The optimal fecal occult blood test (FOBT) and hemoglobin (Hb) threshold for balancing diagnostic accuracy and endoscopic demand in colorectal cancer (CRC) screening among Chinese outpatients remained unclear. A prospective multicenter trial was conducted from January 2017 to April 2021 across eight tertiary hospitals. Eligible outpatients were enrolled, whose stool samples were analyzed using quantitative fecal immunochemical test (FIT), self-administered qualitative FIT, general qualitative FIT, and gFOBT. All participants underwent colonoscopy. The primary outcome was the sensitivity of FOBTs for CRC detection. A total of 2,930 participants were enrolled, with 2,618 participants meeting inclusion criteria and completing FOBTs and colonoscopies. At the threshold of 5.2 µg/g, quantitative FIT demonstrated comparable sensitivity for CRC detection (90.1%) to self-administered qualitative FIT (87.1%), general qualitative FIT (91.1%), and gFOBT (82.2%) (all P > 0.05). The positive rate of quantitative FIT (12.4%) was significantly lower than that of self-administered qualitative FIT (27.5%), general qualitative FIT (24.2%), and gFOBT (23.0%) (all P < 0.05). Quantitative FIT showed superior specificity (93.9%) compared to self-administered qualitative FIT (79.5%), general qualitative FIT (83.6%), and gFOBT (80.7%) (all P < 0.05). Furthermore, quantitative FIT at 5.2 µg/g exhibited higher PPV and LR + for CRC, advanced adenoma (AA) and advanced neoplasia (AN) than other FOBTs. Receiver operating characteristic (ROC) analysis and area under the curve (AUC) revealed excellent accuracy for CRC detection (AUC: 0.951, 95% CI: 0.920-0.981). The quantitative FIT with a threshold of 5.2 µg/g demonstrated superior performance for early CRC screening in Chinese outpatients.

BackgroundLynch Syndrome (LS) is an autosomal dominant disease characterized by germline heterozygous mutations in DNA mismatch repair (MMR) genes. High-risk LS patients may proceed to colorectal cancer (CRC). However, the drivers or biomarkers of LS benign colon tissue approaching malignant CRC are not completely understood. This study aimed to understand the molecular and cellular changes during malignant transition in LS.MethodsSingle-cell RNA sequencing (scRNA-seq) was used to analyze paired fresh biopsy samples from 3 LS patients (carcinoma vs. para-carcinoma, labeled as LS-CA vs. LS-paraCA). Single-nuclear RNA sequencing (snRNA-seq) was used to analyze a frozen biopsy sample of a LS patient. Datasets of Healthy controls and patients diagnosed with sporadic CRC (without LS-related germline or somatic mutations; labeled as nonLS-CRC) were downloaded from the open source. Integrative computational analysis was performed to conclude potential drivers of the malignant transition. Immuno-histo-fluorescence staining (IHF) were also performed for validating the proposed three key markers.ResultsIn the single-cell atlas, we observed an increase of primitive cancer stem-cells with high expression of biomarkers CEACAM5, BACE2, GPRC5A and OLFM4 in the epithelium of the LS. Both infiltration of immune cells and pathways related to DNA repair biological activity in LS are dramatically increased in carcinoma compared to para-carcinoma. The mutation burden in LS is fundamentally elevated compared to that in healthy controls. Furthermore, T cell and macrophage-related tumor immunity in LS is readily mobilized in carcinomas compared to para-carcinoma.ConclusionsThis study provides single-cell transcriptomic resource using affected tissues from patients with Lynch Syndrome and describes an integrative profile covering the alterations of cancer stem cell markers, mutation burden, and tumor immunity during the malignant transition from latency state to Lynch Syndrome and to colorectal cancer at the single-cell level.

Background and study aims Non-magnifying endoscopy remains the most essential tool for detecting early gastric cancer (EGC), but there is still a lack of widely accepted diagnostic methods. We established an optimized EGC detection protocol using non-magnifying gastroscopy-guided targeted biopsy of morphological suspicious lesions and evaluated its effectiveness.Methods This study included 5738 participants across four medical centers in China. Targeted biopsies were performed on the following suspicious lesions for high-grade neoplasia (HGN) under screening non-magnifying gastroscopy: 1) ulcerative lesions; 2) esophagogastric junction reddish lesions outside the atrophic area; 3) pale or well-demarcated lesions outside the atrophic area, except polypoid lesions smaller than 5 mm; 4) elevated lesions with clear borders or uneven top within the atrophic area; and 5) flat/depressed lesions with irregular borders or uneven surface or ocher color under narrow-band imaging (NBI) within the atrophic area. Sensitivity for detecting gastric HGN and the positive predictive value (PPV) of targeted biopsy were calculated.Results The targeted biopsy method demonstrated a sensitivity of 90.9% (50/55, 95% confidence interval [CI] 83.1%-98.8%) and a PPV of 5.4% (50/931, 95% CI 3.9%-6.8%) for diagnosing HGN on per-lesion assessment. Lesions that met the suspicious morphological criteria carried a significant risk to be HGNs, even after adjusting for age, sex, and other risk factors associated with gastric cancer (adjusted odds ratio = 42.03, 95% CI 11.14-158.63, P < 0.001).Conclusions Targeted biopsy of suspicious lesions for HGN with non-magnifying gastroscopy can be used as a primary clue for detecting EGC.

Esophageal squamous cell carcinoma (ESCC) exhibits substantial molecular heterogeneity and unfavorable clinical outcomes. Current transcriptomic advances are shifting the focus from static gene expression profiles to the dynamic architecture of gene interaction networks. However, gene interaction perturbation signatures specific to ESCC remain poorly understood. This study aimed to develop a network-informed prognostic index derived from malignant epithelial cell signatures. In-house single-cell RNA sequencing data from 15 ESCC samples from the First Affiliated Hospital of Zhengzhou University were analyzed to identify dysregulated genes in malignant squamous epithelial cells. Then, a gene interaction perturbation network index (GIPNI) was constructed by systematically evaluating 75 combinations of machine-learning methods and validated across 3 independent cohorts. Associations between the GIPNI and genomic alterations, immune-related characteristics, and therapeutic response were also evaluated. Results showed ESCCs with high-GIPNI scores were associated with advanced clinicopathological features and overactivated mitotic cell cycle and epithelial cell differentiation pathways. Immune profiling suggested that low-GIPNI tumors had a more immune-infiltrated microenvironment. Notably, high-GIPNI ESCCs were associated with higher sensitivity to some common chemotherapeutic agents. Overall, the GIPNI provides a network-informed and malignant squamous cell-oriented framework for prognostic assessment in ESCC. This integrative approach may facilitate risk stratification and provide insights into individualized therapeutic strategies.

BACKGROUND Postoperative recurrence (POR) of Crohn's disease (CD) is a major therapeutic challenge. AIM To evaluate ustekinumab (UST) for the POR management in CD in a Chinese multicenter cohort. METHODS This retrospective analysis included postoperative CD patients with >= 2 high-risk features receiving UST at four tertiary centers. Patients were stratified into a first-line group (biologic-na & iuml;ve, n = 45) and a second-line group (prior biologic failure, n = 26). The primary outcome was endoscopic improvement (>= a 1-point reduction in the Rutgeerts score). Multivariate generalized estimating equations (GEE) were used to identify therapeutic response predictors. RESULTS Overall, 81.7% achieved endoscopic improvement, with 36.6% achieving complete remission. Clinical remission reached 91.5% with a significant Harvey-Bradshaw Index reduction (5.5 +/- 2.8 to 2.1 +/- 1.7, P value < 0.001). The GEE multivariate analysis identified first-line UST therapy (OR = 1.727, 95%CI: 1.042-2.862, P = 0.034) and shorter disease duration (OR = 0.979, 95%CI: 0.967-0.992, P = 0.001) as independent predictors of endoscopic improvement. Significant improvements were observed in nutritional parameters (i.e., albumin and hemoglobin) and inflammatory markers (i.e., C-reactive protein and fecal occult blood positivity). Adverse events occurred in 9.9% of patients. These were all mild-to-moderate severity. CONCLUSION UST demonstrated significant effectiveness and a favorable safety profile for the management of POR in CD. These findings support its use as an effective therapeutic option, particularly under a first-line setting, and provide valuable evidence to optimize postoperative management strategies for CD recurrence in Chinese populations.

ABSTRACT The major challenge in the clinical treatment of gastrointestinal mucosal injury caused by high‐altitude hypoxic environments lies in its unclear underlying mechanisms. In the previous study, we found that hypoxia‐induced gastric and small intestinal damage was mainly attributable to ferroptosis mediated by hypoxia‐inducible factor‐α (HIF‐α; mainly HIF‐1α and HIF‐2α). Both plant exosome‐like nanoparticles and Aquilaria malaccensis Lam. have been reported to have antioxidant properties. In the present study, orally delivered A. malaccensis Lam. exosome‐like nanoparticles (AELNs) reduced HIF‐1α expression and alleviated gastric and small intestinal mucosal ferroptosis induced by hypoxia. We analyzed the compositions of AELNs and hypothesized that ipriflavone was the effector component, as it showed the highest abundance of metabolites. Subsequent experiments demonstrated that ipriflavone downregulated polyunsaturated fatty acid‐phospholipids, NADPH oxidase 4 (NOX4), and arachidonate 5‐lipoxygenase (ALOX5) by inhibiting HIF‐α, consequently alleviating hypoxia‐induced gastric and small intestinal mucosal ferroptosis. Ipriflavone was found to inhibit HIF‐α by targeting prolyl hydroxylase domain protein 2 (PHD2) to induce it to hydroxylate HIF‐α. This study highlights that ipriflavone, a potent HIF‐α inhibitor, significantly ameliorates the gastric and small intestinal mucosal damage caused by hypoxia and has promise in clinical applications for treating disorders characterized by high levels of HIF‐α.

Background and study aims: Research regarding utilization of capsule endoscopy for detecting early esophageal squamous cell carcinoma (ESCC) is limited. This study was designed to preliminarily explore diagnostic performance of magnetically controlled capsule endoscopy with a detachable string (DS-MCCE) for detecting early ESCC. Patients and methods: In this retrospective cross-sectional diagnostic study, 496 asymptomatic individuals with high-risk lesions suspicious for early ESCC in esophagus, suspected neoplastic gastric and duodenal lesions, and all ulcers in the upper gastrointestinal tract first underwent DS-MCCE followed by esophagogastroduodenoscopy (EGD) and biopsy within 1 week. Outcomes included diagnostic performance of DS-MCCE for esophageal mucosal lesions and early ESCC, examination time, patient comfort and preference, and safety. Results: DS-MCCE had a sensitivity of 95.36 % (95% confidence interval [CI] 90.32%-97.95%) and specificity of 88.99% (85.08%-91.99%) for detecting esophageal mucosal lesions, whereas for detecting early ESCC, it showed a sensitivity of 66.67% (95% CI 38.38%-88.18%) and specificity of 99.17% (95% CI 97.88%-99.77%). DS-MCCE demonstrated superiority to EGD without sedation in terms of patient comfort, and participants preferred DS-MCCE to EGD. Median examination time was 9.1 minutes. There were no adverse events associated with DS-MCCE. Conclusions: DS-MCCE has potential in detecting early ESCC, mainly for lesions that are larger in size or exhibit pronounced morphological features. These preliminary findings support a further large-sample prospective study and technical refinement.

OBJECTIVE:Here, we ascertained the clinical characteristics of Chinese patients with autoimmune gastritis (AIG) and determined the correlation of dietary and lifestyle factors with AIG occurrence and development to establish a noninvasive predictive model for AIG. METHODS:In this case-control study, we enrolled 479 patients from seven independent centers nationwide in China; of them, 279 had AIG, 112 had chronic atrophic gastritis mostly in the antrum, and 88 had chronic nonatrophic gastritis. Their clinical and lifestyle data were systematically collected and analyzed. Finally, a multivariate logistic regression disease prediction model was then established and validated. RESULTS:Most of the 279 patients with AIG were middle-aged, older, and female. In the predictive model of AIG, the larger amount of cooking oil used per meal and comorbid autoimmune thyroid disease was considered risk factors, and a diet rich in vitamin B12 was considered a protective factor. We plotted a receiver operating characteristic (ROC) curve of the model in the discovery and validation cohorts, and the areas under the ROC curves were 0.72 and 0.74, respectively. In addition, dietary structure, eating habits, sleep quality, and smoking status were noted to be correlated with the occurrence of gastrointestinal symptoms and complications, as well as histopathological grades of AIG. CONCLUSION:Dietary and lifestyle factors may predict AIG risk in Chinese populations and were related to AIG prognosis.

Objectives: This study aimed to ascertain the effectiveness of using fixed cold snare polypectomy (CSP) specimens, accompanied by endoscopic assessment, in predicting complete resection outcomes. Methods: In this prospective, single-center, observational investigation, patients with colorectal polyps measuring 5-15 mm were enrolled, who underwent CSP between August 2018 and January 2020. Following resection, the specimens were procured and fixed. The primary focus was on evaluating the accuracy of endoscopic margin appraisal of the fixed specimens in forecasting complete resection. The generalized estimating equation model was employed to delve into the potential risk factors contributing to false-positive endoscopic margin assessments of these fixed specimens. Results: A cohort of 150 patients, presenting with 260 polyps, were included in the analysis. The CSP procedure achieved a remarkable complete resection rate of 98.5 %. In assessing the accuracy of endoscopic evaluation for complete resection in fixed specimens with negative margins, we observed a sensitivity of 100.0 %, specificity of 87.1 %, an area under the curve (AUC) of 93.6 %, and an overall accuracy of 87.3 %. Crucial insights from the multivariate regression analysis unveiled sessile serrated lesions (SSL) as an independent risk factor for generating false-positive results during endoscopic margin assessments of fixed specimens, with an odds ratio of 3.5 (95 % CI: 1.3-9.3, P = 0.011). Conclusions: Endoscopic assessment's negative lateral margin could accurately predict complete resection in fixed specimens. The fixed specimens of SSL are not suitable for margin assessment by endoscopy after fixation.

The preferred resection methods for 10–20 mm non-pedunculated lesions remain unclear. This review summarizes the current methods and novel technologies for resecting 10–20 mm non-pedunculated colorectal polyps, mainly focusing on hot snare polypectomy, cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), and endoscopic submucosal dissection (ESD). The application of novel techniques involving bipolar snares and low-power pure-cut is expected to reduce adverse events (AEs) related to thermal damage, but prospective studies are needed to confirm their reliability. CSP, including conventional CSP and submucosal injection CSP (SI-CSP), maintains resection efficacy with dedicated snares or submucosal injection for regular non-pedunculated polyps and serrated lesions with a low AE rate of 0.0%–3.4%. Modified EMR techniques such as underwater EMR, tip-in EMR, and EMR-circumferential precutting demonstrate a 15.0%–20.0% increase in en bloc resection rates compared with conventional EMR while also reducing AEs. ESD is recommended as the preferred method for medium-sized colorectal lesions with suspected submucosal invasion, fibrosis, particularly when the procedure is technically challenging. In addition, optical diagnosis is essential for pathological assessment and precise resection. Also, postoperative follow-up is needed for high-risk lesions and cases with unsatisfactory resection.

Background: Colony-stimulating factor 3 (CSF3) is a cytokine that promotes inflammation by stimulating the maturation, proliferation, and trafficking of myeloid progenitor cells. However, the functional importance of CSF3 in colorectal cancer (CRC) remains unclear. Methods: CSF3 expression levels in CRC cells and tissues were detected by quantitative real-time PCR (qRT-PCR), western blot and immunohistochemistry (IHC). In vitro and in vivo assays were performed to investigate the oncogenic function of CSF3 in the tumor associated malignant phenotypes and the tumorigenic capability of CRC cells. Immunocoprecipitation was performed to verify the regulatory effects of CSF3 on IκBα ubiquitination. Results: We found that CSF3 was overexpressed in CRC tissues compared to adjacent normal tissues, which correlated with poor patient survival. In vitro, silencing CSF3 significantly impaired cell proliferation, colony formation, and migration, while enhancing apoptosis. In vivo, silencing CSF3 resulted in reduced tumor growth, weight, and volume, indicating its potential as a therapeutic target. Mechanistically, CSF3 was found to mediate CRC development by activating the NF-κB signaling pathway, as evidenced by the decreased phosphorylation of p65 and reduced IκBα ubiquitination in CSF3-silenced cells. Furthermore, CSF3 silencing modulated immune infiltration in CRC, promoting an anti-tumor immune response and altering the tumor microenvironment. Conclusion: CSF3 modulated the NF-κB signaling pathway through a distinct mechanism involving p65 phosphorylation and the activation of NF-κB by enhancing IκBα ubiquitination, thereby effectively promoting CRC development, and CSF3 may serve as a potential therapeutic target for repressing CRC advance and metastasis.

Revival stem cells (revSCs) defined by transient induction of clusterin (CLU) expression rapidly expand and differentiate into multiple IEC lineages during intestinal regeneration. Although revSC induction is well-studied, the mechanisms governing their differentiation remain unclear. In this study, we demonstrate that CREPT/RPRD1B, a protein highly expressed in tumors and essential for crypt-base columnar cell (CBC) maintenance, was required for revSC differentiation during intestinal regeneration. Using Villin-Cre-mediated CREPT knockout (Vil-CREPTKO) mice, we found that CREPT deletion leads to regeneration failure following irradiation-induced damage. Interestingly, revSCs were remarkably accumulated, but enterocytes were decreased in Vil-CREPTKO mice. Our single-cell transcriptome analyses demonstrated that CREPT deletion impaired the stem potential of revSCs and inhibited their differentiation into enterocytes and goblet cells. Lineage tracing experiments confirmed the reduced regenerative capacity of CREPT-deficient revSCs in vivo. Together, our findings identified CREPT as an important regulator of revSC differentiation during intestinal regeneration.

Background High heterogeneity of gastric cancer (GC) drives cellular diversity. This complicates liquid biopsies, as detecting tumor markers in bodily fluids may not fully represent the tumor due to uneven marker distribution, compromising test accuracy and sensitivity. Methods Integrative analysis of 43 paired tissues, TCGA, and GEO databases identified 24 key GC-specific DMPs. Combined analysis with cfDNA bisulfite sequencing (79 normal controls and 70 GC) revealed four GC-specific DMPs. We developed GC-mqMSP using cfDNA from 70 normal controls, 106 GC, 41 lung cancer, and 23 colorectal cancer patients, was further validated in an independent cohort (45 GC and 13 normal controls). dCas9-Tet1-CD targeted demethylation assessed functional roles in GC development. Result Based on four GC-specific DMPs common to both tissue and cfDNA, we developed an efficient and convenient GC-mqMSP assay for detection. This assay demonstrated the ability to distinguish early-stage GC patients from normal controls and specifically differentiated GC patients from those with other tumors, achieving an AUCs (0.932 and 0.927), sensitivity (90.54% and 84.38%), and specificity (83.67% and 90.48%) in the training and validation sets. We selected ZNF154 for further study for the high coefficient weights of its two DMPs (Cg05661282 and Cg03234186). DNMT1/UHRF1 complex bind to promoting their hypermethylation and suppressing ZNF154 expression. Hypermethylation of Cg05661282 and Cg03234186 facilitated GC cell proliferation, migration, and tumor formation both in vitro and in vivo. Targeted demethylation at these DMPs reversed tumorigenesis and progression. Conclusion A cfDNA methylation-based integrated score was constructed in this study to predict GC in patients clinically.

Agarwood, a traditional Chinese medicine, has been widely used in the treatment of gastrointestinal diseases. The antibacterial and antioxidant properties of agarwood essential oils (EOs) have been well documented. High-altitude (> 2500 m) regions attract tens of millions of visitors worldwide each year; however, the hypoxic environment poses a threat to the health of the body’s organ systems, including the digestive system. Additionally, hypoxia has been reported to alter the gut microbiota and metabolites. Our previous study demonstrated that hypoxia exposure triggered ferroptosis in the gastric and small intestinal mucosa. This study aimed to explore the therapeutic effects and potential mechanisms of EOs in hypoxia-induced gastric and small intestinal mucosal injury. EO effects were evaluated based on clinical manifestations, histopathological assessments, and lipid peroxidation as determined by reactive oxygen species (ROS) and 4-hydroxynonenal (4-HNE) levels. We also assessed microbiota changes through 16 S rRNA gene amplicon sequencing and analyzed metabolites using untargeted liquid chromatography–mass spectrometry in the gastric and small intestinal contents of mice. EO treatment significantly alleviated hypoxia-triggered mucosal damage in the stomach and small intestine. Notably, EOs reduced hypoxia-induced lipid peroxidation and partially recovered the microbiota and metabolite disruptions induced by hypoxia. Specifically, Candidatus_Saccharimonas and Akkermansia may contribute to mucosal repair via regulating xanthoxic acid and aspartylglycosamine, and guanosine, respectively. EOs may provide a promising approach for treating hypoxia-induced gastric and small intestinal damage by repressing lipid peroxidation and regulating the microbiota and metabolites.

Background Gastrointestinal (GI) tract cancers are the second leading cause of cancer-related mortality, often due to late detection. There is a critical need for non-invasive, highly sensitive biomarkers for early-stage cancer and precancerous lesion detection to enable timely intervention. This study aimed to develop a blood-based method specifically optimized for early GI cancer detection and population-level screening. Methods Using large-scale public tissue methylation data and the Twist probe cfDNA profiles, we developed SPOGIT (Screening for the Presence of Gastrointestinal Tumors), a multi-algorithm model (Logistic Regression/Transformer/MLP/Random Forest/SGD/SVC) for early GI cancer detection. The model was rigorously validated through an internal (n = 83) and multicenter external validation (386 cancers/113 controls/580 precancers), with an interception model assessing its clinical potential. Results SPOGIT demonstrated high accuracy in detecting GI cancers, with a sensitivity of 88.1 % and a specificity of 91.2 %. Notably, it effectively identified early-stage (0-II) cancers with 83.1 % sensitivity. The model also showed significant potential for intercepting premalignant progression, detecting advanced adenomas (AA) and gastric precancerous lesions with sensitivities of 56.5 % and up to 62.4 %, respectively. In the external independent validation cohort, a complementary model CSO (Cancer Signal Origin) demonstrated an accuracy of 83 % for colorectal cancer and 71 % for gastric cancer. Most importantly, simulation analyses projected that SPOGIT implementation could significantly reduce late-stage diagnoses and increase 5-year survival rate by 27.02 % through early interception. Conclusions This study introduced a novel, dual-model blood architecture (SPOGIT/CSO) that enables highly accurate, early detection of GI cancers and their precursors. By facilitating timely clinical intervention, SPOGIT/CSO represented a paradigm-shifting strategy with the potential to significantly improve patient survival outcomes and transform GI cancer management.

Tens of millions of people worldwide travel to high-altitude regions (> 2500 m) every year for short-term work, tourism and pilgrimage. Hypoxia, resulting in a range of gastrointestinal disorders, is a significant physiological challenge in high-altitude environments. The gastrointestinal microbiota is closely linked to the mucosal barrier and our previous research found that hypoxia-induced mucosal injury mainly occurs in stomach and small intestine. This study aimed to characterize the temporal dynamics of gastric and small intestinal microbiota by directly analyzing the luminal contents to elucidate site-specific microbial alterations and their potential role in mucosal damage under hypoxic conditions. C57BL/6 J mice were randomly assigned to four groups: normoxic control, 1-day hypoxic exposure, 3-day hypoxic exposure and 12-day hypoxic exposure. Fresh gastric and small intestinal contents were collected for 16S rRNA sequencing. The operational taxonomic unit (OTU) counts, α/β-diversity and temporal microbial abundance shifts across different durations of hypoxia exposure were analyzed. Our results found that short-term hypoxia (1-3 days) significantly reduced the OTU counts and diminished α/β-diversity in the stomach and small intestine. However, prolonged hypoxia (day 12) reversed the diminished OTU counts and α/β-diversity to near-normoxic levels. In the stomach, short-term hypoxia increased the abundances of the phylum Firmicutes and genus Lactobacillus and suppressed the levels of the phyla Verrucomicrobia, Candidate_division_TM7, Tenericutes, Actinobacteria, and Bacteroidetes and genera S24-7_unclassified and Bifidobacterium. However, at 12 days of hypoxia, these phyla and genera reverted to near-normoxic levels. In the small intestine, the relative abundances of the phylum Firmicutes and genus Lactobacillus increased and those of the phyla Actinobacteria and Verrucomicrobia and genera Bifidobacterium and Akkermansia decreased during short-term hypoxia. However, these altered bacteria returned to near-normoxic levels by day 12 of hypoxia. Temporal clustering revealed persistent taxon shifts; the relative abundances of the phyla Gemmatimonadetes and Acidobacteria and genera Gemmatimonas, Kocuria, Parasutterella, and Saccharopolyspora declined steadily, while Staphylococcus increased consistently in the stomach. In the small intestine, the relative abundance of the genus Stomatobaculum consistently increased in response to prolonged hypoxia. This study provided a time-resolved overview of gastric and small intestinal microbiota adaptations to hypoxia, identified potential candidate taxa involved in mucosal injury caused by hypoxia.

Human umbilical cord mesenchymal stem cells (HUMSCs) are effective therapies for inflammatory bowel disease. However, the mechanisms remain unresolved. We found HUMSCs express CD126 (IL-6 receptor), which indicated CD126 sub-populations might show a distinct response to inflammation. In the present study, we explored whether CD126 is a critical molecule for HUMSCs in regulating inflammation. We assessed the regulatory effects of CD126 high (CD126hi) on the T lymphocyte subpopulations and related cytokines in the dextran sulfate sodium (DSS)-induced colitis model. The effect of CD126hi was evaluated by Hematoxylin and Eosin (H E) staining, fluorescence-activated cell sorting (FACS), and enzyme-linked immunosorbent assay (ELISA) analyses. Statistical significance was typically determined using Student’s t-test or one-way analysis of variance (ANOVA) with Tukey test. The disease symptoms were markedly ameliorated and the interleukin-6 (IL-6), interleukin-17 (IL-17), interferon-γ (IFN-γ), Tumor necrosis factor-α (TNF-α), and interleukin-4 (IL-4) levels were significantly reduced in DSS-treated mice administered with CD126hi HUMSCs but not in DSS-treated mice administered with CD126 low (CD126lo) HUMSCs. Intriguingly, CD126hi HUMSCs significantly increased the levels of transforming growth factor-β (TGF-β1) and interleukin-10 (IL-10) in DSS-treated mice, accompanied by an increase in regulatory T cells (Treg cells). In vitro experiments showed that CD126hi HUMSCs secreted TGF-β1 in response to IL-6 stimulation, while CD126lo HUMSCs were latent in the inflammatory environment. We considered that TGF-β1 secreted by CD126hi HUMSCs regulated the balance of Treg cells and thus promoted the recovery of murine colitis. Our results revealed a mechanism wherein CD126hi HUMSCs function as inflammatory sensors and secrete anti-inflammatory cytokines to rebalance the population of T cells. This study shed light on the potential therapeutic application of CD126hi HUMSCs for inflammatory diseases such as inflammatory bowel disease.

Despite significant advancements in diagnosis and treatment, cancer remains a leading cause of mortality globally. Cancer gene therapy has emerged as a promising strategy, with numerous clinical trials demonstrating its efficacy in targeting tumor cells, vasculature, and immune components. However, precise and selective gene expression regulation remains a challenge. In this study, we demonstrated that the CREPT (cell-cycle related and expression-elevated protein in tumor) promoter holds great potential for targeted cancer gene therapy. CREPT, a tumor-promoting protein as a positive regulator of gene transcription, is highly expressed across various cancer types while exhibiting minimal expression in normal tissues. The CREPT promoter mediated robust and tumor-selective transgene expression in vivo following both local and systemic administration, with only minimal off-target expression detected in blood and none in normal organs. Leveraging this specificity, we engineered an adenovirus encoding diphtheria toxin fragment A under CREPT promoter regulation. This construct was selectively expressed and inhibited protein synthesis, leading cancer cell death in vitro and in vivo. These findings demonstrate that the CREPT promoter may serve as a useful regulatory element for the development of targeted cancer gene therapy.

The aim of this study was to evaluate the clinical outcomes of extensive submucosal dissection involving more than three-fourths of the circumference (eESD) for gastric epithelial neoplasia. Consecutive patients treated by eESD for gastric epithelial neoplasia were retrospectively included at 7 medical centers between 2015 and 2025. Short-term outcomes were en bloc resection, R0 resection, curative resection, procedure time, and adverse events, whereas long-term outcomes were local recurrence rate (LRR), simultaneous multiple carcinomas incidence rate (SMCIR), heterochronous multiple carcinomas incidence rate (HMCIR), and cancer metastasis incidence rate (CMIR). Forty-three patients with 47 lesions (median tumor size: 6.0 cm) were analyzed. The en bloc resection, R0 resection, and curative resection rates were 100, 97.9, and 93.6