Background: T1b gastric cancer (T1b-GC) carries a high risk of lymph node metastasis (LNM), which is a key determinant of treatment choice and prognosis. However, assessing LNM risk in T1b-GC remains challenging. This study aimed to develop machine learning models that integrate clinical data and postoperative hematoxylin and eosin-stained whole-slide images (HE-WSIs) to predict LNM in T1b-GC. Methods: This retrospective, multicenter cohort study analyzed 1023 patients with T1b-GC who underwent radical gastrectomy with lymphadenectomy. Thirteen machine learning algorithms were evaluated to develop a baseline predictive model using clinical variables. A deep learning system (DL-T1b) was trained and validated to predict LNM from histopathological tumor sections. A nomogram combining the baseline model and DL-T1b score was developed and evaluated. Results: Linear discriminant analysis was the optimal baseline model, achieving an area under the curve (AUC) of 0.771 (95% CI: 0.747, 0.813) based on six factors: sex, tumor size, differentiation grade, Laurén classification, tumor location, and lymphovascular invasion. The DL-T1b model demonstrated superior performance (AUC: 0.910; 95% CI: 0.869, 0.945). Incorporating the DL-T1b score with baseline clinical features into a nomogram enhanced its discriminatory performance (AUC: 0.964; 95% CI: 0.949, 0.978), achieving 93.2% sensitivity and 85.1% specificity. Spatial heatmaps of HE-WSIs revealed that the proportion of patches with a 100% predicted probability correlated positively with LNM risk. Conclusion: Derived from HE-WSI tumor regions, the DL-T1b score provides a robust and interpretable tool for individualized LNM risk stratification to guide clinical treatment.

Artificial sweeteners (AS) are widely used food additives, yet their potential role in autoimmune diseases (ADs) remains poorly understood. In this study, we integrated toxicological prediction, Mendelian randomization (MR), bioinformatics analyses, molecular docking, and gut microbiota assessment to investigate the association between AS exposure and ADs and to identify potential underlying mechanisms. Toxicity prediction using the ProTox-II server indicated a high immunotoxic potential for AS (> 0.9). MR analysis revealed a positive association between artificially sweetened cereal consumption and ADs risk (OR = 1.223, 95% CI: 1.005-1.488, p = 0.04). A total of 209 AS-related genes (ARGs) were identified through target prediction databases. Functional enrichment analyses demonstrated that these genes were primarily involved in apoptosis, TNF signaling, and IL-17 signaling pathways, suggesting their contribution to immune dysregulation. By integrating maximal clique centrality (MCC) algorithms with MR evidence, six core targets, including EPHX2, ESR1, ITGB3, MMP9, IL2RA, and PIM1, were identified as potential mediators of AS-associated ADs. Molecular docking further supported the binding affinity between AS compounds and these target proteins. In addition, gut microbiota analysis suggested that AS may suppress beneficial bacteria such as Akkermansia muciniphila, thereby disrupting arachidonic acid metabolism and chemokine signaling pathways involved in autoimmune pathogenesis. Collectively, these findings establish a multi-omics framework linking AS exposure to autoimmune dysregulation and provide novel insights into the immunotoxicological effects of AS and their potential role in the development of ADs.

Fusobacterium nucleatum (F. nucleatum) has been increasingly implicated in the pathogenesis of inflammatory bowel disease (IBD), yet the mechanisms underlying its effects remain incompletely defined. In this study, we integrated human fecal and mucosal samples, comparative metabolomics, multiple experimental colitis models, bacterial genetic manipulation, macrophage functional assays, and host signaling analyses to identify a macrophage-centered mechanism through which F. nucleatum exacerbates colitis. We show that F. nucleatum colonization increases intestinal and systemic levels of its metabolite succinic acid, upregulates the expression of its cognate receptor SUCNR1 on intestinal macrophages, activates NF-κB signaling, and promotes pro-inflammatory macrophage activation. This macrophage inflammatory response is associated with epithelial barrier disruption, increased epithelial apoptosis, and aggravated mucosal and systemic inflammation. A fumarate reductase-deficient (frdA-KO) F. nucleatum strain with impaired succinic acid production showed a markedly reduced capacity to activate macrophage NF-κB signaling, induce macrophage inflammatory activation, and aggravate colitis, whereas exogenous succinic acid restored these effects in the frdA-KO setting. Moreover, siSUCNR1 and pharmacological NF-κB inhibition substantially attenuated succinic acid-induced macrophage inflammatory activation, supporting the involvement of a SUCNR1-NF-κB signaling cascade. Collectively, these findings demonstrate that F. nucleatum exacerbates colitis by producing succinic acid and engaging SUCNR1-NF-κB-dependent inflammatory activation of macrophages, highlighting the F. nucleatum-succinic acid-SUCNR1-NF-κB axis as a potential therapeutic target in IBD.

Aging is a critical risk factor for platelet hyperreactivity and thrombosis, yet the mechanisms involved remain poorly understood. This study investigates the role of ubiquitination in platelet function during aging. We identified heightened platelet reactivity in aged mice and human donors. Proteomic analysis of ubiquitin (Ub)-modified proteins and western blot revealed a reduction in overall ubiquitination in aged platelets, correlated with increased expression of deubiquitinating enzymes. Notably, ubiquitin specific peptidase 25 (USP25) was significantly upregulated in platelets from aged individuals. Functional assays indicated that USP25 deficiency impairs platelet function and delays arterial thrombus formation. Mechanistic investigations integrating Ub-modified proteomics and mass spectrometry demonstrated that USP25 enhances platelet hyperreactivity by stabilizing talin-1 through deubiquitination, maintaining its levels across various tissues, including the liver and spleen. Additionally, AZ1, a USP25/28 inhibitor, effectively sup pressed platelet functions in both aged human and mouse models and decreased age-dependent platelet hyperreactivity and thrombus formation. Collectively, the findings delineate a remodeling of platelet ubiquitination during aging and establish USP25-mediated talin-1 stabilization as a key modulator of platelet hyperactivity in the older population.

The incidence of early-onset colorectal cancer (EOCRC) has been increasing in recent years, the carcinogenesis of which has been linked to oral microbiota alterations. However, it is unknown if the salivary microbiome could help detect EOCRC. Therefore, we aimed to determine whether salivary microbiome profiles can distinguish patients with EOCRC from healthy individuals and to evaluate their diagnostic performance as a non-invasive screening tool. We collected saliva samples from 65 EOCRC patients and 63 control individuals, the microbiota of which was assessed using high-throughput 16S ribosomal RNA gene V3-V4 region sequencing. We then profiled the saliva microbiota and developed EOCRC screening models using machine learning (ML) algorithms. The alpha diversity was comparable between salivary microbiomes of the EOCRC patients and control individuals, while the beta diversity exhibited statistical difference between two groups. A differential analysis of the genus-level saliva microbial communities revealed that, in the EOCRC patients, Prevotella, Actinomyces, and Corynebacterium were more abundant, whereas Fusobacterium, Haemophilus, norank_o__Absconditabacteriales_SR1, norank_c__Gracilibacteria, Peptococcus, Eikenella, and Eubacterium_yurii_group were less abundant. Furthermore, in developing the EOCRC screening model based on the salivary microbiome, the neural network model showed the best performance, achieving an AUC of 0.780 and a recall of 0.929, showing potential for distinguishing EOCRC patients from control individuals in this cohort. This study first highlights the potential dysbiosis of salivary microbiota in EOCRC patients and suggests that salivary microbiome-based biomarkers may serve as potential non-invasive tools for EOCRC screening. Additional research with larger sample sizes would help to further validate these findings. This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR2400087634) on July 31, 2024, retrospectively registered.

BackgroundThe pathogenesis of ulcerative colitis (UC) involves genetic susceptibility and immune dysregulation. However, a more comprehensive understanding of its underlying mechanisms is still required.MethodsWeighted correlation network analysis (WGCNA) and Mendelian randomization (MR) were used to investigate the association and causality between lipid metabolism and UC. Hub genes were identified by applying ensemble machine learning (LASSO, SVM, XGBoost) to the merged transcriptomic data, followed by cell-type-specific localization using public single-cell RNA-seq data from UC tissues. Pathophysiological relevance was confirmed in a DSS-induced colitis mouse model. The mechanistic role of the key hub gene was defined through knockdown LPS challenge in colonic epithelial cells, coupled with transcriptomic profiling.ResultsIntegrated WGCNA and MR analyses established a strong association between UC and lipid metabolic pathways, which was experimentally confirmed by marked intracellular lipid accumulation in UC models. Mechanistically, this dysregulation was traced to lysosomal dysfunction, a finding solidified by pharmacological modulation with Rapamycin (enhancer) and Chloroquine (inhibitor), which directly demonstrated that lysosomal activity governs lipid metabolic disturbance. Subsequent machine-learning-based feature selection from lysosome-related genes pinpointed TRIM29 as a central regulator. Functional and transcriptomic analyses together demonstrated that TRIM29 knockdown attenuates UC progression by rescuing the lysosome-lipid metabolism axis, as evidenced by restored lysosomal function, enhanced cytoskeletal transport, improved lipid catabolism, a resolved pro-inflammatory immune profile, and downregulated inflammatory signaling.ConclusionThis study identifies TRIM29 as a master regulator that drives UC progression by disrupting lysosomal function and reprogramming lipid metabolism. Our work delineates the TRIM29-lysosome-lipid metabolism axis, providing a mechanistic rationale for targeting TRIM29 as a promising therapeutic strategy in UC.

Severe acute pancreatitis (SAP) is a life-threatening abdominal disease. In recent years, multiple studies have suggested that gut microbiota metabolites play a key role in regulating SAP disease outcomes. The gut microbial metabolite phenylacetylglutamine (PAGln) exerts important effects in inflammation and oxidative stress-induced injury; however, its role in SAP remains unexplored. In this study, caerulein and LPS were used to induce experimental SAP models in mice and AR42J cells, followed by histopathological, biochemical, and molecular biological analyses. SAP induced hemorrhagic necrosis of the pancreas, SAP-associated lung injury, intestinal barrier dysfunction, and significantly elevated circulating PAGln levels. Compared to the SAP group, PAGln administration significantly exacerbated inflammation, SAP-associated pulmonary injury, and intestinal barrier dysfunction. Mechanistically, PAGln may influence SAP-induced pancreatic injury and extrapancreatic organ injury by regulating ferroptosis and the TLR4/NF-κB signaling pathway. This study preliminarily demonstrates that PAGln, a gut microbial metabolite, exacerbates pancreatic injury, lung injury, and intestinal barrier dysfunction in SAP, potentially through activation of ferroptosis and the TLR4/NF-κB signaling pathway.

BackgroundUlcerative colitis (UC) is a chronic, multifactorial inflammatory bowel disease. The involvement of small GTPase-related genes (SGRGs) in UC remains poorly defined. This study aims to identify SGRGs associated with UC and elucidate the molecular mechanisms by which they regulate the pathological progression of UC.MethodsMultiple transcriptomic datasets were integrated to identify candidate SGRGs in UC. Four machine learning algorithms were utilized for biomarker screening, followed by the construction of a diagnostic nomogram. The robustness of the identified biomarkers and the nomogram was rigorously evaluated through external validation in multiple independent cohorts. Furthermore, the associations between biomarkers and clinical severity, as well as their capacity for differential diagnosis (UC vs. Crohn’s disease (CD)), were assessed. Functional enrichment, immune infiltration, and cross-dataset single-cell RNA sequencing (scRNA-seq) were employed for in-depth mechanistic investigation. In vivo experiments validated core gene expression.ResultsThree biomarkers (ARHGEF3, S100A8, and RHOU) were successfully identified and validated across multiple independent cohorts. The nomogram constructed based on these biomarkers exhibited excellent diagnostic performance (AUC = 0.991 in the training set, 0.938 and 0.968 in the external validation cohort). Notably, the expression levels of these biomarkers significantly correlated with clinical severity and pathological mucosal states, demonstrating their capacity to reflect disease activity and monitor progression. Furthermore, among the identified biomarkers, ARHGEF3 significantly differentiated UC from CD (p < 0.05), while all three markers exhibited discriminative potential with AUC values exceeding 0.6. Functional annotation illustrated that they were commonly enriched within pathways encompassing “Tight junction” and “Leukocyte transendothelial migration”. Immune infiltration assessment demonstrated 27 differentially expressed immune cells (DEICs) among the UC and control groups. Cross-dataset scRNA-seq analysis further confirmed that macrophages were the key cells, exhibiting significant metabolic reprogramming and functional heterogeneity in UC. In vivo experiments confirmed the expression of above biomarkers in UC.ConclusionThis study systematically identifies ARHGEF3, S100A8, and RHOU as novel UC diagnostic biomarkers, implicating them in disease progression via immune regulation and macrophage function. These findings provide a new basis for precise diagnosis and targeted therapy.

Esophageal cancer (EC) is a frequently diagnosed malignancy with limited available treatment options. Emerging evidence has underscored the significant role of tripartite motif (TRIM) proteins in various cancers. However, the specific role of TRIM11 in EC has not been elucidated. Here, we conducted a comprehensive bioinformatics analysis, along with cell line models and animal culture experiments, to investigate the role of and molecular mechanisms through which TRIM11 contributes to EC progression, and evaluate its potential as a candidate marker associated with adverse clinicopathological features. Transcriptomic analysis was conducted using data from TCGA, GTEx, CCLE, and other publicly available databases to assess TRIM11 expression and its correlation with clinicopathological features, immune infiltration and TRIM11’s relationship with treatment response in EC. In vitro experiments showed that TRIM11 overexpression significantly promoted EC cell proliferation, migration, and invasion. Flow cytometry analysis revealed that TRIM11 increased the proportion of cells entering the S phase. Mechanistically, co-immunoprecipitation assays demonstrated that endogenous TRIM11 directly interacted with Axin2 and GSK3β, two core components of the β-catenin destruction complex. Additionally, TRIM11 knockdown altered the expression of key proteins in the β-catenin signaling pathway, including CyclinD1, GSK3β, Axin2, and β-catenin. Collectively, these findings highlight TRIM11 as a pro-oncogenic factor and suggest that it is a potential functional driver of EC.

The association between proinflammatory dietary patterns and metabolic dysfunction-associated steatotic liver disease (MASLD) has been increasingly recognized; however, the underlying biological mechanisms remain unclear. This study aimed to investigate the relationship between dietary inflammatory potential and MASLD risk and to evaluate the mediating role of insulin resistance (IR)-related biomarkers in this association. A total of 13,675 participants from the National Health and Nutrition Examination Survey were included. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII) and Food Inflammatory Index (FII). Insulin resistance was evaluated using the triglyceride-glucose (TyG) index and its anthropometric-adjusted derivatives, including TyG-BMI, TyG-WC, TyG-WHtR, and TyG-ABSI. Multivariable logistic regression models were applied to examine the associations between DII, FII, and MASLD risk, and mediation analyses were conducted to quantify the proportion of the associations explained by IR-related biomarkers. Participants with MASLD exhibited significantly higher DII and FII scores than those without MASLD (p < 0.001). After adjustment for potential confounders, both DII (OR = 1.07, 95% CI: 1.04-1.10) and FII (OR = 1.04, 95% CI: 1.02-1.06). were independently associated with increased MASLD risk. Furthermore, both dietary inflammatory indices were positively associated with all evaluated IR-related biomarkers. Mediation analyses demonstrated that IR significantly mediated the association between proinflammatory dietary patterns and MASLD, with TyG-WHtR showing the strongest mediating effect, accounting for 73.9% of the association between DII and MASLD and 61.5% of the association between FII and MASLD. These findings indicate that a proinflammatory dietary pattern is associated with an increased risk of MASLD and that insulin resistance may represent a key pathway linking dietary inflammatory exposure to MASLD development. The results highlight the potential importance of targeting diet-induced insulin resistance for MASLD prevention and management.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by persistent colorectal mucosal damage, in which colonic epithelial cell pyroptosis and imbalanced macrophage M1 polarization serve as core pathological features, yet their interaction mechanism remains elusive. Matrix remodeling-associated 7 (MXRA7) has been implicated in inflammatory immune responses and tissue repair, but its role in UC progression is still unclear. In this study, we performed bioinformatics and cell-cell communication analyses using the GSE214695 single-cell RNA sequencing dataset, collected clinical colonic tissues from UC patients, and established a dextran sulfate sodium (DSS)-induced mouse colitis model, complemented by in vitro cell co-culture, gene knockdown/overexpression and molecular biological assays. The results showed that pyroptosis levels, the degree of macrophage M1 polarization, and MXRA7 expression were all significantly upregulated in the colonic tissues of both UC patients and model mice. Mechanistically, macrophage M1 polarization can directly trigger colonic epithelial cell pyroptosis, whereas MXRA7 may, on the one hand, reduce macrophage M1 polarization by inhibiting the NF-κB signaling pathway, and on the other hand, alleviate epithelial cell pyroptosis induced by M1-polarized macrophages. Collectively, MXRA7 may attenuate colonic tissue damage through these dual regulatory mechanisms, thereby serving as a potential regulatory factor or therapeutic target in UC.

Ulcerative colitis (UC), a chronic inflammatory bowel disease, remains difficult to treat due to incomplete understanding of its mechanisms and limited therapeutic options. Diosmin, a natural citrus-derived flavonoid, has shown promising anti-inflammatory effects, but its molecular mechanisms in UC are unclear. In this study, we investigated the protective role of diosmin using dextran sulfate sodium (DSS)-induced colitis in mice and LPS-stimulated HT-29 cells, integrating transcriptomic and network pharmacology analyses. Diosmin treatment significantly alleviated colitis symptoms, reduced inflammation, preserved colon length, and enhanced intestinal barrier integrity, with efficacy comparable to 5-aminosalicylic acid. RNA-seq and network pharmacology identified PI3K-Akt and NF-κB as key pathways associated with diosmin-mediated protection, while molecular docking was used as a supportive computational analysis to explore potential interactions with selected hub-associated proteins. Experimental validation confirmed that diosmin inhibited activation of PI3K-Akt-mTOR and NF-κB signaling, decreased pro-inflammatory cytokines (TNF-α, IL-1β and IL-6), increased IL-10, promoted intestinal barrier repair via upregulation of ZO-1, occludin, and E-cadherin, and suppressed apoptosis of colonic epithelial cells. Together, these findings suggest that diosmin exerts multi-target protective effects against experimental colitis by modulating inflammation, supporting barrier integrity, and regulating key signaling pathways, providing mechanistic insight into the actions of this citrus-derived bioactive compound in colitis.

An elevated risk for inflammatory bowel disease (IBD) has been linked to the intake of high-fat diet (HFD), yet the underlying molecular mechanisms remain unclear. The lysosome and the macroautophagy/autophagy-lysosome pathway (ALP) are critical for maintaining the intestinal epithelial barrier. By employing both an in vivo model of dextran sulfate sodium (DSS)-induced colitis in mice and an in vitro model using lipopolysaccharide (LPS)-treated NCM460 cells, we established that HFD in vivo and palmitic acid (PA) in vitro profoundly impair epithelial barrier function and amplify inflammation, which was linked to the suppression of lysosomal function and the ALP. Mechanistically, HFD in vivo and PA in vitro activated STAT3 (p-STAT3[Y705]) under DSS- and LPS-associated inflammatory stress, respectively. This led to a dual suppression of TFEB: on the one hand, activated STAT3 directly bound to the TFEB promoter to inhibit its transcription; on the other hand, it facilitated the lysosomal recruitment of MTOR and activated MTORC1, which promoted TFEB phosphorylation (p-TFEB[S211]) and hindered its nuclear translocation. This cascade resulted in lysosomal membrane permeabilization (LMP), loss of acidification, and impaired degradative function. Intestinal epithelial-specific knockout of Stat3 or pharmacological activation of TFEB restored lysosomal function, repaired the epithelial barrier, and ameliorated colitis. Conversely, rectal administration of AAV9-shTfeb reversed the protective effects conferred by stat3 knockout. Our study reveals that HFD in vivo and PA in vitro disrupt lysosomal function and the intestinal barrier through the STAT3-TFEB axis, suggesting this signaling pathway as a promising avenue for intervention in diet-associated IBD.Abbreviations: AB-PAS: Alcian blue-periodic acid-Schiff; ALP: autophagy-lysosome pathway; CD: Crohn disease; ChIP: chromatin immunoprecipitation; CLEAR: coordinated lysosomal expression and regulation; DSS: dextran sulfate sodium; HFD: high-fat diet; IBD: inflammatory bowel disease; IF: immunofluorescence; IHC: immunohistochemistry; LAMP: lysosome associated membrane protein; LGALS3/Gal3: galectin 3; LMP: lysosomal membrane permeabilization; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1; PA: palmitic acid; RRAG: Ras-related GTP binding; RRAG-CA: constitutively active RRAG GTPase; RT-qPCR: reverse transcription quantitative PCR; SQSTM1/p62: sequestosome 1; STAT3: signal transducer and activator of transcription 3; TA1: TFEB activator 1; TEM: transmission electron microscopy; TFEB: transcription factor EB; TJ: tight junction; TUNEL: terminal deoxynucleotidyl transferase dUTP nick-end labeling; UC: ulcerative colitis; WB: western blot; WT: wild-type.

Acute pancreatitis (AP) is a common gastrointestinal emergency requiring hospitalization. In recent years, several studies have demonstrated a role for 4-octyl itaconate (4-OI) in anti-inflammatory and oxidative stress injury. However, the potential effects of 4-OI in AP have not been investigated. Caerulein and LPS were used to induce experimental AP models in mice and AR42J cells and then studied by histopathology, biochemical, and molecular analysis. Ferroptosis inhibitor ferrostatin-1 effectively improves pancreatic injury and reduces lipid peroxidation products in experimental AP mice. 4-OI treatment significantly alleviated pancreatic and AP-associated lung injury and inflammation in experimental AP mice by inhibiting ferroptosis. The ferroptosis activator Erastin blocked the protective effect of 4-OI against pancreatic injury in AP, validating that 4-OI alleviates pancreatitis injury through ferroptosis. In vitro experiments further confirmed that 4-OI treatment ameliorated AP-induced pancreatic injury by inhibiting ferroptosis. Our study, for the first time, found that 4-OI ameliorates AP and AP-related lung injury by inhibiting ferroptosis in experimental AP mice, providing a new therapeutic target for alleviating AP.

BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is considered to be an important driver of the increasing burden of chronic liver disease (CLD) worldwide. It is necessary to analyze the burden of CLD due to NAFLD (CLD-NAFLD) systematically. METHODS:Data related to CLD-NAFLD burden from 2012 to 2021 were obtained from the Global Burden of Disease Study (GBD) 2021. The temporal trend of the incidence and disability-adjusted life years (DALYs) was quantified by average annual percentage change (AAPC). The driving factors of the incidence/DALYs change were explored through decomposition analysis. Slope index and concentration index were employed to investigate cross-country health inequalities. RESULTS:During 2012-2021, the global age-standardized incidence rate (ASIR) of CLD-NAFLD increased from 551.52 to 592.78 (per 100,000 population), while the age-standardized DALY rate (ASDR) decreased from 31.92 to 30.90 (per 100,000 population). North Africa and Middle East had the highest age-standardized prevalence rate (ASPR), East Asia experienced the most rapid increase in ASIR, and Caribbean exhibited the most substantial increase in ASDR. Decomposition analysis showed that the main factors driving the increase in incident cases were population growth and epidemiologic changes, whereas population aging and population growth were the main driving factors for the increase of DALYs. There was cross-country health inequality in the DALYs, which showed a decreasing trend from 2012 to 2021. However, the health inequality in incidence was not significant. CONCLUSIONS:The burden of CLD-NAFLD continues to increase. Health policy makers must develop corresponding strategies for the primary health care of metabolic diseases.

Aims: Very early-onset colorectal cancer (EOCRC) was defined as CRC diagnosed before the age of 35 proposed by the latest EOCRC management guideline. Until now, the disease burden of very EOCRC has never been reported. This study aimed to explore the burden of very EOCRC across the past three decades. Methods: We extracted the data from Global Burden of Disease Study to analyze the disease burden of very EOCRC. Risk factors for the burden of deaths and disability-adjusted life years (DALYs) due to very EOCRC were also explored in this study. Additionally, decomposition analysis and frontier analysis were also conducted. Results: Despite regional and gender variations, the global very EOCRC incidence cases increased from 21,874 (95 % UI: 20,386-23,470) to 41,545 (95 % UI: 37,978-45,523). Besides, the deaths cases also increased from 11,445 (95 % UI: 10,545-12,374) to 15,486 (95 % UI: 14,289-16,803), and the DALYs cases increased from 718,136 (95 % UI: 659,858-778,283) to 961,460 (95 % UI: 886,807-1,042,734). Decomposition analysis revealed the epidemiological change contributed most to the incidence burden of very EOCRC. Countries or regions with Sociodemographic Index (SDI) between 0.4 and 0.8 had greater disease burden improvement potential through frontier analysis. Diet low in milk, diet low in calcium, alcohol use, and high body-mass index were the main contributors to deaths and DALYs. Conclusions: The increase in CRC burden among populations younger than 35 years globally requires vigilance from policy makers, physicians, and young individuals themselves, especially those regions experiencing faster growth burden of very EOCRC.

The myriad implications of heavy metal pollution on human health have garnered substantial attention within the academic domain. Nevertheless, a notable research gap persists, as there is currently insufficient direct investigation elucidating the intricate interplay between nickel exposure and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). The data utilized in this study was sourced from the National Health and Nutrition Examination Survey 2017–2020. Hepatic steatosis was evaluated utilizing controlled attenuation parameters (CAP), and nickel exposure level was reflected by urinary nickel concentration. To analyze the association between nickel exposure and MASLD, three multiple logistic regression models with weights were developed. Furthermore, a mediation analysis was performed to examine insulin resistance’s potential mediating role. There were a total of 1,187 participants in the study, of which 548 (46.17

BackgroundThe gut microbiota plays a significant role in the progression of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The recently introduced Dietary Index of Gut Microbiota (DI-GM), which reflects the diversity of the gut microbiota, has yet to be investigated in relation to MASLD.MethodsThis analysis used raw data from the National Health and Nutrition Examination Survey (2001–2018). MASLD was identified using the US-Fatty Liver Index (US-FLI), and dietary recall data were applied to calculate the Dietary Index of Gut Microbiota (DI-GM). Weighted multivariate logistic regression models assessed the relationship between DI-GM and MASLD. Additionally, mediation analysis was performed to evaluate the influence of high-sensitivity C-reactive protein (hs-CRP) and body mass index (BMI) on the relationship between DI-GM and MAFLD. Propensity score matching (PSM) was employed to minimize confounding and reduce bias inherent to observational studies.ResultsA total of 3,473 participants were included in the analysis, among whom 1,247 were diagnosed with MASLD, with a weighted prevalence of 35.90%. After adjusting for demographic, lifestyle, and metabolic syndrome-related variables, a higher score of DI-GM was strongly linked to a lower risk of MASLD (OR = 0.90, 95% CI: 0.85–0.95, p < 0.001). Mediation analysis estimated that BMI accounted for 59.47% of the association (p < 0.001), while hs-CRP explained 15.68%. Even after PSM, a higher score of DI-GM remained significantly associated with a lower incidence of MASLD.ConclusionThe newly proposed DI-GM demonstrated a notable negative correlation with the prevalence of MASLD. Mediation analyses revealed that this relationship was largely influenced by BMI and hs-CRP, highlighting their critical mediating roles.

Aims:This study aimed to evaluate the related research on artificial intelligence (AI) in inflammatory bowel disease (IBD) through bibliometrics analysis and identified the research basis, current hotspots, and future development. Methods:The related literature was acquired from the Web of Science Core Collection (WoSCC) on 31 December 2024. Co-occurrence and cooperation relationship analysis of (cited) authors, institutions, countries, cited journals, references, and keywords in the literature were carried out through CiteSpace 6.1.R6 software and the Online Analysis platform of Literature Metrology. Meanwhile, relevant knowledge maps were drawn, and keywords clustering analysis was performed. Results:According to WoSCC, 1919 authors, 790 research institutions, 184 journals, and 49 countries/regions published 176 AI-related papers in IBD during 1999-2024. The number of papers published has increased significantly since 2019, reaching a maximum by 2023. The United States had the highest number of publications and the closest collaboration with other countries. The clustering analysis showed that the earliest studies focused on "psychometric value" and then moved to "deep learning model," "intestinal ultrasound," and "new diagnostic strategies." Conclusion:This study is the first bibliometric analysis to summarize the current status and to visually reveal the development trends and future research hotspots of the application of AI in IBD. The application of AI in IBD is still in its infancy, and the focus of this field will shift to improving the efficiency of diagnosis and treatment through deep learning techniques, big data-based treatment, and prognosis prediction.

In the context of the global increase in early-onset tumours, investigating the global disease burden caused by early-onset pancreatic cancer (EOPC) is imperative. Data on the burden of EOPC were obtained from the Global Burden of Disease Study 2021. A joinpoint regression model was used to analyse the temporal trend of the EOPC burden, and an age‒period‒cohort (APC) model was used to analyse the influence of age, period, and birth cohort on burden trends. Globally, the number of EOPC cases increased from 24,480 to 42,254, and the number of deaths increased from 17,193 to 26,996 between 1990 and 2021. The results of the APC model showed that the burden of EOPC increases with increasing age, whereas the variations in period and cohort effects exhibited a complex pattern across different sociodemographic index regions. Consequently, the disease burden of EOPC is increasing worldwide, highlighting the need for effective interventions.