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Neutrophils are the most abundant leukocyte population in the human circulatory system and are rapidly recruited to sites of inflammation. Neutrophils play a multifaceted role in intestinal inflammation, as they contribute to the elimination of invading pathogens. Recently, their role in epithelial restitution has been widely recognized; however, they are also associated with bystander tissue damage. The intestinal epithelium provides a physical barrier to prevent direct contact of luminal contents with subepithelial tissues, which is extremely important for the maintenance of intestinal homeostasis. Numerous studies have demonstrated that transepithelial migration of neutrophils is closely related to disease symptoms and disruption of crypt architecture in inflammatory bowel disease and experimental colitis. There has been growing interest in how neutrophils interact with the epithelium under inflammatory conditions. Most studies focus on the effects of neutrophils on intestinal epithelial cells; however, the effects of intestinal epithelial cells on neutrophils during intestinal inflammation need to be well-established. Based on these data, we have summarized recent articles on the role of neutrophil-epithelial interactions in intestinal inflammation, particularly highlighting the epithelium-derived molecular regulators that mediate neutrophil recruitment, transepithelial migration, and detachment from the epithelium, as well as the functional consequences of their crosstalk. A better understanding of these molecular events may help develop novel therapeutic targets for mitigating the deleterious effects of neutrophils in inflammatory bowel disease.

Background To study whether oral presentation (OP) assessment could reflect the novice learners’ interpretation skills and reading behaviour on brain computed tomography (CT) reading. Methods Eighty fifth-year medical students were recruited, received a 2-hour interactive workshop on how to read brain CT, and were assigned to read two brain CT images before and after instruction. We evaluated their image reading behaviour in terms of overall OP post-test rating, the lesion identification, and competency in systematic image reading after instruction. Students’ reading behaviour in searching for the target lesions were recorded by the eye-tracking technique and were used to validate the accuracy of lesion reports. Statistical analyses, including lag sequential analysis (LSA), linear mixed models, and transition entropy (TE) were conducted to reveal temporal relations and spatial complexity of systematic image reading from the eye movement perspective. Results The overall OP ratings [pre-test vs. post-test: 0 vs. 1 in case 1, 0 vs. 1 in case 2, p Conclusion Our results showed OP performance may change concurrently with the medical students’ reading behaviour on brain CT after a structured instruction.

The intestinal tract consists of various types of cells, such as epithelial cells, Paneth cells, macrophages, and lymphocytes, which constitute the intestinal immune system and play a significant role in maintaining intestinal homeostasis by producing antimicrobial materials and controlling the host-commensal balance. Various studies have found that the dysfunction of intestinal homeostasis contributes to the pathogenesis of inflammatory bowel disease (IBD). As a novel mediator, extracellular vesicles (EVs) have been recognized as effective communicators, not only between cells but also between cells and the organism. In recent years, EVs have been regarded as vital characters for dysregulated homeostasis and IBD in either the etiology or the pathology of intestinal inflammation. Here, we review recent studies on EVs associated with intestinal homeostasis and IBD and discuss their source, cargo, and origin, as well as their therapeutic effects on IBD, which mainly include artificial nanoparticles and EVs derived from microorganisms.

Psychosocial stress is a critical inducing factor of inflammatory bowel diseases (IBD), while autophagy is a novel central issue of IBD development. The present study investigated the potential role of autophagy in stress-related IBD in patients and animal model. The correlation between psychosocial stress and intestinal autophagy was determined in 23 patients with IBD. Corticotropin-releasing hormone (CRH), a well-established inducer of psychosocial stress, was administrated in dextran sulfate sodium (DSS)-induced IBD mice and lipopolysaccharide (LPS)-stimulated bone marrow-derived macrophages (BMDM). In IBD patients, the autophagy markers beclin-1, LC3-II/I ratio, Atg16L1, and Atg4B were significantly enhanced. The psychosocial stress score was positively associated with the levels of beclin-1 and the LC3II/I ratio in intestinal biopsy specimens. In IBD mouse model, CRH significantly aggravated intestinal inflammation, increased Paneth cell metaplasia, and enhanced intestinal autophagy (beclin-1, Atg16L1, PIK3R4, and Atg4B upregulation; GAA, CTSD, and PPKAA1 downregulation). Additionally, the CRH-induced gut microbial dysbiosis was evidenced by a marked increase in the number of detrimental bacteria. In LPS-stimulated BMDM, CRH substantially increased M1/M2 polarization and thus promoted inflammation. In both IBD mice and LPS-treated BMDM, blockade of autophagy by chloroquine abrogated the unbeneficial effects of CRH, whereas autophagy inducer rapamycin resulted in a pronounced protective effect against IBD lesion. Our data demonstrate that psychosocial stress may link the enhanced intestinal autophagy by modulating gut microbiota and inflammation to aggravate IBD. These data indicate autophagy as a promising therapeutic target for psychosocial stress-related IBD.

A 67-year-old woman presented with paroxysmal epigastric pain for 3 months, without jaundice. She gave a history of cholecystectomy. Physical examination and blood tests were unremarkable. Magnetic resonance cholangiopancreatography showed cystic dilatation of the common bile duct (CBD), intrahepatic and extrahepatic bile duct dilatation and suspicious intrahepatic bile duct stones (figure 1). CT scan showed intrahepatic and extrahepatic bile duct dilatation and multiple intrahepatic bile duct stones (figure 2). Figure 1 Magnetic resonance cholangiopancreatography showed cystic dilatation of the common bile duct, intrahepatic …

Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the colon and small intestine, comprised of ulcerative colitis and Crohn's disease. Among the complicated pathogenic factors of IBD, the overaction of inflammatory and immune reaction serves as an important factor. Inflammasome is a form of innate immunity as well as inflammation. Among all kinds of inflammasomes, the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is the most studied one, and has been revealed to be involved in the pathogenesis and progression of IBD. Here, in this review, the association between the NLRP3 inflammasome and IBD will be discussed. Furthermore, several NLRP3 inflammasome inhibitors which have been demonstrated to be effective in the alleviation of IBD will be described in this review.

OBJECTIVE Adequate bowel preparation is essential for a successful colonoscopy; clinical studies suggest reinforced education can improve the preparation process. However, there have been no trials to compare WeChat directions (the most widely used social media app in China) with those of the short message service (SMS). This study was aimed to assess the effect of WeChat and SMS on the bowel preparation quality. PARTICIPANTS AND METHODS This was a single-center, prospective, endoscopically blinded, randomized, controlled study. Patients in reinforced education groups received additional reminder messages by WeChat and SMS 2 days before colonoscopy. The primary outcome was bowel preparation quality evaluated by the Boston bowel preparation scale (BBPS) score and the rate of adequacy (BBPS score ≥6). Secondary outcomes included polyp detection rate, adenoma detection rate, and mean total adenomas detected. Patient tolerance level and subjective feelings were also evaluated. RESULTS The total BBPS score and the percentage of adequacy were significantly higher in the reinforced education groups compared with the control (WeChat vs. control, P

BACKGROUND Sorafenib is the first-line treatment for patients with advanced hepatocellular carcinoma (HCC). Y-box binding protein 1 (YB-1) is closely correlated with tumors and drug resistance. However, the relationship between YB-1 and sorafenib resistance and the underlying mechanism in HCC remain unknown. AIM To explore the role and related mechanisms of YB-1 in mediating sorafenib resistance in HCC. METHODS The protein expression levels of YB-1 were assessed in human HCC tissues and adjacent nontumor tissues. Next, we constructed YB-1 overexpression and knockdown hepatocarcinoma cell lines with lentiviruses and stimulated these cell lines with different concentrations of sorafenib. Then, we detected the proliferation and apoptosis in these cells by terminal deoxynucleotidyl transferase dUTP nick end labeling, flow cytometry and Western blotting assays. We also constructed a xenograft tumor model to explore the effect of YB-1 on the efficacy of sorafenib in vivo. Moreover, we studied and verified the specific molecular mechanism of YB-1 mediating sorafenib resistance in hepatoma cells by digital gene expression sequencing (DGE-seq). RESULTS YB-1 protein levels were found to be higher in HCC tissues than in corresponding nontumor tissues. YB-1 suppressed the effect of sorafenib on cell proliferation and apoptosis. Consistently, the efficacy of sorafenib in vivo was enhanced after YB-1 was knocked down. Furthermore, KEGG pathway enrichment analysis of DGE-seq demonstrated that the phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was essential for the sorafenib resistance induced by YB-1. Subsequently, YB-1 interacted with two key proteins of the PI3K/Akt signaling pathway (Akt1 and PIK3R1) as shown by searching the BioGRID and HitPredict websites. Finally, YB-1 suppressed the inactivation of the PI3K/Akt signaling pathway induced by sorafenib, and the blockade of the PI3K/Akt signaling pathway by LY294002 mitigated YB-1-induced sorafenib resistance. CONCLUSION Overall, we concluded that YB-1 augments sorafenib resistance through the PI3K/Akt signaling pathway in HCC and suggest that YB-1 is a key drug resistance-related gene, which is of great significance for the application of sorafenib in advanced-stage HCC.

BACKGROUND Artificial intelligence in colonoscopy is an emerging field, and its application may help colonoscopists improve inspection quality and reduce the rate of missed polyps and adenomas. Several deep learning-based computer-assisted detection (CADe) techniques were established from small single-center datasets, and unrepresentative learning materials might confine their application and generalization in wide practice. Although CADes have been reported to identify polyps in colonoscopic images and videos in real time, their diagnostic performance deserves to be further validated in clinical practice. AIM To train and test a CADe based on multicenter high-quality images of polyps and preliminarily validate it in clinical colonoscopies. METHODS With high-quality screening and labeling from 55 qualified colonoscopists, a dataset consisting of over 71000 images from 20 centers was used to train and test a deep learning-based CADe. In addition, the real-time diagnostic performance of CADe was tested frame by frame in 47 unaltered full-ranged videos that contained 86 histologically confirmed polyps. Finally, we conducted a self-controlled observational study to validate the diagnostic performance of CADe in real-world colonoscopy with the main outcome measure of polyps per colonoscopy in Changhai Hospital. RESULTS The CADe was able to identify polyps in the test dataset with 95.0% sensitivity and 99.1% specificity. For colonoscopy videos, all 86 polyps were detected with 92.2% sensitivity and 93.6% specificity in frame-by-frame analysis. In the prospective validation, the sensitivity of CAD in identifying polyps was 98.4% (185/188). Folds, reflections of light and fecal fluid were the main causes of false positives in both the test dataset and clinical colonoscopies. Colonoscopists can detect more polyps (0.90 vs 0.82, P < 0.001) and adenomas (0.32 vs 0.30, P = 0.045) with the aid of CADe, particularly polyps < 5 mm and flat polyps (0.65 vs 0.57, P < 0.001; 0.74 vs 0.67, P = 0.001, respectively). However, high efficacy is not realized in colonoscopies with inadequate bowel preparation and withdrawal time (P = 0.32; P = 0.16, respectively). CONCLUSION CADe is feasible in the clinical setting and might help endoscopists detect more polyps and adenomas, and further confirmation is warranted.

Although current quality indicators of colonoscopy recommend 6 minutes as the minimum standard for withdrawal time (WT), the impact of a WT longer than 6 minutes on neoplasia detection is unclear.A multicenter randomized controlled trial involving 1027 patients was conducted from January 2018 to July 2019. Participants were randomly divided into a 9-minute (n = 514) and 6-minute (n = 513) WT group, and a timer was used to adjust the withdrawal speed. The primary outcome was the adenoma detection rate (ADR).Intention-to-treat analysis showed a significantly higher ADR in the 9-minute versus 6-minute WT group (36.6% vs. 27.1%, P = .001). Prolonging WT from 6 to 9 minutes significantly increased ADR of the proximal colon (21.4% vs. 11.9%, P.001) as well as of the less experienced colonoscopists (36.8% vs. 23.5%, P = .001). Improvements were also observed in the polyp detection rate (58.0% vs. 47.8%, P.001), and mean number of polyps and adenomas detected per colonoscopy (1.1 vs. 0.9, P = .002; 0.5 vs. 0.4, P = .008, respectively). The higher ADRs in 9-minute WT were also confirmed by the per-protocol (PP) analysis and subgroup analyses, with an increased rate of sessile serrated lesion detection in the 9-minute WT by PP analysis (4.0% vs. 1.3%, P = .04). Multivariate logistic regression demonstrated that the 9-minute WT was independently associated with increased ADR (P = .005).Prolonging WT from 6 to 9 minutes significantly improved ADR, especially in the proximal colon and for less experienced colonoscopists. A 9-minute WT benchmark should be considered as one of the quality indicators of colonoscopy. ClinicalTrials.gov (identifier, NCT03399045).

Background and aim Endoscopic transmural drainage has been recognized as the first-line treatment for pancreatic fluid collection (PFC). Currently, three different types of stents have been extensively applied, including double pigtail plastic stent (PS), fully covered self-expanding metal stent (FCSEMS), and novel lumen-apposing metal stent (LAMS). Nonetheless, limited data are available about the comparison among them in terms of their clinical outcomes and safety for endoscopic ultrasound-guided drainage of PFC. Methods The current retrospective study was carried on 160 PFC patients undergoing endoscopic ultrasound-guided drainage from 2010 to 2018 at a single tertiary care center. Patients were divided into three groups based on different drainage ways: drainage using PS, FCSEMS, or LAMS. Results A total of 160 PFC patients (104 male and 56 female) were analyzed in this retrospective study, including 62 patients drained with PS, 28 with FCSEMS, and 70 with LAMS. Typically, the technical success (93.5% vs 96.4% vs 94.3%, P = 1.000) and treatment success rates (84.6% vs 85.2% vs 89.2%, P = 0.763) were similar between PS, FCSEMS, and LAMS. With regard to major adverse events, four patients (FCSEMS: n = 2 and LAMS: n = 2) with pseudoaneurysms developed severe bleeding; among them, 75% (3/4) of patients were observed within 2 weeks after intervention, and two patients in LAMS group died. Conclusions There are no significant differences in the clinical outcomes of PFC patients treated with PS, FCSEMS, or LAMS. Nonetheless, severe (or even fatal) bleeding may occur at the early stage after metal stent placement, which should be paid particular attention to.

Background Endoscopic retrograde cholangiopancreatography (ERCP) is one of the most frequently performed procedures for the treatment of biliary-pancreatic diseases. The most frequent complications of ERCP include pancreatitis, haemorrhage, perforation and cholangitis. While post-ERCP biliary bleeding leading to biliary obstruction is rare. Case presentation We herein report a case of exceptional post-ERCP cholangitis due to a blood clot in the common bile duct (CBD). This case involves a 75-year-old woman with a history of recurring upper abdominal pain. Abdominal computerized tomography (CT) revealed dilatation of the extrahepatic bile duct with stones at the lower CBD. After ERCP, clearance of stones was obtained. The post-ERCP course was symptomatic with upper abdominal pain and a significant increase in cholestatic parameters. A second CT scan demonstrated a markedly dilated biliary tree with a longitudinal high-density image at the middle CBD. The patient was successfully treated with a repeated ERCP, and a blood clot was extracted. We also present a review of the literature published between 1985 and 2016 in PubMed. Four similar cases were reported during this period from France, Turkey, the USA and the UK, separately. Our case is the first reported in China. Conclusions Post-ERCP biliary bleeding leading to biliary obstruction is rare. We describe a rare case of post-ERCP cholangitis due to a blood clot in the common bile duct (CBD), which is consistent with most clinical presentations of similar cases already described. An analysis of the possible pathophysiological mechanisms and a review of the current literature are provided. We attempt to attract clinicians’ attention to the differential diagnosis of post-ERCP obstruction. The complications might be severe or even fatal. The diagnosis of blood clot is based on clinical and laboratory data, particularly imaging. Repeated ERCP is often necessary and effective.

Objective Colonoscopy performed in the afternoon, rather than morning, has been reported to be associated with lower rates of adenoma and polyp detection (ADR and PDR) and cecal intubation (CIR). This meta-analysis evaluated the efficacy of afternoon colonoscopy relative to morning colonoscopy. Methods The databases MEDLINE, Web of Science, EMBASE, and the Cochrane Library were searched to identify potential relevant studies. The primary outcome was ADR and the secondary outcomes were CIR and PDR. The outcomes were estimated by relative risk (RR) and 95% confidence interval (CI) with a random effects model. Results Sixteen studies with 38,063 participants met the inclusion criteria. The pooled analyses indicated that ADR (RR: 1.08, 95% CI: 1.00–1.17) and CIR (RR: 1.01, 95% CI: 1.00–1.02) were stable during the whole day. In subgroup analyses, the effect of full-day block or inferior bowel preparation were more prominent, reflected by a significant reduction of ADR (RR: 1.18, 95% CI: 1.09–1.28; RR: 1.12, 95% CI: 1.01–1.24) and CIR (RR: 1.08, 95% CI: 1.02–1.13; RR: 1.02, 95% CI: 1.01–1.03) in the afternoon, respectively. Conclusions Colonoscopy quality, as indicated by the ADR and CIR, is not affected by the time of day for procedures performed in block shifts. However, endoscopists’ working full-day blocks and inferior bowel preparation are associated with a significant decrease in ADR and CIR in the afternoon.

Gastric cancer (GC) is one of the most common malignancies that threatens human health. As the molecular mechanisms unerlying GC are not completely understood, identification of genes related to GC could provide new insights into gene function as well as potential treatment targets. We discovered that UGT2B15 may contribute to the pathogenesis and progression of GC using GEO data and bioinformatic analysis. Using TCGA data, UGT2B15 mRNA was found to be significantly overexpressed in GC tissues; patients with higher UGT2B15 had a poorer prognosis. It was further discovered that UGT2B15 and FOXA1 were both upregulated, and UGT2B15 and Foxa1 were positively correlated in GC. It is known that Foxa1 is a vital threshold to activate the Hippo‑YAP signaling pathway. In addition, we suggest that a potential molecular mechanisms includes UGT2B15 which may upregulate Foxa1, activate the Hippo‑YAP signaling pathway and contribute to the development of GC. Taken together, our findings demonstrate that UGT2B15 may be an oncogene in GC and is a promising therapeutic target for cancer treatment.

Background and Aims Gum chewing can accelerate motility in the GI tract; clinical studies suggested gum chewing can reduce postoperative ileus. However, no trial has investigated the effect of gum chewing on bowel preparation for colonoscopy in addition to polyethylene glycol (PEG). The objective of this study was to investigate whether gum chewing before colonoscopy can increase the quality of bowel preparation. Methods This was a single-center, randomized controlled trial. Consecutive patients undergoing colonoscopy were randomized to the gum group or the control group. Patients in the gum group chewed sugar-free gum every 2 hours for 20 minutes each time from the end of drinking 2 L of PEG to the beginning of colonoscopy. Patients in the control group only received 2 L of PEG before colonoscopy. The quality of bowel preparation, procedure time, adenoma detection rate, patients' tolerance, and adverse events were compared. Results Three hundred patients were included in the study (150 in the control group, 150 in the gum group). More than 90% of patients in both groups were satisfied with the process of bowel preparation, and the incidence of adverse events was comparable in the 2 groups (41.3% vs 46.0%, P = .42). The mean Boston Bowel Preparation Scale score was 6.2 ± 1.4 and 6.1 ± 1.2 in the control group and the gum group, respectively, and the difference between the 2 groups was not significant ( P = .51). Conclusions This study indicates that gum chewing does not improve the quality of bowel preparation for colonoscopy, but it can improve patients' satisfaction with the process of bowel preparation and does not have negative effects on cleanliness. (Clinical trials registration number: NCT02507037.)

Turmeric (Curcuma longa L, Zingiberaceae) rhizomes exhibit versatile biological activities including the significant anti-cancer property. As an herbal medicine, the therapeutic effects of turmeric may be expressed by multi-components which have complicated integration effects on multi-targets. Therefore, having previously found three A549 cell-binding curcuminoids (curcumin, Cur; demethoxycurcumin, DMcur; bisdemethoxycurcumin, BMcur) from turmeric, studies were undertaken in this paper to determine the anti-cancer mechanism and integration effects of these curcuminoids by using chemical markers' knockout and UHPLC-LTQ Orbitrap MS-based metabolomics. Four curcuminoid-containing fractions including a mixture of 3 cell-binding curcuminoids (CE), and three individual curcuminoids with natural proportion in turmeric were prepared by chemical markers' knockout method. CE, Cur, DMcur and BMcur fractions showed significant anti-cancer activity on A549 cells. The activities of CE, Cur and BMcur fractions were comparative with the turmeric crude extract (TcE). In the metabolomics study, CE and three individual curcuminoid fractions changed the expression of 25 metabolites in A549 cells, which were involved in glycerophospholipid catabolism, sphingolipid metabolism and fatty acid metabolism, etc. Among them, glycerophospholipid catabolism was disordered greatly in CE group, while sphingolipid metabolism was suggested to be closely related to DMcur and BMcur activity. Furthermore, the metabolomics data showed that three curcuminoids existed synergistic and antagonistic actions and the use of multi-curcuminoids is more powerful than use of single curcuminoid on the metabolic alterations of A549 cells.

OBJECTIVE We conducted a randomized trial aiming at improving patients' informed consent for undergoing endoscopic retrograde cholangiopancreatography (ERCP) in clinical care by comparing the efficacy of an additional educational video to written informed consent with that of written informed consent alone. METHODS This was a single-center, randomized controlled trial. Consecutive patients undergoing ERCP were randomized to a video education or a control group. An educational video detailing ERCP procedure plus standard written informed consent was administered to the video education group, while the control group reviewed standard written informed consent only. The primary outcome was the patients' perception of the risk or possibility of ERCP complications. Their perception of the benefits of ERCP, alternative treatments and overall satisfaction with the process of informed consent were also compared. RESULTS In total 205 patients were included in the study (104 in the control group and 101 in the video education group). Patients' comprehension of ERCP-related complications in the video education group was significantly increased (P

We performed a systematic review and meta-analysis to comprehensively estimate adenoma miss rate (AMR) and advanced AMR (AAMR) and explore associated factors.We searched the PubMed, Web of Science, and Ovid EMBASE databases for studies published through April 2018 on tandem colonoscopies, with AMR and AAMR as the primary outcomes. We performed meta-regression analyses to identify risk factors and factors associated with outcome. Primary outcomes were AMR and AAMR and secondary outcomes were AMR and AAMR for different locations, sizes, pathologies, morphologies, and populations.In a meta-analysis of 43 publications and more than 15,000 tandem colonoscopies, we calculated miss rates of 26% for adenomas (95% confidence interval [CI] 23%-30%), 9% for advanced adenomas (95% CI 4%-16%), and 27% for serrated polyps (95% CI 16%-40%). Miss rates were high for proximal advanced adenomas (14%; 95% CI 5%-26%), serrated polyps (27%; 95% CI 16%-40%), flat adenomas (34%; 95% CI 24%-45%), and in patients at high risk for colorectal cancer (33%; 95% CI 26%-41%). Miss rates could be decreased by adequate bowel preparation and auxiliary techniques (P = .06; P = .04, and P = .01, respectively). The adenoma detection rate (ADR), adenomas per index colonoscopy, and adenomas per positive index colonoscopy (APPC) were independently associated with AMR (P = .02, P = .01, and P = .008, respectively), whereas APPC was the only factor independently associated with AAMR (P = .006). An APPC value greater than 1.8 was more effective in monitoring AMR (31% vs 15% for AMR P.0001) than an ADR value of at least 34% (27% vs 17% for AMR; P = .008). The AAMR of colonoscopies with an APPC value below 1.7 was 35%, vs 2% for colonoscopies with an APPC value of at least 1.7 (P = .0005).In a systematic review and meta-analysis, we found that adenomas and advanced adenomas are missed (based on AMR and AAMR) more frequently than previously believed. In addition to ADR, APPC deserves consideration as a complementary indicator of colonoscopy quality, if it is validated in additional studies.

Endoscopic biliary sphincterotomy (EST) is commonly performed during therapeutic endoscopic retrograde cholangiopancreatography (ERCP), but is an independent risk factor for post-ERCP pancreatitis, bleeding and duodenal perforation. These are partly ascribed to the electrosurgical current mode used for EST, and currently the optimal current model for EST remains controversial. In this study, we aimed to compare the rate of complications undergoing EST using the Endocut versus the blended current. A systematic search of databases was performed for relevant published and prospective studies including randomized clinical trials (RCTs) to compare Endocut with blended current modes for EST. Data were collected from inception until 1 July 2018, using post-ERCP pancreatitis, bleeding and perforation as primary outcomes. Three RCTs including a total of 594 patients met the inclusion criteria. Our meta-analysis results showed the rate of post-ERCP pancreatitis, primarily mild to moderate pancreatitis, was no different between Endocut versus blended current modes [risk ratio (RR) 0.61, 95% confidence interval (CI) 0.25–1.52, P = 0.29]. However, the risk of endoscopically bleeding events, primarily mild bleeding, was lower in studies using Endocut versus blended current (RR 0.54, 95% CI 0.31–0.95, P = 0.03). Notably, none of the patients experienced perforation in these three trials. The rate of post-ERCP pancreatitis was not significantly different when using the Endocut versus blended current during EST. Nevertheless, compared with the blended current, Endocut reduced the incidence of endoscopically evident bleeding; however, the available data were insufficient to assess the perforation risk.

Objective Over the past decades, carbohydrate antigen 72-4 (CA72-4) was thought to be a tumor marker that was elevated in healthy individuals and patients with malignancies, including gastrointestinal (GI), ovarian, endometrial and lung malignancies. Furthermore, studies found that elevated serum CA72-4 might predict digestive tumors, especially gastric tumors, although there was still neither a sensitive nor specific tumor biomarker for gastric cancer (GC). This study aimed to evaluate the diagnostic accuracy of CA72-4 in predicting malignancies, especially GC. Methods Altogether 403 patients underwent a CA72-4 test after admission to the Department of Gastroenterology in Changhai Hospital, the Second Military Medical University, from 1 June 2015 to 31 October 2015. Their age and sex, main symptoms, and final diagnoses were summarized. Results The positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio of CA72-4 for diagnosing GC were 31.58%, 79.17%, 1.70, and 0.97, respectively. In the receiver operating characteristic (ROC) curve analysis, the area under the ROC curve for discriminating between patients with GC and those without was 0.62. Conclusion Performing a CA72-4 test on its own is of little use for predicting malignances, especially GC, in patients with GI diseases.

Objective Cancer recurrence is a complicated problem for clinicians that contributes to poor prognosis. This study aimed to use advanced gastric carcinoma genes profiles to predict increased risk of cancer recurrence in order to identify patients in need of adjuvant therapy for prognosis improvement. Methods Differentially expressed genes were identified for advanced gastric carcinoma by analyzing the GSE2685 from the Gene Expression Omnibus database (GEO) using R package. The candidate genes were then obtained by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction analysis and survival analysis. Logistic regression analysis was performed to determine the relationship between candidate genes and the recurrence of gastric carcinoma. Results Collagen type IV alpha 1 (COL4A1) was overexpressed in gastric carcinoma tissue by analyzing the GSE2685 gene expression profiles from the Gene Expression Omnibus database. COL4A1 was also overexpressed in gastric carcinoma tissue from the Cancer Genome Atlas dataset and further determined that higher COL4A1 expression led to poorer overall survival. A univariate analysis suggested that COL4A1 was strongly correlated with T stage and gastric carcinoma recurrence (P = 0.014 and 0.041, respectively). Moreover, a multiple logistic regression analysis indicated that COL4A1 was significantly associated with gastric carcinoma recurrence (hazard ratio 1.605, 95% confidence interval 1.063-2.677, P = 0.008). Conclusions COL4A1 may promote gastric carcinoma recurrence and could be used as a therapeutic target for gastric carcinoma recurrence.

Pressure injuries increase the cost of medical care and prolong hospitalization. The incidence of pressure injury at the target coronary care unit (CCU) from January to August 2016 was 1.1%, which was significantly higher than the 0.4% defined in the 2015 Taiwan Clinical Performance Indicators (TCPI) system. Medical device related pressure injury (MDRPI) accounted for 73.1% of the pressure injuries (incidence: 0.8%). The main causes of the high incidence of MDRPI were: (1) inadequate decompression dressing and restraint equipment, (2) incomplete implementation of prevention interventions in the CCU, (3) inadequate knowledge of MDRPI prevention among nurses, (4) deficient standards for preventing MDRPI, (5) ineffective MDRPI-related education, and (6) insufficient auditing frequencies.To reduce the incidence of MDRPI in the target CCU to 0.4% or less.Promote a seed-teacher system and a care bundle that "increased skin tolerance, decompression, medical dressing, change, and removal" using education, the adoption of PE-foam binding gloves, and regular audits.The incidence of MDRPI was reduced from 0.8% to 0.3% between October 2016 and April 2017 and further reduced to 0.1% during the maintenance phase between May and July 2017.The results indicate that the improvement program effectively reduced the incidence of MDRPI and thus increased the quality of nursing care. Therefore, the use of a care bundles should be promoted in intensive care units.運用組合式照護降低心臟加護病房醫療裝置相關壓傷發生密度.壓傷發生會增加醫療成本、延長住院，2015年台灣臨床成效指標（Taiwan clinical performance indicators, TCPI）心臟內科加護病房（coronary care unit, CCU）壓傷總發生密度0.4%；而本院CCU 2016年1~8月壓傷總發生密度1.1%，遠高於TCPI，其中醫療裝置相關壓傷（medical device related pressure injury, MDRPI）佔73.1%，發生密度0.8%；導因為預防壓傷設備不完善且敷料不足、未落實執行壓傷預防措施、護理師MDRPI認知不足、預防MDRPI照護之標準化程序未詳盡、MDRPI相關教育學習成效低及未定期稽核壓傷預防措施。.降低本心臟內科加護病房MDRPI發生密度至≤ 0.4%。.透過教育、推動種子教師與「耐、壓、用、換、除」組合式照護、改用PE（polyethylene）泡棉約束手套並定期稽核。.改善後2016年10月～2017年4月MDRPI發生密度由0.8%降至0.3%，維持期2017年5～7月降為0.1%。.顯示專案有效降低MDRPI，建議平行推廣此組合式照護概念，藉此經驗提供臨床照護參考。.

Endoscopic retrograde cholangiopancreatography (ERCP) is associated with risk of complications. Methods to facilitate ductal cannulation may reduce complications. Intraduodenal acid infusion is a physiological approach to stimulate secretin release in human body and may facilitate cannulation. The objective of this study was to investigate the effect of intraduodenal acid infusion on pancreatic duct cannulation during ERCP.It was a single center, double-blind, randomized controlled trial. Consecutive patients undergoing first ERCP for pancreatic diseases were randomized toreceive 50 mL acetic acid intraduodenal infusion at ERCP (acetic acid group) or 50 mL saline (control group). The primary outcome, difficult cannulation rate (cannulation time5 min), in the two groups was compared.Two hundred ten patients were included in the final analysis (105 in each group). The difficult cannulation rate were 39.1% in the control group and 20.9% in the acetic acid group, and the difference was statistically significant (P = 0.004). The overall successful deep cannulation rate was 89.5% and 85.7%, respectively (P = 0.402). The cannulation time was remarkably shortened (182 vs 286 s, P = 0.018), and the cannulation attempts were significantly decreased (3.4 vs 4.4, P = 0.008). The fluoroscopy time was also significantly reduced (60 vs 86 s, P = 0.028). The incidence of post-ERCP pancreatitis and hyperamylasemia was comparable (7.6% vs 10.5% and 10.5% vs 19.1%, P 0.05).Intraduodenal acetic acid infusion can significantly decrease difficult pancreatic cannulation rate, facilitate pancreatic duct cannulation, and reduce radiation exposure (ClinicalTrials.gov number, NCT02800772).

Background: Electronic learning (e-learning) through mobile technology represents a novel way to teach emergent otorhinolaryngology-head and neck surgery (ORL-HNS) disorders to undergraduate medical students. Whether a cognitive style of education combined with learning modules can impact learning outcomes and satisfaction in millennial medical students is unknown. Objective: The aim of this study was to assess the impact of cognitive styles and learning modules using mobile e-learning on knowledge gain, competence gain, and satisfaction for emergent ORL-HNS disorders. Methods: This randomized controlled trial included 60 undergraduate medical students who were novices in ORL-HNS at an academic teaching hospital. The cognitive style of the participants was assessed using the group embedded figures test. The students were randomly assigned (1:1) to a novel interactive multimedia (IM) group and conventional Microsoft PowerPoint show (PPS) group matched by age, sex, and cognitive style. The content for the gamified IM module was derived from and corresponded to the textbook-based learning material of the PPS module (video lectures). The participants were unblinded and used fully automated courseware containing the IM or PPS module on a 7-inch tablet for 100 min. Knowledge and competence were assessed using multiple-choice questions and multimedia situation tests, respectively. Each participant also rated their global satisfaction. Results: All of the participants (median age 23 years, range 22-26 years; 36 males and 24 females) received the intended intervention after randomization. Overall, the participants had significant gains in knowledge (median 50%, interquartile range [IQR]=17%-80%, P

Intestinal mucosal barrier, mainly consisting of the mucus layer and epithelium, functions in absorbing nutrition as well as prevention of the invasion of pathogenic microorganisms. Paneth cell, an important component of mucosal barrier, plays a vital role in maintaining the intestinal homeostasis by producing antimicrobial materials and controlling the host-commensal balance. Current evidence shows that the dysfunction of intestinal mucosal barrier, especially Paneth cell, participates in the onset and progression of inflammatory bowel disease (IBD). Autophagy, a cellular stress response, involves various physiological processes, such as secretion of proteins, production of antimicrobial peptides, and degradation of aberrant organelles or proteins. In the recent years, the roles of autophagy in the pathogenesis of IBD have been increasingly studied. Here in this review, we mainly focus on describing the roles of Paneth cell autophagy in IBD as well as several popular autophagy-related genetic variants in Penath cell and the related therapeutic strategies against IBD.

Colonoscopy insertion is technically challenging, time-consuming, and painful, especially for the sigmoid. Several pilot studies indicated that the (left) tilt-down position could facilitate the insertion procedure, but no formal trials have been published to demonstrate its efficacy. We performed this study to verify the benefits of the left lateral tilt-down position (LTDP) on the insertion process.This 2-center prospective trial randomized unsedated patients to the LTDP or left lateral horizontal position (LHP) to aid insertion. The primary outcome measure was cecal intubation time (CIT). Secondary outcome measures included decending colon intubation time (DIT), pain score of insertion, acceptance of unsedated colonoscopy for future examinations, difficulty score for insertion, and the adverse event rate of colonoscopy.Two hundred fifty-eight patients were randomized to the LTDP (128) or LHP (130) in 2 centers. The median CIT and DIT were shorter with patients positioned in LTDP than in LHP (CIT, 280.0 vs 339.5 s, P .001; DIT, 53.0 vs 69.0 s, P .001, respectively) and patients with high and low body mass index (BMI) benefited more from LTDP than from LHP, as opposed to patients with normal BMI. In addition, colonoscopy insertion in LTDP was less painful (3.4 ± 1.6 vs 4.0 ± 1.7, P = .02) and less difficult (3.1 ± 1.9 vs 3.7 ± 1.4, P .001), showing a higher tendency to acceptance of unsedated colonoscopy (82.9% vs 73.8%, P = .08). The rates of adverse events were extremely low and did not differ significantly in the 2 groups.LTDP for colonoscopy insertion can reduce insertion time and pain, and potentially improves patients' acceptance of unsedated colonoscopy. (Clinical trial registration number: NCT02842489.).

Colonoscopy insertion is painful for some patients and is one of the main barriers to screening colonoscopy. Few studies have assessed the impact of the supine position (SP) on colonoscopy insertion, especially for unsedated patients. The aim of this randomized controlled trial was to clarify this issue.Unsedated patients were randomized to SP or left horizontal position (LHP) as the starting position of colonoscopy insertion. The primary outcome measure was cecal intubation time (CIT), and the secondary outcome measures were descending colon intubation time (DIT), pain score of patients, difficulty score according to the endoscopist, and patients' acceptance of unsedated colonoscopy.A total of 347 patients were randomized to the SP group (175) or the LHP group (172). The CIT in the SP group was significantly shorter than that in the LHP group (275.0 seconds [interquartile range (IQR), 234.0-328.5 seconds] versus 316.0 seconds [IQR, 261.0-370.0 seconds], P .001). The DIT was also shorter in the SP group (64.5 seconds [IQR, 52.0-86.3 seconds] versus 74.0 seconds [IQR, 62.0-92.0 seconds], P = .001). Compared with the LHP, the SP had a lower pain score (3.3 versus 3.9, P = .002), a lower difficulty score (3.1 versus 3.7, P .001), a lower frequency of position change (7.1% versus 38.0%, P .001), and less need for abdominal compression (39.1% versus 45.5%, P = .02). SP was the only modifiable and independent factor identified to reduce CIT and pain score and improve patients' acceptance of unsedated colonoscopy.As an economical and convenient method, SP can reduce CIT, ease pain, and improve patients' acceptance of unsedated colonoscopy. (Clinical trial registration number: NCT03289442.).

Lidamycin (LDM, also known as C-1027) as an anti-cancer agent inhibits growth in a variety of cancer cells by inducing apoptosis and cell cycle arrest. In this study we demonstrated that inhibition of mouse embryonic carcinoma (EC) cell growth using LDM at low concentrations can be attributed to a loss of the cell's self-renewal capability but not to apoptosis or cell death, which can be correlated to the down-regulation of embryonic stem (ES) cell-like genes Oct4, Sox2 and c-Myc. MTT assays showed that LDM inhibited the growth of mouse P19 EC cells in a time- and dose-dependent manner. The EC cells exposed to a low dose (0.01 nM) of LDM lost their capability to generate colonies, as evidenced by the colony forming assay. Flow cytometer analyses demonstrated that LDM induced G1 arrest in exposed EC cells without apoptosis. Real-time qPCR, Western blotting and immunocytochemistry revealed that Oct4, Sox2 and c-Myc were down-regulated in LDM-exposed EC cells, but not adriamycin (ADM)-exposed cells. Furthermore, a combination of the low dose of LDM and ADM significantly reduced the proliferation of the cancer cells than single-agent treatment. This suggested that synergy of ADM and LDM improved chemotherapy. Taking together, our results indicate that LDM can reduce the capability for self-renewal that mouse EC cells possess through the repression of ES cell-like genes, thereby inhibiting carcinoma cell growth. This data also suggests that LDM might have potential for application in CSC-based therapy and be a useful tool for studying ES cell pluripotency and differentiation.

To investigate the expression of vacuole membrane protein 1 (Vmp1) and its prognostic value in invasive ductal carcinoma (IDC) and concomitant ductal carcinoma in situ (DCIS) of the breast.The expression and location of Vmp1 in the breast tissues from 102 patients with IDC and 32 concomitant DCIS were detected by immunohistochemical SP method, and the relationship with clinicopathologic parameters was analyzed.Vmp1 expression was observed in the cytoplasm of the cancer cells in 57.8% (59/102) cases, and correlated with grade (χ(2) = 12.644, P = 0.002), pTNM stage (χ(2) = 11.987, P = 0.001), node status (χ(2) = 9.341, P = 0.002), tumor diameter (χ(2) = 7.630, P = 0.022) as well as Nottingham Prognostic Index (NPI;χ(2) = 15.561, P = 0.000). The expression of Vmp1 in concomitant DCIS was higher than that in IDC (81.3% vs 56.3%; χ(2) = 4.655, P = 0.031). In this cohort, the mean disease-free survival was 81.2 months; the 5-year overall survival rate was 90.2% (92/102) and the disease-free survival rate was 81.4% (83/102). Vmp1 expression had significant influence on disease-free survival time, with Vmp1-negative patients showing poor prognosis (χ(2) = 11.192, P = 0.001). COX's proportional hazards regression model revealed that Vmp1 was a protective factor, with relative risk1.The detection of Vmp1 in IDC may be helpful for prognosis prediction; the patients with Vmp1 expression may have a better prognosis.

Peroxisome proliferator-activated receptor α (PPARα) is a nuclear hormone receptor that regulates energy metabolism, but its precise mechanisms remain unknown. Here, we demonstrate that the PPARα agonist fenofibrate activated expression of the glucose transporter Glut4. Moreover, PPARα was associated with the Glut4 promoter through GATA sites upon fenofibrate stimulation in cardiomyocytes. This occupancy is achieved through an interaction between amino acids 1–136 of PPARα with amino acids 276–443 of the cardiac transcription factor GATA-6. In addition, the interaction of PPARα with GATA-6 activated Glut4 gene expression, improved glucose consumption, and enhanced activity of mitochondrial citrate synthase in C2C12 myoblasts; both mutants of PPARα (1–101 aa) and GATA-6 (227–331 aa) were unable to cooperate in Glut4 activation. Thus, GATA-6 is an important component of the transcription network required for energy metabolism mediated by PPARα, and these findings provide a molecular basis for understanding the role of GATA-6 proteins in muscle development and disease.

To investigate the expression of FOXA1 in breast invasive ductal carcinomas, observe its expression in all molecular subtypes of breast invasive ductal carcinomas and understand its diagnostic and prognostic significance.Tissue specimens were obtained from 213 cases of breast invasive ductal carcinoma (IDC) and their expressions of FOXA1 and Ki67 detected by immunohistochemistry. And the expressions of CK5/6 and CK14 were detected to distinguish between normal breast-like subtype and basal-like subtype.The expression of FOXA1 was observed in 150 cases (70.4%). It correlated positively with ER and PR. But there was a negative correlation with histological grade, Nottingham prognostic index, p53 and Ki67. The expression of FOXA1 had difference between luminal and non-luminal subtypes. In luminal subtype, the expression of FOXA1 was associated with histological grade, PR, NPI, Ki67 and A subtype. In terms of prognosis, the expression of FOXA1 predicted a long disease-free survival and overall survival.The expression of FOXA1 is associated with a good prognosis. FOXA1 is a promising candidate for clinical identification of luminal A subtype. Prognostic analysis of FOXA1 in low-risk breast cancers may prove to be useful in clinical treatment decision-making.

The aim of this study was to investigate drug resistance and the genetic relatedness of erythromycin-resistant Streptococcus spp. from different animals and humans in Taiwan. Cumulatively, 248 isolates were collected from 15 animal species and human patients and the susceptibilities of the isolates to six antimicrobial agents including azithromycin (AZI), clarithromycin (CLAR), erythromycin (ERY), spiramycin (SPIR), amoxicillin (AMO), and enrofloxacin (ENRO) were determined by the agar dilution method. The results indicated that resistance among the 248 strains was highest for SPIR, followed by ENRO, CLAR, ERY, AZI, and AMO. The most common resistotypes of the isolates from mammals and aquatic animals were AZI-CLAR-ERY-SPIR (27.5%) and SPIR (55.1%), respectively. The presence of ERY-resistant genes was confirmed by PCR. The erm gene was amplified from 28 isolates (20.6%) by PCR for further investigation. The predominant erm gene in the ERY-resistant isolates was the erm(B) gene. The phylogenetic analysis of the erm(B) gene results indicated that there was a close genetic relationship among all the strains but the genotypic clusters did not show clear segregation of the isolates according to the source or region.

To examine the expression of nestin and neurogenin 3 (Ngn3), the markers of pancreatic stem cells, in the human fetal pancreas.The human fetal pancreas tissue of 12 and 14 weeks were examined for the expression of nestin and Ngn3 using the techniques of immunofluorescence dye and RT-PCR.Both nestin and Ngn3 expressed widely in 12 and 14 weeks before in human fetal pancreatic tissue. In these positive cells there was no co-expressing insulin or glucagon. There were nestin and Ngn3 co-expressing cells in ducts but not in the islets. The results of RT-PCR also indicated the expression of nestin and Ngn3.There was no expression of the markers of mature endocrine cells in the nestin and Ngn3 positive cells, and they were the marks of no-differentiation cells in the human fetal pancreatic tissue.

Chitosan nanoparticles are good drug carriers because of their good biocompatibility and biodegradability, and can be readily modified. As a new drug delivery system, they have attracted increasing attention for their wide applications in, for example, loading protein drugs, gene drugs, and anticancer chemical drugs, and via various routes of administration including oral, nasal, intravenous, and ocular. This paper reviews published research on chitosan nanoparticles, including its preparation methods, characteristics, modification, in vivo metabolic processes, and applications.