{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:14:20Z","timestamp":1788264860991,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2026,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Jingtong Granules is a clinically approved seven\u2010herb formula for CSR, a condition in which radicular pain is sustained partly by inflammatory and immune processes, yet the immune\u2010cellular state of CSR and the immune\u2010level mechanism of the formula remain poorly defined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Using peripheral\u2010blood transcriptomes from GSE223227 (7 controls, 9 CSR, and 30 degenerative cervical myelopathy), we profiled nine immune lineages by signature scoring, prioritized CSR\u2010associated features with six machine\u2010learning methods under permutation\u2010based specificity testing, localized signature genes on the Human Protein Atlas sorted immune\u2010cell reference, and linked the immune program to mass\u2010spectrometry\u2010confirmed constituents of Jingtong Granules by network pharmacology, molecular docking, molecular dynamics, and MM\u2010GBSA. Two\u2010level Mendelian randomization against cervical\u2010specific FinnGen endpoints tested genetic causal directionality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CSR blood showed a bidirectional immune\u2010rebalancing pattern: reduced NK\u2010cell activity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0164), increased M1\u2010macrophage activity (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0311), and directionally higher neutrophil and lower CD8\u2010cytotoxic scores. The neutrophil\/myeloid effector program discriminated CSR from controls (AUROC 0.79), exceeding a size\u2010matched random\u2010panel null, whereas a generic\n                      <jats:italic>NF\u2010\u03baB\/TNF<\/jats:italic>\n                      panel performed near chance; a composite rebalancing score reached a preliminary AUROC of 0.90 (95% CI 0.71\u20131.00). Network pharmacology nominated\n                      <jats:italic>MPO<\/jats:italic>\n                      as a formula\u2010associated immune target, whereas patient\u2010upregulated, neutrophil\u2010localized\n                      <jats:italic>ELANE<\/jats:italic>\n                      and\n                      <jats:italic>CTSG<\/jats:italic>\n                      were prioritized as structurally tractable granule enzymes. The validated quality markers nodakenin and paeoniflorin docked favorably to\n                      <jats:italic>ELANE<\/jats:italic>\n                      and\n                      <jats:italic>CTSG<\/jats:italic>\n                      and remained in their catalytic pockets during molecular dynamics, with MM\u2010GBSA binding free energies of \u221216.0 to \u221233.5\u2009kcal\/mol. Both markers also showed favorable drug\u2010like physicochemical profiles. Mendelian randomization gave no support for an upstream genetic\u2010causal role of the myeloid\u2010skewed immune state in cervical disk disorders or radiculopathy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These exploratory, single\u2010cohort findings characterize CSR peripheral blood as myeloid\u2010skewed and cytotoxic\u2010attenuated and nominate a traceable constituent\u2010to\u2010enzyme hypothesis in which mass\u2010spectrometry\u2010confirmed Jingtong Granules markers may engage patient\u2010upregulated neutrophil granule enzymes, warranting replication and experimental validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.70145","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T16:37:26Z","timestamp":1784824646000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mass\u2010Spectrometry\u2010Identified Quality Markers of Jingtong Granules Are Predicted to Engage Upregulated Neutrophil Granule Enzymes in Cervical Spondylotic Radiculopathy: An Integrative Machine\u2010Learning and Molecular\u2010Dynamics Study"],"prefix":"10.1002","volume":"40","author":[{"given":"Guangyi","family":"Yang","sequence":"first","affiliation":[{"name":"Graduate School Beijing University of Chinese Medicine  Beijing China"},{"name":"Wangjing Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changxiao","family":"Han","sequence":"additional","affiliation":[{"name":"Wangjing Hospital China Academy of Chinese Medical Sciences  Beijing China"},{"name":"Beijing Key Laboratory of Digital and Intelligent Traditional Chinese Medicine for the Prevention and Treatment of Degenerative Bone and Joint Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9377-6734","authenticated-orcid":false,"given":"Hongtao","family":"Li","sequence":"additional","affiliation":[{"name":"Wangjing Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijie","family":"Chang","sequence":"additional","affiliation":[{"name":"Wangjing Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenlong","family":"Qiu","sequence":"additional","affiliation":[{"name":"Wangjing Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Wangjing Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bochen","family":"Peng","sequence":"additional","affiliation":[{"name":"Graduate School Beijing University of Chinese Medicine  Beijing China"},{"name":"Wangjing Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanbin","family":"Liu","sequence":"additional","affiliation":[{"name":"Graduate School Beijing University of Chinese Medicine  Beijing China"},{"name":"Wangjing Hospital China Academy of Chinese Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xunlu","family":"Yin","sequence":"additional","affiliation":[{"name":"Wangjing Hospital China Academy of Chinese Medical Sciences  Beijing China"},{"name":"Beijing Key Laboratory of Digital and Intelligent Traditional Chinese Medicine for the Prevention and Treatment of Degenerative Bone and Joint Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1134-6087","authenticated-orcid":false,"given":"Minshan","family":"Feng","sequence":"additional","affiliation":[{"name":"Wangjing Hospital China Academy of Chinese Medical Sciences  Beijing China"},{"name":"Beijing Key Laboratory of Digital and Intelligent Traditional Chinese Medicine for the Prevention and Treatment of Degenerative Bone and Joint Diseases  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12178\u2010016\u20109349\u20104"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2665\u20109913(23)00321\u20101"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00586\u2010006\u20100271\u20100"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpain.2008.07.008"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neucir.2020.01.001"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1719293"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s12276\u2010024\u201001168\u20104"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.19540\/j.cnki.cjcmm.20221230.501"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.13286\/j.1001\u20105213.2025.16.05"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.01.041"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1010933404324"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v036.i11"},{"key":"e_1_2_11_15_1","first-page":"2825","article-title":"Scikit\u2010Learn: Machine Learning in Python","volume":"12","author":"Pedregosa F.","year":"2011","journal-title":"Journal of Machine Learning Research"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758\u20102946\u20106\u201013"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1277"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz382"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa1063"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep42717"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.1.235"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758\u20102946\u20103\u201033"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.5b00255"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20035"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.10128"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.445869"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp8001614"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.softx.2015.06.001"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/ct300418h"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.08.008"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.06.045"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010020\u20100684\u20104"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010022\u201005473\u20108"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010021\u201000913\u2010z"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.18236"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1515\/znc\u20102007\u20105\u2010607"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1590\/1519\u20106984.252936"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5AY02031J"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.157431"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1155\/mi\/2808908"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573409919666230605123129"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1103509"}],"container-title":["Rapid Communications in Mass Spectrometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rcm.70145","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/rcm.70145","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rcm.70145","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:26:29Z","timestamp":1788261989000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/rcm.70145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":43,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2026,10,15]]}},"alternative-id":["10.1002\/rcm.70145"],"URL":"https:\/\/doi.org\/10.1002\/rcm.70145","archive":["Portico"],"relation":{},"ISSN":["0951-4198","1097-0231"],"issn-type":[{"value":"0951-4198","type":"print"},{"value":"1097-0231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]},"assertion":[{"value":"2026-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70145"}}