Background and purpose: Pancreatic intraepithelial neoplasia (PanIN) is thought to be a precursor lesion of infiltrating pancreatic ductal adenocarcinoma. The mutation of the phenotypic impact of K-ras G12D alone, silencing of p53 and p16 could promote this process. The role of Smad4 in this progression was poorly understood. In the present study, we investigated the role of Smad4 in the development of pancreatic tumor, based on PanIN cell line from mice with K-ras G12D mutation in order to investigate the effect of Smad4 silencing on PanIN cells in the development and malignant transformation in nude mice. Methods: Smad4 knock-down PanIN cells (PanIN-S) were established by stable transfeetion with lentiviral-mediated Smad4 RNA interference (RNAi). In xenograft model experiments, BALB/c nude mice were randomly divided into 2 groups (5 mice per group) implanted with PanIN or PanlN-S cells subcutaneously. Two weeks after tumor cells inoculation, tumor volume and weight were estimated. PCNA staining was used to evaluate cell proliferation and CD31 polyclonal antibody was used to assess micro-vessel density (MVD) in tumors. Results: Effect of siRNA of Smad4 gene in PanlN cells was confirmed by RT-PCR and Western blot. Compared with PanlN groups, there was a dramatic increase in tumor volume and weight in PanIN-S groups (P<0.05). Furthermore, immunohistochemical analysis of the harvested tumors suggested that Smad4 silencing was associated with 'increased tumor cell proliferation (PCNA reactivity) and angiogenesis (micro-vessel density, MVD). The percentage of PCNA-positive cells in the PanlN-S groups were significantly increased than PanIN groups (P<0.05). CD31 staining revealed a significant increase in the PanlN-S groups compared to the PanlN groups (P<0.05). Conclusion: Silencing of Smad4 in PanlN cells with endogenous expression of K-ras G12D, enhanced progression to invasive adenocarcinomas. Cell proliferation and vascularization may be its important mechanisms.

Objective: To clarify the feasibility and safety of magnetically guided capsule endoscopy (MGCE) in minors. Methods: A descriptive cohort study was carried out to retrospectively collect the data of minors (<18 years) who underwent MGCE in Ruijin Hospital from April 2015 to October 2018. Exclusion criteria: patients with dysphagia, obvious gastrointestinal bleeding, diagnosed or suspected gastrointestinal obstruction, or congenital gastrointestinal malformations or intestinal fistula; patients with previous bowel surgery, or in poor general condition; patients with implants; pregnant patients; patients with incomplete data or without data. A total of 218 patients, including 122 males and 96 females, with mean age of (12.0±3.1) (5-17) years and 236 times of examination were included. The capsule size of the Ankon MGCE system was 11.8 mm×27 mm, taking two pictures per second, with a viewing angle of 140 degrees. Data of gastric visualization (0% to 100%), gastric cleanliness (satisfactory cleanliness was defined as a clear display of the gastric mucosa; the effect of bubbles or mucus on the visual field was negligible, or the gastric mucosa was slightly blurred; a small amount of air bubbles or mucus affected slightly the field of view), gastric or small bowel examination time, lesion detection rate, etc. were recorded. All the patients were followed up for 2 weeks to confirm capsule excretion and to record adverse events. Results: A total of 202 patients (217 times) completed gastric examination and 112 patients (125 times) completed small bowel examination. The median gastric visualization of cardia, fundus, body, angulus, antrum and pylorus was 100%, 90% (75%,100%), 100% (80%,100%), 100%, 100%, and 100%, respectively. The cleanliness of the gastric cardia, fundus, body, angle, antrum, and pylorus was assessed to be satisfactory in 100.0%, 76.5% (153/200), 92.5% (185/200), 97.5% (195/200), 99.5% (199/200), and 100.0% of patients, respectively. In 202 patients undergoing gastric examination, the median gastric exanimation time was 10.5 (7.3, 13.9) minutes. In 112 patients undergoing small bowel examination, the median gastric transit time was 51.5 (20.6, 112.0) minutes and the median small bowel transit time was 232.4 (181.8, 321.6) minutes. The small bowel transit rate was 91.1% (102/112). The lesion detection rates of stomach, duodenum and jejunoileum were 18.8% (38/202), 8.1% (10/124) and 26.8% (30/112) respectively. No complications or adverse events occurred. Conclusion MGCE is feasible and safe to detect both gastric cavity and small bowel in minors.

Bacteria-mediated anti-tumor therapy has received widespread attention due to its natural tumor-targeting ability and specific immune-activation characteristics. It has made significant progress in breaking the limitations of monotherapy and effectively eradicating tumors, especially when combined with traditional therapy, such as radiotherapy. According to their different biological characteristics, bacteria and their derivatives can not only improve the sensitivity of tumor radiotherapy but also protect normal tissues. Moreover, genetically engineered bacteria and bacteria-based biomaterials have further expanded the scope of their applications in radiotherapy. In this review, we have summarized relevant researches on the application of bacteria and its derivatives in radiotherapy in recent years, expounding that the bacteria, bacterial derivatives and bacteria-based biomaterials can not only directly enhance radiotherapy but also improve the anti-tumor effect by improving the tumor microenvironment (TME) and immune effects. Furthermore, some probiotics can also protect normal tissues and organs such as intestines from radiation via anti-inflammatory, anti-oxidation and apoptosis inhibition. In conclusion, the prospect of bacteria in radiotherapy will be very extensive, but its biological safety and mechanism need to be further evaluated and studied.