BackgroundObservational studies highlighted a link between the appendix and inflammatory bowel disease (IBD), but proving causality has been difficult due to the lack of a clear temporal sequence.MethodsThis research used a two-sample bidirectional univariable Mendelian randomization (MR), multivariable MR and linkage disequilibrium score regression (LDSC) analyses to explore the relationship between acute appendicitis, appendectomy, and IBD. Eligible instrumental variables were screened from previous genome-wide association studies (GWAS) of European ancestry for analysis. The inverse variance-weighted method was used for the primary analysis. Sensitivity analyses were used to detect and correct pleiotropy. LDSC analysis determined SNP-based heritability (h2) for acute appendicitis, IBD, Crohn's disease (CD), and ulcerative colitis (UC). Following that, cross-trait LDSC analysis assessed genetic correlations (rg) between these traits using GWAS summary data.ResultsGenetically predicted UC was significantly associated with a lower risk of acute appendicitis (OR = 0.933, 95% CI 0.911-0.957, p < 0.001) and appendectomy (OR = 0.954, 95% CI 0.932-0.976, p < 0.001). Conversely, no causal effect was observed from acute appendicitis or appendectomy on IBD, UC, or CD. While a suggestive association was noted for CD with appendectomy in univariable analysis, it did not remain significant after multivariable adjustment for the influence of UC. A significant negative genetic correlation further supported the inverse relationship between UC and acute appendicitis (rg = -0.205, p = 0.005).ConclusionsIn conclusion, genetically predicted UC was causally associated with a decreased risk of acute appendicitis and appendectomy, but neither acute appendicitis nor appendectomy has a causal impact on the risk of IBD, UC, or CD. These findings suggest that ulcerative colitis (UC) may confer a protective effect against the development of acute appendicitis, offering valuable insights into the shared genetic architecture and potential biological mechanisms underlying these conditions.

Efforts to improve the survival rates of patients with severe hemorrhage are highly dependent on hemostatic materials to achieve rapid and timely hemostasis. Zeolites have demonstrated their superb procoagulant properties and been made into various forms of commercial hemostatic dressings, including zeolite granules, zeolite-cotton gauze, and zeolite-cotton balls. In this work, a zeolite-polyvinyl alcohol (PVA) composite sponge was fabricated without using any additional organic binders via an in situ hydrothermal synthesis method. This spongiform zeolite-based hemostatic material conforms well to irregular wound surfaces and provides sustained pressure on the entire surface, making it more applicable to hemostasis of wounds with irregular concave-convex surfaces compared with current zeolite hemostatic materials. In a rabbit model of lethal massive hemorrhage, the hemostasis time of the zeolite-PVA group (195 s) was significantly shorter than that of the reference cotton gauze group (307 s). And the blood loss in the zeolite-PVA group (13.0 g) was approximately half of that in the cotton gauze group (23.8 g). Consequently, the zeolite-PVA group achieved 100% survival rate in this severe hemorrhage model, while the survival rate in the cotton gauze group was only 75%. This new zeolite-based hemostatic material expands the practical usage of zeolite composite materials and provides a promising solution for massive hemorrhage control in pre-hospital trauma treatment.

INTRODUCTION:Endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging, with high operator radiation exposure, physical strain, and a steep learning curve, necessitating a robotic solution. This study evaluated robotic-assisted ERCP feasibility and efficacy in an animal model. METHODS:In this randomised controlled crossover study, three experienced endoscopists performed 24 ERCP procedures (12 robotic-assisted vs. 12 manual) on four beagles using the YunSRobot system. Primary outcomes included papilla positioning maintenance, cannulation time, and success rate. RESULTS:Robotic-assisted ERCP demonstrated superior papilla positioning (95.74% vs. 77.25%, p < 0.01), indicating more endoscopic stability during cannulation. The successful cannulation rate was identical in both groups (83.3%). The robotic group required fewer attempts (2.0 vs. 3.5) and experienced no scope dislocations (0 vs. 5). No severe adverse events occurred in either group. CONCLUSIONS:Robotic-assisted ERCP is feasible, safe, and effective, offering significantly improved endoscopic stability with comparable cannulation success to manual techniques.

Blood transfusion plays a crucial role in the emergency care of trauma patients, significantly impacting their survival rates and prognoses, thereby saving millions of lives annually. Early and rapid recognition of transfusion needs in trauma patients is essential. This study aims to establish a predictive model for emergency transfusions in patients with severe trauma using machine learning (ML). Data were obtained from a comprehensive and anonymized set of medical records. LASSO regression was employed for feature selection. Six ML algorithms were utilized to develop predictive models. The performance of these models was assessed based on their identification accuracy, calibration, and clinical utility. Additionally, the SHapley Additive exPlanations (SHAP) method was applied to visualize model features and predictions on an individual case basis. A total of 1716 trauma patients were included in the study and 278 (16.2%) receive blood transfusion after emergency room admission. A model with 11 variables was built, with XGBoost performing best, achieving an area under the curve of 0.884 (95% CI: 0.847–0.921) and brier score of 0.0878 (0.0734–0.1071). Key predictors included, shock index, systolic blood pressure, heart rate, traumatic brain injury, hepatic insufficiency, age, gender, respiratory rate, percutaneous arterial oxygen saturation, pelvic fracture, and femoral fracture. The model also showed robust net benefit across a threshold probability (0.1–0.75). We developed a ML model to predict the need of transfusion in trauma patients and conducted a comprehensive assessment of 6 models in terms of discrimination, calibration, and clinical utility. The SHAP method was employed to visually interpret the influence of each variable, thereby enabling clinicians to better understand the underlying mechanisms of ML.

Rapid and effective bleeding control is essential for saving lives from severe hemorrhage. Currently, expandable hemostatic materials are in urgent demand for narrow and deep wounds because they can be quickly packed into a wound cavity and expand internally to generate pressure that promotes hemostasis. In this work, a zeolite-poly(vinyl alcohol) (PVA) composite sponge was first prepared by decorating zeolite powders onto a commercial medical PVA sponge, and it was further fabricated into small tablets in a compressed state. The small tablets can be easily loaded inside a syringe-like applicator for rapidly injecting into deep wounds in less than 3 s, and they can quickly expand six times in less than 30 s when they come into contact with blood. This material shows outstanding hemostatic efficiency and excellent biosafety. In a New Zealand rabbit severe femoral artery hemorrhage model, the short average hemostasis time (123 s) and the small total blood loss (9.9 g) for the zeolite-PVA sponge group clearly demonstrate its outstanding hemostatic efficiency, compared to the commercial Celox sponge group (220 s and 22.9 g) and the gauze group (333 s and 28.5 g). Consequently, the timely and effective hemostasis led to a 100% survival rate for the zeolite-PVA sponge group in this severe femoral artery hemorrhage model. On the contrary, the survival rates of the gauze group and the Celox sponge group were only 67% and 83%, respectively. This rapidly expandable zeolite-PVA sponge material provides a promising solution for meeting the challenge of massive hemorrhage in narrow and deep wounds.

Honeybees (Apis mellifera), as social insects, exhibit complex social behaviors and cognitive functions. The short lifespan and stable gut microorganisms of honeybees provide certain availability as a rapid and high-flux animal model for aging research. This study explored the effect of D-galactose, a common aging inducer, on honeybees and investigated the associated effects and mechanisms, with particular focus on the potential protective role of sodium butyrate. Experimental cohorts were established as follows: conventional (CV) group, D-galactose-treated (DG) group, and sodium butyrate-treated (SB) group. The CV group was fed sucrose solution; the DG group was fed D-galactose solution; and the SB group was fed D-galactose and sodium butyrate solution. A comprehensive assessment was conducted on day 15 post-treatment, including survival analysis, starvation test, motor, learning and memory ability tests, malondialdehyde test, and Smurf test. Potential mechanisms through the microbiome and metabolome were investigated. Compared to the honeybees from the CV group, those in the DG group showed a shortened lifespan, a weaker energy storage ability, impaired motor, learning, and memory abilities, reduced weight, increased oxidation, and a disrupted gut barrier. These phenotypic changes were associated with microbial dysbiosis characterized by Lactobacillus enrichment and diminished butyrate levels. Notably, sodium butyrate supplementation extended the honeybees' lifespan and improved their learning and memory abilities damaged by D-galactose. Our findings establish honeybees as a valuable model system for aging research and highlight the crucial role of butyrate metabolism in senescence regulation.IMPORTANCEThis study presents a novel approach to investigating aging processes by establishing a D-galactose-induced aging model in honeybees. Our findings demonstrate that butyrate supplementation effectively attenuates D-galactose-induced senescence phenotypes, suggesting its potential as a therapeutic intervention for age-related decline. This research provides a unique model system for aging studies and highlights the significant role of butyrate in modulating senescence progression. The results contribute to our understanding of the molecular mechanisms underlying aging and offer new insights into potential anti-aging strategies.

BackgroundImmune checkpoint inhibitors (ICIs) represent an effective treatment for various malignant tumors. However, the utilization of ICIs is frequently accompanied by immune-related adverse events (irAEs), among which immune checkpoint inhibitor (ICI)-induced colitis is a notable complication. Current clinical guidelines recommend corticosteroids as the first-line therapy for ICI-induced colitis. Nevertheless, subset of patients fails to respond adequately to corticosteroid therapy, resulting in steroid refractoriness. At present, studies investigating the risk factors for steroid-refractory remain limited.Patients and methodsA retrospective analysis was conducted on patients diagnosed with ICI-induced colitis after malignant tumor treatment with ICIs. Data collected included demographics, tumor and ICIs types, time to colitis onset, number of ICIs treatments, clinical manifestations (diarrhea, abdominal pain, bloody stool, fever), endoscopic findings (ulcerative lesions, extent of lesion distribution), laboratory results, grades of diarrhea and colitis, and corticosteroid treatment response. Patients were stratified into steroid-responsive and steroid-refractory groups. Multivariate logistic regression analysis was employed to identify risk factors related to steroid-refractory. Kaplan-Meier survival analysis and log-rank tests were conducted to compare survival time differences between the two groups.ResultsA total of 57 patients were included, with 45 patients in the steroid-responsive group and 12 patients in the steroid-refractory group. Univariate analysis revealed differences between the two groups in the time to colitis onset (median days: 97 vs. 141, P = 0.037), presence of fever (4.4% vs. 25.0%, P = 0.045), presence of ulcerative lesions (26.9% vs. 34.6%, P = 0.036), grades of colitis (P = 0.011), and serum interleukin-6 (IL-6) level (24.1 ± 20.5 pg/mL vs. 81.7 ± 38.7 pg/mL, P < 0.001). Multivariate regression analysis indicated that serum IL-6 level was an independent risk factor for steroid-refractory. Kaplan-Meier survival analysis showed no significant difference in survival time between the two groups.ConclusionsFor patients with ICI-induced colitis, serum IL-6 level at colitis onset could serve as an independent risk indicator for predicting the efficacy of corticosteroid therapy. Early consideration of selective immunosuppressive therapy (SIT) may be warranted with caution for patients with high serum IL-6 level.

With the increasing richness of medical images and clinical data, abundant data support is provided for multimodal chest disease diagnosis methods. However, traditional multimodal fusion methods are often relatively simple, leading to insufficient exploitation of crossmodal complementary advantages. At the same time, existing multimodal chest disease diagnosis methods usually focus on two modalities, and their scalability is poor when extended to three or more modalities. Moreover, in practical clinical scenarios, missing modality problems often arise due to equipment limitations or incomplete data acquisition. To address these issues, this paper proposes a novel multimodal chest disease classification model, MDFormer. This model designs a crossmodal attention fusion mechanism, MFAttention, and combines it with the Transformer architecture to construct a multimodal fusion module, MFTrans, which effectively integrates medical imaging, clinical text, and vital signs data. When extended to multiple modalities, MFTrans significantly reduces model parameters. At the same time, this paper also proposes a two-stage masked enhancement classification and contrastive learning training framework, MECCL, which significantly improves the model’s robustness and transferability. Experimental results show that MDFormer achieves a classification precision of 0.8 on the MIMIC dataset, and when 50% of the modality data are missing, the AUC can reach 85% of that of the complete data, outperforming models that did not use two-stage training.

Colitis-associated colorectal cancer (CAC) develops as a result of prolonged colitis in patients with inflammatory bowel disease. In recent years, the role of the gut microbiota in colitis-associated colorectal carcinogenesis has begun to be recognized. Specific microbes, such as enterotoxigenic Bacteroides fragilis, Fusobacterium nucleatum, and pks+ Escherichia coli, promote carcinogenesis by regulating oncogenic signaling, epithelial-mesenchymal transition, autophagy induction, and the immune microenvironment. Conversely, commensal fungi and probiotics exert tumor-suppressive effects by inhibiting inflammatory pathways and immune cell recruitment. Emerging microbiota-targeted strategies, including precision probiotics and fecal microbiota transplantation, can restore ecological homeostasis, attenuate inflammation, and enhance the efficacy of conventional therapies. This review summarizes the current understanding of the mechanisms underlying microbiota-driven CAC pathogenesis and assesses the potential applications of gut microbiota in the development of diagnostic tools and therapeutic interventions.

ABSTRACT Background The increasing incidence of inflammatory bowel disease (IBD) presents significant medical and societal challenges. A well‐designed IBD database is crucial for both epidemiological studies and clinical management. However, inconsistencies between regional databases hinder cross‐institutional and international research, especially between Eastern and Western societies. Methods We developed a new IBD database, the 301 IBD database, integrating the IBD clinical characteristics from the Penn IBD database (USA) and the latest IBD guidelines and consensus and clinical practices of the Chinese PLA General Hospital (PLAGH). We applied this database to analyze clinical data of IBD inpatients at PLAGH from 2008 to 2023. Results The 301 IBD database contains 490 items in 6 sections including demographic characteristics, personal history, clinical phenotype, disease activity, laboratory tests and examinations, and treatment. Features of the 301 IBD database include inpatient focus, biochemical indicators and opportunistic infection focus, and more about ulcerative colitis (UC)‐associated complications. Single‐center analysis revealed an increasing hospitalization trend, from 2.35% in 2008 to 3.94% in 2023. We found that the clinical characteristics of our UC inpatients are predominantly male (62.5%), extensive lesions (55.1%), low usage of biologics (4.1%), and a high incidence of UC‐CRC (3.0%). The clinical characteristics of CD inpatients included male predominance (68.39%), early onset age (35.43 ± 14.75‐year‐old), and high rate of surgery (25.81%). Conclusion The 301 IBD database, integrating Eastern and Western clinical data, provides a valuable tool for IBD clinical research. Future international, multicenter collaborations are expected to further enhance its utility.

Background The gut microbiota is closely associated with autism spectrum disorders (ASD), but the specific microorganism involved is not well understood. Bacteroides fragilis has been implicated in ASD in rodent models, though the evidence is inconclusive. B. fragilis exhibits remarkable genetic diversity and can be categorized into enterotoxigenic B. fragilis (ETBF) or non-toxigenic B. fragilis (NTBF). We aimed to investigate the potential role of B. fragilis in the ASD population. Methods Fecal samples were collected from 70 individuals with ASD, 45 individuals with Tic disorder (TD) as disease controls, and 64 healthy controls (HC) for PCR analysis to identify B. fragilis and ETBF. In five ASD children who were ETBF (+) and received fecal microbiota transplantation (FMT) treatment, we compared the ETBF copy number by quantitative PCR before and after FMT. Results There was no significant difference in the detection of B. fragilis between the ASD, TD, and HC groups, whereas ETBF was higher in ASD than in TD (21.43% vs. 6.67%, P = 0.0335) and HC (21.43% vs. 7.81%, P = 0.0272) (IDDF2024-ABS-0172 Figure 1. Stacked histogram of B. fragilis and subtype in ASD TD and HC children). Among five ASD children who tested positive for ETBF and received FMT treatment, 80% (4/5) showed a clinical response, a 4.5-point decrease in the CARS-2 score. Four cases had a reduction in their CARS-2 score by 5.5-6.5 and a decrease in ETBF copy number by over 90%. One non-responding case had a 2-point decrease in their CARS-2 score and a 49.88% decrease in ETBF copy number (IDDF2024-ABS-0172 Figure 2. Cars 2 scores and fecal ETBF copy number was reduced after FMT treatment in five ASD children). Conclusions The detection rate of ETBF was higher in ASD than in TD and HC children. FMT efficacy was correlated with ETBF, which may be a predictor of FMT efficacy for ASD. ETBF is a potential intestinal pathogen and biomarker for diagnostic and therapeutic targets for ASD.

ABSTRACTThe present study aimed to characterize the gut microbiota and serum metabolome changes associated with sleep deprivation (SD) as well as to explore the potential benefits of multi-probiotic supplementation in alleviating SD-related mental health disorders. Rats were subjected to 7 days of SD, followed by 14 days of multi-probiotics or saline administration. Open-field tests were conducted at baseline, end of SD (day 7), and after 14 days of saline or multi-probiotic gavage (day 21). Metagenomic sequencing was conducted on fecal samples, and serum metabolites were measured by untargeted liquid chromatography tandem-mass spectrometry. At day 7, anxiety-like behaviors, including significant decreases in total movement distance (P = 0.0002) and staying time in the central zone (P = 0.021), were observed. In addition, increased levels of lipopolysaccharide (LPS; P = 0.028) and decreased levels of uridine (P = 0.018) and tryptophan (P = 0.01) were detected in rats after 7 days of SD. After SD, the richness of the gut bacterial community increased, and the levels of Akkermansia muciniphila, Muribaculum intestinale, and Bacteroides caecimuris decreased. The changes in the host metabolism and gut microbiota composition were strongly associated with the anxiety-like behaviors caused by SD. In addition, multi-probiotic supplementation for 14 days modestly improved the anxiety-like behaviors in SD rats but significantly reduced the serum level of LPS (P = 0.045). In conclusion, SD induces changes in the gut microbiota and serum metabolites, which may contribute to the development of chronic inflammatory responses and affect the gut-brain axis, causing anxiety-like behaviors. Probiotic supplementation significantly reduces serum LPS, which may alleviate the influence of chronic inflammation.IMPORTANCEThe disturbance in the gut microbiome and serum metabolome induced by SD may be involved in anxiety-like behaviors. Probiotic supplementation decreases serum levels of LPS, but this reduction may be insufficient for alleviating SD-induced anxiety-like behaviors.

Observational studies highlighted an association between the appendix and inflammatory bowel disease (IBD). However, it's unclear whether the identified association is causal because of difficulties in establishing a clear temporal sequence. We investigated the association between acute appendicitis, appendectomy, and IBD by using two-sample bidirectional univariable Mendelian randomization (UVMR), multivariable MR (MVMR) and linkage disequilibrium score regression (LDSC) analyses. Eligible instrumental variables were screened from previous genome-wide association studies (GWAS) of European ancestry for analysis. The inverse variance-weighted (IVW) method was used for the primary analysis. Sensitivity analyses were used to detect and correct pleiotropy. LDSC analysis determined SNP-based heritability (h2) for acute appendicitis, IBD, Crohn's disease (CD), and ulcerative colitis (UC). Following that, cross-trait LDSC analysis assessed genetic correlations (rg) between these traits using GWAS summary data. Genetically predicted UC was associated with a significantly lower risk of acute appendicitis (OR = 0.933, P < 0.001) and appendectomy (OR = 0.954, P < 0.001), but conversely, acute appendicitis or appendectomy had no causal effect on IBD, UC or CD (all P > 0.05). CD had a suggestive association with appendectomy (OR = 0.981, P = 0.018) but was not significant after excluding the effect of UC by MVMR (OR = 0.999, P = 0.889). Furthermore, LDSC suggested a negative genetic correlation between UC and acute appendicitis (rg = -0.205, P = 0.005). In conclusion, our study confirms UC casually leads to a decreased risk of acute appendicitis and appendectomy, but neither acute appendicitis nor appendectomy reduces the risk of IBD, UC, and CD.

Colitis-associated colorectal cancer (CAC) is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease (IBD). Patients with IBD, including ulcerative colitis and Crohn's disease, are known to have an increased risk of developing CAC. Although the incidence of CAC has significantly decreased over the past few decades, individuals with CAC have increased mortality compared to individuals with sporadic colorectal cancer, and the incidence of CAC increases with duration. Chronic inflammation is generally recognized as a major contributor to the pathogenesis of CAC. CAC has been shown to progress from colitis to dysplasia and finally to carcinoma. Accumulating evidence suggests that multiple immune-mediated pathways, DNA damage pathways, and pathogens are involved in the pathogenesis of CAC. Over the past decade, there has been an increasing effort to develop clinical approaches that could help improve outcomes for CAC patients. Colonoscopic surveillance plays an important role in reducing the risk of advanced and interval cancers. It is generally recommended that CAC patients undergo endoscopic removal or colectomy. This review summarizes the current understanding of CAC, particularly its epidemiology, mechanisms, and management. It focuses on the mechanisms that contribute to the development of CAC, covering advances in genomics, immunology, and the microbiome; presents evidence for management strategies, including endoscopy and colectomy; and discusses new strategies to interfere with the process and development of CAC. These scientific findings will pave the way for the management of CAC in the near future.