DNA Hydrogels for Cancer Diagnosis and Therapy.

Nucleic acids, because of their precise pairing and simple composition, have emerged as excellent materials for the formation of gels. The application of DNA hydrogels in the diagnosis and therapy of cancer has expanded significantly through research on the properties and functions of nucleic acids. Functional nucleic acids (FNAs) such as aptamers, Small interfering RNA (siRNA), and DNAzymes have been incorporated into DNA hydrogels to enhance their diagnostic and therapeutic capabilities. This review discusses various methods for forming DNA hydrogels, with a focus on pure DNA hydrogels. We then explore the innovative applications of DNA hydrogels in cancer diagnosis and therapy. DNA hydrogels have become essential biomedical materials, and this review provides an overview of current research findings and the status of DNA hydrogels in the diagnosis and therapy of cancer, while also exploring future research directions.

Potential Risk Factors of Disorders of Gut-Brain Interaction in Undergraduates and Postgraduates: Partially Mediated by Life Stress and Lifestyle.

INTRODUCTION: This study aimed to investigate the prevalence of disorders of gut-brain interaction (DGBI) and life stress in college students, and explore risk factors of DGBI in college students and the role of life stress. METHODS: A total of 2,578 college students filled up validated questionnaires assessing GI symptoms, lifestyle, and life stress. Participants were diagnosed as DGBI based on the Rome III criteria. Multivariate ordinal logistic regression analysis and mediation effect model were employed to explore potential risk factors of DGBI and the mediating role of life stress and lifestyle in DGBI. RESULTS: A total of 437 of 2,578 (17.0%) college students were diagnosed with DGBI. College students with DGBI had higher levels of life stress, including eight specific categories. Females (1.709 [1.437, 2.033]), staying up late (1.519 [1.300, 1.776]), and life stress (1.008 [1.006, 1.010]) were risk factors for DGBI, while postgraduates (0.751 [0.578, 0.976]) and regular diet (0.751 [0.685, 0.947]) were protective factors. Males and poor family economic were associated with a higher risk of DGBI after controlling stress, while an association between grade and DGBI was mediated by stress, regular diet, and sleep habits. CONCLUSION: DGBI was common among college students. Life stress and lifestyle were associated with DGBI and mediated partial association between grade and DGBI in college students. More attention should be paid to undergraduates.

Efficacy and Safety of Vonoprazan-Based Quadruple Therapy for the Eradication of Helicobacter pylori in Patients with Peptic Ulcers: A Pooled Analysis of Two Randomized, Double-Blind, Double-Dummy, Phase 3 Trials.

Helicobacter pylori eradication is crucial in the treatment of peptic ulcers caused by H. pylori infection, a disease highly prevalent in Asia. We present a pooled analysis of two randomized, double-blind, double-dummy, phase 3 studies evaluating the efficacy and safety of vonoprazan-based bismuth-containing quadruple therapy for H. pylori eradication. Patients aged ≥18 years with endoscopically confirmed duodenal or gastric ulcers were randomized 1 : 1 to receive vonoprazan 20 mg or lansoprazole 30 mg once daily for up to 6 (duodenal ulcers) or 8 weeks (gastric ulcers). H. pylori-positive patients received vonoprazan- or lansoprazole-based bismuth-containing quadruple therapy for the first 2 weeks. H. pylori eradication was determined using the carbon-13 urea breath test at a follow-up visit 4 weeks post-treatment. The H. pylori eradication rate was 90.6% with vonoprazan vs. 85.2% with lansoprazole (difference: 5.4%; 95% confidence interval (CI): -0.1, 10.8). H. pylori eradication rates were 7.1% (95% CI: 1.4, 12.8) and 12.6% (95% CI: 3.9, 22.0) higher in patients aged <65 years and current smokers, respectively, with vonoprazan vs. lansoprazole. In the Chinese subpopulation, the H. pylori eradication rate was 92.0% with vonoprazan vs. 86.0% with lansoprazole (difference: 6.1%; 95% CI: 0.5, 11.7). Treatment-emergent adverse events occurred in 72.7 vs. 62.6% of H. pylori-positive patients at baseline in the vonoprazan vs. lansoprazole arm. H. pylori eradication with vonoprazan-based quadruple therapy was noninferior to lansoprazole-based quadruple therapy and exceeded 90%, a clinically relevant threshold for determining the efficacy of H. pylori eradication regimens (ClinicalTrials.gov identifier: NCT03050359; NCT03050307).

Potassium-competitive acid blockers and proton-pump inhibitors for healing of erosive esophagitis: a systematic review and network meta-analysis.

Background: Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are recommended for erosive esophagitis (EE), with good safety and tolerance. However, it is unclear which is the best treatment option for EE. Objectives: This study aimed to evaluate the comparative efficacy of P-CABs and PPIs for healing EE patients, seeking an appropriate treatment choice in the 4- or 8-week treatment and standard or double dose. Design: A systematic review and network meta-analysis. Data sources and methods: Relevant databases were searched to collect randomized controlled trials of PPIs and P-CABs in the treatment of EE up to 31 May 2023. Studies on standard or double-dose PPIs or P-CABs which were published in English and assessed 4- or 8-week healing effects in EE were included. A network meta-analysis was performed to evaluate the efficacy of the treatments under the frequentist framework. Sensitivity and subgroup analyses of patients with different baseline EE were also conducted. Results: In all, 34 studies involving 25,054 patients and 9 PPIs, 6 P-CABs, or placebo treatment interventions were included. The pooled 4-week healing rate was significantly statistically lower than the pooled 8-week healing rate for most treatments. Besides, the higher healing rate of double-dose treatment than standard-dose treatment was not observed in the initial treatment of most drugs. The main analysis only included studies conducted for both patients with and without severe EE at baseline, and the proportion of severe EE included in the study was >10%, Keverprazan 20 mg qd ranked best with a surface under the cumulative ranking curve (SUCRA) value of 84.7, followed by Ilaprazole 10 mg qd with a SUCRA value of 82.0, for the healing rate at 8 weeks. Sensitivity analysis showed that the results were robust. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, particularly for patients with severe EE. And the healing rate of Keverprazan 20 mg qd at 8 weeks ranked best in the subgroup without or with severe EE at baseline. Conclusion: This study showed that an 8-week treatment seemed more effective than the 4-week treatment for healing EE patients. The healing effect of Keverprazan (20 mg qd) ranked best in 8-week treatment, for both severe and non-severe EE patients. Trial registration: The study protocol was registered with INPLASY (registration number INPLASY2023120053).

A review and network meta-analysis of different medications for treating erosive esophagitis: potassium-competitive acid blockers and proton-pump inhibitors Why was the study done? Proton-pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are commonly used to treat Erosive esophagitis (EE) due to their good safety and tolerance. This study aimed to compare the effectiveness of P-CABs and PPIs in healing EE patients. We wanted to determine the best treatment choice in terms of the duration of treatment (4 or 8 weeks) and the dosage (standard or double-dose). What did the researchers do? The researchers searched relevant databases for randomized controlled trials that studied the use of PPIs and P-CABs in treating EE up until May 31, 2023. They included studies that evaluated the healing effects of standard or double-dose PPIs or P-CABs over a period of 4 or 8 weeks. A network meta-analysis was performed to compare the effectiveness of these treatments. They also conducted sensitivity analysis and subgroup analysis to examine the effects on patients with different levels of EE. What did the researchers find? The results showed that the healing rate after 4 weeks of treatment was significantly lower than the healing rate after 8 weeks for most treatments. Additionally, the higher healing rate observed with double-dose treatment compared to standard-dose treatment was not seen in the initial treatment of most drugs. In the main analysis, which included studies with patients both with and without severe EE at the beginning, Keverprazan 20mg qd was ranked as the most effective treatment with a healing rate of 84.7, followed by Ilaprazole 10mg qd with a healing rate of 82.0 at 8 weeks. The results were robust in sensitivity analysis. Subgroup analysis showed that most P-CABs had higher healing rates than PPIs, especially for patients with severe EE. What do the findings mean? Treating EE patients for 8 weeks was more effective than treating them for 4 weeks. Keverprazan (20mg once a day) with the 8-week treatment is the optimal method.

Identification of CXC Chemokine Receptor 2 (CXCR2) as a Novel Eosinophils-Independent Diagnostic Biomarker of Pediatric Eosinophilic Esophagitis by Integrated Bioinformatic and Machine-Learning Analysis.

Background: Eosinophilic esophagitis (EoE) is a complex allergic condition frequently accompanied by various atopic comorbidities in children, which significantly affects their life qualities. Therefore, this study aimed to evaluate pivotal molecular markers that may facilitate the diagnosis of EoE in pediatric patients. Methods: Three available EoE-associated gene expression datasets in children: GSE184182, GSE 197702, GSE55794, along with GSE173895 were downloaded from the GEO database. Differentially expressed genes (DEGs) identified by "limma" were intersected with key module genes identified by weighted gene co-expression network analysis (WGCNA), and the shared genes went through functional enrichment analysis. The protein-protein interaction (PPI) network and the machine learning algorithms: least absolute shrinkage and selection operator (LASSO), random forest (RF), and XGBoost were used to reveal candidate diagnostic markers for EoE. The receiver operating characteristic (ROC) curve showed the efficacy of differential diagnosis of this marker, along with online databases predicting its molecular regulatory network. Finally, we performed gene set enrichment analysis (GSEA) and assessed immune cell infiltration of EoE/control samples by using the CIBERSORT algorithm. The correlations between the key diagnostic biomarker and immune cells were also investigated. Results: The intersection of 936 DEGs and 1446 key module genes in EoE generated 567 genes, which were primarily enriched in immune regulation. Following the construction of the PPI network and filtration by machine learning, CXCR2 served as a potential diagnostic biomarker of pediatric EoE with a perfect diagnostic efficacy (AUC = ~1.00) in regional tissue/peripheral whole blood samples. Multiple infiltrated immune cells were observed to participate in disrupting the homeostasis of esophageal epithelium to varying degrees. Conclusion: The immune-correlated CXCR2 gene was proved to be a promising diagnostic indicator for EoE, and dysregulated regulatory T cells (Tregs)/neutrophils might play a crucial role in the pathogenesis of EoE in children.

Identifying MS4A6A+ macrophages as potential contributors to the pathogenesis of nonalcoholic fatty liver disease, periodontitis, and type 2 diabetes mellitus.

Purpose: Concrete epidemiological evidence has suggested the mutually-contributing effect respectively between nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), and periodontitis (PD); however, their shared crosstalk mechanism remains an open issue. Method: The NAFLD, PD, and T2DM-related datasets were obtained from the NCBI GEO repository. Their common differentially expressed genes (DEGs) were identified and the functional enrichment analysis performed by the DAVID platform determined relevant biological processes and pathways. Then, the STRING database established a PPI network of such DEGs and topological analysis through Cytoscape 3.7.1 software along with the machine-learning analysis by the least absolute shrinkage and selection operator (LASSO) algorithm screened out hub characteristic genes. Their efficacy was validated by external datasets using the receiver operating characteristic (ROC) curve, and gene expression and location of the most robust one was determined using single-cell sequencing and immunohistochemical staining. Finally, the promising drugs were predicted through the CTD database, and the CB-DOCK 2 and Pymol platform mimicked molecular docking. Result: Intersection of differentially expressed genes from three datasets identified 25 shared DEGs of the three diseases, which were enriched in MHC II-mediated antigen presenting process. PPI network and LASSO machine-learning analysis determined 4 feature genes, of which the MS4A6A gene mainly expressed by macrophages was the hub gene and key immune cell type. Molecular docking simulation chosen fenretinide as the most promising medicant for MS4A6A+ macrophages. Conclusion: MS4A6A+ macrophages were suggested to be important immune-related mediators in the progression of NAFLD, PD, and T2DM pathologies.

Fut2 Deficiency Promotes Intestinal Stem Cell Aging by Damaging Mitochondrial Functions via Down-Regulating α1,2-Fucosylation of Asah2 and Npc1.

Fut2-mediated α1,2-fucosylation is important for gut homeostasis, including the intestinal stem cell (ISC). The stemness of ISC declines with age, and aging-associated ISC dysfunction is closely related to many age-related intestinal diseases. We previously found intestinal epithelial dysfunction in some aged Fut2 knockout mice. However, how Fut2-mediated α1,2-fucosylation affects ISC aging is still unknown. On this basis, the herein study aims to investigate the role of Fut2-mediated α1,2-fucosylation in ISC aging. Aging models in ISC-specific Fut2 knockout mice were established. ISCs were isolated for proteomics and N-glycoproteomics analysis. ISC functions and mitochondrial functions were examined in mice and organoids. Ulex europaeus agglutinin I chromatography and site-directed mutagenesis were used to validate the key target fucosylated proteins of Fut2. As a result, Fut2 knockout impaired ISC stemness and promoted aging marker expression in aged mice. Proteomics analysis indicated mitochondrial dysfunction in Fut2 knockout ISC. More injured mitochondria, elevated levels of reactive oxygen species, and decreased levels of adenosine 5'-triphosphate (ATP) in Fut2 knockout ISC were found. Moreover, respiratory chain complex impairment and mitophagy dysfunction in Fut2 knockout ISC were further noted. Finally, Fut2 was demonstrated to regulate mitochondrial functions mainly by regulating the α1,2-fucosylation of N-acyl sphingosine amidohydrolase 2 (Asah2) and Niemann-Pick type C intracellular cholesterol transporter 1 (Npc1). In conclusion, this study demonstrated the substantial role of Fut2 in regulating ISC functions during aging by affecting mitochondrial function. These findings provide novel insights into the molecular mechanisms of ISC aging and therapeutic strategies for age-related intestinal diseases.

Significant improvement of physicians' knowledge and clinical practice: an opportune, effective, and convenient continuing medical education program on functional dyspepsia.

Aims: This cohort study aimed to explore the effect of a one-day online continuing medical education (CME) on the improvement of physicians' knowledge and clinical practice on functional dyspepsia (FD). Methods: Physicians were invited to participate in this CME via medical education applications. FD training videos made in advance were sent to participants via a weblink. Before and after training, participants were required to finish the FD knowledge test and provide case information of FD patients. McNemar test, Wilcoxon rank-sum test, Freidman test, Chi-square test, quantile regression, and generalized estimating equations (GEE) were used to perform statistical analysis. Results: There were 397 of 430 (92.33%) physicians finished this CME program. The total score of the FD knowledge test after training was significantly higher compared with before training [488.3 (468.3-510.0) vs. 391.7 (341.7-450.0), p < 0.001]. Particularly, physicians from primary hospitals show more increase in total scores than physicians from secondary and tertiary hospitals. According to the GEE model, receiving this online training was an independent predictor of physicians' choice of upper gastrointestinal endoscopy in patients with FD [OR 1.73, 95%CI (1.09-2.73), p = 0.020], especially in PDS. Also, it was an independent predictor of physicians' choice of acid-suppressive drugs in patients with FD [OR 1.30, 95%CI (1.03-1.63), p = 0.026], especially in EPS and PDS overlapping EPS. Conclusion: This one-day online CME program effectively and conveniently improved physicians' knowledge and clinical practice, providing new ideas for future CME and facilitating precise clinical management of FD patients with different subtypes especially in primary hospitals.

Efficacy and safety of peroral endoscopic myotomy for pediatric achalasia: A nationwide study.

Achalasia, a rare esophageal motility disorder characterized by the inability of the lower esophageal sphincter to relax and loss of esophageal peristalsis, significantly impacts pediatric patient quality of life through symptoms like dysphagia, chest pain, and weight loss. This nationwide retrospective cohort study evaluates the efficacy and safety of peroral endoscopic myotomy (POEM) for pediatric achalasia in Mongolia, contributing to the limited global data on this minimally invasive treatment in children. Conducted between February 2020 and March 2022 at 2 tertiary centers, the study included symptomatic achalasia patients, treatment-naive or those with unsatisfactory outcomes from previous esophageal dilations. The POEM procedure was assessed for its impact on esophageal structure and function, symptom severity via the Eckardt score, and procedure-related safety, with outcomes measured at baseline, 3 days, and 12 months post-procedure. The study demonstrated notable post-procedure improvements across all measured outcomes: abnormal contraction length and esophageal width significantly reduced, underscoring the procedure's effectiveness. More precisely, the integrated relaxation pressure showed a significant improvement from a mean of 26.8 mm Hg (standard deviation [SD], 5.4 mm Hg) pre-procedure to 10.8 mm Hg (SD, 1.1 mm Hg) 12 months (P < .001). Similarly, Eckardt scores, which assess symptom severity, improved significantly from a pre-procedure mean of 7.0 (SD, 1.0) to a substantially lower score post-procedure (P < .001), reflecting enhanced patient quality of life and symptom alleviation. This study underscores POEM's role as an effective, minimally invasive option for pediatric achalasia management within the Mongolian population, offering significant symptomatic relief and improved esophageal function.

Tongue Biting Event in Patients with Sleep-Related Facial Mandibular Myoclonus: A Case Series Study.

Background: Sleep-related facial mandibular myoclonus (SRFMM) remains rare in clinical practice. The aim of this study was to provide a comprehensive understanding of the electroclinical manner, therapeutic regimen, and prognosis of SRFMM. Methods: Twenty-three patients who were diagnosed with SRFMM by clinical manifestation, video-electroencephalography (EEG) and electromyography over bilateral masseter and temporalis muscles were enrolled. Clinical and electrophysiological evaluation as well as follow-up information were recorded and analyzed. Results: The cohort involved 4 infants and 19 adults with a mean onset age of 43.5 years for SRFMM, among whom 19 were male. Twenty-one patients complained of tongue injuries and disturbed night-time sleep. SRFMM in 4 patients were ascribed to oral aripiprazole, brainstem ischemia and brain trauma. In 62 SRFMM episodes, 93.5% occurred in NREM sleep and 6.5% in REM sleep, and all events were associated with EEG arousals. In 13 patients with or without clonazepam, the motor events gradually disappeared, and the rest turned to be sporadic. Conclusion: SRFMM is a characteristic parasomnia manifested by tongue biting and accompanying facial mandibular myoclonus, leading to disrupted sleep. Besides adults, infants can also experience SRFMM with spontaneous remission. Most patients respond well to clonazepam, eventually with favorable prognosis.

Age over sex: evaluating gut microbiota differences in healthy Chinese populations.

Age and gender have been recognized as two pivotal covariates affecting the composition of the gut microbiota. However, their mediated variations in microbiota seem to be inconsistent across different countries and races. In this study, 613 individuals, whom we referred to as the "healthy" population, were selected from 1,018 volunteers through rigorous selection using 16S rRNA sequencing. Three enterotypes were identified, namely, Escherichia-Shigella, mixture (Bacteroides and Faecalibacterium), and Prevotella. Moreover, 11 covariates that explain the differences in microbiota were determined, with age being the predominant factor. Furthermore, age-related differences in alpha diversity, beta diversity, and core genera were observed in our cohort. Remarkably, after adjusting for 10 covariates other than age, abundant genera that differed between age groups were demonstrated. In contrast, minimal differences in alpha diversity, beta diversity, and differentially abundant genera were observed between male and female individuals. Furthermore, we also demonstrated the age trajectories of several well-known beneficial genera, lipopolysaccharide (LPS)-producing genera, and short-chain fatty acids (SCFAs)-producing genera. Overall, our study further elucidated the effects mediated by age and gender on microbiota differences, which are of significant importance for a comprehensive understanding of the gut microbiome spectrum in healthy individuals.

EphB2 promotes enteric nitrergic hyperinnervation and neurogenic inflammation in DSS-induced chronic colitis in mice.

BACKGROUND: Enteric nervous system (ENS) has been closely associated with the neuro-immune response and is currently considered a reliable target for intestinal inflammation. Neuronal nitric oxide synthase (nNOS) nerves are involved in inflammatory diseases by releasing nitric oxide (NO). EphB2 expression and density of innervation of the mucosal layer are positively correlated with the severity of intestinal inflammatory responses. In this study, we hypothesized that a EphB2-mediated mechanism may regulate enteric immunity through modulation of nNOS nerves. METHODS: Firstly, the Western blot (WB) method was employed to quantify EphB2 expression in the intestinal mucosal layer of DSS mice and assess alterations in nerve fiber activation and density. Immunofluorescence (IF) double staining with nNOS and neuronal marker PGP9.5 was conducted to measure nNOS nerve fiber density within the intestinal mucosal layer of mice. Subsequently, in vivo experiments were performed to investigate the inhibitory or activatory effect of EphB2Fc or EphrinB2Fc on EphB2 expression and activation. Immunoprecipitation experiments confirmed the interaction between EphB2 and nNOS nerves. WB and IF experiments were carried out to evaluate both inflammatory conditions of mouse colonic mucosa following intervention with EphB2Fc/EphrinB2Fc as well as changes in nNOS nerve fibers expression. Finally, in vitro experiments, neurally-mediated inflammation was assessed in the organ bath system by activating intestinal mucosal innervation through Veratridine (VER) and electrical field stimulation (EFS) techniques for 3 h. The activation of nNOS nerves was inhibited by nitroindazole (7NI). WB was employed to detect changes in the expression of inflammatory factors in the intestinal mucosal layer in EphB2Fc/EphrinB2Fc treated mice and control group. KEY RESULTS: We found that the expression of EphB2 and density nNOS nerve fibers in the intestinal mucosa were positively correlated with the colitis response. Blocking (EphB2Fc)/activating (EphrinB2Fc) EphB2 in vivo significantly reduced/increased the density of nNOS nerve fibers and expression of inflammatory factors in colonic mucosa of DSS treated mice. In vitro, blocking nNOS nerves activation attenuated the inflammatory reaction induced by either EFS or EphB2. CONCLUSIONS: Our findings provided evidence that EphB2 mediated regulation of innate immunity-ENS crosstalk might represent an attractive target for novel therapeutic strategies in ulcerative colitis.

Psychological factors may affect the quality of life in irritable bowel syndrome patients more than the gut itself? A multicenter cross-sectional study.

Background and Aim: Both intestinal symptoms and comorbidities exist in irritable bowel syndrome (IBS) patients and influence their quality of life (QOL). More research is needed to determine how these variables impact the QOL of IBS patients. This study aimed to determine which specific factors had a higher influence on QOL and to further compare the effects of intestinal symptoms and comorbidities on QOL. Methods: IBS patients were recruited from six tertiary hospitals in different regions of China. QOL, gastrointestinal symptoms, and comorbidities were assessed by different scales. Correlation analysis, multiple linear regression, and mediation model were used for statistics. Results: Four hundred fifty-three IBS patients (39.7% women, mean age 45 years) were included and no significant differences in QOL were found across demographic characteristics. Abnormal defecation (r = -0.398), fatigue (r = -0.266), and weakness (r = -0.286) were found to show higher correlation with QOL. More than 40% of IBS patients were found to suffer from varying degrees of anxiety or depression, and anxiety (r = -0.564) and depression (r = -0.411) were significantly negatively correlated with QOL (P < 0.001). Psychological factors showed the strongest impact (ß' = -0.451) and play a strong mediating role in the impact of physiological symptoms on QOL. Anxiety was found to be the strongest factor (ß' = -0.421). Conclusion: Compared with other symptoms, psychological symptoms, particularly anxiety, are more common and have a more negative influence on QOL. The QOL of IBS patients is also significantly impacted by abnormal defecation, abdominal distension, and systemic extraintestinal somatic symptoms. In the treatment of IBS patients with unhealthy mental status, psychotherapy might be prioritized.

Integrating clinical and cross-cohort metagenomic features: a stable and non-invasive colorectal cancer and adenoma diagnostic model.

Background: Dysbiosis is associated with colorectal cancer (CRC) and adenomas (CRA). However, the robustness of diagnostic models based on microbial signatures in multiple cohorts remains unsatisfactory. Materials and Methods: In this study, we used machine learning models to screen metagenomic signatures from the respective cross-cohort datasets of CRC and CRA (selected from CuratedMetagenomicData, each disease included 4 datasets). Then select a CRC and CRA data set from the CuratedMetagenomicData database and meet the requirements of having both metagenomic data and clinical data. This data set will be used to verify the inference that integrating clinical features can improve the performance of microbial disease prediction models. Results: After repeated verification, we selected 20 metagenomic features that performed well and were stably expressed within cross-cohorts to represent the diagnostic role of bacterial communities in CRC/CRA. The performance of the selected cross-cohort metagenomic features was stable for multi-regional and multi-ethnic populations (CRC, AUC: 0.817-0.867; CRA, AUC: 0.766-0.833). After clinical feature combination, AUC of our integrated CRC diagnostic model reached 0.939 (95% CI: 0.932-0.947, NRI=30%), and that of the CRA integrated model reached 0.925 (95%CI: 0.917-0.935, NRI=18%). Conclusion: In conclusion, the integrated model performed significantly better than single microbiome or clinical feature models in all cohorts. Integrating cross-cohort common discriminative microbial features with clinical features could help construct stable diagnostic models for early non-invasive screening for CRC and CRA.