Although nanomedicine has enabled significant advances in drug delivery, the clinical translation of conventional synthetic nanocarriers is limited by immune clearance, non-specific biodistribution, and gastrointestinal instability. This poses major challenges for therapy targeting the intestines. Cell membrane-coated nanotechnology (CMCT) and membrane vesicle-based systems have emerged as biomimetic platforms integrating synthetic nanomaterials with naturally derived biological interfaces. These biohybrid systems inherit biological functions originating from cells, including immune evasion, prolonged circulation, lesion homing, and microenvironment-responsive interactions, through the direct transfer of intact membrane components. This review summarizes recent advances in CMCT and membrane vesicle-based strategies for intestinal drug delivery. It covers fabrication methodologies, programmable manufacturing approaches, and functional regulation enabled by diverse membrane sources and hybrid engineering designs. Applications in inflammatory bowel disease, colorectal cancer, and intestinal infections are highlighted, emphasizing key therapeutic mechanisms, such as targeting inflammation, neutralizing toxins, modulating the immune system, and regulating the microbiome. We also discuss the major challenges of translation, such as preserving membrane and coating integrity, ensuring oral stability, achieving batch reproducibility, and ensuring biosafety. Overall, this review establishes a conceptual and engineering framework to guide the transition of membrane-based nanocarriers from passive biomimicry to adaptive, clinically translatable intestinal delivery systems.

Thalidomide, once withdrawn due to teratogenicity, has re-emerged as a repurposed agent to treat a broad spectrum of diseases because of its anti-inflammatory, immunomodulatory, and anti-angiogenic properties. Over the past two decades, thalidomide has also been increasingly used in digestive diseases, including gastrointestinal and hepatobiliary–pancreatic disorders. Despite these expanding indications, its broader clinical use remains restricted by safety concerns and the absence of standardized, evidence-based guidance. In particular, practical strategies for optimizing efficacy while minimizing toxicity have not been systematically summarized. This review aims to provide an updated, integrated, and clinically oriented overview of thalidomide in digestive diseases, summarizing the expanded applications from immune-mediated to non-immune-related conditions, highlighting real-world applications, therapeutic strategies, and approaches to risk mitigation. Furthermore, we discuss structural analogs and novel delivery systems that may enhance safety and efficacy, paving the way for thalidomide’s rational and safe use as a modern “phoenix drug”.

Introduction: Lenalidomide is an immunomodulatory drug. Its repurposing for refractory Behcet’s Disease is a promising strategy. Behcet’s Disease is a rare and complex autoinflammatory condition. Current treatment options are limited. This study explored the drug’s therapeutic potential using clinical and computational analyses. Methods: This study included a systematic review of clinical case reports. Computational methods included toxicological predictions, network pharmacology to screen common targets of lenalidomide and Behcet’s Disease, and the construction of protein-protein interaction networks utilizing tools such as ProTox-3.0, ADMETlab 3.0, and Cytoscape. Additionally, molecular docking (AutoDock Vina) and molecular dynamics simulations (GROMACS) were used to assess binding and stability. Results: Clinical data showed low-dose lenalidomide provided rapid symptom relief and appeared to be well tolerated. Computational toxicology revealed a complex, dose-dependent safety profile. Network analysis identified 63 common targets. Seven core genes were found, including IL6, TNF, and JAK1. These genes were enriched in immune pathways, particularly the JAK-STAT cascade. Molecular docking and dynamics confirmed stable binding to key targets like IL6 and JAK1. Discussion: Lenalidomide appears potentially effective in Behcet’s Disease. Its action likely involves multi-target regulation of core immune pathways. Multi-target regulation of the JAKSTAT and TNF signaling cascades directly addresses the core autoinflammatory pathology of Behcet's Disease. The concordance between clinical efficacy and computational findings highlights its repurposing potential. The findings also stress the importance of dose optimization for safety, generating a promising low-dose safety hypothesis. conclusion: Lenalidomide is a viable repurposed therapeutic candidate for refractory Behçet’s Disease. This old drug new use strategy offers a practical and mechanistically supported treatment avenue for this rare disease, demonstrating the value of computational and clinical integration in rare disease therapy development. Conclusion: Lenalidomide is a viable repurposing candidate warranting further clinical investigation for refractory Behcet’s Disease. This strategy provides a mechanistically supported treatment for this rare disease. Combining network pharmacology and molecular dynamics provides a robust preclinical rationale for repurposing lenalidomide in Behcet's Disease.

Background and aim: The sedative role of dexmedetomidine (DEX) in gastrointestinal endoscopic procedures is unclear, highlighting the need to compare DEX with conventional sedatives for a full evaluation. We performed this systematic review and meta-analysis to assess the efficacy and safety of sedation with DEX alone or in combination during gastrointestinal endoscopic procedures with a view to providing guidance for clinical application. Methods: The PubMed, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov databases were searched for randomized controlled trials from inception to July 1, 2022. Standardized mean difference and weighted mean difference with 95% confidence interval or pooled risk ratios with 95% CI was used for continuous outcomes or dichotomous outcomes, respectively, and a random-effect model was selected regardless of the significance of the heterogeneity. Results: Forty-one studies with 3,015 patients were assessed, of which 1,363 patients were in the DEX group and 1,652 patients were in the control (without DEX) group. We found that DEX administration decreased the risk of body movements or gagging, hypoxia, and cough, reduced the additional requirement for other sedatives, and increased the endoscopist satisfaction level, however, induction time, and risk of bradycardia, and without statistical differences in RSS score, patient satisfaction level, recovery time, hypotension, nausea, and vomiting. Conclusion: DEX may benefit patients undergoing gastrointestinal endoscopic procedures in some clinical outcomes, whilst some potential disadvantages also exist. Remarkably, DEX was non-inferior to midazolam and propofol in terms of sedation level. In conclusion, DEX is an alternative option for sedation in gastrointestinal endoscopic procedures.