Inflammatory bowel disease (IBD) is a heterogeneous group of disorders characterized primarily by chronic relapsing intestinal inflammation, encompassing Crohn’s disease (CD) and ulcerative colitis (UC), affecting individuals across age groups with variable clinical manifestations. With the advancement of global industrialization, its incidence continues to rise, particularly in newly industrialized regions, which not only severely impairs patients' quality of life but also emerges as a major public health concern threatening digestive system health, accompanied by a substantial healthcare burden, thus necessitating the development of more effective and safer individualized treatment strategies. This review summarizes the pathogenesis of IBD, including intestinal mucosal immune dysregulation, intestinal barrier damage, gut microbiota dysbiosis, reactive oxygen species (ROS) homeostasis imbalance, and the complex crosstalk between genetic and environmental factors; however, clinical treatment still faces numerous challenges: 30%-40% of patients exhibit primary or secondary non-response to existing therapeutic regimens such as biologics and small-molecule drugs, and prolonged administration tends to induce significant side effects. Further integrated herein are emerging strategies such as ROS modulators, novel immune-targeted modulation, intestinal barrier repair agents, microbiota-directed interventions, multi-omics-based precision medicine, and artificial intelligence (AI)-assisted therapy, which represent key directions to address the limitations of traditional treatments. This article begins with an overview of basic pathological mechanisms and offers a comprehensive overview of relevant therapeutic approaches and future development directions, aiming to facilitate the transition of the field from traditional generalized therapies to personalized precision medicine and to bridge the long-standing gap between basic research and clinical practice.

Background: Patients with ulcerative colitis (UC) usually display cognitive impairments, such as memory loss, attention deficit and declining executive function, especially during active disease. However, the potential neurological mechanisms of these symptoms remain unclear. Method: Forty-one patients with mildly to moderately active UC, as well as forty-two matched healthy controls, were recruited for examination using psychological scales, cognitive function testing and resting-state functional magnetic resonance imaging (rs-fMRI). Seed points were identified via amplitude of low-frequency fluctuation (ALFF) analysis, and whole-brain functional connectivity (FC) was calculated based on the graph theoretical. Correlation analyses were performed among clinical indexes, neuropsychological assessments and neuroimaging data. Result: Compared with the healthy controls, UC patients exhibited lower ALFF values in the bilateral hippocampal/parahippocampal region and higher ALFF values in the left posterior cingulate cortex and left middle frontal gyrus. With HIPP/ParaHIPP as the seed point, activity in the FC in the bilateral middle frontal gyrus, anterior cingulate cortex, and left caudate nucleus increased; these brain regions are mainly related to working memory. Using the PCC.L as the seed point, activity in the FC in the middle cingulate cortex and the left angular gyrus increased; these brain regions are mainly related to the attention network and executive functions. Conclusion: These results indicated that the limbic lobe might be the core of the brain-gut axis and play an important role in cognitive impairments, suggesting potential mechanisms for cognitive impairment in UC patients during active disease.

Cathepsins are lysosomal peptidases belonging to the papain family, and based on their catalytic sites, these enzymes can be divided into serine, cysteine and aspartic proteases. The studies conducted to date have identified, 15 types of cathepsins that are widely distributed in intracellular and extracellular spaces. These proteases participate in various pathological activities, including the occurrence and development of human cancers. Several recent studies suggest that cathepsins, particularly cathepsins B, D, E and L, contribute to digestive tumorigenesis. Cathepsins were found to promote the development of most digestive cancers except liver cancer, in which they might have the opposite effects. Due to their important roles in digestive tumors, cathepsins might be therapeutic targets for the treatment of digestive cancers.

Currently, WeChat is widely used in disease education for patients with Crohn’s disease (CD) in China. It is beneficial for the patients to actively engage in their disease management. In this study, we examined the source and expectations of disease information for Chinese CD patients, analysing the content of popular WeChat public accounts and their potential association with medication adherence. Between November 24th, 2017 and April 10th, 2018, online questionnaires were sent to CD patients from eight different large urban hospitals in China. In all, 436 patients with CD were surveyed, and 342 patients responded. Patients most frequently visited Baidu (65%), WeChat (61%) and medical websites such as Haodaifu (35%) when searching for IBD-related information. Among ten WeChat IBD public accounts, the China Crohn’s and Colitis Foundation (CCCF) (73%), “IBD Academic Officer” (21%) and “IBD in love” (21%) were the most popular. CD patients were most interested in information from the internet about diet and day-to-day health-related living with IBD (83%), an introduction to the disease (80%), and medication advances and side effects (80%). The correlation between the information provided by the top five WeChat public accounts and patients’ expectations was low. Additionally, most patients (64%) had greater confidence in overcoming the disease after learning about CD through their internet searches. Medical adherence was also related to internet access and income (p < 0.05). WeChat has become a major source of information for IBD education in China, but the content of WeChat didn’t fully meet patients’ expectations. Therefore, future initiatives should aim to provide high-quality information that based on patients’ demands.

Inflammatory bowel disease (IBD) is a chronic, inflammatory, and autoimmune disorder, and its incidence of comorbid with major depressive disorder (MDD) is significantly higher than the general population. However, many patients lack proper recognition and necessary psychological health treatments. We aimed to identify potential biomarkers and mechanisms involved in the development of IBD comorbid with MDD (IBD-MDD). We utilized IBD and MDD-related datasets from the GEO database for differential gene expression analysis, protein-protein interaction (PPI) and pathway enrichment analysis, random forest algorithm, LASSO regression analysis, and construction of a disease prediction model. We assessed the accuracy of the model using ROC curve, explored potential mechanisms through immune infiltration analysis, and validated candidate biomarkers using peripheral blood samples from patients in our center’s cohort. We identified 484 IBD-related secreted proteins and 142 key module genes associated with MDD. PPI analysis revealed two crucial modules primarily involved in inflammation and immune regulation. We identified four diagnostic genes (HGF, SPARC, ADAM12, and MMP8) from the 21 shared genes between IBD-related secreted proteins and MDD key module genes, constructed a nomogram model and confirmed its accuracy using ROC curve from an external independent dataset. Immune infiltration analysis revealed significant associations between the four diagnostic genes, and cellular immune dysregulation in MDD. Finally, we validated the expression patterns of the four diagnostic genes in our cohort. Our study discovered four candidate biomarkers for IBD-MDD, providing new insights for the diagnosis and therapeutic intervention of serum-based IBD comorbid with MDD.

Helicobacter pylori (H. pylori) infection remains a global public health issue, especially in Asia. Due to the emergence of antibiotic-resistant strains and the complexity of H. pylori infection, conventional vaccination is the best way to control the disease. Our previous study found that the N-acetyl-neuroaminyllactose-binding hemagglutinin protein (HpaA) is an effective protective antigen for vaccination against H. pylori infection, and intranasal immunization with the immunodominant HpaA epitope peptide (HpaA 154-171, P22, MEGVLIPAGFIKVTILEP) in conjunction with a CpG adjuvant decreased bacterial colonization in H. pylori-infected mice. However, to confer more robust and effective protection against H. pylori infection, an optimized delivery system is needed to enhance the P22-specific memory T cell response. In this study, an intranasal nanoemulsion (NE) delivery system offering high vaccine efficacy without obvious cytotoxicity was designed and produced. We found that this highly stable system significantly prolonged the nasal residence time and enhanced the cellular uptake of the epitope peptide, which powerfully boosted the specific Th1 responses of the NE-P22 vaccine, thus reducing bacterial colonization without CpG. Furthermore, the protection efficacy was further enhanced by combining the NE-P22 vaccine with CpG. This epitope-loaded nanoemulsion delivery system was shown to extend antigen release and elicit potent Th1 response, it is an applicable delivery system for intranasal vaccine against H. pylori.