Osteoporosis is a bone disorder characterized by low bone mass density and impaired microarchitecture that is accompanied by multiple metabolic disorders, especially metabolic dysfunction-associated steatotic liver disease (MASLD). Inulin has been proposed as a treatment for MASLD, but its role in MASLD-related bone loss has not been determined. This study aimed to investigate the effect of inulin on MASLD-induced bone loss and the underlying mechanisms. To establish a MASLD model, C57BL/6 mice were fed a high-fat high-fructose high-glucose diet for 16 weeks. Inulin treatment was administered by incorporating 5

Helicobacter pylori (H. pylori) infection is a major risk factor for gastric carcinogenesis, requiring holistic endoscopic assessment of distributed mucosal abnormalities. While patient-level diagnostic labels are accessible, obtaining large-scale fine-grained annotations is constrained due to high inter-observer variability and the labor-intensive nature of the process. This naturally formulates the task as a multiple instance learning (MIL) problem. Existing image-level approaches often rely on noisy supervisory signals without modeling sequence context, while standard embedding-based MIL methods suffer from suboptimal feature representations and insufficient integration of H. pylori-specific phenotypes. To address these challenges, we propose PhenoMIL, a two-stage framework emulating clinical hierarchical reasoning. First, the Fine-grained Phenotype-level Semi-Supervised Learning (FPS-SL) stage uses multi-label supervised contrastive learning and prototype-based pseudo-label generation to acquire phenotype-specific knowledge and learn transferable representation from limited instance-level annotations. Subsequently, the Clinically Informed MIL (CIMIL) stage performs holistic bag-level diagnosis using Consensus-aware Feature Modulation (CFM) to exploit latent neighborhood structures, and Phenotype-guided Attention Aggregation (PAA) to align instance weighting with diagnostic priors. Extensive evaluation on a large-scale multi-center dataset (303,910 images from 6388 patients) demonstrates PhenoMIL’s superiority in both multi-label phenotype classification and H. pylori infection diagnosis. Notably, in a real-world reader study, PhenoMIL achieved 81.63% sensitivity and 87.84% specificity, outperforming both junior and senior endoscopists.

ABSTRACT Background Stomach cancer has become one of the most common types of cancer, with its mortality rate ranking third in the world. Currently, the main treatments for gastric cancer are surgery, radiation therapy, and chemotherapy. Although current treatments can effectively prevent postoperative metastasis and recurrence of gastric cancer, they may also bring various adverse reactions in the gastrointestinal tract and side effects such as bone marrow suppression. Years of research have confirmed that traditional Chinese medicine treatment for gastric and other cancers has distinct characteristics and advantages. Combined treatment can increase the tumor inhibition rate, reduce the side effects of radiation and chemotherapy, improve patients' quality of life, and prolong the survival prognosis. Aims This study explores the anti‐tumor effect and specific molecular mechanism of Hairyvein Agrimonia Herb on gastric cancer. Methods and Results The combination of network pharmacology technology and various experimental techniques, including in vitro cell verification, was carried out throughout the whole study. The results show that five active components in the Hairyvein Agrimonia Herb can act on 160 carcinogenic targets in gastric cancer. String correlation analysis, Cytoscape network topology analysis, core target screening, protein molecule docking, immunohistochemical expression levels, and survival immune correlation analysis revealed that the carcinogenic genes JUN, HIF1A, and PTGS2 may be the primary drug targets for Hairyvein Agrimonia Herb in treating gastric cancer. The active component quercetin shows the best inhibitory effect on the docking of the PTGS2 protein. Furthermore, the prognostic models constructed by the carcinogenic genes JUN, HIF1A, and PTGS2 are significantly correlated with the survival time of gastric cancer patients. Conclusion This study provides a new ethical basis and research direction for understanding the mechanism of action of Hairyvein Agrimonia Herb in treating gastric cancer.

BACKGROUND:Etrasimod is an oral, once-daily sphingosine 1-phosphate (S1P) receptor modulator for the treatment of active ulcerative colitis. In the randomised, placebo-controlled, double-blind phase 3 ENLIGHT UC study, also known as the ES101002 study, we aimed to evaluate the efficacy and safety of etrasimod in patients with moderately to severely active ulcerative colitis in East Asia. METHODS:Using a central interactive web response system, in the 12-week induction period, adults (aged 18-75 years, inclusive) with moderately to severely active ulcerative colitis (modified Mayo score [MMS] 4-9 with an endoscopic subscore ≥2 and a rectal bleeding subscore ≥1) and an inadequate response, loss of response, or intolerance to at least one ulcerative colitis treatment were randomly assigned (2:1) to once-daily oral etrasimod 2 mg or placebo. Patients and study staff were masked to treatment assignment. Patients were enrolled from 52 hospitals across China, Taiwan, and Souh Korea. Randomisation was stratified by previous treatment status and baseline disease activity. Patients who had an MMS clinical response at induction period week 12 were re-randomly assigned (1:1) to once-daily oral etrasimod 2 mg or placebo for the 40-week maintenance period. Randomisation was stratified by induction period treatment, previous exposure to biologicals or JAK inhibitors, and concomitant use of oral corticosteroids at induction period baseline. The primary efficacy outcome was MMS clinical remission (stool frequency subscore=0 [or stool frequency subscore=1 with a ≥1 point decrease from induction period baseline], rectal bleeding subscore=0, and endoscopic subscore ≤1 [excluding friability]), assessed in the induction and maintenance periods separately (at induction period week 12 and maintenance period week 40). The primary efficacy analyses used the full analysis set (FAS), which included all patients who were randomly assigned and received at least one dose of study treatment for the induction period, and all re-randomly assigned patients who showed clinical response at induction period week 12 and received at least one dose of study treatment for the maintenance period. The safety analyses for each treatment period used the safety analysis set (SAF), which included all patients who received any amount of study drug in the corresponding treatment period. ENLIGHT UC is registered with ClinicalTrials.gov (NCT04176588) and the study is complete. FINDINGS:606 patients were screened between Sept 25, 2019, and April 27, 2023, and 340 were randomly assigned for the induction period and treated (FAS: 228 patients [88 female and 140 male] assigned to etrasimod and 112 patients [44 female and 68 male] assigned to placebo). 157 patients who showed clinical response in the induction period were re-randomly assigned and treated in the maintenance period (FAS: 77 patients [35 female and 42 male] assigned to etrasimod and 80 patients [32 female and 48 male] assigned to placebo). A significantly greater proportion of patients treated with etrasimod than those treated with placebo, showed clinical remission at induction week 12 (57 [25·0%] of 228 patients vs six [5·4%] of 112 patients; adjusted difference 20·4%; 95% CI 13·4%-27·4%; p<0·0001) and maintenance period week 40 (37 [48·1%] of 77 patients vs 10 [12·5%] of 80 patients; adjusted difference 35·9%; 95% CI 22·5%-49·2%; p<0·0001). In the induction period, the most frequently reported treatment-emergent adverse event (TEAE) was increased ALT (22 [10%] in the etrasimod group vs one [1%] in the placebo group). In the maintenance period, the most frequently reported TEAE was upper respiratory tract infection (14 [18%] in the etrasimod group vs 14 [17%] in the placebo group). Across the induction and maintenance periods, most TEAEs were mild to moderate in severity. Five (2%) of 228 patients treated with etrasimod and four (4%) of 112 patients treated with placebo discontinued study treatment due to TEAEs during the induction period, and one (1%) of 77 patients treated with etrasimod and one (1%) of 81 patients treated with placebo discontinued study treatment due to TEAEs during the maintenance period. No grade 4 or higher TEAE, malignancies, or deaths were reported. INTERPRETATION:Etrasimod was effective and well tolerated as an oral induction and maintenance treatment in patients with moderately to severely active ulcerative colitis in East Asia. FUNDING:Everest Medicines. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section.

Deep learning algorithm-based artificial intelligence (AI) has significantly advanced the domain of endoscopic diagnosis; however, its utilization for detecting Helicobacter pylori (H. pylori) infections remains constrained. We aimed to develop and validate the AI diagnostic system (HOPE AI) for diagnosing H. pylori infection by analyzing extensive imaging data obtained from clinical endoscopies. This multicenter diagnostic study was carried out across seven hospitals in China. Eligible patients were individuals aged 18 years or older who underwent upper gastrointestinal gastroendoscopy. The endoscopic images were randomly allocated (7:3) to the training and internal validation datasets for the development of HOPE AI, utilizing a multi-instance learning (MIL) framework and long short-term memory (LSTM) architectures, and the prospective external validation dataset for assessing its diagnostic efficacy. The performance of HOPE AI was also benchmarked against endoscopists. The diagnostic accuracy, sensitivity, specificity, and area under the curve of HOPE AI were assessed to detect H. pylori infection. A total of 308,887 endoscopic images and 197 videos from 6207 patients were utilized to develop and evaluate HOPE AI. Our AI system demonstrated outstanding performance, achieving an AUC of 0.932 (95

ObjectiveCircular RNAs belong to a category of noncoding RNAs that feature a unique continuous, covalently bonded ring configuration. Recent research indicates that circular RNAs are essential for the development of metabolic dysfunction-associated steatotic liver disease. This study sought to examine the functional role and molecular mechanism of circDock6 in metabolic dysfunction-associated steatotic liver disease.MethodsQuantitative reverse transcription polymerase chain reaction was performed to determine circDock6 expression patterns in liver tissues from high-fat diet- and standard diet-fed mice in vivo. Triglyceride detection, western blot analysis, and oil red O staining were performed to evaluate the regulatory effect of circDock6 on metabolic dysfunction-associated steatotic liver disease in vitro.ResultsCircDock6 was found to be markedly overexpressed in high-fat diet liver tissues compared with that in standard diet tissues. Moreover, knockdown of circDock6 expression lowered triglyceride content and lipid droplet formation. Mechanistically, circDock6 acted as a molecular sponge for mmu-let-7g-5p, which regulated insulin-like growth factor 1 receptor expression and contributed to the progression of metabolic dysfunction-associated steatotic liver disease. CircDock6 knockdown suppressed metabolic dysfunction-associated steatotic liver disease progression by modulating insulin-like growth factor 1 receptor via mmu-let-7g-5p targeting.ConclusionOur study identified circDock6 as a novel regulator of metabolic dysfunction-associated steatotic liver disease pathogenesis through the mmu-let-7g-5p/insulin-like growth factor 1 receptor axis, indicating its potential as a therapeutic target for metabolic dysfunction-associated steatotic liver disease intervention.

Abstract Background With advances in endoscopic submucosal dissection (ESD) technique, an increasing number of the Chinese population are being diagnosed with early gastric cancers (EGCs) at gastric angulus. However, the relationship between gastric angulus and EGCs remains obscure. Objectives We aimed to unveil the unreported location characteristics of gastric angulus in Chinese EGC patients and the correlation between the degree of submucosal fibrosis and ESD outcomes. Methods We retrospectively reviewed the medical records of EGC patients treated with ESD from January 2010 to March 2023. We retrospectively investigated and analyzed 740 EGC patients using multiple analyses. Results Following gastric antrum (53.1%), the gastric angulus (21.8%) emerged as the second-most prevalent site for EGCs. It had highest incidence of severe submucosal fibrosis and ulceration than the other parts. Multivariate analysis showed independent associations of submucosal fibrosis at the angulus with ulceration (OR: 3.714, 95% CI: 1.041–13.249), procedure duration (OR: 1.037, 95% CI: 1.014–1.061), and perforation complication (OR: 14.611, 95% CI: 1.626-131.277) (all P < 0.05). Conclusions The gastric angulus demonstrates the highest incidence of severe submucosal fibrosis and ulceration for EGCs identified by ESD. This condition is linked to unfavorable outcomes, typically increased perforation risks and prolonged operation duration. Therefore, meticulous dissection is crucial for patients with EGCs in the gastric angulus.

Ulcerative colitis (UC) is an inflammatory bowel disease with an unclear etiology that can lead to irreversible changes in distal colonic function in chronic patients. This study investigated anorectal function in recurrent UC patients and identified influencing factors. This prospective study enrolled 33 recurrent UC patients and 40 newly diagnosed patients from January 2019 to December 2022. Data collection included clinical records, scores, and anorectal function assessments. Regression analyses were used to identify factors impacting anorectal function. Recurrent UC patients had higher baseline CRP and fecal calprotectin levels, increased anxiety and depression, and more severe fecal incontinence. They also had lower BMIs, serum Hb and albumin (ALB) levels, and Inflammatory Bowel Disease Questionnaire scores than did initial-onset UC patients. Multivariate linear regression analysis revealed that long disease duration (coef. − 0.376, P < 0.001) and high fecal calprotectin level (coef. − 0.656, P < 0.001) independently influenced the initial sensation threshold in recurrent UC patients. Additionally, high fecal calprotectin (coef. − 0.073, P = 0.013) and high Zung Self-Rating Anxiety Scale score (coef. − 0.489, P = 0.001) were identified as two independent determinants of the defecation volume threshold. For the defecation urgency threshold, the independent factors included high disease duration (coef. − 0.358, P = 0.017) and high fecal calprotectin level (coef. − 0.499, P = 0.001). Similarly, the sole independent factor identified for the maximum capacity threshold was high fecal calprotectin (coef. − 0.691, P = 0.001). Recurrent UC patients had increased rectal sensitivity and compromised anorectal function, which significantly impacted quality of life. Proactively managing the disease, reducing UC relapses, and addressing anxiety are effective measures for improving anorectal function in these patients.

Objectives: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. Materials and Methods: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. Results: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). Conclusions: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.

BACKGROUND:Nonalcoholic fatty liver disease (NAFLD) may contribute to osteoporosis. Berberine is a traditional Chinese medicine and was recently shown to be beneficial in NAFLD. However, little is known about its impact on bone loss induced by NAFLD. AIM:We aimed to explore the role of berberine in bone loss and determine its underlying mechanisms in NAFLD. METHODS:C57BL/6 mice were fed a high-fat high-fructose high-glucose diet (HFFGD) for 16 weeks to establish a NAFLD mouse model. The mice were administered berberine (300 mg/kg/d) by gavage, and fatty liver levels and bone loss indicators were tested. RESULTS:Berberine significantly improved HFFGD-induced weight gain, hepatic lipid accumulation and increases in serum liver enzymes, thereby alleviating NAFLD. Berberine increased trabecular number (Tb. N), trabecular thickness (Tb. Th), bone volume to tissue volume ratio (BV/TV), and decreased trabecular separation (Tb. Sp) and restored bone loss in NAFLD. Mechanistically, berberine significantly inhibited ferroptosis and 4-hydroxynonenal (4-HNE), prostaglandin-endoperoxide synthase 2 (PTGS2), and transferrin (TF) levels and increased ferritin heavy chain (FTH) levels in the femurs of HFFGD-fed mice. Moreover, berberine also activated the solute carrier family 7 member 11 (SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) signaling pathway. CONCLUSION:Berberine significantly ameliorates bone loss induced by NAFLD by activating the SLC7A11/GSH/GPX4 signaling pathway and inhibiting ferroptosis. Therefore, berberine may serve as a therapeutic agent for NAFLD-induced bone loss.

OBJECTIVES:This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. MATERIALS AND METHODS:From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. RESULTS:Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). CONCLUSIONS:Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.

Abstract Circular RNAs (circRNAs) are a novel kind of noncoding RNA with a closed ring structure. An increasing number of studies have shown that it plays an important role in NAFLD. In this study, we used circDock6 to explore its role and molecular mechanism in the progression of NAFLD. qRT‒PCR was used to detect the circDock6 expression level in SD liver tissues and HFD tissues. The regulatory effects of circDock6 in NAFLD were evaluated by Oil Red “O” staining, triglyceride detection, and western blot (WB) analysis. CircDock6 was significantly upregulated in HFD liver tissues compared to SD tissues. Additionally, Oil Red “O” staining and triglyceride detection revealed that decreased expression levels of circDock6 inhibited lipid droplet formation and reduced triglyceride content. CircDock6 acts as a mmu-let-7 g-5p sponge to promote the progression of NAFLD by regulating IGF1R. Our data demonstrated that circDock6 was expressed at high levels in HFD tissues. Knockdown of circDock6 expression inhibited NAFLD progression by regulating IGF1R through targeting mmu-let-7 g-5p.

Question: A 75-year-old man was hospitalized in the Gastroenterology Department with a 14-day history of intermittent right upper quadrant abdominal pain and low-grade fever, without chills and other systemic symptoms. He had a past medical history of polymyalgia rheumatica (PMR), benign prostatic hyperplasia, and hypertension. The patient had history of methylprednisolone and methotrexate use, which was administered for 2 years, and he had no history of smoking or alcohol consumption. On hospital admission, the patient showed stable vital signs and his body temperature was 37.7°C. Physical examination showed moderate right upper quadrant tenderness and negative Murphy sign. Laboratory tests on presentation showed a serum amylase concentration of 1387 U/L, an alanine aminotransferase (ALT) concentration of 3127 U/L, an aspartate aminotransferase (AST) concentration of 4554 U/L (Table 1), and a hypersensitive C-reactive protein level of 29.65 mg/L. Immunologic evaluations showed that antinuclear antibody was positive (1:100), and other immune-associated indexes were negative. No abnormal blood markers were revealed for cancer and virus infection. Multiple imaging tests including abdominal doppler ultrasound examination, plain abdominal computed tomography (CT), and magnetic resonance cholangiopancreatography demonstrated the existence of cholecystitis (Figures A, B), but there were no abnormalities on the pancreas (Figures C, D).Table 1Changes in Liver Enzymes, Amylase, and Lipase Levels in the Patients2 y before hospitalizationDay of hospitalization7 d after hospitalization2 mo after hospitalizationALT (U/L)1431275517AST (U/L)1445543325Amylase (U/L)10813871510454Lipase (U/L)49913524 Open table in a new tab One week after hospitalization, the concentrations of ALT and AST and hypersensitive C-reactive protein decreased significantly (Table 1). Abdominal CT also showed the recovery of cholecystitis (Figure E), and no pancreatic abnormalities were noted (Figure F). However, at the 7th day after hospitalization, the patient still had persistent slight right upper quadrant abdominal pain, without fever and chills. In this case, abdominal pain did not require medical interventions. To identify the causes of abdominal pain, the patient still required hospitalization. The level of serum amylase kept high at 1510 U/L, with a lipase level was decreased from 91–35 U/L (Table 1). Given the present clinical test results and imaging pictures, what is the diagnosis? What will you do next to establish the diagnosis? Look on page 381 for the answer and see the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult. Elevated serum amylase is commonly observed in patients with various pancreatic diseases, such as chronic pancreatitis, pancreatic pseudocyst, and pancreatic tumors, particularly acute pancreatitis. The diagnostic criteria for acute pancreatitis include the presentation of at least 2 of the following: (1) upper abdominal pain, (2) elevated serum amylase or lipase, and/or (3) imaging (CT, magnetic resonance imaging, or ultrasonography). The patient developed upper abdominal pain and elevated serum amylase; acute pancreatitis was considered. However, significant elevation of the serum lipase level was not observed, and the elevated serum amylase persisted from hospitalization to more than 7 days. Both abdominal CT (Figure C) and magnetic resonance cholangiopancreatography (Figure D) did not show any pancreatic abnormality. Therefore, pancreatic diseases may not be the cause contributing to the elevated serum amylase. Few studies have reported an association of elevated serum amylase with lung cancer, ovarian cancer, multiple myeloma, diabetic ketoacidosis, pneumonia, and kidney dysfunction. In this patient, laboratory tests on cancer, metabolic diseases, and virus infection had not demonstrated abnormality. Renal function was normal throughout. Also, chest CT did not support pneumonia or lung cancer diagnoses. Macroamylasemia, when serum amylase combines with plasma proteins (usually immunoglobulins) to form complexes that cause hyperamylasaemia, is one cause of elevated serum amylase. Currently, diagnosis of macroamylasemia is determined primarily through amylase/creatinine clearance ratio (ACCR) and polyethylene glycol precipitation.1Gillett M.G. Gunneberg A. Goldie D.J. Demonstration of macroamylasemia by polyethylene glycol (PEG) precipitation requires correct PEG concentration.Clin Chem. 1995; 41: 956-957Crossref PubMed Scopus (7) Google Scholar,2Levitt M.D. Ellis C. A rapid and simple assay to determine if macroamylase is the cause of hyperamylasemia.Gastroenterology. 1982; 83: 378-382Abstract Full Text PDF PubMed Scopus (64) Google Scholar In this patient, ACCR was 0.20%, <1%. The precipitation rate of amylase was 93.47%, which revealed that the elevated amylase in serum belonged to macroamylase. Based on previous history, laboratory and imaging data, the diagnosis of macroamylasemia was confirmed in this patient. As a rare cause of hyperamylasemia, macroamylasemia was first reported as early as 1967 in the United States, characterized by occasional abdominal pain.3Berk J.E. Kizu H. Wilding P. et al.Macroamylasemia: a newly recognized cause for elevated serum amylase activity.N Engl J Med. 1967; 277: 941-946Crossref PubMed Scopus (128) Google Scholar The etiology and pathogenesis of macroamylasemia remained to be elucidated until now. It can occur alone or accompany multiple diseases, such as liver diseases, carcinoma, and a variety of autoimmune disorders. An increase of amylase levels and a decrease of ACCR are crucial at diagnosis. Furthermore, polyethylene glycol precipitation is a feasible way to provide clinical evidence and is considered one of the diagnostic criteria.4Sakallıoğlu O. Macroamylasemia; a dilemma in morbidity.Balkan Med J. 2015; 32: 330Crossref PubMed Scopus (2) Google Scholar The patient had PMR previously, presenting as polyarthralgia, proximal muscle stiffness, and polymyalgia. After 2 years of use of methylprednisolone and methotrexate, the above clinical symptoms improved and both of the drugs were terminated. To our knowledge, there has been no study on the connections between macroamylasemia and PMR so far. The occurrence and development of PMR are always associated with immunologic derangements.5Matteson E.L. Dejaco C. Polymyalgia rheumatica.Ann Intern Med. 2017; 166: ITC65-65ITC80Crossref PubMed Scopus (44) Google Scholar Hence, we speculate that PMR may be the cause of macroamylasemia in this patient after excluding other factors. Currently, there is no defined time for the course of macroamylasemia, and the manifestations in patients may persist for a long time, even many years. Given the self-healing ability of macroamylasemia, no special treatments are found today. After another week of supportive care, the abdominal pain in this patient was improved dramatically and the patient was discharged from the hospital. Within a 2-month follow-up, the patient had no symptoms. The serum amylase concentrations were gradually reduced to 454 U/L, accompanied by normal AST and ALT levels. In the future, the disease activity of PMR should be monitored, and further follow-up is needed for clinical symptoms and serum amylase levels.

BackgroundEndoscopic submucosal dissection (ESD) for early gastric cancer (EGC) does not always lead to curative resection. Risk factors of lymph node metastasis (LNM)/local cancer residue after non-curative ESD for EGC have not been fully elucidated. We therefore aimed to clarify them and evaluate whether the "eCura system" is reliable for the risk stratification of LNM after non-curative ESD.MethodsWe conducted a multicenter retrospective study at seven institutions in Zhejiang, China, on 128 patients who underwent non-curative ESD for EGC. We divided the patients into two groups according to their therapeutic regimen after non-curative ESD. We analyzed the risk factors for LNM, local cancer residue, cancer recurrence, and cancer-specific mortality. Furthermore, we compared the outcomes in each risk category after applying the "eCura system".ResultsAmong 68 patients undergoing additional surgery, LNM was found in three (4.41%) patients, while local cancer residue was found in eight (11.76%) patients. Multivariate analysis showed that upper third location and deep submucosal invasion were independent risk factors of LNM and local cancer residue. Among 60 patients who underwent simple follow-up, local cancer recurrence was found in four (6.67%) patients and cancer-specific mortality was found in one (1.67%) patient. There were no independent risk factors of cancer recurrence and cancer-specific mortality in our study. During the follow-up period, 5-year overall survival (OS) and disease-free survival (DFS) were 93.8% and 88.9%, respectively. Additionally, LNM and cancer recurrence were significantly associated with the eCura scoring system (p = 0.044 and p = 0.017, respectively), while local cancer residue and cancer-specific mortality were not (p = 0.478 and p = 0.131, respectively).ConclusionClinicians should be aware of the risk factors for the prognosis of patients with non-curative ESD to determine subsequent treatment. Through the application of the "eCura system", additional surgery should be performed in patients with intermediate/high risk of LNM.

Aims:To evaluate the value of endoscopic screening during endoscopic submucosal dissection (ESD) in the detection of synchronous multiple early gastric cancer (SMEGC) and the risk factors for missed diagnosis of SMEGC.Methods:We conducted gastric endoscopic screening during ESD operation in 271 patients with early gastric cancer (EGC) referred for ESD, and endoscopic follow-up within 1 year after the operation. The detection and characteristics of SMEGC were analyzed in three stages: before ESD, during ESD operation, and within 1 year after ESD.Results:SMEGC was detected in 37 of 271 patients (13.6%). Among them, 21 patients with SMEGC (56.8%) were diagnosed before ESD, 9 (24.3%) were diagnosed with SMEGC by endoscopic screening during ESD operation, and 7 (18.9%) were found to have EGC lesions in the stomach during postoperative endoscopic follow-up within 1 year. The preoperative missed detection rate of SMEGC was 43.2%, and the rate of missed detection could be reduced by 24.3% (9/37) with endoscopic screening during ESD operation. Missed SMEGC lesions were more common in flat or depressed type and smaller in size than the lesions found before ESD. The presence of severe atrophic gastritis and age ≥60 years were significantly correlated with SMEGC (P < 0.05), while multivariate analysis showed that age ≥60 years was an independent risk factor (OR = 2.63, P < 0.05) for SMEGC.Conclusions:SMEGC lesions are apt to be missed endoscopically. Special attention should be paid to small, depressed, or flat lesions in detecting SMEGC, especially in elderly patients or (and) patients with severe atrophic gastritis. Endoscopic screening during ESD operation can effectively reduce the missed diagnosis rate of SMEGC.

BACKGROUND Ulcerative colitis (UC) is an idiopathic, chronic inflammatory disorder of the colonic mucosa with increasing prevalence and limited management. Ruxolitinib is a new anti- JAK/STAT3 biologic agent that has shown potential in protecting against colitis. METHODS We first constructed an in vivo UC model and an in vitro colonic epithelial cell inflammation model. Ruxolitinib was administered via gavage in mice. After treatment, colon tissues, cells, and cell lysates were collected and prepared for histological evaluation, immunohistochemistry, immunofluorescence staining, quantitative reverse-transcriptase polymerase chain reaction, Western blotting, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining, and cytokine analysis. STAT3 expression was silenced and overexpressed via small interfering RNA and overexpression plasmid transfection, respectively, and quantitative reverse-transcriptase polymerase chain reaction was used to examine the downstream effects. RESULTS Ruxolitinib administration significantly alleviated colitis both in vivo and in vitro, as manifested by reduced body weight loss, shortened colon lengths, relieved disease activity (measured by the disease activity index), and prolonged survival. A mechanistic study showed that ruxolitinib attenuated nuclear factor kappa B-induced inflammation, reduced apoptosis, and ameliorated epithelial barrier leakage, and thereby reduced colitis activity in vivo. STAT3 knockdown partially reversed the protective effect of ruxolitinib against colitis, while STAT3 overexpression exaggerated the reductions in proinflammatory cytokine levels upon ruxolitinib treatment. CONCLUSIONS We demonstrate that ruxolitinib alleviates colitis by inhibiting nuclear factor kappa B-related inflammation and apoptosis in addition to restoring epithelial barrier function via STAT3, providing a new strategy for UC treatment.

Transfer RNA-derived small RNAs (tsRNAs) are newly discovered noncoding RNAs (ncRNAs). According to the specific cleavage of nucleases at different sites of tRNAs, the produced tsRNAs are divided into tRNA-derived stress-inducible RNAs (tiRNAs) and tRNA-derived fragments (tRFs). tRFs and tiRNAs have essential biological functions, such as mRNA stability regulation, translation regulation and epigenetic regulation, and play significant roles in the occurrence and development of various tumors. Although the roles of tsRNAs in some tumors have been intensively studied, their roles in gastric cancer are still rarely reported. In this review, we focus on recent advances in the generation and classification of tsRNAs, their biological functions, and their roles in gastric cancer. Sixteen articles investigating dysregulated tsRNAs in gastric cancer are summarized. The roles of 17 tsRNAs are summarized, of which 9 were upregulated and 8 were downregulated compared with controls. Aberrant regulation of tsRNAs was closely related to the main clinicopathological factors of gastric cancer, such as lymph node metastasis, Tumor-Node-Metastasis (TNM) stage, tumor size, and vascular invasion. tsRNAs participate in the progression of gastric cancer by regulating the PTEN/PI3K/AKT, MAPK, Wnt, and p53 signaling pathways. The available literature suggests the potential of using tsRNAs as clinical biomarkers for gastric cancer diagnosis and prognosis and as therapeutic targets for gastric cancer treatment.

背景:微小息肉(≤5 mm)和小息肉(6～9 mm)是临床上最常见的结直肠息肉,其中少数具有进展期组织学.目的:分析具有进展期组织学的微小和小结直肠息肉的内镜下特征.方法:回顾性收集2016年6月—2021年9月在宁波市第一医院行结肠镜下息肉切除术的病例,采集临床、内镜和病理资料.采用倾向性评分匹配法为进展期组织学微小和小息肉1:1匹配对照组,以单因素和多因素分析筛选与进展期组织学相关的内镜下特征.结果:2950例患者检出直径10 mm以下的腺瘤性息肉3631个,14个(1.2％)微小息肉存在进展期组织学,均为高级别上皮内瘤变(HGIN);114个(4.6％)小息肉存在进展期组织学,包括109个HGIN和5个黏膜下浸润性癌.504例患者检出直径10 mm以下的锯齿状病变755个,均未发现进展期组织学.多因素Logistic回归分析显示,在微小和小息肉中,鸡皮征(OR=3.790,95％CI:1.767～8.128)、充血(OR=2.802,95％CI:1.450～5.415)、出血(OR=5.074,95％CI:1.511～17.035)、分叶改变(OR=2.522,95％CI:1.247～5.098)和相对凹陷(OR=5.317,95％CI:1.376～20.550)是进展期组织学的独立危险因素,而JNET高风险和内镜下病变形态为隆起型与进展期组织学无关.结论:结肠镜检查时如发现微小或小息肉有鸡皮征、充血、出血、分叶改变和相对凹陷表现,应警惕可能存在进展期组织学.

To the Editor: In China, colorectal cancer (CRC) ranks third in cancer incidence and fifth in cancer-related deaths.[1] Most CRCs arise from adenomatous polyps. Colonoscopy can detect and remove polyps early to prevent CRC. However, the polyp miss rate in conventional colonoscopy may be more than 40%.[2] New endoscopic devices for detecting polyps have made some progress over the past few decades,[3] but are still operator-dependent and require additional costs. Therefore, artificial intelligence (AI)-assisted polyp detection systems have emerged in recent years. This study aimed to evaluate the effectiveness of our newly developed AI-assisted polyp detection system for colonoscopy in a preclinical manner. We conducted a controlled study comparing the polyp detection results of AI video analysis and conventional colonoscopy. Adult patients scheduled for colonoscopy at Ningbo Hospital of Zhejiang University were considered for inclusion. The exclusion criteria were emergency colonoscopy, colonoscopic polypectomy, history of colorectal polyps, and patients with severe intestinal diseases or contraindications for colonoscopy. This study is a part of a multi-center project including Ningbo Hospital and the First Affiliated Hospital, College of Medicine, Zhejiang University; this protocol was approved by the Research Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University (IRB No. 2018-524). The informed consent was waived. Eligible patients underwent conventional detection first, followed by AI detection [Supplementary Figure 1, https://links.lww.com/CM9/B248]. For conventional detection, patients underwent conventional colonoscopy by a gastroenterology physician, who was blinded to subsequent video analysis. Patients with unqualified colonoscopy (no cecal intubation, Boston bowel preparation scale score <6, or withdrawal time from cecum to anus [excluding biopsy time] <6 min) or impaired colonoscopy video were excluded. Subsequently, videos of conventional colonoscopy were used for AI detection [Supplementary Figure 2, https://links.lww.com/CM9/B248]. Finally, five assessors from the First Affiliated Hospital, College of Medicine, Zhejiang University reviewed AI-analyzed videos and ruled out false-positive diagnoses. Details of our AI system are shown in Supplementary Materials, https://links.lww.com/CM9/B248. The primary outcome is polyp detection rate (PDR), which is the number of positive patients (those with ≥1 polyp detected during colonoscopy) divided by the total number of patients. Secondary outcomes include polyps per colonoscopy (PPC), calculated as the number of polyps detected during colonoscopy divided by the number of colonoscopies, and polyps per colonoscopy-plus (PPC-Plus), calculated as the number of non-first polyps (polyps detected after the first polyp during colonoscopy) divided by the number of colonoscopies. In addition, we analyzed the characteristics of detected polyps, including location, size, and morphology. All results were analyzed using SPSS 20.0 software (IBM Inc., Chicago, IL, USA). The McNemar test was used to compare the PDR of AI detection and conventional detection, and a comparison between groups was performed using the χ2 test. The PPC and PPC-Plus were compared between conventional detection and AI detection using the Wilcoxon signed-rank test. A P-value <0.05 was considered statistically significant. A total of 764 patients who underwent colonoscopy at Ningbo Hospital of Zhejiang University from May to August 2018 were included in the final analysis. Most (90.4%, 691/764) patients were asymptomatic and underwent colonoscopy for screening or an annual medical examination (Patient characteristics are shown in Supplementary Table 1, https://links.lww.com/CM9/B248). A total of 554 polyps were found in 271 patients by conventional colonoscopy, and 813 polyps were found in 348 patients by AI system. For the primary outcome, the PDR of AI detection was statistically significantly higher than that of conventional detection (45.5% vs. 35.5%, P < 0.001). In addition to the first-found polyps, there were 283 non-first polyps found in conventional detection and 465 in AI detection. For secondary outcomes, PPC (1.1 vs. 0.7, P < 0.001) and PPC-Plus (0.6 vs. 0.4, P < 0.001) were significantly higher in AI detection than in conventional detection [Table 1]. Table 1 - Primary and secondary outcomes for conventional detection and AI detection. Outcomes Conventional detection AI detection Statistical values P values Positive patients∗, n 271 348 Total polyps detected, n 554 813 Non-first polyps† detected, n 283 465 PDR 35.5% 45.5% 16.101 <0.001 PPC 0.7 1.1 −10.957 <0.001 PPC-Plus 0.4 0.6 −8.530 <0.001 ∗Positive patients represent patients with ≥1 polyp detected during conventional detection or AI detection.†Non-first polyps represent polyps detected after the first polyp during colonoscopy. AI: Artificial intelligence; PDR: Polyp detection rate; PPC: Polyps per colonoscopy; PPC-Plus: Polyps per colonoscopy-plus. Further comparing the polyp characteristics of AI and conventional detection, we found that the polyp location distribution was similar, while AI-detected polyps were more likely to be diminutive and flat than conventionally detected polyps [Supplementary Table 2, https://links.lww.com/CM9/B248]. Subanalysis found that the PDR of senior operators was relatively higher than that of junior operators [Supplementary Table 3, https://links.lww.com/CM9/B248]. More critically, the PDR of AI detection was significantly higher than that of conventional detection by both junior (43.9% vs. 34.2%, P < 0.001) and senior operators (47.6% vs. 37.0%, P < 0.001). In this study, we found that more positive patients and additional polyps were detected with AI detection than with conventional colonoscopy, providing strong support for the real-time application of the AI-assisted system. In an early study, Karkanis et al[4] first developed a computer-aided polyp detection system through static image assessment. Here, the AI-assisted dynamic polyp detection system used in the study was developed by ourselves. We conducted a preliminary comparative study on human polyp detection and AI detection, and demonstrated the promise of AI polyp detection through offline video analysis. Compared with conventional colonoscopy, the AI system had better performance in polyp detection, especially for polyps located in the left colon, diminutive and flat, and non-first polyps that are easily missed in conventional colonoscopy. Nowadays, there are several single-center randomized control trials (RCTs) showing the feasibility and effectiveness of online AI-assisted polyp detection.[5] Compared with these systems, our AI system achieves faster real-time detection speeds of 25.8 ms per frame, which motivates us to go a step further by using our system in multicenter RCTs. There are still some limitations of our study. First, the AI failed to detect the 18 polyps found by conventional colonoscopy, suggesting that the AI system cannot fully cover all the findings by the human eye. But when we put this system into live use, it will play an additional role acting as the colonoscopist's “third eye.” Second, there were some false-positive diagnoses due to protruding folds, sucked mucosa, and residual fluid in AI detection. If the system is used for on-site examinations, colonoscopists can check for suspected polyps in real-time and rule out misdiagnosis. Moreover, we did not obtain the histology of the additionally found polyps by AI because the results were analyzed offline. Finally, since all colonoscopies were performed using an OLYMPUS CV-290SL colonoscope, it may cause some biases. In conclusion, our newly developed AI-assisted system has the potential to improve colorectal polyp detection and to reduce operator dependence, which supports the real-time use of this system in colonoscopy and its potential to improve CRC screening and prevention. Funding This study was supported by grants from the Medical Health Science and Technology Project of the Zhejiang Provincial Health Commission (No. 2020KY125) and the National Natural Science Foundation of China (No. 81800511).