Prospects of polyglycolic acid sheets for the treatment of esophageal stricture after esophageal endoscopic submucosal dissection.

Esophageal cancer is the seventh most common type of cancer and the sixth leading cause of cancer -related mortality worldwide. Endoscopic submucosal dissection (ESD) is widely used for the resection of early esophageal cancer. However, post-ESD esophageal stricture is a common long-term complication, which requires attention. Patients with post-ESD esophageal stricture often experience dysphagia and require multiple dilatations, which greatly affects their quality of life and increases healthcare costs. Therefore, to manage post-ESD esophageal stricture, researchers are actively exploring various strategies, such as pharmaceutical interventions, endoscopic balloon dilation, and esophageal stenting. Although steroids-based therapy has achieved some success, steroids can lead to complications such as osteoporosis and infection. Meanwhile, endoscopic balloon dilatation is effective in the short term, but is prone to recurrence and perforation. Additionally, esophageal stenting can alleviate the stricture, but is associated with discomfort during stenting and the complication of easy displacement also present challenges. Tissue engineering has evolved rapidly in recent years, and hydrogel materials have good biodegradability and biocompatibility. A novel type of polyglycolic acid (PGA) sheets has been found to be effective in preventing esophageal stricture after ESD, with the advantages of a simple operation and low complication rate. PGA membranes act as a biophysical barrier to cover the wound as well as facilitate the delivery of medications to promote wound repair and healing. However, there is still a lack of multicenter, large-sample randomized controlled clinical studies focused on the treatment of post-ESD esophageal strictures with PGA membrane, which will be a promising direction for future advancements in this field.

Nomogram model predicting the overall survival for patients with primary gastric mucosa-associated lymphoid tissue lymphoma.

BACKGROUND: Increasingly extranodal marginal B-cell lymphoma of mucosa-associated lymphoid tissue, known as mucosa-associated lymphoid tissue (MALT) lymphoma, is a type of non-Hodgkin's lymphoma. The prognosis of primary gastric MALT (GML) patients can be affected by many factors. Clinical risk factors, including age, type of therapy, sex, stage and family hematologic malignancy history, also have significant effects on the development of the disease. The available data are mainly focused on epidemiology; in contrast, few studies have investigated the prognostic variables for overall survival (OS) in patients with primary GML. Based on the realities above, we searched a large amount of data on patients diagnosed with primary GML in the Surveillance, Epidemiology and End Results (SEER) database. The aim was to develop and verify a survival nomogram model that can predict the overall survival prognosis of primary GML by combining prognostic and determinant variables. AIM: To create an effective survival nomogram for patients with primary gastric GML. METHODS: All data of patients with primary GML from 2004 to 2015 were collected from the SEER database. The primary endpoint was OS. Based on the LASSO and COX regression, we created and further verified the accuracy and effectiveness of the survival nomogram model by the concordance index (C-index), calibration curve and time-dependent receiver operating characteristic (td-ROC) curves. RESULTS: A total of 2604 patients diagnosed with primary GML were selected for this study. A total of 1823 and 781 people were randomly distributed into the training and testing sets at a ratio of 7:3. The median follow-up of all patients was 71 mo, and the 3- and 5-year OS rates were 87.2% and 79.8%, respectively. Age, sex, race, Ann Arbor stage and radiation were independent risk factors for OS of primary GML (all P < 0.05). The C-index values of the nomogram were 0.751 (95%CI: 0.729-0.773) and 0.718 (95%CI: 0.680-0.757) in the training and testing cohorts, respectively, showing the good discrimination ability of the nomogram model. Td-ROC curves and calibration plots also indicated satisfactory predictive power and good agreement of the model. Overall, the nomogram shows favorable performance in discriminating and predicting the OS of patients with primary GML. CONCLUSION: A nomogram was developed and validated to have good survival predictive performance based on five clinical independent risk factors for OS for patients with primary GML. Nomograms are a low-cost and convenient clinical tool in assessing individualized prognosis and treatment for patients with primary GML.

LINC01116 modulates EMT process via binding with AGO1 mRNA in oesophageal squamous cell carcinoma.

Recent researches have uncovered that long non-coding RNAs (lncRNAs) are closely correlated with the development of different diseases, while biological functions and hidden molecular mechanisms of antisense lncRNAs in oesophageal squamous cell carcinoma (OSCC) remain unclear. Here, we identified upregulation of LINC01116 in RNA sequencing data, online database, and in OSCC and intraepithelial neoplasia (IEN) specimens. Functionally, LINC01116 facilitates OSCC advancement and metastasis in vitro and vivo. Mechanistically, elevated expression of LINC01116 in OSCC cells other than tumor stroma and cytoplasmic enables it to activate AGO1 expression via complementary binding with AGO1 mRNA to facilitate EMT process of OSCC.

Machine learning-based automated sponge cytology for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction: a nationwide, multicohort, prospective study.

BACKGROUND: Oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction have a dismal prognosis, and early detection is key to reduce mortality. However, early detection depends on upper gastrointestinal endoscopy, which is not feasible to implement at a population level. We aimed to develop and validate a fully automated machine learning-based prediction tool integrating a minimally invasive sponge cytology test and epidemiological risk factors for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction before endoscopy. METHODS: For this multicohort prospective study, we enrolled participants aged 40-75 years undergoing upper gastrointestinal endoscopy screening at 39 tertiary or secondary hospitals in China for model training and testing, and included community-based screening participants for further validation. All participants underwent questionnaire surveys, sponge cytology testing, and endoscopy in a sequential manner. We trained machine learning models to predict a composite outcome of high-grade lesions, defined as histology-confirmed high-grade intraepithelial neoplasia and carcinoma of the oesophagus and oesophagogastric junction. The predictive features included 105 cytological and 15 epidemiological features. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC) and average precision. The performance measures for cytologists with AI assistance was also assessed. FINDINGS: Between Jan 1, 2021, and June 30, 2022, 17 498 eligible participants were involved in model training and validation. In the testing set, the AUROC of the final model was 0·960 (95% CI 0·937 to 0·977) and the average precision was 0·482 (0·470 to 0·494). The model achieved similar performance to consensus of cytologists with AI assistance (AUROC 0·955 [95% CI 0·933 to 0·975]; p=0·749; difference 0·005, 95% CI, -0·011 to 0·020). If the model-defined moderate-risk and high-risk groups were referred for endoscopy, the sensitivity was 94·5% (95% CI 88·8 to 97·5), specificity was 91·9% (91·2 to 92·5), and the predictive positive value was 18·4% (15·6 to 21·6), and 90·3% of endoscopies could be avoided. Further validation in community-based screening showed that the AUROC of the model was 0·964 (95% CI 0·920 to 0·990), and 92·8% of endoscopies could be avoided after risk stratification. INTERPRETATION: We developed a prediction tool with favourable performance for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction. This approach could prevent the need for endoscopy screening in many low-risk individuals and ensure resource optimisation by prioritising high-risk individuals. FUNDING: Science and Technology Commission of Shanghai Municipality.

Endoscopic debulking resection with additive chemoradiotherapy: Optimal management of advanced inoperable esophageal squamous cell carcinoma.

BACKGROUND: There is no remedial strategy other than definitive chemoradiotherapy for patients with advanced esophageal squamous cell carcinoma (ESCC) who are not eligible to undergo surgical treatment. AIM: To introduce a novel therapy called endoscopic debulking resection (EdR) followed by additive chemoradiotherapy (CRT) and evaluate its efficacy and safety. METHODS: Advanced, inoperable ESCC patients between 1 January 2015 and 30 December 2019 were investigated retrospectively. Patients who received EdR followed by CRT were deemed the EdR + CRT group and those without CRT were deemed the EdR group. Overall survival (OS), progression-free survival (PFS), and adverse events were evaluated. RESULTS: A total of 41 patients were enrolled. At a median follow-up of 36 mo (range: 1-83), the estimated 1-, 2-, and 3-year cumulative OS rates of patients who underwent EdR plus additive CRT were 92.6%, 85.2%, and 79.5%, respectively, which were higher than those of patients who underwent EdR alone (1-year OS, 83.3%; 2-year OS, 58.3%; 3-year OS, 50%; P = 0.05). The estimated 2-year cumulative PFS rate after EdR + CRT was 85.7%, while it was 61.5% after EdR (P = 0.043). According to the univariate and multivariate Cox regression analyses, early clinical stage (stage ≤ IIB) and additive CRT were potential protective factors for cumulative OS. No severe adverse events were observed during the EdR procedure, and only mild to moderate myelosuppression and radiation pneumonia were observed in patients who underwent additive CRT after EdR. CONCLUSION: EdR plus CRT is an alternative strategy for selective advanced inoperable ESCC patients.

Efficacy of keverprazan for duodenal ulcer: A phase II randomized, double-blind, parallel-controlled trial.

BACKGROUND AND AIM: Considering the limitation of varying acid suppression of proton pump inhibitors, this study was aimed to assess the efficacy, safety, and dose-effect relationship of keverprazan, a novel potassium-competitive acid blocker, in the treatment of duodenal ulcer (DU) compared with lansoprazole. METHODS: A randomized, double-blind, double-dummy, multicenter, low-dose, high-dose, and positive-drug parallel-controlled study was conducted to verify the non-inferiority of keverprazan (20 or 30 mg) to lansoprazole of 30 mg once daily for 4 to 6 weeks and dose-effect relationship of keverprazan in the treatment of patients with active DU confirmed by endoscopy. RESULTS: Of the 180 subjects randomized, including 55 cases in the keverprazan_20 mg group, 61 cases in the keverprazan_30 mg group, and 64 cases in the lansoprazole_30 mg group, 168 subjects (93.33%) completed the study. The proportions of healed DU subjects in the keverprazan_20 mg, keverprazan_30 mg, and lansoprazole_30 mg groups were respectively 87.27%, 90.16%, and 79.69% at week 4 (P = 0.4595) and were respectively 96.36%, 98.36%, and 92.19% at week 6 (P = 0.2577). The incidence of adverse events in the keverprazan_20 mg group was lower than that in the lansoprazole_30 mg (P = 0.0285) and keverprazan_30 mg groups (P = 0.0398). CONCLUSIONS: Keverprazan was effective and non-inferior to lansoprazole in healing DU. Based on the comparable efficacy and safety data, keverprazan of 20 mg once daily is recommended for the follow-up study of acid-related disorders. (Trial registration number: ChiCTR2100043455.).

Hepatitis E Virus Capsid as a Carrier of Exogenous Antigens for the Development of Chimeric Virus-Like Particles.

INTRODUCTION: Virus-like particles (VLPs), self-assembled multiprotein structures, can stimulate robust immune responses due to their structural similarity to native virions that allow the presentation of multiple copies of the target epitopes. Utilizing VLPs as vaccine platforms to present exogenous antigens is a promising and challenging approach in the vaccine development field. This study investigates the potential of the truncated hepatitis E virus (HEV) capsid as a VLP platform to present foreign antigens. METHODS: The S and M domains of the HEV capsid protein were selected as the optimal carrier (CaSM). The exogenous antigen Seq8 containing 3 neutralizing epitopes from 3 different foot-and-mouth disease virus (FMDV) strains was linked to the C-terminal of CaSM to construct a chimeric VLP (CaSM-Seq8). The chimeric particles were produced in Escherichia coli, and their morphology, physicochemical properties, antigenicity, and immunogenicity were analyzed. RESULTS: Morphological analysis showed that CaSM-Seq8 self-assembled into VLPs similar to CaSM VLPs (∼26 nm in diameter) but smaller than native HEV virions. Further, the thermal stability and the resistance to enzymatic proteolysis of Seq8 were enhanced when it was attached to the CaSM carrier. The antigenicity analysis revealed a more robust reactivity against anti-FMDV antibodies when Seq8 was presented on CaSM particles. Upon injection into mice, FMDV-specific IgGs induced by CaSM-Seq8 appeared earlier, increased faster, and maintained higher levels for a longer time than those induced by Seq8 alone or the inactivated FMDV vaccine. CONCLUSION: This study demonstrated the potential of utilizing the truncated HEV capsid as an antigen-presenting platform for the development of chimeric VLP immunogens.

Feasibility and Accuracy of Artificial Intelligence-Assisted Sponge Cytology for Community-Based Esophageal Squamous Cell Carcinoma Screening in China.

INTRODUCTION: Screening is the pivotal strategy to relieve the burden of esophageal squamous cell carcinoma (ESCC) in high-risk areas. The cost, invasiveness, and accessibility of esophagogastroduodenoscopy (EGD) necessitate the development of preliminary screening methods. METHODS: Residents aged 40-85 years were recruited in a high-risk area of ESCC. Esophageal cells were collected using an approved novel capsule sponge, and cytology slides were scanned by a trained artificial intelligence (AI) system before cytologists provided confirmation. Atypical squamous cell or more severe diagnosis was defined as positive cytology. AI-based abnormal cell counts were also reported. EGD was performed subsequently with biopsy as needed. Diagnostic accuracy, adverse events, and acceptability of cytology testing were assessed. Esophageal high-grade lesions (ESCC and high-grade intraepithelial neoplasia) were the primary target lesions. RESULTS: In total, 1,844 participants were enrolled, and 20 (1.1%) high-grade lesions were confirmed by endoscopic biopsy. The AI-assisted cytologist-confirmed cytology showed good diagnostic accuracy, with a sensitivity of 90.0% (95% confidence interval [CI], 76.9%-100.0%), specificity of 93.7% (95% CI, 92.6%-94.8%), and positive predictive value of 13.5% (95% CI, 7.70%-19.3%) for detecting high-grade lesions. The area under the receiver operation characteristics curve was 0.926 (95% CI, 0.850-1.000) and 0.949 (95% CI, 0.890-1.000) for AI-assisted cytologist-confirmed cytology and AI-based abnormal cell count, respectively. The numbers of EGD could be reduced by 92.5% (from 99.2 to 7.4 to detect 1 high-grade lesion) if only cytology-positive participants were referred to endoscopy. No serious adverse events were documented during the cell collection process, and 96.1% participants reported this process as acceptable. DISCUSSION: The AI-assisted sponge cytology is feasible, safe, and acceptable for ESCC screening in community, with high accuracy for detecting esophageal squamous high-grade lesions.

Biological and clinical implications of metastasis-associated circular RNAs in oesophageal squamous cell carcinoma.

Oesophageal squamous cell carcinoma (OSCC) is a prevalent malignancy with high morbidity and mortality as a result of early metastasis and poor prognosis. Metastasis is a multistep process, involving various signalling pathways. Circular RNAs (circRNAs) are a class of covalently closed noncoding RNAs, the aberrant expression of which is reported to be involved in several biological events, including cell transformation, proliferation, migration, invasion, apoptosis and metastasis. Several studies have reported interactions between circRNAs and metastasis-associated signalling pathways. The abundance, stability and highly specific expression of candidate circRNAs make them potential biomarkers and therapeutic targets in OSCC. In this review article, we comprehensively describe metastasis-related circRNAs and their interactions with epithelial-mesenchymal transition-associated molecules. We also describe the molecular mechanisms and clinical relevance of circRNAs in OSCC progression and metastasis.

The number of biopsy specimens can influence the non-lifting sign in colorectal laterally spreading tumors.

BACKGROUND: Although the problem of whether to perform a biopsy before endoscopic treatment for colorectal laterally spreading tumor (LST) troubles clinicians, about 50 % of lesions still undergo a preceding biopsy. We aimed to explore factors affecting the non-lifting sign in LST and examine the influence of "biopsy-related factors", such as the number of biopsy specimens and the interval after biopsy on non-lifting sign in cases with a history of biopsy. METHODS: Clinical data of 159 LSTs regarding age, gender, history of biopsy, tumor location, tumor size, the depth of submucosal invasion, tumor configuration, histologic type, location with respect to the fold, and result of non-lifting sign testing were investigated retrospectively. For patients with a history of biopsy, the period after biopsy and the number of biopsy specimens also were analyzed. RESULTS: Among 159 cases of LST, 112 were positive and 47 were negative for lifting signs. Biopsy history (p = 0.008), tumor size (p = 0.010), and location with respect to the fold (p = 0.022) were identified as factors affecting the non-lifting sign in multivariate analyses. In 75 LST cases with a history of biopsy, only the number of biopsies (p = 0.003) was identified as a factor affecting the non-lifting sign in multivariate analyses. CONCLUSIONS: For LST, lesions with larger size, being across the fold, and biopsy history were predictive factors for non-lifting signs. Reducing the number of biopsies would reduce the occurrence of non-lifting signs when biopsy is necessary. The impact of the interval after the biopsy on the non-lifting sign will require further study.

Markers of gastric intestinal metaplasia under digital chromoendoscopy: systematic review and meta-analysis.

Diagnosis of gastric intestinal metaplasia (GIM) under digital chromoendoscopy presents various markers. The diagnostic yield of each marker has shown variable results. A systematic review and meta-analysis were performed to evaluate the following markers: light blue crest (LBC), marginal turbid band (MTB), groove type (GT), white opaque substance (WOS). Discussion of their joint diagnosis, reliability, assessment of local GIM severity and influencing factors was also provided. PubMed, EMBASE, Cochrane Library and Web of science were searched. The Meta-DiSc and Stata software were used to analyze the data. Fourteen studies were included with a total of 3081 lesions. There were 12 studies for LBC, six for GT, four for MTB and one for WOS, respectively. The pooled results showed that the diagnostic sensitivity and specificity of LBC were 0.79 [95% confidence interval (CI) 0.76-0.81] and 0.95 (95% CI 0.94-0.96). The sensitivity of GT and MTB were 0.49 (95% CI 0.43-0.54) and 0.47 (95% CI 0.40-0.53), and the specificity were 0.92 (95% CI 0.89-0.94) and 0.92 (95% CI 0.89-0.95). The area under the summary receiver operating characteristic curve was 0.9532, 0.7791 and 0.9553 for LBC, GT and MTB, respectively. LBC resulted the most classic marker. Proper combined diagnosis can improve the diagnostic efficiency. Reliability of these markers was acceptable. These markers can help endoscopic to assess the severity of local GIM. Besides intestinal metaplasia, many factors can potentially interfere with the diagnosis.

Efficacy and Safety of Endoscopic Treatment for Gastrointestinal Stromal Tumors in the Upper Gastrointestinal Tract.

BACKGROUND/AIMS: Endoscopic treatment (ET) has been applied for decades to treat subepithelial tumors, including gastrointestinal stromal tumors (GISTs). However, the efficacy of ET remains debatable. In this study, we evaluated the efficacy and safety of ET for GISTs in the upper gastrointestinal tract. METHODS: This retrospective single-center study included 97 patients who underwent ET. All patients were enrolled from July 2014 to July 2018. Parameters such as demographics, size, resection margin, complications, pathological features, procedure time, total cost, and follow-up were investigated and analyzed. RESULTS: Our study achieved 100% en bloc resection and 77.4% (72/93) R0 resection. The most common location was the fundus with a mean tumor size of 2.1±1.43 cm. The mean age, procedure time, hospital stay, and cost were 59.7±11.29 years, 64.7±35.23 minutes, 6.8 days, and 5,337 dollars, respectively. According to National Institutes of Health classification, 63 (64.9%), 26 (26.8%), 5 (5.2%), and 3 (3.1%) patients belonged to the very low, low, intermediate, and high risk classification, respectively. Immunohistochemistry results showed a 100% positive rate of CD34, DOG-1, CD117, and Ki67. A mean follow-up of 21.3±13.0 months showed no recurrence or metastasis. CONCLUSION: ET is effective and safe for curative removal of GISTs in the upper gastrointestinal tract, and it can be a treatment of choice for patients with no metastasis.

Bleeding after endoscopic submucosal dissection of gastric lesions.

Endoscopic submucosal dissection (ESD) is generally used to treat gastric mucosal and submucosal lesions. Nevertheless, ESD is more difficult and complicated to perform than a traditional endoscopic mucosal resection, which can increase the incidence of various complications including hemorrhage, perforation and infection. Hemorrhage is a major post-ESD complication. Prevention and early diagnosis of post-ESD bleeding for gastric lesions are closely associated with the efficacy and safety of the operation. Many studies have reported the risks of and the preventative measures for hemorrhage after gastric ESD, but there remain some issues to be solved. We thus reviewed the risk factors, precautions and treatments for hemorrhage after ESD of gastric lesions.

lncRNACNN3-206 activates intestinal epithelial cell apoptosis and invasion by sponging miR-212, an implication for Crohn's disease.

BACKGROUND: Statistics indicate that the incidence of Crohn's disease (CD) is rising in many countries. The poor understanding on the pathological mechanism has limited the development of effective therapy against this disease. Previous studies showed that long noncoding RNAs (lncRNAs) could be involved in autoimmune diseases including CD, but the detailed molecular mechanisms remain unclear. AIM: To identify the differentially expressed lncRNAs in the intestinal mucosa associated with CD, and to characterize their pathogenic role(s) and related mechanisms. METHODS: The differential expression of lncRNAs was screened by high-throughput RNA sequencing, and the top candidate genes were validated in an expanded cohort by real-time PCR. The regulatory network was predicted by bioinformatic software and competitive endogenous RNA analysis, and was characterized in Caco-2 and HT-29 cell culture using methods of cell transfection, real-time PCR, Western blotting analysis, flow cytometry, and cell migration and invasion assays. Finally, these findings were confirmed in vivo using a CD animal model. RESULTS: The 3' end of lncRNACNN3-206 and the 3' UTR of Caspase10 contain high-affinity miR212 binding sites. lncRNACNN3-206 expression was found to be significantly increased in intestinal lesions of CD patients. Activation of the lncRNACNN3-206-miR-212-Caspase10 regulatory network led to increased apoptosis, migration and invasion in intestinal epithelial cells. Knockdown of lncRNACNN3-206 expression alleviated intestinal mucosal inflammation and tissue damage in the CD mouse model. CONCLUSION: lncRNACNN3-206 may play a key role in CD pathogenesis. lncRNACNN3-206 could be a therapeutic target for CD treatment.

Development and validation of a clinical prediction model to estimate the probability of malignancy in solid pancreatic lesions and explore its value in the atypical diagnostic category after endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA).

BACKGROUND: The diagnosis of solid pancreatic lesions is still a thorny problem for clinicians, even endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) still face problems like false negative. The present study aimed to first establish a model to predict the malignancy in solid pancreatic lesions and then explored its validity with atypical diagnostic category diagnosed by cytologists after EUS-FNA. METHODS: Clinical information of 360 cases diagnosed with solid pancreatic lesions between June 2013 and July 2019, and another 20 cases with atypical diagnostic category were collected retrospectively. These cases were divided into group A and group B according to the order of admission. Using the data of group A, multivariate logistic regression analysis was performed to construct a malignancy prediction model which was then verified using group B. Furthermore, the characteristics of the malignancy between the group with atypical diagnostic category and group A were compared in order to evaluate the rationality of the model used in the atypical diagnostic category group, and its predictive ability in these lesions. RESULTS: Multivariate logistic regression analysis revealed that age, density, CA19-9 and carcinoembryonic antigen (CEA) grade, pancreatic duct, swollen lymph nodes, pancreas calcification, and weight loss were independent factors in predicting malignancy (P<0.05). The verification results showed that the area under the receiver operating characteristic (ROC) curve was 0.854±0.042; 95% CI: 0.771-0.936. Univariate analysis showed no significant difference between the malignancy in atypical diagnostic category group and that in group A. For the atypical diagnostic category group, the sensitivity of this model was 83.33%, specificity 100%, positive predictive value (PPV) 100%, negative predictive value (NPV) 40%. CONCLUSIONS: Advanced age, low density of lesions, high CA19-9 and CEA grade, dilatation of pancreatic duct, swollen lymph nodes and weight loss were risk factors for malignancy, while calcification was a protective factor. The model had a relatively high predictive ability on malignancy in both solid pancreatic lesions and atypical diagnostic category group.

Risk Factors and Nomogram for Pancreatic Stone Formation in Chronic Pancreatitis over a Long-Term Course: A Cohort of 2,153 Patients.

BACKGROUND: Pancreatic stones are pathognomonic of chronic pancreatitis (CP). This study aimed to determine the incidence, identify risk factors, and develop a nomogram for pancreatic stones in CP patients. METHODS: Patients with CP admitted to our center from January 2000 to December 2013 were enrolled. Cumulative rates of pancreatic stones after the onset of CP and after the diagnosis of CP were calculated. Patients were randomly assigned, in a 2:1 ratio, to the training and validation cohort. Based on the training cohort, risk factors were identified through Cox proportional hazards regression model, and nomogram was developed. Internal and external validations were performed based on the training and validation cohort, respectively. RESULTS: With a total of 2,153 CP patients, pancreatic stones were detected in 1,626 (75.5%) patients, with a median follow-up of 7.8 years. Age at the onset of CP, body mass index, smoking, diabetes mellitus, pancreatic pseudocyst, biliary stricture, severe acute pancreatitis, and type of pain were identified risk factors for pancreatic stones development. The nomogram with these 8 factors achieved good accuracy. CONCLUSIONS: The nomogram achieved an individualized prediction of pancreatic stones development in CP. It may help the management of pancreatic stones.

Clinical Overview of GIST and Its Latest Management by Endoscopic Resection in Upper GI: A Literature Review.

AIMS: To review the clinical presentation, diagnosis, assessment of risk of malignancy, and recent advances in management (mainly focusing on the role of endoscopic resection) of gastrointestinal stromal tumors (GISTs) in upper GI. METHOD: We searched Embase, Web of science, and PubMed databases from 1993 to 2018 by using the following keywords: "gastrointestinal stromal tumors," "GIST," "treatment," and "diagnosis." Additional papers were searched manually from references of the related articles. FINDINGS: The improvement of endoscopic techniques in treating upper gastrointestinal subepithelial tumors especially gastrointestinal tumors has reduced the need for invasive surgery in patients unfit for surgery. Many studies have concluded that modified endoscopic treatments are effective and safe. These treatments permit minimal tissue resection, better dissection control, and high rates of en bloc resection with an acceptable rate of complications.

Updated review on immune factors in pathogenesis of Crohn's disease.

Although the incidence of Crohn's disease (CD) in China is not as high as that in European and American countries, there has been a clear increasing trend in recent years. Little is known about its pathogenesis, cause of deferment, and the range of complications associated with the disease. Local and international scholars have presented many hypotheses about CD pathogenesis based on experimental and clinical studies, including genetic susceptibility, immune function defects, intestinal microflora disorders, delayed hypersensitivity, and food antigen stimulation. However, the specific mechanism leading to this immune imbalance, which causes persistent intestinal mucosal damage, and the source of the inflammatory cascade reaction are still unclear. So far, the results of research studies differ locally and internationally. This paper presents the most current research on immune factors in the pathogenesis of CD.

MiR-26b regulates 5-FU-resistance in human colorectal cancer via down-regulation of Pgp.

Chemotherapy resistance frequently drives tumor progression. However, the underlying molecular mechanisms remain unclear. In this study, we found that the expression level of miR-26b was down-regulated in the human colorectal cancer tissues and the resistant cells strains: HT-29/5-FU and LOVO/5-FU cells. Meanwhile, we showed that miR-26b improved sensibility of colorectal cancer cells to 5-FU in vitro and enhanced the potency of 5-FU in the inhibition of tumor growth in vivo. We further demonstrated that the tumor suppressive role of miR-26b was mediated by negatively regulating P-glycoprotein (Pgp) protein expression. Furthermore, studies of colorectal cancer specimens indicated that the expression of miR-26b and Pgp had inverse correlation. Importantly, we found that CpG islands in the miR-26b promoter region were hypermethylated in 5-FU resistant cells. Our study is the first to identify the tumor suppressive role of over-expressed miR-26b in chemo-sensitivity. Identification of a novel miRNA-mediated pathway that regulates chemo-sensitivity in colorectal cancer will facilitate the development of novel therapeutic strategies in the future.