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.

Background/Aims: Enteroenteric intussusception in Peutz-Jeghers syndrome (EI-PJS) is traditionally treated by surgery. However, enteroscopic treatment is a minimally invasive approach worth attempting. We aimed to develop a risk scoring system to facilitate decision-making in the treatment of EI-PJS. Methods: This was a single-center case-control study, including 80 patients diagnosed with PJS and coexisting intussusception between January 2015 and January 2021 in Air Force Medical Center. We performed logistic regression analysis to identify independent risk factors and allocated different points to each subcategory of risk factors; the total score of individuals ranged from 0 to 9 points. Then, we constructed a risk stratification system based on the possibility of requiring surgery: 0–3 points for “low-risk,” 4–6 points for “moderate-risk,” and 7–9 points for “high-risk.” Results: Sixty-one patients (76.25%) were successfully treated with enteroscopy. Sixteen patients (20.0%) failed enteroscopic treatment and subsequently underwent surgery, and three patients (3.75%) received surgery directly. Abdominal pain, the diameter of the responsible polyp, and the length of intussusception were independent risk factors for predicting the possibility of requiring surgery. According to the risk scoring system, the incidence rates of surgery were 4.44% in the low-risk tier, 30.43% in the moderate-risk tier, and 83.33% in the high-risk tier. From low- to high-risk tiers, the trend of increasing risk was significant (p<0.001). Conclusions We developed a risk scoring system based on abdominal pain, diameter of the responsible polyps, and length of intussusception. It can preoperatively stratify patients according to the risk of requiring surgery for EI-PJS to facilitate treatment decision-making.

Transjugular intrahepatic portosystemic shunt (TIPS) is a safe and effective method for the treatment of portal hypertension complications in patients with decompensated liver cirrhosis. At present, there are many prognostic scoring tools for risk stratification of poor prognosis after TIPS. This article briefly introduces seven prognostic scoring tools commonly used for TIPS and summarizes the clinical research evidence of each scoring tool. The literature review shows that there is currently no sufficient research evidence to determine the optimal prognostic scoring tool after TIPS. Future clinical studies should comprehensively explore the advantages and disadvantages of different scoring tools in predicting short- and long-term adverse prognostic events after TIPS and develop new prognostic scoring tools in combination with new prognostic markers.

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 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.

Data of 7 patients with complex benign esophageal strictures (CBESs) who underwent endoscopic longitudinal incision combined with local injection of bleomycin were retrospectively reviewed at Air Force Medical Center from August 2018 to November 2019.The length of preoperative esophageal stenosis was 4-14 cm and the minimum diameter of esophageal stenosis was 0.2-0.4 cm in 7 cases. The procedure was successful for all 7 patients.No adverse events occurred during 5-14 months of follow-up period.Restenosis and dysphagia occurred in 5 cases.The interval between the first endoscopic treatment and the recurrence of esophageal stenosis was 30-120 days.Among the 5 cases of recurrence, 4 cases remained unobstructed after 2 treatments and 1 case remained unobstructed after 4 treatments. The dysphagia scores of 7 patients were graded from 0 to 1 by the end of follow-up. Endoscopic longitudinal incision combined with bleomycin therapy in treatment of CBESs is safe and effective.

Objective:To evaluate the value of blood urea nitrogen (BUN)/creatinine (Cr) ratio for guiding the access route of double balloon enteroscopy (DBE) for small intestinal bleeding.Methods:The clinical information was collected from 105 patients who underwent DBE for suspected small intestinal bleeding at Air Force Medical Center from January 2015 to October 2019. Patients were divided into the elevated BUN/Cr group ( n=52) and the normal BUN/Cr group ( n=53), with a cut-off value of 81. Comparison was made for the detection rate of lesions between the oral route and anal route separately in the two groups using Chi-square test. Results:Among the 105 patients with suspected small intestinal bleeding, definite causes of bleeding were identified in 79 patients by DBE, and the overall lesion detection rate was 75.24% (79/105). In the elevated BUN/Cr group, the overall lesion detection rate was 76.92% (40/52), among which 79.49% (31/39) was through oral and 47.37% (9/19) through anal enteroscopy. In the normal BUN/Cr group, the overall lesion detection rate was 73.58% (39/53), and 63.64% (21/33) was transoral and 51.43% (18/35) transanal. The lesion detection rate of transoral enteroscopy in the elevated group was significantly higher than that in the normal group ( χ2=6.576, P=0.010). There was no significant difference in the lesion detection rate of transanal enteroscopy between the two groups ( χ2=2.230, P=0.135). Conclusion:For patients with active small intestinal bleeding (active bleeding within 48 hours), the BUN/Cr ratio higher than 81 may indicate that DBE should be performed firstly via oral route.

Objective:To evaluate the efficacy and safety of balloon-assisted enteroscopy (BAE) in the follow-up treatment of small intestinal polyps in patients with Peutz-Jeghers syndrome (PJS).Methods:From February 2005 to September 2019, the clinical data of patients with PJS who visited Air Force Medical Center many times and underwent BAE for small intestinal polyps surveillance and treatment were collected. The number of follow-up treatment times under BAE, operation-related complications and conservative theragy or surgical treatment were observed. Spearman rank correlation analysis was used to analyze the correlation between follow-up treatment times under BAE and the number and maximum diameter of small intestinal polyps.Results:A total of 165 PJS patients were enrolled, including 98 males and 67 females, and the mean age of first visit was (22.5±9.4) years. A total of 664 BAE operations were performed in the 165 PJS patients. The number of BAE operations and the number of follow-up treatments for each patient were 4.0±1.8 and 2.8±1.1, respectively. There were 26, 52, 35, 28, 12, 4, 2, 2, 2 and 2 patients who underwent 2, 3, 4, 5, 6, 7, 8, 9, 10 and 11 BAE operations, respectively. There were 165, 76, 30, 12, 4 and 4 patients who received 2, 3, 4, 5, 6 and 7 follow-up treatments, respectively. During the first to the fifth times of BAE follow-up treatment, the numbers of small bowel polyps resected under BAE of each patient were 7.0 (2.0, 11.0), 4.0 (2.0, 10.0), 3.0 (1.0, 8.5), 5.5 (1.8 , 10.3) and 3.0 (2.0, 6.8), respectively; and the maximum diameters of resected small intestinal polyps were 4.5 cm(3.0 cm, 6.0 cm), 3.0 cm(1.5 cm, 4.0 cm), 2.0 cm (1.5 cm, 3.0 cm), 3.0 cm(2.5 cm, 4.0 cm) and 2.5 cm(1.5 cm, 4.0) cm, respectively. The results of Spearman rank correlation analysis indicated that the number of follow-up treatment under BAE was negatively correlated with the number and maximum diameter of resected small intestinal polyps ( r s=-0.141, P=0.003; r s=-0.400, P<0.01). The total incidence of operation-related complications of small intestinal polyps resection under BAE was 3.2% (21/664), and 61.9%(13/21)of the complications were cured by conservative therapy. During the follow-up period, there were 26 cases of PJS complicated with intestinal intussusception, of which 20 cases (76.9%, 20/26) disappeared after BAE resection of small intestinal polyps. A total of 13 patients received surgery for intussusception (6 cases) or large polyps blocking the intestinal lumen (7cases). Conclusions:BAE is safe and effective in the follow-up treatment of small intestinal polyps in PJS. It can reduce the number and maximum diameter of small intestinal polyps, prevent and treat the complications related to small intestinal polyps, and effectively reduced surgical treatments.

Objective:To investigate the efficacy of double balloon enteroscopy (DBE) in the treatment of bleeding from small intestinal vascular lesion and risk factors of bleeding recurrence .Methods:From April 2013 to May 2020, at Air Force Medical Center, the clinical data of 65 patients with confirmed or suspected bleeding from small intestinal vascular lesion were retrospectively analyzed. The patients were divided into DBE treatment group (patients of Yano classification 1a and 1b received argon plasma coagulation, and patients of Yano classification 2 and 3 accepted combination of titanium clip and submucosal injection of lauromacrogol sclerosing agent) and non-DBE treatment group (traditional treatments such as stopping anticoagulant or antiplatelet drugs, blood transfusion, and iron supplementation). The bleeding recurrence of patients with single small intestinal vascular lesion between DBE treatment group and non-DBE treatment group, and patients with single or mulitiple vascular lesion of DBE treatment group were compared. Univariate analysis was used to analyze the clinical data of patients with or without recurrent bleeding. Multivariate logistic regression model was used to analyze the independent risk factors and protective factors of recurrent bleeding in small intestinal vascular lesion. Independent sample t test, chi-square test and Fisher exact probability method were used for statistical analysis. Results:Forty-four (25 of single vascular lesion and 19 of multiple vascular lesion) patients were diagnosed with small intestinal vascular lesions and received DBE treatment (DBE treatment group). Twenty-one patients with single vascular lesion accepted traditional treatment (non-DBE treatment group). The recurrent rate of bleeding in patients with single vascular lesion of DBE treatment group was lower than that in patients with single vascular lesion of non-DBE treatment group and patients with multiple vascular lesion of DBE treatment group (24.0%, 6/25 vs. 71.4%, 15/21 and 12/19), and the differences were statistically significant ( χ2=10.348 and 6.848, P=0.001 and 0.009). The results of univariate analysis showed that the proportion of blood transfusion, hypertension, complicated with valvular heart disease and DBE treatment in patients with rebleeding or not rebleeding from small intestinal vascular lesion was different with statistically significant (69.7%(23/33) vs. 37.5%(12/32), 51.5%(17/33) vs. 18.8%(6/32), 42.4%(14/33) vs. 12.5%(4/32) and 54.5%(18/33) vs. 81.2%(26/32), χ2=6.777, 7.628, 7.265, and 5.298, all P<0.05). The results of multivariate logistic regression analysis indicated that blood transfusion during the course of disease (odds ratien ( OR)=3.736, 95% confidence interval ( CI) 1.082 to 12.898, P=0.037) and complication with valvular heart disease ( OR=4.916, 95% CI 1.107 to 21.829, P=0.036) were independent risk factors of bleeding recurrence in patients with small intestinal vascular lesions. DBE treatment was the protective factor of bleeding recurrence in patients with small intestinal vascular lesion ( OR=0.214, 95% CI 0.057 to 0.808, P=0.023). Conclusions:DBE is effective in the treatment of small intestinal vascular lesion bleeding, especially for single vascular lesion. Blood transfusion during disease course and complication with valvular heart disease are independent risk factors for bleeding recurrence in patients with small intestinal vascular lesion.

Objective:To analyze the relationship between STK11 mutation and the cumulative risk of intussusception in patients with Peutz-Jeghers syndrome (PJS). Methods:From December 2017 to June 2019, the clinical data of 167 patients with PJS in Air Force Medical Center were collected, including gender, age, family history, age of first intussusception and results of gene test. Kaplan-Meier was used to analyze the cumulative risk of intussusception in patients with different mutation types. Wilcoxon rank sum test and log-rank test were used for statistical analysis.Results:Among 167 patients, 89.8% patients (150/167) had S TK11 mutation, and 50.7% of the mutation sites were found in exons 1, exon 4 and exon 5. And 70.6% patients (118/167) developed intussusception. The median age of patients with intussusception for the first time was 15 years (ranged from 2 to 52 years). Among 118 PJS patients with intussusception, 53 patients had family history and 65 patients had no family history; 70 cases were male and 48 cases were female. There were no statistically significant differences in the cumulative risk of intussusception between PJS patients with and without family history, and between male and female PJS patients (both P>0.05). There were 107 cases (90.7%) with STK11 mutation ( STK11 mutation group) and 11 cases (9.3%) without STK11 mutation ( STK11 non-mutation group). The median age of first intussusception of STK11 gene mutation group was younger than that of STK11 non-mutation group, and the difference was statistically significant ( Z=-2.108, P=0.035). In STK11 mutation group, 29 cases (27.1%) were nonsense mutations (nonsense mutation group), 23 cases (21.5%) were frameshift mutations (frameshift mutation group), 21 cases (19.6%) were missense mutations (missense mutation group), 26 cases (24.3%) were splicing mutations (splicing mutation group) and 8 cases (7.5%) of other mutations. There were statistically significant differences in the cumulative risk of intussusception between the STK11 mutation group and the STK11 non-mutation group, the STK11 splicing mutation group and the STK11 non-mutation group, STK11 missense mutation group and the STK11 non-mutation group ( χ2=5.570, 10.167 and 6.653, all P<0.05). There were no statistically significant differences in the cumulative risk of intussusception between STK11 nonsense mutation group and STK11 non-mutation group, between STK11 frame-shift mutation group and STK11 non-mutation group, among groups with different mutation types of STK11 gene (all P>0.05). Conclusions:The younger the age of first intussusception in PJS patients with STK11 mutation, the higher the cumulative risk. The mutation type of STK11 gene has potential value for the risk assessment of intussusception in PJS patients.