ObjectiveTo investigate the effects of forkhead box protein O4 （FOXO4） expression on gastric precancerous lesions （GPL）， and to clarify its mechanism in mediating the therapeutic effect of Celastrus orbiculatus extract （COE） on GPL by regulating aerobic glycolysis. MethodsReferring to the previously established combined modeling protocol in our research group， a rat model of gastric precancerous lesions （GPL） was constructed through the following procedures： rats were given free access to 170 μg/mL N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） solution for ad libitum drinking， fed with a diet supplemented with 0.03% ranitidine hydrochloride， and treated with a cycling regimen of “2-day feeding followed by 1-day fasting”. Specifically， on the afternoon of each fasting day， the rats received intragastric administration of 2% sodium salicylate at a dose of 10 mL/kg body weight. FOXO4-silenced and overexpression model rats were constructed by tail vein injection of plasmids. The rats were randomly divided into control， model， COE， overexpression negative control （OE-NC）， FOXO4 overexpression （OE-FOXO4）， OE-FOXO4+COE， silencing negative control （shNC）， FOXO4 silencing （shFOXO4） and shFOXO4+COE groups. Gastric mucosal histopathological changes were observed in each group. Lactic acid content in gastric mucosal tissues was detected by colorimetry. The expression levels of FOXO4， HK2， PKM2， LDHA and GLUT1 were evaluated by immunohistochemistry （IHC）， and their mRNA levels were determined by RT-PCR.Results Compared with the control group， the COE， OE-FOXO4 and OE-FOXO4+COE groups exhibited significantly improved gastric mucosal lesions， reduced lactic acid levels， weakened expression of aerobic glycolysis-related proteins （PKM2， HK2， LDHA， GLUT1）， and enhanced FOXO4 expression. The OE-FOXO4+COE group showed the lowest lactic acid level and more pronounced changes in related protein expression compared with the COE and OE-FOXO4 groups. In contrast， the shFOXO4 and shFOXO4+COE groups displayed increased lactic acid levels， enhanced expression of aerobic glycolysis-related proteins， and reduced FOXO4 expression compared with the model group.ConclusionFOXO4 expression is involved in the inhibitory effect of COE on GPL， possibly by regulating the aerobic glycolysis process.

Objective : To observe the effect of Celastrus orbiculatusextract(COE) on gastric precancerous lesions(GPL) and to explore its role in the Notch-1 signaling pathway. Methods : GPL rat models were established using a composite model replication method, and the rats were randomly divided into a control group, a model group, and COE low, medium and high dose groups [COE at 12.5, 25, and 50 mg/(kg·d)]. After 4 weeks of intervention, gastric tissue was collected, and immunohistochemistry(IHC) was performed to detect the expression of mucins(MUC2, MUC5AC, and MUC6), Leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5), Proliferating Cell Nuclear Antigen(Ki67), and Notch-1. Polymerase chain reaction(PCR) was used to determine the mRNA levels of the aforementioned mucins. Human gastric epithelial cells(GES-1) were induced with N-Methyl-N′-nitro-N-nitrosoguanidine(MNNG) to establish a GPL cell model. The cells were randomly divided into control, model, and COE low, medium, and high concentration groups(COE at 5, 10, and 20 μg/ml). After 24 hours of corresponding interventions, changes in cell morphology were observed under an inverted microscope. Western blot was used to measure the expression of Notch-1 and Lgr5, and immunofluorescence(IF) was employed to detect Notch-1 expression. Results : Compared to the control group, the expression of MUC2, Lgr5, Notch-1, and Ki67 in the gastric tissue of the model group rats significantly increased(P<0.000 1), while the expression of MUC5AC and MUC6 decreased(P<0.000 1). In comparison to the model group, the expressions of MUC2, Lgr5, Notch-1, and Ki67 were significantly reduced in the COE groups(P<0.01), while the expression of MUC5AC and MUC6 significantly increased(P<0.01). In the GES-1 model group, the cells exhibited irregular morphology, loose intercellular connections, and disorganized arrangement compared to the control group. In contrast, the cells in the COE groups displayed a more regular morphology and a more organized arrangement than those in the model group. Additionally, compared to the control group, the expression of Lgr5 and Notch-1 in the model group were significantly elevated(P<0.000 1), whereas after COE treatment, their expressions were markedly reduced(P<0.001). Conclusion COE can alleviate GPL, and its mechanism may be associated with the downregulation of the Notch-1 signaling pathway, which improves gastric mucosal mucin barrier function and inhibits the abnormal proliferation of gastric mucosal stem cells.

Familial adenomatous polyposis is characterized by the multiple and adenomatous polyps in the colorectum combined with polyps in the stomach and duodenum, while it is rarely seen in the common bile duct (CBD).In July 2013, 1patient with FAP combined with adenomas in the CBD was admitted to the Fujian Provincial Hospital.The patient underwent laparoscopic CBD exploration and resection of masses due to acute pancreatitis 11 months ago, and was confirmed as with adenoma in the distal CBD by postoperative pathological examination.Multiple polyps were found in the stomach, duodenum,CBD, colorectum after admission to hospital, biopsy confirmed that polyps were tubular adenoma.The patient received pancreaticduodenectomy and was diagnosed as with duodenum-CBD tubular adenoma in postoperative pathological examination.The patient was followed up by telephone interview and outpatient examination and had a full recovery, in addition to the increasing of stools frequency and occasioned hematochezia, and then was treated by total colectomy at postoperative month 7.The tubular adenoma was confirmed by postoperative pathological examination.

Objective To investigate the expression of hypoxia inducible factor-1α(HIF-1α) and vascular endothelial growth factor C(VEGF-C) in colon carcinoma,and their relation with clinical pathological parameters and prognosis. Methods Immunohistochemistry was used to detect the expression of HIF-1α and VEGF-C in 65 tissues of colon carcinoma. Results In all cases,the expression of HIF-1α had a positive correlation with the expression of VEGF-C(r= 0.638,P＜0.01).The expressions of HIF-1α and VEGF-C had significant correlation with clinical stage and nodal metastasis(P＜0.05) ,but had no relationship with sex,age and tumor size(P＞0.05). Conclusion The expression of HIF-1α and VEGF-C was correlated with nodal metastasis, tumorigenesis and prognosis of colon/carcinoma.