{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T10:33:31Z","timestamp":1772274811508,"version":"3.50.1"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&D Program of China","doi-asserted-by":"crossref","award":["2023YFC2410200"],"award-info":[{"award-number":["2023YFC2410200"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Shenzhen Science and Technology Program","award":["JCYJ20240813150209013"],"award-info":[{"award-number":["JCYJ20240813150209013"]}]},{"name":"Shenzhen Major Science and Technology Projects","award":["KJZD20240903104105007"],"award-info":[{"award-number":["KJZD20240903104105007"]}]},{"name":"Sun Yat-sen University Higher Education Teaching Research and Reform Project","award":["2021A10321030"],"award-info":[{"award-number":["2021A10321030"]}]},{"name":"Inner Mongolia Autonomous Region science and technology plan project","award":["2025SYFSH0536"],"award-info":[{"award-number":["2025SYFSH0536"]}]},{"name":"Inner Mongolia Autonomous Region Innovation Platform Construction Plan","award":["2025SKYPT0053"],"award-info":[{"award-number":["2025SKYPT0053"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Chronic rhinosinusitis with nasal polyps (CRSwNP) comprises multiple molecular endotypes that only partly align with the clinical phenotype, which complicates target selection and interpretation of treatment effects. Human omics and biomarker studies define candidate pathways, but causal attribution of specific nodes to lesion formation and remodeling requires perturbable in vivo systems. Here, we present a \u201cmodule-first\u201d framework that links murine induction paradigms to epithelial\u2013immune\u2013stromal circuits and to a minimal, module-matched endpoint set for reproducible causal inference. We summarize commonly used CRSwNP-like protocols (allergen\/protease \u00b1 SEB, aeroallergen + SEB, innate trigger-enriched paradigms, and modifier layers), emphasize operational pathology terminology (\u201cpolyp-like lesion\u201d versus \u201ctrue polyp\u201d), and propose a uniform causal template for validated pathway modules (alarmins\/IL-33\u2013NF-\u03baB, type 2\/ILC2\u2013eosinophil, IL-17A\/neutrophil, Wnt\/EMT remodeling, and JAK\/STAT kinase convergence). Finally, we organize chemical and molecular interventions by leverage point and propose an ARRIVE-aligned Minimum Reporting Set to standardize model anchoring, target engagement, and cross-study comparability. This module-first roadmap is intended to accelerate mechanism-linked discovery and preclinical validation of tractable drug targets in CRSwNP. Importantly, this module-first roadmap is intended as a heuristic organizing principle rather than an exhaustive taxonomy, because pathway modules can overlap and shift dynamically across time and tissue compartments in vivo.<\/jats:p>","DOI":"10.3390\/molecules31050781","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:51:29Z","timestamp":1772117489000},"page":"781","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chronic Rhinosinusitis with Nasal Polyps: A \u201cModule-First\u201d Review of Murine Models and Chemical Interventions"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5391-7221","authenticated-orcid":false,"given":"Yunfei","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Otolaryngology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3165-6946","authenticated-orcid":false,"given":"Gengluan","family":"Liu","sequence":"additional","affiliation":[{"name":"Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Department of Respiratory and Critical Care Medicine, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0820-3350","authenticated-orcid":false,"given":"Caiyan","family":"An","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Allergic Diseases, Foundational and Translational Medical Research Center, Hohhot First Hospital, Hohhot 010030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4375-995X","authenticated-orcid":false,"given":"Hesen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1779-8674","authenticated-orcid":false,"given":"Huaixiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8206-7409","authenticated-orcid":false,"given":"Junjing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Inner Mongolia Key Laboratory of Allergic Diseases, Foundational and Translational Medical Research Center, Hohhot First Hospital, Hohhot 010030, China"},{"name":"Department of Hepato-Biliary Surgery, Department of Surgery, Hohhot First Hospital, Hohhot 010030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5989-4266","authenticated-orcid":false,"given":"Yunping","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0414-5878","authenticated-orcid":false,"given":"Ningning","family":"Li","sequence":"additional","affiliation":[{"name":"Tomas Lindahl Nobel Laureate Laboratory, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen 518107, China"},{"name":"Department of Hepato-Biliary Surgery, Department of Surgery, Hohhot First Hospital, Hohhot 010030, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1016\/j.jaci.2013.02.036","article-title":"Endotypes and Phenotypes of Chronic Rhinosinusitis: A PRACTALL Document","volume":"131","author":"Akdis","year":"2013","journal-title":"J. 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