Discoidin domain receptor 2 (DDR2), a tyrosine kinase receptor belonging to DDRs family, is associated with progression of various cancers. Studies have indicated that DDR2 expression is upregulated in various cancer tissues, which could promote tumors proliferation, invasion, and metastases. Furthermore, patients with high DDR2 expression showed poor 5-year overall survival rate. In addition, DDR2 point mutation can enhance the sensitivity of tumor cells to small molecule tyrosine kinase inhibitor dasatinib, which suggests that DDR2 mutation may be a promising target for cancer therapy.

Objective To investigate the effect of melatonin against cerebral ischemia reperfusion injury (CIRI) in mice and its mechanism.Methods Thirty male C57BL/6 mice were randomly divided into sham operation group,CIRI group,and melatonin treatment group (n =10 in each group).A middle cerebral artery occlusion model was induced by suture method.The degree of brain injury was evaluated by neurological function score,brain water content,and cerebral infarction volume.Western blot analysis was used to detect apoptosis-related proteins Bim,Bcl-2,and endoplasmic reticuhm stress-related molecules C/ EBP homologous protein (C/EBP) expression.Results Compared with the CIRI group,the neurological function score was significantly improved,the degree of cerebral edema was significantly reduced,and the volume of cerebral infarction was significantly reduced in the melatonin treatment group (all P ＜0.05).In addition,the expression of Bcl-2 was significantly up-regulated in the melatonin treatment group,and the expression of Bim and CHOP was significantly down-regulated (all P ＜ 0.05).Conclusion Melatonin may play an anti-CIRI role by regulating CHOP,and endoplasmic reticulum stress plays an important role in CIRI.

Objective:To evaluate the efficacy and safety of combination of sufficient argon plasma coagulation(APC) cauterization and clipping in the treatment of colonic diverticular bleeding.Methods:From June 2018 to April 2022, the clinical data of patients were retrospectively analyzed, who visited Department of Gastroenterology of Air Force Medical Center due to overt gastrointestinal bleeding, and were confirmed or suspected to have colonic diverticular bleeding and received combination of sufficient APC cauterization and clipping treatment. The deadline for follow-up was September 30, 2022. During the follow-up after endoscopic treatment, the re-bleeding rate, hemoglobin level difference between the last follow-up and before treatment, wound healing under colonoscopy as well as the intraoperative and postoperative complications of patients were statistically analyzed. Descriptive analysis was used for statistical analysis.Results:A total of 15 patients were enrolled, including 13 males and 2 females, aged (60.8±14.8) years old. The course of the disease was 1 day to 13 years. A total of 145 colonic diverticula of 15 patients were treated under endoscopy. The median follow-up time was 14.5 months (5.3 to 49.5 months) months. Among the 15 patients, 12 patients received endoscopic therapy once and no bleeding occurred till the end of follow-up. Three patients suspected with diverticular bleeding received a second endoscopic treatment because of bleeding at the 12 days, 3 months and 8 months after the first treatment, respectively.No rebleeding occurred after the second endoscopic therapy till the end of follow-up. The re-bleeding rate of the first treatment was 3/15 and the re-bleeding rate of re-treatment was 0. At the end of follow-up, the hemoglobin concentration increased (35.9±26.3) g/L compared with that before the treatment. Two patients had perforation during operation and were closed with multiple titanium clips. There was no abdominal pain or other symptoms after operation. And the patients were discharged 3 and 4 days after treatment, respectively. Two patients suffered short-term postoperative wound bleeding and successful hemostasis was achieved after endoscopic treatment. One patient developed postoperative infection and the symptoms disappeared after anti-infection treatment.Conclusions:Combination of sufficient APC cauterization and titanium clipping is safe and effective in the treatment of colonic diverticular bleeding. For patients with dominant diverticular hemorrhage, or patients with recurrent gastrointestinal bleeding, if other etiology are excluded and colonic diverticular bleeding is highly suspected, the combination of sufficient APC cauterization and titanium clipping under endoscopy is feasible.

Objective:To evaluate the efficacy and safety of endoscopic stricturotomy (EST) under balloon-assisted enteroscopy (BAE) in treatment of benign jejuno-ileal stenosis.Methods:From December 2015 to August 2021, at the Air Force Medical Center, 41 patients who were diagnosed with benign jejuno-ileal stenosis underwent BAE deep small bowel EST and/or surgery due to ineffective or ineffective drug treatment were retrospectively analyzed. Twenty-one patients were treated with EST (EST group) and 20 patients were treated with surgery (surgery group). The etiology and follow-up time were analyzed, the general conditions (male proportion and age), the immediate technical success rate (the percentage of the stenosis that the enteroscope could pass through after EST in the total number of treated stenoses), the incidence of complications (including perforation, bleeding, etc.), the symptom remission rates at 3-month, 6-month, and 1-year after treatment (the percentage of patients with complete or partial remission in the total number of patients), cumulative symptom-free survival rate (no obstruction-related symptoms after EST or surgery till the last follow-up) and cumulative surgery-free survival rate of two groups were compared. Chi-square test, independent t-test, Fisher′s exact probability method and Kaplan-Meier analysis were used for statistical analysis. Results:The main etiology of stricture of EST group and surgery group was Crohn′s disease (71.4%, 15/21 and 60.0%, 12/20, respectively), and the median follow-up time was 12 months (6 to 46 months) and 45 months (14 to 73 months), respectively. There were no significant differences in male proportion, age, immediate technical success rate and incidence of complication between EST group and surgery group (57.1%, 12/21 vs. 65.0%, 13/20; (45.2±17.4) years old vs. (43.1±20.3) years old; 95.3%, 41/43 vs. 100.0%, 30/30; 26.9%, 7/26 vs. 10.0%, 2/20, all P>0.05). In the EST group, 9.5% (2/21) of the patients received surgery because of perforation during EST, 76.2% (16/21) of the patients did not need surgery after EST, and the median symptom-free survival time of patients without symptoms in EST group was 13.3 months. There was no significant difference in the symptom remission rate at 3-month after treatment between EST group and the surgery group (17/19 vs. 100.0%, 20/20, P>0.05). The symptom remission rate at 6-month and 1-year of EST group were lower than those of the surgery group (15/19 vs. 100.0%, 20/20; 8/11 vs. 100.0%, 20/20), and the differences were statistically significant (both were Fisher′s exact probability method, P=0.047 and 0.037). The cumulative symptom-free survival rates at 3-month, 6-month and 1-year of EST group and surgery group were 66.0% vs. 90.0%, 61.0% vs. 85.0% and 54.0% vs. 80.0%, respectively.The results of Kaplan-Meier analysis indicated that there was no significant difference in the symptom-free survival curve between two groups ( P>0.05). The 3-month, 6-month and 1-year cumulative surgery-free survival rates after treatment in EST group were 90.0%, 81.0% and 73.0%, respectively. The 3-month, 6-month and 1-year cumulative surgery-free survival rates after treatment in surgery group were all 100.0%. Conclusion:EST under BAE is technically feasible, and safe in the treatment of benign jejuno-ileal stenosis, and can effectively relieve clinical obstruction symptoms and avoid or delay surgery in the short term.

Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2(Nrf2)in the process of pterostilbene acting on LoVo cells.Methods LoVo cells were treated with different concentrations(5,10,20,40,60,80,100 panol/L)of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Tran-swell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochon-drial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlo-rofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic pro-teins(Bcl2 and Bax)were determined by Western blotting.In addition,cell viability,Nrf2 expression,and ap-optosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane.Results Compared with the control group,40,60,80,100 μmol/L pterostilbene reduced the viability of LoVo cells(P=0.014,P＜0.001,P＜0.001,P＜0.001).Pterostilbene at 5,10,20 μmol/L did not show effects on cell viability but inhibited cell migration(P=0.008,P＜0.001,P＜0.001)and invasion(all P＜0.001).Pterostilbene at 40,60,80 μmol/L increased apoptosis(P=0.014,P＜0.001,P＜0.001),promoted mitochondrial membrane potential depolarization(P=0.026,P＜0.001,P＜0.001)and reactive oxygen species accumula-tion(all P＜0.001),and down-regulated the expression of phosphorylated Nrf2(P=0.030,P＜0.001,P＜0.001),heme oxygenase 1(P=0.015,P＜0.001,P＜0.001),and Bc12(P=0.039,P＜0.001,P＜0.001)in LoVo cells.Pterostilbene at 60,80 μmol/L down-regulated Nrf2 expression(P=0.001,P＜0.001)and up-regulated Bax expression(both P＜0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability(P＜0.001),apoptosis(P＜0.001),and Nrf2 expression(P=0.022).Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.