Mechanism Underlying Metformin Action and Its Potential to Reduce Gastric Cancer Risk.

Diabetes mellitus is associated with a high risk of developing gastric cancer (GC). Metformin, which is conventionally used to treat type 2 diabetes, induces AMP-activated protein kinase signaling and suppresses gluconeogenesis. Recent studies have reported that metformin is associated with beneficial effects in cancer prevention and treatment owing to its anti-tumor effects. This makes metformin a potential medication for GC therapy. However, contradicting reports have emerged regarding the efficacy of metformin in reducing the risk of GC. This review summarizes the impact of metformin on mitigating GC risk by analyzing clinical databases. The mechanism underlying the anti-tumor effect of metformin on GC is also discussed.

Helicobacter pylori eradication with high-dose proton pump inhibitor-amoxicillin dual therapy: A systematic review and meta-analysis.

BACKGROUND: Resistance of Helicobacter pylori to many antibiotics, which lowers the efficacy of eradication therapy, is increasingly prevalent. High-dose proton pump inhibitor (PPI)-amoxicillin dual therapy (HDDT) has been used for H. pylori eradication for years, and resistance to amoxicillin is relatively rare. Although many studies have compared the eradication rate of HDDT with that of guideline therapies, the reported efficacy of HDDT varies greatly and is inconsistent. AIMS: This study investigated the eradication rate and adverse effects of HDDT compared with the guidelines at the time of the study. METHODS: Several open public databases, including Cochrane, EMBASE, PubMed, and MEDLINE, were searched. The results of the current literature on the eradication and adverse event rates of HDDT compared with the latest recommended first-line therapies were analysed. Notably, 14 out of the 16 included studies were conducted in Asian regions. RESULTS: The eradication rate of HDDT was lower but not significantly different from those of control therapies (odds ratio [OR] = 0.92, 95% confidence interval [CI] = 0.67-1.26) in the intent-to-treat (ITT) analysis. A similar trend was observed in the per-protocol (PP) analysis (OR = 0.88, 95% CI = 0.47-1.63). Notably, the adverse effect risk in HDDT was significantly lower than in other therapies (I2 = 67.75%, OR = 0.42, 95% CI = 0.33-0.54, P = 0.00004). When the eradication rate of the control group was lower than 81%, HDDT was significantly better than control therapies (OR = 2.44, 95% CI = 1.23-4.84). CONCLUSION: HDDT used four times a day for 14 days showed better efficacy and safety than the guideline treatments for H. pylori infection in areas with high antimicrobial resistance.

Meperidine as the single sedative agent during esophagogastroduodenoscopy, a double-blind, randomized, controlled study.

BACKGROUND AND AIM: In Taiwan, unsedated esophagogastroduodenoscopy (EGD) is widely used, but it is uncomfortable for some patients. While meperidine has been adopted in colonoscopy, its use in EGD has not received extensive attention. This was a prospective study to investigate the use of meperidine as a single sedative agent during EGD. METHODS: One hundred and forty patients were randomized to receive either 25-mg meperidine (n = 70) or placebo (n = 70) by intramuscular injection before EGD. The primary outcome was patient discomfort scores. The secondary outcomes included patient, endoscopist, and EGD-related variables. RESULTS: Patients in the meperidine group reported less discomfort during esophageal intubation (median score of 2.0 and interquartile range [IQR] of 0-4.0 vs median score of 4.8 and IQR of 1.7-7.0, respectively; P < 0.001) and during the procedure (median score of 1.0 [IQR 0-3.1] vs 3.5 [IQR 0-5.6], P = 0.001) than patients in the placebo group. The endoscopist found patients in the meperidine group had better tolerance during esophageal intubation (median score of 1.0 [IQR 0-2.0] vs 2.0 [IQR 1.0-3.0], P = 0.021) and during the procedure (median score of 0 [IQR 0-1.0] vs 1.0 [IQR 0-3.0], P < 0.001). After the procedure more patients in the meperidine group (71.4% vs 35.7%, P < 0.001) experienced self-limited dizziness that prolonged recovery by ∼3.7 min. CONCLUSIONS: After receiving meperidine injection, patients had better tolerance and less discomfort during diagnostic EGD (NCT01547520).

Ceramide and Toll-like receptor 4 are mobilized into membrane rafts in response to Helicobacter pylori infection in gastric epithelial cells.

Helicobacter pylori infection is thought to be involved in the development of several gastric diseases. Two H. pylori virulence factors (vacuolating cytotoxin A and cytotoxin-associated gene A) reportedly interact with lipid rafts in gastric epithelial cells. The role of Toll-like receptor (TLR)-mediated signaling in response to H. pylori infection has been investigated extensively in host cells. However, the receptor molecules in lipid rafts that are involved in H. pylori-induced innate sensing have not been well characterized. This study investigated whether lipid rafts play a role in H. pylori-induced ceramide secretion and TLR4 expression and thereby contribute to inflammation in gastric epithelial cells. We observed that both TLR4 and MD-2 mRNA and protein levels were significantly higher in H. pylori-infected AGS cells than in mock-infected cells. Moreover, significantly more TLR4 protein was detected in detergent-resistant membranes extracted from H. pylori-infected AGS cells than in those extracted from mock-infected cells. However, this effect was attenuated by the treatment of cells with cholesterol-usurping agents, suggesting that H. pylori-induced TLR4 signaling is dependent on cholesterol-rich microdomains. Similarly, the level of cellular ceramide was elevated and ceramide was translocated into lipid rafts after H. pylori infection, leading to interleukin-8 (IL-8) production. Using the sphingomyelinase inhibitor imipramine, we observed that H. pylori-induced TLR4 expression was ceramide dependent. These results indicate the mobilization of ceramide and TLR4 into lipid rafts by H. pylori infection in response to inflammation in gastric epithelial cells.

Oral versus intravenous proton pump inhibitors in preventing re-bleeding for patients with peptic ulcer bleeding after successful endoscopic therapy.

BACKGROUND: High dose intravenous proton pump inhibitor after endoscopic therapy for peptic ulcer bleeding has been recommended as adjuvant therapy. Whether oral proton pump inhibitor can replace intravenous proton pump inhibitor in this setting is unknown. This study aims to compare the clinical efficacy of oral and intravenous proton pump inhibitor after endoscopic therapy. METHODS: Patients with high-risk bleeding peptic ulcers after successful endoscopic therapy were randomly assigned as oral lansoprazole or intravenous esomeprazole group. Primary outcome of the study was re-bleeding rate within 14 days. Secondary outcome included hospital stay, volume of blood transfusion, surgical intervention and mortality within 1 month. RESULTS: From April 2010 to Feb 2011, 100 patients were enrolled in this study. The re-bleeding rates were 4% (2/50) in the intravenous group and 4% (2/50) in the oral group. There was no difference between the two groups with regards to the hospital stay, volume of blood transfusion, surgery or mortality rate. The mean duration of hospital stay was 1.8 days in the oral lansoprazole group and 3.9 days in the intravenous esomeprazole group (p > 0.01). CONCLUSION: Patients receiving oral proton pump inhibitor have a shorter hospital stay. There is no evidence of a difference in clinical outcomes between oral and intravenous PPI treatment. However, the study was not powered to prove equivalence or non-inferiority. Future studies are still needed. TRIAL REGISTRATION: NCT01123031.

Which should go first during same-day bidirectional endosocopy with propofol sedation?

BACKGROUND AND AIM: Same-day bidirectional endoscopy, including esophagogastroduodenoscopy (EGD) and colonoscopy, is frequently performed to screen for cancer and gastrointestinal bleeding. However, the optimal sequence for the procedures is unclear thus far. The aim of this study was to evaluate the optimal sequence for same-day bidirectional endoscopy. METHODS: Consecutive patients undergoing same-day bidirectional endoscopy under propofol sedation were randomized to either the colonoscopy-first group (colonoscopy followed by EGD, n = 87) or the EGD-first group (EGD followed by colonoscopy, n = 89). We evaluated the propofol dose, procedure duration, patient tolerance and recovery, adverse events, and endoscopic findings. The patient tolerance was assessed with a 0-10 visual analog scale. RESULTS: Total procedure times, patients' tolerance and recovery, adverse events, and endoscopic findings were similar between the two groups. The total propofol dose was significantly higher for the colonoscopy-first group than for the EGD-first group (mean 95% credibility limit: 135.7 [70-201.4] mg vs 124.7 [64.1-185.3] mg, respectively, P = 0.024). Patients in the colonoscopy-first group moved significantly more during colonoscopy than those in the EGD-first group: 1.1 (0-3.8) versus 0.6 (0-2.9) scores, respectively (P = 0.024). CONCLUSION: The optimal sequence for same-day bidirectional endoscopy is EGD followed by colonoscopy. In this order, the procedure is better tolerated, and patients require a lower overall dose of propofol.

Helicobacter pylori cholesterol-α-glucosyltransferase manipulates cholesterol for bacterial adherence to gastric epithelial cells.

Helicobacter pylori infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcers, and gastric cancer. Infection of cells with H. pylori is dependent on lipid rafts, which are cholesterol-rich microdomains located in the cell membrane. H. pylori cholesterol-α-glucosyltransferase (CGT) catalyzes the conversion of membrane cholesterol to cholesteryl glucosides, which can be incorporated into the bacterial cell wall, facilitating evasion from immune defense and colonization in the host. However, the detailed mechanisms underlying this process remain to be explored. In this study, we discovered for the first time that H. pylori CGT could promote adherence to gastric epithelial cells in a cholesterol-dependent manner. Externalization of cell membrane phosphatidylserine (PS) is crucial for enhancement of binding of H. pylori to cells by CGT and for cytotoxin-associated gene A (CagA)-induced pathogenesis. Furthermore, exogenous cholesterol interferes with the actions of H. pylori CGT to catalyze cellular cholesterol, which impedes bacterial binding to cells and attenuates subsequent inflammation, indicating that the initial attachment of H. pylori to cells is closely dependent on host cholesterol. These results provide evidence that CGT contributes to H. pylori infectivity and it may serve as a key target for the treatment of H. pylori-associated diseases.

Mosapride as an adjunct to lansoprazole for symptom relief of reflux oesophagitis.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Reflux oesophagitis is a common clinical disorder associated with significant morbidity. Proton pump inhibitors are the current pharmacotherapy of choice, but not all treated patients achieve symptom relief. Little is known about the efficacy of mosapride, a prokinetic agent which decreases episodes of gastro-oesophageal reflux, as an adjunct to proton pump inhibitors in improving the symptoms of reflux oesophagitis. WHAT THIS STUDY ADDS Mosapride was generally not more effective than placebo as an adjunct therapy to a standard dose of lansoprazole in decreasing the symptom burden of patients with reflux oesophagitis. However, in a subgroup with more severe symptoms, combination therapy with lansoprazole and mosapride was possibly superior to monotherapy with lansoprazole. AIMS To investigate if mosapride, a prokinetic agent, was an effective adjunct to acid suppression in improving the symptoms of reflux oesophagitis. METHODS Patients (n= 96) with reflux oesophagitis were randomly assigned to either mosapride (5 mg three times daily) or placebo for 4 weeks. Symptom severity was assessed by a validated questionnaire at enrolment, 4 and 8 weeks after medication. The primary outcome for the first 4 weeks was decrease in symptom scores. After a 3 day washout period, patients initially allocated to mosapride crossed over to placebo and vice versa for the next 4 weeks. The outcome of the second phase was maintenance of symptom control. All patients received lansoprazole (30 mg once daily) throughout study. RESULTS The decreased symptom score after 4 weeks of treatment with lansoprazole and mosapride (n= 50) was 13.42 +/- 1.16 (mean +/- SEM), similar to that of lansoprazole plus placebo (10.85 +/- 1.03, n= 46), with an insignificant difference of 2.57 (95% CI -0.53, 5.67, P= 0.103). However, a sub-group analysis for patients with pre-treatment scores of >18 points (n= 48) revealed that lansoprazole plus mosapride achieved a greater reduction of symptom score than lansoprazole plus placebo (18.22 +/- 1.91 vs. 12.88 +/- 1.65; mean difference of 5.34, 95% CI 0.28, 10.40, P= 0.039). In the second phase, there was no difference between lansoprazole with mosapride or placebo in maintaining symptom control (39/44 or 86.64% vs. 41/50 or 82%, P= 0.401). Subgroup analysis for those with substantial residual symptoms revealed similar results. CONCLUSION Compared with placebo, mosapride generally does not provide additional benefit to a standard dose of lansoprazole in patients with reflux oesophagitis, except possibly in the subgroup of severely symptomatic patients.

A randomized controlled trial comparing two different dosages of infusional pantoprazole in peptic ulcer bleeding.

AIM: The optimal dosage of proton pump inhibitor in bleeding peptic ulcers remains controversial. The aim was to compare the clinical effectiveness of two doses of infusional pantoprazole in peptic ulcer bleeding. METHODS: Peptic ulcer patients (n= 120) with bleeding stigmata were enrolled after successful endoscopic therapy. After an initial bolus injection of 80 mg pantoprazole, patients were randomized to receive continuously infused pantoprazole at either 192 mg day(-1) or 40 mg every 6 h (i.e. 160 mg day(-1)) for 3 days. Clinical outcomes between the two groups within 14 days were compared, with 14-day recurrent bleeding regarded as the primary end-point. RESULTS: Both groups (n= 60 each) were well matched in demographic and clinical factors upon entry. Bleeding totally recurred in 11 (9.2%) patients, with six (10%) in the 192 mg day(-1) group and five (8.3%) in the 160 mg day(-1) group (relative risk of bleeding recurrence between two treatments 1.2; 95% CI 0.39, 3.72). All secondary outcomes between the two groups were similar, including the amount of blood transfusion (mean 1179 ml vs. 1203 ml, P > 0.1), hospital stay (mean 9.5 days vs. 9.9 days, P > 0.1), need for surgery (n= 1 vs. n= 0, P > 0.1), and mortality (n= 1 vs. n= 0, P > 0.1). CONCLUSIONS: Following endoscopic haemostasis, infusional pantoprazole at either 192 mg day(-1) or 40 mg every 6 h appear similar.

Limited low-air insufflation is optimal for colonoscopy.

BACKGROUND: Air insufflation is essential in routine colonoscopy, but obtaining optimal insufflation levels has not been discussed in the literature. The aim of this study was to determine optimal air insufflation during colonoscopic examination. METHODS: Consecutive patients who underwent colonoscopy were randomized to receive high-air insufflation (group A, n = 83), low-air insufflation (group B, n = 84), or low-air insufflation limited to the rectum and sigmoid colon (group C, n = 83). Completion rate, cecal intubation time, propofol dose, need for abdominal compression, and turning of patients, were evaluated. The post-procedure abdominal bloating was assessed with a 0-10 visual analog scale. RESULTS: The completion rates were similar among the three groups. The cecal intubation time was significantly shorter in group C than in group B (4.1 +/- 1.7 min vs. 5.2 +/- 3.0 min, mean +/- SD, p = 0.005). The dose of propofol was significantly less in group C than in group A (11.7 +/- 3.2 mg vs. 12.7 +/- 3.6 mg, mean +/- SD, p = 0.045). Group C needed the least manual abdominal compression (group A, B, and C: 81.9, 69, and 59%, respectively, p = 0.005) and had the least post-procedure abdominal bloating (group A, B, and C: 2.2 +/- 2.4, 2.2 +/- 2.1, and 1.5 +/- 1.9, respectively, p = 0.04). CONCLUSIONS: We found that limited use of low-air insufflation in the rectum and sigmoid is the procedure of choice for colonoscopic examination.

Campylobacter jejuni Cytolethal Distending Toxin C Exploits Lipid Rafts to Mitigate Helicobacter pylori-Induced Pathogenesis.

Helicobacter pylori infection is associated with several gastrointestinal diseases, including gastritis, peptic ulcer, and gastrointestinal adenocarcinoma. Two major cytotoxins, vacuolating cytotoxin A (VacA) and cytotoxin-associated gene A (CagA), interact closely with lipid rafts, contributing to H. pylori-associated disease progression. The Campylobacter jejuni cytolethal distending toxin consists of three subunits: CdtA, CdtB, and CdtC. Among them, CdtA and CdtC bind to membrane lipid rafts, which is crucial for CdtB entry into cells. In this study, we employed recombinant CdtC (rCdtC) to antagonize the functions of H. pylori cytotoxin in cells. Our results showed that rCdtC alleviates cell vacuolation induced by H. pylori VacA. Furthermore, rCdtC reduces H. pylori CagA translocation, which decreases nuclear factor kappa-B activation and interleukin-8 production, resulting in the mitigation of gastric epithelial cell inflammation. These results reveal that CdtC hijacks cholesterol to compete for H. pylori cytotoxin actions via lipid rafts, ameliorating H. pylori-induced pathogenesis.

Fine Particulate Matter Exposure Alters Pulmonary Microbiota Composition and Aggravates Pneumococcus-Induced Lung Pathogenesis.

Exposure to fine particulate matter (PM) with aerodynamic diameter ≤2.5 µm (PM2. 5) is closely correlated with respiratory diseases. Microbiota plays a key role in maintaining body homeostasis including regulation of host immune status and metabolism. As reported recently, PM2. 5 exposure causes microbiota dysbiosis and thus promotes disease progression. However, whether PM2. 5 alters pulmonary microbiota distribution and aggravates bacteria-induced pathogenesis remains unknown. In this study, we used mouse experimental models of PM2. 5 exposure combined with Streptococcus pneumonia infection. We characterized the airway microbiota of bronchoalveolar lavage fluid (BALF) by sequencing the 16S rRNA V3-V4 amplicon on the Illumina MiSeq platform, followed by a combination of bioinformatics and statistical analyses. Shannon-diversity index, observed ASVs, and Fisher's diversity index indicated that microbiota richness was significantly decreased in the mice treated with either PM2. 5 or pneumococcus when compared with the control group. The genera Streptococcus, Prevotella, Leptotrichia, and Granulicatella were remarkably increased in mice exposed to PM2. 5 combined with pneumococcal infection as compared to mice with pneumococcal infection alone. Histopathological examination exhibited that a more pronounced inflammation was present in lungs of mice treated with PM2. 5 and pneumococcus than that in mouse groups exposed to either PM2. 5 or pneumococcal infection alone. Our results demonstrate that PM2. 5 alters the microbiota composition, thereby enhancing susceptibility to pneumococcal infection and exacerbating lung pathogenesis.

Psychopathology and personality trait in subgroups of functional dyspepsia based on Rome III criteria.

OBJECTIVES: Functional dyspepsia is a heterogeneous symptom complex that may be subdivided into postprandial distress syndrome and epigastric pain syndrome. We aimed to investigate differences among these subgroups in psychopathological factors and personality traits. METHODS: We enrolled 187 consecutive outpatients (72.2% female patients, mean age 42.6 years) with functional dyspepsia based on the Rome III criteria. Patients were interviewed and evaluated by the Brief Symptom Rating Scale and the short-form Maudsley personality inventory for severity of psychopathology and personality traits. Multiple linear regression models were built for each psychopathological dimension and personality trait to assess the independent association with each subclass diagnosis of functional dyspepsia. RESULTS: There was an overlap (n=64, 34.2%) between the patients diagnosed with epigastric pain syndrome (n=157, 84.0%) and those with postprandial distress syndrome (n=94, 50.3%). Patients with symptoms compatible with both syndromes were psychopathologically more severe than either subgroup without overlapping. Multiple linear regression analysis demonstrated that the diagnosis of postprandial distress syndrome was independently associated with higher scores in overall psychopathological stress, and specifically in somatization (P=0.034), depression (P=0.028), phobia (P=0.044), and additional symptoms (P<0.001). However, epigastric pain syndrome was not associated with psychopathology. Postprandial distress was univariately associated with neuroticism, but the association was insignificant in the multivariate analysis (P=0.136). CONCLUSIONS: The Rome III subgroups of functional dyspepsia significantly overlap. Patients fulfilling criteria for both subgroups had symptoms that were psychopathologically more severe than those of patients without overlapping. Diagnosis of postprandial distress syndrome, but not epigastric pain syndrome, is independently associated with psychopathological factors.

Oral or intravenous proton pump inhibitor in patients with peptic ulcer bleeding after successful endoscopic epinephrine injection.

AIMS: We aimed to assess the clinical effectiveness of oral vs. intravenous (i.v.) regular-dose proton pump inhibitor (PPI) after endoscopic injection of epinephrine in patients with peptic ulcer bleeding. METHODS: Peptic ulcer patients with active bleeding, nonbleeding visible vessels, or adherent clots were enrolled after successful endoscopic haemostasis achieved by epinephrine injection. They were randomized to receive either oral rabeprazole (RAB group, 20 mg twice daily for 3 days) or i.v. omeprazole (OME group, 40 mg i.v. infusion every 12 h for 3 days). Subsequently, the enrolled patients receive oral PPI for 2 months (rabeprazole 20 mg or esomeprazole 40 mg once daily). The primary end-point was recurrent bleeding up to 14 days. The hospital stay, blood transfusion, surgery and mortality within 14 days were compared as well. RESULTS: A total of 156 patients were enrolled, with 78 patients randomly allocated in each group. The two groups were well matched for factors affecting the clinical outcomes. Primary end-points (recurrent bleeding up to 14 days) were reached in 12 patients (15.4%) in the OME group and 13 patients (16.7%) in the RAB group [95% confidence interval (CI) of difference -12.82, 10.22]. All the rebleeding events occurred within 3 days of enrolment. The two groups were not different in hospital stay, volume of blood transfusion, surgery or mortality rate (1.3% of the OME group and 2.6% of the RAB group died, 95% CI of difference -5.6, 3.0). CONCLUSIONS: Oral rabeprazole and i.v. regular-dose omeprazole are equally effective in preventing rebleeding in patients with high-risk bleeding peptic ulcers after successful endoscopic injection with epinephrine.

Propofol alone versus propofol in combination with meperidine for sedation during colonoscopy.

BACKGROUND: Despite the increasing popularity of propofol for sedation in colonoscopy, the optimal regimen is still controversial. Both propofol alone and propofol in combination with meperidine are frequently used during colonoscopy, but the impact of adding meperidine has not been evaluated. This study aimed to investigate if adding meperidine to propofol offers any advantage in terms of patient tolerance, recovery time, and postcolonoscopy discomforts. METHOD: Consecutive patients admitted to the physical checkup department of our hospital were randomized to receive either meperidine plus propofol (combination group, n=100) or propofol alone (propofol group, n=100) for sedated colonoscopy. The patients' tolerance and postcolonoscopy discomforts (pain, bloating, dizziness, and nausea/vomiting) were assessed with a 0-10 visual analog scale. The recovery times were assessed with 5-minute and 10-minute Aldrete scores. RESULTS: The dose of propofol was less in the combination group than the propofol group (129.80+/-37.93 mg vs. 147.90+/-47.85, mean+/-SD, P=0.003). The endoscopists, anesthetists, and nurses all rated patients' tolerance in favor of the combination group than the propofol group (mean+/-SD, endoscopists, 9.17+/-1.23 vs. 8.49+/-1.60, P=0.001; anesthetists, 9.21+/-1.08 vs. 8.63+/-1.37, P=0.001; nurses, 9.18+/-1.34 vs. 8.71+/-1.47, P=0.019, respectively). Patients in the combination group recovered earlier than the placebo group (5-min Aldrete scores: 9.48+/-1.09 vs. 9.05+/-1.32, mean+/-SD, P=0.013; short intervals to speak: 4.29+/-4.05 min vs. 6.30+/-5.22 min, P=0.003; and departure: 18.62+/-5.28 min vs. 20.28+/-5.68 min, P=0.034). There was also less abdominal bloating in the combination group after colonoscopy (1.23+/-1.79 vs. 2.19+/-2.12, mean+/-SD, P=0.004). Incidences of hypoxemia, hypotension, and overall satisfaction scores were comparable between the 2 groups. CONCLUSIONS: For sedated colonoscopy, propofol in combination with meperidine is better than propofol alone in improving patients' tolerance and recovery.

Retrospective analysis of endoscopic management of foreign bodies in the upper gastrointestinal tract of adults.

BACKGROUND: Foreign body impaction in the upper gastrointestinal (UGI) tract is considered an emergency worldwide. This article reports our experience in the endoscopic management of foreign bodies in the UGI tract of adults. METHODS: A retrospective chart review was conducted on adult patients (aged >18 years) who received endoscopic management of foreign bodies in the UGI tract at Shuang Ho Hospital between November 2008 and November 2016. RESULTS: A total of 280 patients (male/female: 107/178; mean age: 56 years) were included. Fish bones were the most common ingested foreign bodies (n = 162; 56.8%), and the esophagus was the most common lodgment site (n = 222; 77.9%). The presence of symptoms indicated that the ingested foreign bodies were lodged in the hypopharynx or esophagus rather than in the stomach or duodenum (p < 0.01). The detection rate of ingested foreign bodies in the UGI tract through plain radiography was 53% (122/230). The average "door-to-scope" was 5.9 hours, and 99.2% of the patients received endoscopic management of the ingested foreign bodies within 24 hours. The complication rate was relatively low (n = 14; 4.9%). No patient received surgical intervention or died of endoscopic management. CONCLUSION: Endoscopic management is a safe and highly effective procedure for extracting ingested foreign bodies. Rapid endoscopic intervention should be provided to reduce the risk of complications.

Clinical Evaluation of CA72-4 for Screening Gastric Cancer in A Healthy Population: A Multicenter Retrospective Study.

Early detection is important for improving the survival rate of patients with gastric cancer (GC). Serum tumor markers have been widely used for detecting GC. However, their clinical values remain controversial. This study aims to investigate the role of serum cancer antigen 72-4 (CA72-4) in the diagnosis of GC in a healthy population. A total of 7757 adults who underwent upper gastrointestinal endoscopy and serum CA72-4 level measurement in multicenters in Taiwan from January 2006 to August 2016 were recruited in this retrospective study. Risk factors for GC, serum tumor markers, and esophagogastroduodenoscopy (EGD) findings were evaluated. High serum levels of CA72-4 were found in 7.2% of healthy adults. CA72-4 level showed lower sensitivity (33.3%) but higher specificity (92.8%); however, the positive predictive value was quite low (0.18%). After adjustment of clinical risk factors for GC using EGD findings, gastric ulcer (adjusted odds ratio (aOR) = 2.11), gastric polyps (aOR = 1.42), and atrophic gastritis (aOR = 1.27) were significantly associated with high serum CA72-4 levels. Furthermore, both age (OR = 1.01) and Helicobacter pylori infection (OR = 1.44) exhibited a significant association with high serum CA72-4 levels. These results indicate that routine screening of CA72-4 levels for diagnosing GC in asymptomatic patients may be ineffective due to low sensitivity and low positive predictive value. The clinical utility of EGD findings along with serum CA72-4 level for screening healthy individuals with GC is warranted.

Coalescence of RAGE in Lipid Rafts in Response to Cytolethal Distending Toxin-Induced Inflammation.

The receptor for advanced glycation end products (RAGE) interacts with various molecules in the cell membrane to induce an inflammatory response. The cytolethal distending toxin (CDT) produced by Campylobacter jejuni contains three subunits: CdtA, CdtB, and CdtC. Amongst, CdtA and CdtC interact with membrane lipid rafts, by which CdtB enters the nucleus to induce pathogenesis. In this study, we first explored the relationships between RAGE, lipid rafts, and inflammation in gastrointestinal epithelial cells exposed to CDT. Our results showed that CDT activated the expression of RAGE and high mobility group box 1 (HMGB1), followed by the recruitment of RAGE into lipid rafts. In contrast, RAGE antagonist inhibited CDT-induced inflammation via the RAGE-HMGB1 axis. Disruption of lipid rafts decreased CDT-induced downstream signaling, which in turn attenuated the inflammatory response. Furthermore, in vivo studies revealed severe inflammation and upregulation of RAGE and IL-1ß in the intestinal tissues of CDT-treated mice. These results demonstrate that mobilization of RAGE to lipid rafts plays a crucial role in CDT-induced inflammation.

Antibacterial activity of ovatodiolide isolated from Anisomeles indica against Helicobacter pylori.

Helicobacter pylori infection is associated with high incidence of gastric diseases. The extensive therapy of H. pylori infection with antibiotics has increased its resistance rates worldwide. Ovatodiolide, a pure constituent isolated from Anisomeles indica, has been demonstrated to possess bactericidal activity against H. pylori. In this study, ovatodiolide inhibited the growth of both H. pylori reference strain and clinical multidrug-resistant isolates. Docking analysis revealed that ovatodiolide fits into the hydrophobic pocket of a ribosomal protein, RpsB. Furthermore, ovatodiolide inhibited bacterial growth by reducing levels of RpsB, which plays a crucial role in protein translation. Our results demonstrate that ovatodiolide binds to a ribosomal protein and interferes with protein synthesis. This study provides evidence that ovatodiolide has the potential to be developed into a potent therapeutic agent for treating H. pylori infection.