{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T18:04:54Z","timestamp":1780769094905,"version":"3.54.1"},"reference-count":97,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T00:00:00Z","timestamp":1777334400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170577"],"award-info":[{"award-number":["82170577"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Functional dyspepsia (FD) is a common gastrointestinal disorder lacking established molecular targets. Symptom\u2010based classification into epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS) often fails to guide effective therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To identify molecular subtypes of FD using proteomics to better understand disease heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using 4D\u2010DIA proteomics, we analyzed gastric and duodenal biopsies from 47 FD patients and 10 healthy controls. Non\u2010negative matrix factorization was applied separately to each site for unsupervised clustering. Subtypes were characterized by clinical profiles, pathway enrichment, immune infiltration analysis, and validated via histology and immunostaining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Two gastric (G1: 17%, G2: 83%) and three duodenal subtypes (D1: 13%, D2: 70%, D3: 17%) were identified. G1 showed strong immune activation linked to\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>H. pylori<\/jats:italic>\n                      <\/jats:styled-content>\n                      infection, while G2 was enriched for metabolic pathways. Duodenal subtypes revealed distinct mechanisms: D1 featured eosinophil\u2010predominant inflammation, D2 showed ROS metabolism and ferroptosis correlated with pain, and D3 exhibited mast cell infiltration. Gastric and duodenal subtypes were independent of each other. No significant association was found between molecular subtypes and EPS\/PDS clinical classification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      FD involves heterogeneous molecular mechanisms across gastric and duodenal sites. Duodenal profiling exhibited disease\u2010relevant immune and oxidative pathways, while gastric patterns are largely distinguished by\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>H. pylori<\/jats:italic>\n                      <\/jats:styled-content>\n                      infection status. Conventional symptom\u2010based subtyping fails to capture this complexity, underscoring the need for mechanism\u2010based stratification to guide personalized treatment in FD.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/nmo.70333","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:52:21Z","timestamp":1777438341000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multi\u2010Site Proteomics Reveals Distinct Molecular Patterns Within Functional Dyspepsia"],"prefix":"10.1111","volume":"38","author":[{"given":"Ruiqi","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, the First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianjun","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, the First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6866-8066","authenticated-orcid":false,"given":"Zhanye","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, the First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junnan","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, the First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yubin","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, the First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"},{"name":"Institute of Precision Medicine, the First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niandi","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, the First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2838-1103","authenticated-orcid":false,"given":"Mengyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, the First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4223-4943","authenticated-orcid":false,"given":"Yinglian","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, the First Affiliated Hospital Sun Yat\u2010sen University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,28]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-54716-3"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.03.035"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.1998.00410.x"},{"key":"e_1_2_12_5_1","first-page":"CD011194","article-title":"Proton Pump Inhibitors for Functional Dyspepsia","volume":"11","author":"Pinto\u2010Sanchez M. I.","year":"2017","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"e_1_2_12_6_1","first-page":"CD009431","article-title":"Prokinetics for Functional Dyspepsia","volume":"10","author":"Pittayanon R.","year":"2018","journal-title":"Cochrane Database of Systematic Reviews"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30469-4"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1051632"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1080\/14789450.2017.1317600"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2020.103995"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0273853"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.TIR118.000900"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312518"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-023-04326-w"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13058-020-01296-5"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-024-02017-8"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2982.2008.01164.x"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.179.6.540"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2036.2001.00900.x"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v26.i5.466"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-021-01843-7"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-11-367"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308531101"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6485871"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.93975"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00438-024-02170-1"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fsurg.2022.1013794"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-14964-7"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.881809"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-017-1349-1"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110710"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.9.3601-3608.1996"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/15548627.2021.1985338"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-017-0504-1"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2004.01974.x"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.3109\/01913123.2011.606964"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-5378.2009.00679.x"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1177\/039463201302600308"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aninu.2021.09.010"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.916661"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2013.05.017"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1508730"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a040584"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25126498"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-024-00931-2"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00824-4"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-023-01098-7"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13304"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2022.10.012"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903778"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.01.042"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2022.01.014"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2024.07.018"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz210"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cotox.2017.10.003"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-72284-0"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1816317116"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mam.2012.07.010"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e13316"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2020.118675"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST0350876"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/25.10.1010"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plipres.2013.12.001"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10252"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2021.12.006"},{"key":"e_1_2_12_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/352126a0"},{"key":"e_1_2_12_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2021.145575"},{"key":"e_1_2_12_69_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a018267"},{"key":"e_1_2_12_70_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2000.6501"},{"key":"e_1_2_12_71_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology12050694"},{"key":"e_1_2_12_72_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0113057"},{"key":"e_1_2_12_73_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10020401"},{"key":"e_1_2_12_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.70005"},{"key":"e_1_2_12_75_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-023-01338-3"},{"key":"e_1_2_12_76_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1442555"},{"key":"e_1_2_12_77_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40291-022-00588-0"},{"issue":"5","key":"e_1_2_12_78_1","first-page":"4789","article-title":"SORBS1 Inhibits Epithelial to Mesenchymal Transition (EMT) of Breast Cancer Cells by Regulating PI3K\/AKT Signaling and Macrophage Phenotypic Polarization","volume":"16","author":"Feng K.","year":"2024","journal-title":"Aging (Albany NY)"},{"key":"e_1_2_12_79_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2008.01.010"},{"key":"e_1_2_12_80_1","doi-asserted-by":"publisher","DOI":"10.34172\/mejdd.2021.243"},{"key":"e_1_2_12_81_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0493-1"},{"key":"e_1_2_12_82_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-019-01550-4"},{"key":"e_1_2_12_83_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000000740"},{"key":"e_1_2_12_84_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-307843"},{"key":"e_1_2_12_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-23620-y"},{"key":"e_1_2_12_86_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-019-5470-8"},{"key":"e_1_2_12_87_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11894-011-0197-5"},{"key":"e_1_2_12_88_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2012-303857"},{"key":"e_1_2_12_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2007.05.015"},{"key":"e_1_2_12_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.512"},{"key":"e_1_2_12_91_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2020.12.016"},{"key":"e_1_2_12_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101780"},{"key":"e_1_2_12_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-020-00324-8"},{"key":"e_1_2_12_94_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-023-02878-8"},{"key":"e_1_2_12_95_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0b013e318031457a"},{"key":"e_1_2_12_96_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1549554"},{"key":"e_1_2_12_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116253"},{"key":"e_1_2_12_98_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-020-2298-2"}],"container-title":["Neurogastroenterology &amp; Motility"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.70333","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/nmo.70333","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/nmo.70333","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:16:13Z","timestamp":1780546573000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/nmo.70333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,28]]},"references-count":97,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/nmo.70333"],"URL":"https:\/\/doi.org\/10.1111\/nmo.70333","archive":["Portico"],"relation":{},"ISSN":["1350-1925","1365-2982"],"issn-type":[{"value":"1350-1925","type":"print"},{"value":"1365-2982","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,28]]},"assertion":[{"value":"2025-12-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70333"}}