Despite pharmacological advancements of oral ulcer treatment, developing sustained-release delivery systems remains a challenge. To address this, we designed a bioinspired microneedle platform integrating Turkish gall extract for targeted ulcer therapy. Drawing on the structural principles of octopus suckers, we fabricated a 3D-printed microneedle array with suction-enhanced morphology, replicated into a hydrogelbased mold. The microneedle matrix was synthesized by combining Turkish gall extract, polydopamine, and hyaluronic acid methacrylate, leveraging polydopamine's catechol chemistry for robust mucoadhesion. Pharmacological evaluations confirmed the dual functionality of the herbal component, demonstrating dose-dependent anti-inflammatory and anti-oxidant effects in vitro and in rodents. Applied to oral ulcer lesions in rats, the microneedle system exhibited prolonged mucosal retention with sustained drug release, significantly accelerating epithelial regeneration. These findings establish the sucker-inspired herbal microneedle platform as a mechanochemically optimized therapeutic strategy and provide a translational framework for modernizing traditional herbal delivery.

BACKGROUND AND STUDY AIMS:Colorectal serrated lesions are precursors to colorectal cancer, with a high recurrence risk after endoscopic resection. Identifying risk factors for recurrence and establishing a prediction model are crucial for optimizing surveillance strategies. PATIENTS AND METHODS:A single-center retrospective study included 164 patients with colorectal serrated lesions who had endoscopic follow-up information after the surgery. These cases were divided into a polyp recurrence group (79 cases) and a non-recurrence group (85 cases). Demographic data, medical histories, laboratory findings, endoscopic characteristics of the lesions, and follow-up durations were therefore collected. Cox regression identified independent risk factors, which were incorporated into a nomogram. Model performance was evaluated using C-index, calibration curves, and decision curve analysis. RESULTS:Multivariate analysis identified non-alcoholic fatty liver disease (HR 1.813, 95%CI 1.080-3.045), atrophic gastritis (HR 1.733, 95%CI 1.087-2.760), history of gallbladder abnormalities (HR 1.791, 95%CI 1.107-2.898) and elevated total bile acid levels (HR 1.023, 95%CI 1.003-1.043) as independent predictors of recurrence. The nomogram demonstrated good discrimination (C-index: 0.703-0.820) and clinical applicability (decision curve analysis net benefit: 27-80% threshold). CONCLUSIONS:This study established a validated prediction model for colorectal serrated lesions recurrence, highlighting metabolism-related factors as key determinants. Targeting these factors and applying the nomogram may enhance risk stratification and postoperative surveillance, potentially reducing colorectal cancer progression. Limitations include the retrospective design, single-center data, and lacking further validations.

Gastrointestinal stenosis following endoscopic intervention remains a major clinical challenge, largely driven by excessive fibrotic remodeling rather than persistent inflammation alone. Although glucocorticoids are widely used to suppress acute inflammatory responses, their therapeutic benefit is limited since the core profibrotic circuitry governed by the TGF-β/Smad signaling pathway. In fibrotic lesions throughout the gastrointestinal tract, activated myofibroblasts and dense extracellular matrix deposition increase tissue stiffness, reinforce mechanotransduction-dependent TGF-β activation, and restrict effective intralesional drug retention, thereby establishing a self-sustaining profibrotic microenvironment. To address this mechanistic barrier, we developed an octopus-inspired suction-cup microneedle patch with a mechanically decoupled architecture composed of rigid PLGA microneedles (MN) and a flexible pectin-based substrate. This design enables efficient penetration into stiffened mucosa and stable adhesion within the moist, dynamic luminal environment. The system achieves localized co-delivery of Budesonide (BUD) and SMAD7, an endogenous intracellular antagonist of TGF-β/Smad signaling. Comprehensive in vitro mechanistic studies and in vivo wound-healing models demonstrate effective intralesional retention, significant suppression of fibrotic remodeling, and promotion of mucosal regeneration. By simultaneously targeting inflammation and the core fibrotic signaling cascade, this bioinspired microneedle platform offers a mechanistically informed and clinically translatable strategy for the prevention and treatment of post-endoscopic gastrointestinal stenosis.

BACKGROUND:Accurate prediction of lymph node metastasis (LNM) is crucial for treatment decisions in early gastric cancer (EGC). Current preoperative methods for LNM prediction are often insufficient. PATIENTS AND METHODS:This multicenter retrospective study enrolled 605 EGC patients who underwent endoscopic submucosal dissection (ESD) and/or surgery across five institutions between 2013 and 2023. We developed a deep learning model, LNMate, to predict LNM before ESD and evaluated its impact on endoscopists' diagnostic performance. We also conducted immunohistochemical (IHC) analysis on tissue samples from 32 patients. Additionally, we constructed a deep learning-based endoscopic nomogram (DLEN) to estimate LNM risk after ESD, validated through comparison with the eCura system. RESULTS:LNMate showed high predictive performance with area under the curves (AUCs) ranging from 0.843 (95% confidence interval [CI], 0.782-0.904) to 0.875 (95% CI, 0.814-0.936). With LNMate assistance, endoscopists improved diagnostic accuracy by 13.8%, particularly in specificity (mean increase of 0.17, P = 0.03). IHC analysis showed associations between CD8+ and CD20+ cell enrichment with non-LNM predictions, and CD68+ macrophage infiltration with LNM. The DLEN outperformed the eCura system (AUC, 0.91 [95% CI, 0.86-0.97] vs. 0.71 [95% CI, 0.58-0.83], P < 0.01), reducing oversurgery by 24.2%, with no false negatives. CONCLUSIONS:The deep learning-based intelligent system for the entire treatment process of EGC showed excellent performance in predicting LNM, offering valuable decision support for both endoscopists in pre-ESD treatment planning and surgeons in post-ESD surgical decision-making.

BACKGROUND:Recently, several endoscopic techniques have been used to improve the R0 resection rate of rectal neuroendocrine neoplasms (R-NENs). However, none of these methods can achieve 100% complete resection (CR), particularly in the vertical direction. Endoscopic full-thickness resection (EFTR) has proven to be an effective method for the treatment of submucosal tumors but is seldom utilized in the eradication of R-NENs. AIM:To review cases of R-NENs removed using EFTR and to evaluate the safety and efficacy of this technique. METHODS:This retrospective cohort study enrolled 160 patients with pathologically confirmed R-NENs, including 132 who underwent endoscopic submucosal dissection (ESD) and 28 who underwent EFTR. Lesions were categorized as < 1 cm, 1-2 cm, and > 2 cm in size. CR rate, en bloc resection rate, operation time, and complications were evaluated. Subgroup analyses and follow-up were also performed. RESULTS:EFTR achieved 100% CR rates for lesions < 1 cm and 1-2 cm, compared with 67.0% and 50.0%, respectively, in the ESD group. En bloc resection and successful removal of the R-NENs were achieved in all patients. Meanwhile, EFTR showed performance comparable to ESD in terms of operation time, hospitalization cost, and postoperative adverse events, except for a one-day longer hospital stay. We also analyzed the invasion depth of R-NENs based on full-thickness specimens. The data showed that 80% of lesions (< 1 cm) and 85.7% of lesions (1-2 cm) had invaded the SM3 level or deeper at the time of resection. For ESD specimens, 46.6% (< 1 cm) and 89.3% (1-2 cm) of lesions had infiltrated more than 2000 μm beneath the muscularis mucosae. CONCLUSION:EFTR has shown superior performance in the resection of small R-NENs compared with that of ESD.

In cancer therapy, tumor cells can diminish their signals through mechanisms such as immune escape, thereby evading recognition and elimination by the immune system. Providing tumor signals to enhance the recognition of tumor sites is considered a crucial approach in cancer treatment. Inspired by the decoy-induced directed feeding of fish, we propose a biomimetic nanoparticle system for tumor signal amplification. This biomimetic system comprises magnetically responsive nanoparticles and immune-inducing bacterial membranes. These designs work together to create a baiting effect at the tumor site, attracting and activating immune cells to attack. It has been demonstrated that the generated nanoparticles have the potential to be targeted and delivered to the tumor site under the influence of an external magnetic field, as demonstrated in preliminary in vitro and in vivo studies. Moreover, the nanoparticles utilize the bacterial membrane and cell membrane-translocated calreticulin to induce an immune response, simulating a decoy mechanism to recruit immune cells. The nanoparticles were proved to be effective in recruiting macrophages and neutrophils and reducing tumor size in animal experiments. These features make the nanoparticles an ideal candidate for treating tumors.

Severe acute pancreatitis (SAP) is distinguished by an uncontrolled systemic pro-inflammatory response caused by the activation of trypsin within the pancreatic tissue, leading to the occurrence of multiple organ failure (MOF). Gasdermin D (GSDMD)-induced pyroptosis represents a form of programmed cell death characterised by robust inflammatory responses. This indicates that directing efforts towards pyroptosis could potentially offer a remedy for SAP and its related MOF. Our objective was to examine the impact of disulfiram (DSF), a potent inhibitor of pyroptosis, and its potential therapeutic mechanism in SAP. The biochemical and histological assessments provided clear evidence that DSF effectively hindered necrosis, infiltration, oedema and cellular demise within pancreatic tissues. As a result, DSF effectively suppressed acute pancreatitis. Significantly, DSF hindered the process of GSDMD-mediated pyroptosis in pancreatic cells within the context of SAP. This is evident through the observed decrease in the number of SYTOX-positive cells, the prevention of LDH release and the restriction of expression of full-length GSDMD, N-terminal GSDMD and p-NF-ĸB p65. Subsequently, we assessed the mRNA levels of the pro-inflammatory cytokines Il-18, Il-1β, Il-6, Tnf-α, Hmgb1 and Ccl2. Our findings revealed a significant rise in the levels of these pro-inflammatory cytokines in SAP mice, whereas DSF remarkably inhibited the release of them. It is noteworthy that DSF also mitigated the resultant damage to remote vital organs (lungs, liver, and kidneys). Thus, GSDMD-mediated pyroptosis has been significantly involved in the pathogenesis of SAP, and DSF could potentially serve as an alternative therapeutic agent for SAP and its associated MOF.

The selection of optimal first-line biologic therapy for treatment-naïve Crohn’s disease (CD) patients continues to present a clinical dilemma. Existing evidence remains limited by its predominant focus on anti-TNF-exposed populations or reliance on clinical endpoints alone. Our investigation provides a comprehensive comparative effectiveness analysis of ustekinumab (UST) versus infliximab (IFX) as first-line therapies in biologic-naïve CD, incorporating advanced cross-sectional imaging characteristics and specifically evaluating differential rates of endoscopic mucosal healing (MH) across longitudinal follow-up. This retrospective cohort study enrolled 210 biologic-naïve CD patients. Primary outcome was MH at 1, 1.5, and 2 years. Subgroup analyses were performed to explore potential treatment heterogeneity among different patient subgroups. Furthermore, logistic regression analyses were conducted to identify MH-related factors. While 1-year and 1.5-year MH rates were comparable (27.8

Background:The precancerous lesion of colorectal cancer (CRC), colorectal sessile serrated lesion (SSL), takes an average of 15 years to germinate from no cell dysplasia to CRC, and 2 years for SSL with dysplasia (SSL-D). To date, the impacts of endoscopic and pathological features of SSL and SSL-D on the development of dysplasia remain unclear. In this study, we explored these impacts, striving to provide reference for its classification, detection, and diagnosis. Methods:Retrospectively, a cross-sectional analysis was conducted to compare 414 SSL and 59 SSL-D, which had been diagnosed under colonoscopy in the Affiliated Drum Tower Hospital of Nanjing University. Results:A total of 454 participants were enrolled with a mean age of 58.43±13.94 years and a male-to-female ratio of 0.91:1. There were significant differences between the SSL and SSL-D groups in the gender distribution (P=0.044). The proportion of patients with hypertension (33.33% vs. 17.13%, P=0.004) was higher in the SSL-D group. Significantly higher indexes in lipid metabolism were observed in the SSL-D group. SSL-D had a greater number of lesions ≥10 mm (86.44% vs. 57.00%, P<0.001), 0-IIa morphology (55.93% vs. 41.55%, P=0.049), and kermesinus surface (22.03% vs. 7.49%, P<0.001). Conclusions:Female SSL patients with a history of hypertension are more prone to developing into dysplasia, whereas morphological discriminations between SSL and SSL-D are vague. Lipid metabolism might have certain impact on the germination of SSL to SSL-D. Studies with larger sample sizes are warranted.

Berberine has been reported as a safe and effective pharmacological agent to reduce colorectal adenoma recurrence after polypectomy. This retrospective cohort study is an extended follow-up of a previous clinical trial (NCT02226185) during the post-treatment observational phase. We aim to evaluate the long-term protective effects of berberine on adenoma recurrence. Among 895 patients who finished the previous 2-year randomized trial, we recruited 781 patients at 7 clinical centers across 6 provinces in China. The primary outcome is adenoma recurrence. Between December 29, 2018, and October 10, 2024, 648 patients underwent at least one colonoscopy during the follow-up. The protective effects of berberine persist for at least 6 years after treatment cessation, with lower adenoma recurrence rate (34.7% vs. 52.1%) and lower neoplasm occurrence rate (63.4% vs. 71.0%). Berberine may serve as a potential long-term preventive agent against adenoma recurrence after polypectomy.

Colorectal cancer (CRC) is a leading cause of cancer deaths worldwide and in recent years its incidence is increasing rapidly in China, which constitutes a major public health burden. Almost 90% of CRC cases develop from precursor adenomatous polyps, through a series of genetic changes known as adenoma-carcinoma sequence during at least 10 years. Detection and removal of colorectal adenoma (CRA) could reduce CRC mortality risk by colonoscopy, but the recurrence rate is high. Our previous RCT study (NCT02226185) found that oral Berberine (BBR), a natural isoquinoline alkaloid extracted from the Chinese herb Coptis chinensis for 2 years significantly reduced recurrence after endoscopic removal of CRA (RR 0.77, 95% CI 0.66-0.91; p=0.001). The study recruited 895 participants who had undergone complete polypectomy within 6 months in seven hospital centers across six provinces in China between Nov 14, 2014, and Dec 30, 2016. Participants were randomly assigned (1:1) to receive BBR (0·3 g twice daily) or placebo tablets via block randomization for 2 years. After the end of randomized treatment, we continued this Follow-up Study to track adenoma recurrence for an average of 6 years till Sep 30, 2024. Besides 114 participants lost to follow up, we obtained follow-up information for 781 participants, 648 of whom underwent at least one colonoscopy after the end of study treatment and were included in this analysis. Mantel-Haenszel test was used to compute relative risks (RRs) and 95% confidence intervals (CIs) for the effect of BBR on risk of adenoma recurrence. Cox proportional-hazards model and Andersen-Gill model were used to analyze multi-recurrence by time. The study is registered with ClinicalTrials.gov, number NCT06629051. During the average 6 years follow up, we found that participants in the BBR group still had a substantially and statistically significantly lower risk of CRA than those in the placebo group (34.7% versus 52.1%; adjusted RR = 0.639, 95% CI = 0.508 to 0.785, P<0.001) and a reduction in risk of any neoplasm including inflammatory polyps, serrated lesions and colorectal cancer (adjusted RR = 0.874, 95% CI = 0.775 to 0.983, P = 0.022). Meanwhile the risk of non-advanced CRA in BBR group was lower than that in placebo group (adjusted RR = 0.634, 95% CI = 0.497 to 0.790, P<0.001). The incidence of adenoma recurrence was significantly lower in participants receiving BBR (HR= 0.601; 95% CI = 0.473-0.765; P<0.001). And in every year after treatment ended, the risk of adenoma recurrence in BBR group was lower than placebo group for all RRs<1.0 but some of which were not statistically significant. Generally, the protective effect of berberine on risk of colorectal recurrence extends up to 6 years after cessation of active treatment, even in the absence of continued supplementation.

Gastric cancer (GC) is a prevalent malignant tumor of the digestive system that is often diagnosed at advanced stages owing to inconspicuous early symptoms and a lack of specific examination methods. Effective treatment of advanced stages remains challenging, emphasizing the need for new therapeutic targets. Metabolic reprogramming, a hallmark of tumors, plays a pivotal role in tumor progression, immune evasion, and immune surveillance. DNA damage-regulated autophagy modulator 1 (DRAM1) encodes a hexameric transmembrane protein that is predominantly located in lysosomes and induces autophagy; however, its mechanism of action in gastric cancer remains unclear. Our study found that elevated DRAM1 expression in patients with GC correlated with survival and prognosis. DRAM1 knockdown suppressed energy metabolism in GC cells through the PI3K/AKT/mTOR signaling pathway, thereby mitigating GC progression. Atorvastatin, a focus of recent tumor research, significantly enhanced apoptosis levels in DRAM1 knockdown GC cells compared to the control group. Therefore, through metabolic reprogramming, DRAM1 may serve as a potential therapeutic target for GC prevention.

Background:Autoimmune enteropathy (AIE) is a rare autoimmune disorder characterized primarily by villous atrophy of the small intestinal mucosa. This article presents a case of adult-onset AIE featuring intractable diarrhea and severe malnutrition, along with a review of the existing literature to summarize its clinical characteristics, aiming to provide insights for the diagnosis and management of AIE. Case Description:A 60-year-old male was admitted due to intermittent abdominal pain, diarrhea, and weight loss. Laboratory tests revealed gliadin immunoglobulin A (IgA) (+) and immunoglobulin G (IgG) (+), but tissue transglutaminase IgA (-) and IgG (-). Endoscopy revealed that the mucous membrane of the small intestine was congested and edematous, the villi were atrophied and prone to bleeding after biopsy, and some of the villi exhibited a white mossy appearance. Pathologically, the villi of many segments of the small intestine presented diffuse and obvious atrophy, and there was lymphocytic infiltration in the intestinal glands. After exclusionary diagnosis, the patient was considered to have AIE. After effective initial treatment with corticosteroid, the patient exhibited recurrent symptoms and poor nutritional status, and eventually died of sepsis. Conclusions:For patients with refractory diarrhea and intestinal villous atrophy, a comprehensive diagnosis should be made based on medication history, epidemiological factors, gluten dietary response, serological markers, and histopathological findings. Early intervention with corticosteroids combined with nutritional support is critical, while vigilance against severe adverse events such as life-threatening infections is essential.

An increasing number of patients with oesophageal or gastric cancer are being diagnosed with colorectal lesions. This single-centre, retrospective study assessed the risk of colorectal lesions in patients with early oesophagogastric cancer. 170 patients were enrolled in the early oesophagogastric cancer group, of whom 113 (66.47%) had colorectal lesions. 238 individuals were included in the control group, among whom 38 (15.97%) were diagnosed with colorectal lesions. The incidence of colorectal lesions between the two groups was statistically significant (P < 0.05), and patients with early oesophagogastric cancer had a risk of colorectal lesions (odds ratio = 10.434, 95% confidence interval = 6.516–16.708). Multivariate analysis identified three independent risk factors: faecal occult blood test positivity, oesophagogastric lesion diameter >2 cm, and the presence of multiple oesophagogastric lesions. These findings suggest that the early oesophagogastric cancer increased the risk of colorectal lesions, particularly among individuals with the identified risk factors.

Missed early gastric cancer (MEGC) is prevalent during esophagogastroduodenoscopy (EGD), which is the first-line recommended strategy for detecting early gastric cancer (EGC). Hence, we explored the risk factors for MEGC and different types of MEGC, based on the endoscopic resected population. This retrospective, case–control study was conducted at Nanjing Drum Tower Hospital (NJDTH). We included patients who were diagnosed with EGC during screening EGD, underwent endoscopic resection, and were confirmed by postoperative pathology at the NJDTH from January 2014 to December 2021, and classified them into different types according to the different root causes of misses. Univariable, multivariable, subgroup and propensity score analyses were used to explore the risk factors for MEGC and different types of MEGC. A total of 447 patients, comprising 345 with initially detected early gastric cancer (IDEGC) and 102 with MEGC, were included in this study. Larger size (≥ 1 cm) (OR 0.45, 95

Abstract Background This study aimed to create a simulation-based assessment system for evaluating endoscopist proficiency due to the absence of evidence-based scoring systems. Methods After feasibility and clinical relevance assessments of simulator modules by gastroenterology experts, a colonoscopy module with relatively high operational difficulty was chosen for testing and underwent preliminary validation. Additionally, a questionnaire was designed to collect information about endoscopist experience, including the number of colonoscopy and gastroscope performed, insertion time, cecal intubation rate, early colorectal cancer detection rate. Subsequently, 38 physicians from our hospital's endoscopy center completed the questionnaire and underwent virtual reality simulator training. The endoscopist's proficiency was assessed in real-time based on scoring criteria, including total operation time, percentage of examined mucosa, time to reach the cecum, screening efficiency, proportion of time with clear vision, and total time spent on colonoscope looping. Results In our study, no statistically significant differences were found among endoscopy experts, specialist attending physicians, and resident physicians in terms of their experience and early cancer detection rates (P > 0.05). However, the VR system scores, including operational completion time, time to reach the cecum, and the percentage of observed mucosa, were correlated with the number of colonoscopies completed by the endoscopists (P < 0.05). Operational completion time and time to reach the cecum were strongly correlated with usual insertion times (P < 0.001), and the percentage of observed mucosa score was related to early disease detection rates. Notably, screening efficiency and endoscopic clarity scores were not correlated with physicians' disease detection rates (P > 0.05). Conclusion Virtual reality endoscopy can be utilized to assess endoscopist proficiency and provide targeted guidance to enhance their clinical practice. Based on these findings, further expansion and enrichment of simulator content, as well as optimization of training methods, can be pursued promisingly in the future.

Pancreatic ductal adenocarcinoma (PDAC) is recognized as the most aggressive and fatal malignancy. A previous study reported that PDAC patients who exhibit elevated levels of DDX3X have a poor prognosis and low overall survival rate. However, the underlying molecular mechanism remains unclear. This study aimed to investigate the specific roles of DDX3X in PDAC. Multiple bioinformatics analyses were used to evaluate DDX3X expression and its potential role in PDAC. In vitro and in vivo studies were performed to assess the effects of DDX3X on PDAC cell growth. Furthermore, Western blotting, quantitative PCR, immunohistochemistry, immunofluorescence, mass spectrometry, coimmunoprecipitation and multiplexed immunohistochemical staining were conducted to identify the specific regulatory mechanism in PDAC. The results verified that DDX3X expression is notably upregulated in the tumor tissue vs. normal tissue of PDAC patients. DDX3X knockdown markedly suppressed the proliferation, invasion and migration of PDAC cells in vitro and inhibited tumor growth in vivo. Conversely, overexpression of DDX3X induced the opposite effect. Further studies supported that the DDX3X protein can associate with sirtuin 7 (SIRT7) to stimulate PDAC carcinogenesis and progression. Furthermore, SIRT7 inhibition significantly impeded DDX3X-mediated tumor growth both ex vivo and in vivo. The results also revealed that programmed death ligand 1 (PD-L1) expression is positively correlated with DDX3X expression. These results reveal significant involvement of the DDX3X-SIRT7 axis in the initiation and advancement of PDAC and offer previously undiscovered therapeutic options for PDAC management.

The gut has been a focal point in the research of digestive system disorders. The internal microbiota generates metabolites that function as signaling molecules and substrates, interacting with the intestinal wall and influencing host physiology and pathology. Besides, the gut microbiota and metabolites owe highly diverse types and quantities, posing challenges for quantitative analysis, and monitoring frequent interactions between digestive tract metabolites and the intestinal wall remains a challenge. However, research targeting gut microbiota metabolites has elucidated their relevance to digestive diseases. By modulating metabolites such as short-chain fatty acids, bile acids, and lipopolysaccharides, it is possible to intervene in the progression of diseases such as inflammatory bowel disease and non-alcoholic fatty liver disease. Currently, research on gut microbiota is advancing, and more work is required to explore the interactions between host, microbes and underlying mechanisms. In this review, we have revisited the generation of gut microbiota-related metabolites, their impact on diseases, and modes of interaction, emphasizing the significant role of metabolites in digestive system disorders. It is believed that the linkage between gut microbiota and diseases in current research can be established through metabolites, providing a framework and foundation for research in the field of metabolomics and fundamental mechanisms.