Objective: To investigate the value of magnetically guided capsule endoscopy (MGCE) and magnetic resonance enterography (MRE) in assessing the activity of pediatric Crohn’s disease.Methods: Clinical data from 82 subjects with pediatric Crohn’s disease, who underwent MGCE and MRE from October 2018 to March 2021 were analyzed retrospectively. Pairwise comparisons of several indexes, including MaRIA, CECDAI, PCDAI, and SES-CD, were performed by Spearman’s rank correlation test and kappa consistency analysis. CECDAI and MaRIA values predicted whether patients were moderately or severely active (PCDAI ≥30) clinically by logistic regression analysis. The area under the receiver operating characteristic curve (AUC) quantified the evaluation value of moderate to severe activity of pediatric CD.Results: In judging the severity of CD in the small intestine, the correlation coefficient between CECDAI and MaRIA was 0.406 (p < 0.05), and the kappa value of the consistency analysis was 0.299 (p < 0.05). MaRIA was weakly correlated with PCDAI (r = 0.254, p < 0.05), and they were weakly consistent in assessing the activity of Crohn’s disease (kappa = 0.135, p < 0.05). For predicting clinically moderate to severe activity, the fitted AUC based on CECDAI and MarRIA was 0.917, which was higher than applying a single parameter (CECDAI = 0.725, MarRIA = 0.899, respectively). MaRIA and serum albumin were significantly and negatively correlated (r = −1.064, p < 0.05). The consistency of the detection rate of gastric ulcers by MGCE and gastroscopy was moderate (kappa = 0.586, p < 0.05), and the detection rate of ulcers in the terminal ileum between MGCE and colonoscopy showed high consistency (kappa = 0.609, p < 0.05).Conclusions: MGCE and MRE are valuable, non-invasive methods for evaluating small bowel lesions in children with CD. The combined application of MGCE and MRE can better characterize the disease activity.

Background and Aims. Screening for gastric diseases in symptomatic outpatients with conventional esophagogastroduodenoscopy (C-EGD) is expensive and has poor compliance. We aimed to explore the efficiency and safety of magnetic-controlled capsule gastroscopy (MCCG) in symptomatic outpatients who refused C-EGD. Methods. We performed a retrospective study of 76794 consecutive symptomatic outpatients from January 2014 to October 2019. A total of 2318 adults (F/M=1064/1254) in the MCCG group who refused C-EGD were matched with adults in the C-EGD group using propensity-score matching (PSM). The detection rates of abnormalities were analyzed to explore the application of MCCG in symptomatic patients. Results. Our study demonstrated a prevalence of gastric ulcers (GUs) in patients with functional dyspepsia- (FD-) like symptoms of 8.14%. The detection rate of esophagitis and Barrett’s esophagus was higher in patients with typical gastroesophageal reflux disease (GERD) symptoms than in patients in the other four groups (P<0.01). The detection rates of gastric ulcers in the five groups (abdominal pain, bloating, heartburn, follow-up, and bleeding) were significantly different (P=0.015). The total detection rate of gastric ulcers in symptomatic patients was 9.7%. A total of 7 advanced carcinomas were detected by MCCG and confirmed by endoscopic or surgical biopsy. The advanced gastric cancer detection rate was not significantly different between the MCCG group and the C-EGD matched group in terms of nonhematemesis GI bleeding (2 vs. 2, P=1.00). In addition, the overall focal lesion detection rate in the MCCG group was superior to that in the C-EGD matched group (224 vs. 184, P=0.038). MCCG gained a clinically meaningful small bowel diagnostic yield of 54.8% (17/31) out of 31 cases of suspected small bowel bleeding. No patient reported capsule retention at the two-week follow-up. Conclusion. MCCG is well tolerated, safe, and technically feasible and has a considerable diagnostic yield. The overall gastric diagnostic yield of gastric focal lesions with MCCG was comparable to that with C-EGD. MCCG offered a supplementary diagnosis in patients who had a previously undiagnostic C-EGD, indicating that MCCG could play an important role in the routine monitoring and follow-up of outpatient. MCCG shows its safety and efficiency in symptomatic outpatient applications.

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.

Background and Aims. Magnetically guided capsule endoscopy (MGCE) offers a noninvasive method of evaluating both the gastric cavity and small intestine; however, few studies have evaluated MGCE in pediatric patients. We investigated the diagnostic efficacy of MGCE in pediatric patients with abdominal pain. Patients and Methods. We enrolled 48 patients with abdominal pain aged 6-18 years. All patients underwent MGCE to evaluate the gastric cavity and small intestine. Results. The cleanliness of the gastric cardia, fundus, body, angle, antrum, and pylorus was assessed satisfactorily in 100%, 85.4%, 89.6%, 100%, 97.9%, and 100% of patients, respectively. The subjective percentage visualization of the gastric cardia, fundus, body, angle, antrum, and pylorus was 84.8%, 83.8%, 88.5%, 87.7%, 95.2%, and 99.6%, respectively. Eighteen (37.5%) patients had 19 gastrointestinal tract lesions: one esophageal, three in the gastric cavity, and 15 in the small intestine. No adverse events occurred during follow-up. Conclusions. MGCE is safe, convenient, and tolerable for evaluating the gastric cavity and small intestine in pediatric patients. MGCE can effectively diagnose pediatric patients with abdominal pain.

Objective. This study aimed at investigating the clinical value of magnetic-guided capsule endoscopy (MGCE) in the diagnosis of gastrointestinal diseases in minors. Methods. Eighty-four minor patients hospitalized in the pediatric department at Ruijin Hospital between June 2015 and January 2018 were enrolled for this study. Following bowel preparation, all patients underwent MGCE. The feasibility, safety, diagnostic yield, and sensitivity of MGCE were analyzed. Patients were followed up for more than 2 weeks. Results. The main indications for MGCE in minors were Crohn's disease, gastrointestinal bleeding, and abdominal pain. The main causes of gastric disease were gastric inflammatory hyperplasia, exudative gastritis, and polyps. The most common small bowel diseases in minors were Crohn's disease, Henoch-Schonlein purpura, and polyps. The diagnostic yield in the stomach and small intestine was 13.1% and 28.6%, respectively, and the sensitivity was 100% and 96.0%, respectively. No adverse events occurred. Conclusion. MGCE is a safe, effective, and well-tolerated procedure with good sensitivity and has a potential clinic value for the diagnosis of gastrointestinal diseases in minors.

Magnetically controlled capsule endoscopy (MCE) has emerged as a feasible and efficient diagnostic modality for gastric diseases in adults. This study aims to assess the feasibility and safety of MCE in the diagnosis and management of pediatric patients.

The importance of Pituitary homeobox 2 (Pitx2) in malignancy remains enigmatic, and Pitx2 has not been previously implicated in pancreatic ductal adenocarcinoma (PDAC). In this study, we performed gene expression profiling of human PDAC tissues and identified Pitx2 as a promising candidate. Pitx2 expression was decreased from 2.6- to 19-fold in human PDAC tissues from microarray units. Immunochemistry staining showed that Pitx2 expression was moderate to intense in normal pancreatic and pancreatic intraepithelial neoplastic lesions, whereas low in human PDAC tissues. The Pitx2 levels correlated with overall patient survival post-operatively in PDAC. Induction of Pitx2 expression partly inhibited the malignant phenotype of PDAC cells. Interestingly, low Pitx2 expression was correlated with Smad4 mutant inactivation, but not with Pitx2 DNA-methylation. Furthermore, Smad4 protein bound to Pitx2 promoter and stimulated Pitx2 expression in PDAC. In addition, Pitx2 protein bound to the promoter of the protein phosphatase 2A regulatory subunit B55α (PPP2R2A) and upregulated PPP2R2A expression, which may activate dephosphorylation of Akt in PDAC. These findings provide new mechanistic insights into Pitx2 as a tumor suppressor in the downstream of Smad4. And Pitx2 protein promotes PPP2R2A expression which may inhibit Akt pathway. Therefore, we propose that the Smad4-Pitx2-PPP2R2A axis, a new signaling pathway, suppresses the pancreatic carcinogenesis.

Rab11‐FIP2 can interact with MYO5B and plays an important role in regulating plasma membrane recycling. Our previous study has shown that MYO5B is epigenetically silenced and associated with c‐Met signaling in human gastric cancer. However, little is known of the function of Rab11‐FIP2 in gastric cancer. In this study, we investigated Rab11‐FIP2 expression by immunohistochemistry in 86 patients with gastric cancer. We found that the expression level of Rab11‐FIP2 was significantly increased in gastric cancer tissues and high expression of Rab11‐FIP2 was closely correlated with nodal metastasis in gastric cancer patients. Rab11‐FIP2 overexpression promoted epithelial–mesenchymal transition (EMT) in a manner associated with gastric cancer metastasis in vitro and in vivo. We also found that hypoxia could enhance the expression of Rab11‐FIP2 through HIF‐1α. Inactivation of Rab11‐FIP2 dramatically decreased hypoxia‐induced migration of gastric cancer cells. Suppression of the internalization of EGFR, at least in part, plays an important role in EMT induced by overexpression of Rab11‐FIP2 in gastric cancer cells. Finally, we demonstrated that Rab11‐FIP2 could regulate actin cytoskeleton dynamics. In conclusion, our findings reveal a novel mechanism underlying the role of Rab11‐FIP2 in gastric cancer dissemination, suggesting that Rab11‐FIP2 may be a promising candidate target for gastric cancer treatment.

Background The transformation of healthy gastric tissue into intestinal metaplasia (IM) is thought to be a critical premalignant step in the development of intestinal-type gastric adenocarcinoma (GA). How such premalignancies contribute to the development of GA is, however, poorly understood. Methods In this study, the extent and clonal complexity in IM tissue from patients without gastric cancer were analysed by measuring variations of multiple microsatellite (MS) markers. Results Even though these tissues are generally regarded as clinically benign, we found extensive MS length heterogeneity between and within individual IM glands, indicating that complex genome diversity is already pervasive in these tissues. Based on a clonal relationship analysis, we found that there exist multiple clones within individual IM glands and that MS alterations can accumulate in these clones. Moreover, we found spatially distant IM glands with the same MS phenotype, suggesting that these MS alterations were progressed by gland fission. Conclusions These results provide evidence that genetic instability is an early event, present within metaplastic tissues of otherwise non-cancer patients, and such frequent genetic alterations can be part of the pathophysiological rationale for the requirement of this phase during gastric carcinogenesis.

Study the contribution of long non-coding RNAs (lncRNAs) to progression of pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC). We explored lncRNAs profilings in PanIN cell line (SH-PAN) isolated from Pdx-1-Cre; LSL-Kras G12D/+ mice and PDAC cell line (DT-PCa) isolated from Pdx-1-Cre; LSL- Kras G12D/+ ; LSL- Tp53 R172H/+ mice by lncRNAs microarray, and detected expression of lncRNAs and genes in PDAC by Real-time PCR, Western blot, ChIP and immunohistochemistry. Eight lncRNAs and five protein-coding genes, associated with Wnt pathway, were identified with more than five-fold changes between DT-PCa cells and SH-PAN cells. Of them, lincRNA1611 and Ppp3ca were validated significantly high expression in DT-PCa cells and in 22 of 26 fresh resected human PDAC tissues, compared to SH-PAN cells and normal pancreatic tissues, respectively. Moreover, Tp53 mutation status displayed a positive correlation with lincRNA1611 or Ppp3ca level. Immunohistochemical staining for Ppp3ca was weak or lack in 91 of 107 normal pancreatic tissues, 24 of 29 PanIN-I and 13 of 16 PanIN-II tissues, however, was strong in 10 of 27 PanIN-III and 62 of 107 PDAC tissues post operation. LincRNA1611 and Ppp3ca were high expression in PDAC and may serve as new potential targets for intervention of the disease.

[目的]对胃黏膜上皮内瘤变(IEN)患者开展胃镜的定期随访和筛查胃癌的研究,探索提高临床胃癌检出的有效性.[方法]收集2009年1月～2014年12月间,经胃镜活检病理诊断为胃黏膜IEN患者505例,其中低级别上皮内瘤变(LGIEN)465例,高级别上皮内瘤变(HGIEN) 40例,进行定期随访、胃镜复查及病灶活检病理学检查,病理学证实胃癌或有确切病灶的HGIEN者行外科、腹腔镜手术或内镜黏膜剥离术(ESD)治疗,切除标本作病理学检查及胃癌分期.[结果]505例胃黏膜IEN患者经平均21.33个月的随访以及平均3.88次的胃镜复查,共检出胃癌81例,检出胃癌占全组的16.0％,其中早期胃癌51例,占检出胃癌的63.0％;进展期胃癌22例,占检出胃癌的27.2％.另外经胃镜活检病理检出的8例胃癌失访.465例LGIEN患者,检出胃癌57例(12.3％),其中早期胃癌38例(66.7％);40例HGIEN患者,检出胃癌24例(60.0％),其中早期胃癌13例(54.2％).[结论]通过对胃黏膜IEN患者的定期胃镜随访及病理活检,能有效提高胃癌的检出率,尤其能够在LGIEN中筛查出漏诊的胃癌患者;具有确切病灶的HGIEN者,手术病理证实大多为胃癌患者,因此对胃黏膜IEN患者的定期复查必须实施制度化管理.

TIP30 is a putative tumor suppressor that can promote apoptosis and inhibit angiogenesis. However, the role of TIP30 in esophageal squamous cell carcinoma (ESCC) biology has not been investigated. Immunohistochemistry was used to investigate the expression of TIP30 in 70 ESCC. Hypermethylation of TIP30 was evaluated by the methylation specific PCR (MSP) method in ESCC (tumor and paired adjacent non-tumor tissues). Lost expression of TIP30 was observed in 50 of 70 (71.4%) ESCC. 61.4% (43 of 70) of primary tumors analyzed displayed TIP30 hypermethylation, indicating that this aberrant characteristic is common in ESCC. Moreover, a statistically significant inverse association was found between TIP30 methylation status and expression of the TIP30 protein in tumor tissues (p = 0.001). We also found that microRNA-10b (miR-10b) targets a homologous DNA region in the 3'untranslated region of the TIP30 gene and represses its expression at the transcriptional level. Reporter assay with 3'UTR of TIP30 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-10b, providing strong evidence that miR-10b is a direct regulator of TIP30. These results suggest that TIP30 expression is regulated by promoter methylation and miR-10b in ESCC. (C) 2014 Elsevier Inc. All rights reserved.

>患者男,48岁,因"自觉排便后有无痛性肿块脱出肛门,便血间歇性发作10年,肛门流脓3个月"前来检查。患者于10年前发现便后有无痛性坠胀物,并伴有里急后重感,于当地医院诊断为痔疮并行手术治疗,1年后复发再次手术。3个月前直肠指检发现直肠占位,于2011年7月19日行内镜检查发现距肛门4 cm处齿状线上方巨大球形增殖性病灶,病灶表面黏膜较粗糙(图1a);并于距肛门10 cm处见另一环形狭窄伴结节状增生病灶,局部可见不规则溃疡性改变,表面覆坏死物质(图1b)。EUS提示齿状线起至距肛门10 cm范围内肠壁明显增厚及结构消失,最厚处达1.5 cm,呈不均匀中-低回声,肌层部分残留,外膜不规则(图1c);病变肠段与前列腺包膜分界清楚,精囊腺等邻近器官未累及,肠外未见明显肿大淋巴结,内外括约肌分界欠规则(图1d)。

Our previous study has shown that MYO5B is downregulated in gastric cancer. However, the mechanism by which the expression of MYO5B was inhibited remains unknown.

Pancreatic intraepithelial neoplasia (PanIN) is the most common premalignant lesion of the pancreas. Further understanding of the biological behavior and molecular genetic alterations in the stepwise progression of PanINs is necessary toward the development of pancreatic ductal adenocarcinoma (PDAC) interventions. In this study, we analyzed the morphological characteristics, molecular alterations, and biological behavior of pancreatic wild-type and neoplasia tissues, including analysis of PanIN cell line SH-PAN (isolated from Pdx-1-Cre; LSL-KrasG12D/+ mouse) and PDAC cell line DT-PCa (isolated from Pdx1-Cre; LSL-KrasG12D/+; LSL-Tp53R172H/+ mouse. Results show that KrasG12D induces ductal lesion PanINs. Increased expression of EGFR, Her-2/Neu, p-MAPK and β-Catenin was observed in low-grade PanINs. Tp53 was not expressed in wild-type and low-grade PanINs, however, increased expression was observed in high-grade PanINs. Furthermore, SH-PAN cells did not exhibit any colony formation and showed significantly lower migration and invasion ability compared with DT-PCa cells. Notably, we first found PPP2R2A (protein phosphatase 2, regulatory subunit B, alpha) expression was significantly higher in SH-PAN cells than DT-PCa cells, and was high in 96 of 172 peritumoral normal human pancreatic tissues and 20 of 36 human low- or middle-grade PanIN tissues, whereas, was weak or negligible in 12 of 20 human high-grade PanIN tissues and 124 of 172 human PDAC tissues post-operation. The expression of PPP2R2A appears to be correlated with clinical survival. Taken together, Kras(G12D) - driven PanIN showed the tumorigenic ability, however, did not undergo a malignant transformation, and decreased expression of PPP2R2A in PDACs may provided a new target for pancreatic carcinoma intervention.

Background: The aim of the present study was to investigate the indications, clinical utility, feasibility and safety of double-balloon enteroscopy (DBE) in the diagnosis and management of small intestinal diseases in pediatric patients.Methods: This is a retrospective analysis of pediatric patients younger than 18 years referred to Shanghai Rui Jin Hospital from May 2003 to June 2008 for investigation of suspected small bowel disorders. Demographic, clinical, procedural and outcome data were collected for analysis.Results: A total of 35 DBE were carried out in 30 children with a mean age of 13 years. Indications for DBE were obscure gastrointestinal (GI) bleeding (n = 22), chronic abdominal pain (n = 4), chronic diarrhea (n = 3), and incomplete small bowel obstruction (n = 1). DBE evidenced pathological findings in 29 patients (96.7%). DBE altered management in 90% of patients with positive findings. Follow up was obtained on all patients with a mean (range) of 40 months (14- 75 months). The procedure was successful in all patients and there were no serious complications related to sedation.Conclusion: DBE is feasible and safe and has a high diagnostic yield and therapeutic impact on the diagnosis and management of small bowel disorders in selected pediatric patients.

<正>胃镜直视下识别病灶以及钳取活组织的病理学检查是诊断胃癌的首选方法,而临床工作中胃癌患者被漏诊或误诊也主要与胃镜检查这一重要环节有关。日本有关研究认为病灶过小无法窥清与确实存在明显胃癌病灶却仍被遗漏的频率相等;而贲门附近胃癌的漏诊大多为胃镜观察不充

High levels of SOX4 expression have been found in a variety of human cancers, such as lung, brain and breast cancers. However, the expression of SOX4 in gastric tissues remains unknown. The SOX4 expression was detected using immunohistochemical staining and semi-quantitative RT-PCR, and our results showed that SOX4 was up-regulated in gastric cancer compared to benign gastric tissues. To further elucidate the molecular mechanisms underlying up-regulation of SOX4 in gastric cancers, we analyzed the expression of microRNA-129-2 (miR-129-2) gene, the epigenetic repression of which leads to overexpression of SOX4 in endometrial cancer. We found that up-regulation of SOX4 was inversely associated with the epigenetic silencing of miR-129-2 in gastric cancer, and restoration of miR-129-2 down-regulated SOX4 expression. We also found that inactivation of SOX4 by siRNA and restoration of miR-129-2 induced apoptosis in gastric cancer cells.

Objective To investigate the relationship between the expression of c-ski in human gastric cancer and the clinicopathological parameters. Methods The expression of c-ski protein and mRNA were detected by immunohis-tochemistry and reverse transcriptase-polymerase chain reaction in adjacent normal tissues ( n = 28) and gastric cancer tissues ( n = 28) . Results The positive rate of c-ski protein and the level of c-ski mRNA in gastric cancer tissues were significantly higher than those in adjacent normal tissues ( P 0. 01) . The positive rate of c-ski protein in intestinal gastric cancer was higher than that in diffuse gastric cancer ( P 0. 05) ,but it was not related to sex,depth of tumor invasion,tumor size,lymph node,distant metastasis and 1-year survival time ( P 0. 05) . Conclusion The c-ski was overexpression in gastric cancer tissues and the positive rate of c-ski was obviously different between intestinal gastric cancer and diffuse gastric cancer.