level of GLP-1 increases which significantly inhibit the apoptosis of islet B cells in rats with type 2 diabetes mellitus.