Obesity is growing rapidly and becomes an important public health problem worldwide. Epidemiologic data revealed that obesity increased the risk of a variety of disease,including digestive system tumor. Therefore,investigating the molecular mechanism of carcinogenic effect of obesity may provide new clues for management of obesity-associated digestive system tumor. In this article,the progress in research on effect of obesity on digestive system tumorigenesis and its potential mechanism were summarized.

Based on our school's specific conditions, to make full use of the laboratory, improve students' ability of practice and innovation, for the past few years, Medical College of Dalian University has intensified the soft and hard ware construction of the labs, has done some exploration in the management structure and mechanism innovation of laboratory, and has constructed various experimental and innovative platform and experimental teaching reform etc.The effect of lab construction has been em erging and the quality of students has been bettered greatly.

Background:Accumulating evidence links colorectal cancer (CRC) with the gut microbiota.Fusobacterium nucleatum (F.nucleatum) has been revealed to be involved in the development of CRC, however, the mechanism of F.nucleatum in mediating colorectal tumorigenesis is still poorly understood.Aims:To investigate the effect and potential mechanism of F.nucleatum on CRC.Methods:Wild type C57BL/6 mice and APC(Min/+) mice characterized by multiple intestinal neoplasia were used in this animal study.After administered with F.nucleatum intragastrically and/or 1,2-dimethylhydrazine (DMH, a carcinogen) subcutaneously, the aberrant crypt foci (ACF) and colonic tumor were counted at 8th and 20th week, respectively.Structural alteration of intestinal microbiota and mucosal immune factors were detected in wild type C57BL/6 mice receiving different interventions by using Roche 454 GS FLX pyrosequencing and Bio-Plex ProTM cytokine assay, respectively.Results:In DMH-treated wild type C57BL/6 mice or APC(Min/+) mice, number of ACF and colonic tumor in those administered with F.nucleatum were significantly higher than those without (P<0.05).F.nucleatum colonization significantly altered the lumen microbial structure, with decreased Cyanobacterium and increased Tenericutes and Verrucomicrobia (P all <0.05).Furthermore, F.nucleatum up-regulated expressions of tumor-related immune factors in colonic mucosa, such as IL-21, IL-22, IL-31 and CD40L (P<0.05).Conclusions:F.nucleatum colonization in intestine may prompt colonic tumorigenesis in mice via inducing intestinal dysbiosis and modulating tumor-related immune factors expression.

Objective To investigate the effects of Saccharomyces boulardii ( S. boulardii) on the col-onization of Helicobacter suis ( H. suis) in stomach and the formation of gastric mucosa associated lymphoid tissue (MALT) during H. suis infection. Methods Sixty C57BL/6 wild type mice were randomly divided into six groups. The mice in group A and group B were respectively given sterile distilled water and S. boulardii twice by gavage and then infected with H. suis for one week. The mice in group C and group E were given sterile phos-phate buffer saline by gavage for one week and then respectively given sterile distilled water and S. boulardii by gavage twice a week for 12 weeks. The mice in group D and group F were infected with H. suis for one week and then respectively given sterile distilled water and S. boulardii by gavage twice a week for 12 weeks. Serum and gastric tissue samples were collected from each mouse. Results The bacterial loads of H. suis in the stomachs of mice in group B were significantly lower than those in group A. No significant differences in the levels of se-creted IgA( sIgA) in serum and gastric tissue samples and the expression of IFN-γat mRNA level in gastric mu-cosa samples were found between the two groups. The expression of H. suis 16S RNA and the formation of gastric lymphoid follicles were detected in mice in groups D and F. The levels of sIgA in serum and gastric tissue sam-ples and the expression of IFN-γ and CXCL13 at mRNA level in gastric mucosa samples increased significantly in groups D and F as compared with groups C and E. Compared with the mice in group D, the bacterial loads of H. suis in stomachs, the numbers of MALT per unit length of gastric mucosa and the expression of IFN-γ and CXCL13 at mRNA level in gastric mucosa decreased significantly in mice from group F, but the levels of sIgA in serum and gastric tissue samples increased significantly. Conclusion S. boulardii could inhibit the colonization of H. suis in stomach and suppress the formation of gastric MALT during H. suis infection.

Objective To evaluate the clinical application value of serum high sensitive α-fetoprotein variant ratio (hs-AFP-L3％) in the diagnosis and treatment of hepatocellular carcinoma.Methods From October 2016 to March 2018,at Affiliated Hospital of Qingdao University,160 patients diagnosed with hepatocellular carcinoma,32 patients with intrahepatic cholangiocarcinoma (ICC),52 patients with post-hepatitis B liver cirrhosis,53 patients with chronic hepatitis B and 50 healthy controls were enrolled.The serum levels of hs-AFP-L3％ and α-fetoprotein were measured.Mann-Whitney U test,Spearman correlation analysis,Wilcoxon signed rank test and chi-square test were performed for statistical analysis.Results The serum levels of hs-AFP-L3％ and α-fetoprotein in hepatocellular carcinoma group were 24.90％ (4.68％ to 61.85％) and 113.45 μg/L (11.18 μg/L to 1 803.48 μg/L),respectively,which were higher than those in ICC group (0.50％,0.50％ to 0.50％;and 2.79 μg/L,1.72 μg/L to 4.04 μg/L),cirrhosis group (0.50％,0.50％ to 5.25％;and 18.35 μg/L,3.95 μg/L to 31.93 μg/L),chronic hepatitis group (0.50％,0.50％ to 4.25％;and 2.70 μg/L,1.80 μg/L to 17.00 μg/L),and healthy control group (0.50％,0.50％ to 0.50％;and 1.94 μg/L,1.46 μg/L to 2.63 μg/L),and the differences were statistically significant (U =461.00,1 485.50,1 141.00,625.00;401.50,2 207.00,1 254.00,266.00;all P ＜0.01).The sensitivity of hs-AFP-L3％ and α-fetoprotein in the diagnosis of hepatocellular carcinoma was 66.3％ and 70.0％,respectively;and the difference was not statistically significant (x2 =0.54,P ＞ 0.05).The sensitivity of the combined detection was 82.5％,which was higher than that of the separate detection,and the differences were statistically significant (x2 =24.04 and 18.05,both P ＜0.01).The specificity of hs-AFP-L3％ was 95.2％,which was higher than that of α-fetoprotein (68.6％),and the difference was statistically significant (x2 =26.04,P ＜ 0.01).The specificity of the combined detection of these two markers was 68.6％,which was lower than that of hs-AFP-L3％ alone (95.2％),and the difference was statistically significant (x2 =26.04,P ＜ 0.01).There was no statistically significant difference in the specificity between the combined detection and α-fetoprotein detection alone (68.6％,P ＞ 0.05).The sensitivity of hs-AFP-L3％ in the diagnosis of patients with α-fetoprotein-negative (α-fetoprotein ＜ 20 μg/L) hepatocellular carcinoma was 41.7％.The serum levels of hs-AFP-L3％ and α-fetoprotein were both positively correlated with tumor size and clinical stage (hs-AFP-L3％ r =0.272 and 0.436;α-fetoprotein r =0.375 and 0.458;all P ＜ 0.01).The reduction of serum hs-AFP-L3％ in 38 patients with hepatocellular carcinoma after operation was 82.2％,which was higher than that of oα-fetoprotein (69.2％),and the difference was statistically significant (U =532.50,P =0.049).There was no correlation between serum level of hs-AFP-L3％ and α-fetoprotein level (r =0.077,P ＞ 0.05).Conclusions The sensitivity of hs-AFP-L3％ is similar to that of α-fetoprotein in the diagnosis of hepatocellular carcinoma,while the specificity of hs-AFP-L3％ is higher than that of α-fetoprotein.The combined detection of the two markers can improve the diagnostic rate of hepatocellular carcinoma.The hs-AFP-L3％ has a high diagnostic value in α-fetoprotein-negative hepatocellular carcinoma.

PURPOSE: This study was aimed to investigate the effect of pseudolaric acid B (PAB) on proliferation, invasion and epithelial-to-mesenchymal transition (EMT) in pancreatic cancer cells and to explore the possible mechanism. MATERIALS AND METHODS: The pancreatic cancer cell line SW1990 was cultured and treated with PAB dose- and time-dependent manners. Cell proliferation and invasion ability were measured by MTT assay and Matrigel/Transwell test, respectively. Semi-quantitative real-time polymerase chain reaction and Western blotting were conducted to detect the expression of EMT markers and the key molecules. Finally, nude mice subcutaneous transplantation tumor model was used to confirm the therapy efficacy of PAB. RESULTS: PAB could inhibit SW1990 cell proliferation and invasion in time- and dose-dependent manners. Vimentin, fibronectin, N-cadherin, Snail, Slug, YAP, TEAD1, and Survivin were down-regulated (p < 0.01), while E-cadherin, caspase-9, MST1, and pYAP were up-regulated (p < 0.05). Combined PAB and gemcitabine treatment markedly restricted the tumor growth compared with gencitabin or PAB alone groups. CONCLUSION: PAB could inhibit the proliferation and invasion ability of pancreatic cancer cells through activating Hippo-YAP pathway and inhibiting the process of EMT.
Animals ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/metabolism ; Cadherins ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation/drug effects ; Cytokines ; Deoxycytidine/analogs & derivatives ; Deoxycytidine/pharmacology ; Deoxycytidine/therapeutic use ; Diterpenes/pharmacology ; Diterpenes/therapeutic use ; Epithelial-Mesenchymal Transition/drug effects ; Female ; Humans ; Mice, Nude ; Neoplasm Invasiveness ; Pancreatic Neoplasms/diet therapy ; Pancreatic Neoplasms/pathology ; Real-Time Polymerase Chain Reaction ; Signal Transduction/drug effects ; Vimentin/metabolism