{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T18:47:58Z","timestamp":1776451678519,"version":"3.51.2"},"reference-count":44,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"16","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81902167"],"award-info":[{"award-number":["81902167"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National High Level Hospital Clinical Research Funding","award":["2022-PUMCH-A-152"],"award-info":[{"award-number":["2022-PUMCH-A-152"]}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,4,17]]},"abstract":"<jats:p>\n                    Primary aldosteronism (PA), a leading cause of secondary hypertension, remains vastly underdiagnosed due to unreliable screening tools. We developed an integrated platform combining a high-gradient magnetic separation three-dimensional (HGMS-3D) chip and locked nucleic acid (LNA)\u2013enhanced droplet digital polymerase chain reaction (ddPCR) for noninvasive detection of potassium inwardly rectifying channel subfamily J member 5 (\n                    <jats:italic toggle=\"yes\">KCNJ5<\/jats:italic>\n                    ) mutations in plasma small extracellular vesicles (sEVs). The HGMS-3D chip uses a nickel mesh\u2013based stereoscopic immunoaffinity capture system, achieving a vesicle isolation efficiency 4.4-fold higher than ultracentrifugation. Coupled with LNA-ddPCR, the platform detects\n                    <jats:italic toggle=\"yes\">KCNJ5<\/jats:italic>\n                    hotspot mutations [p.Gly151Arg, (G151R); p.Leu168Arg (L168R)] at minor allele frequencies of \u22640.05% (\n                    <jats:italic toggle=\"yes\">R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    \u2265 0.99), overcoming plasma-derived noise. Clinical validation in 106 patients with PA demonstrated 64.58% sensitivity and 96.88% specificity for sEV-based mutation profiling. The assay identified one aldosterone-producing adenoma (APA) case missed by tissue genotyping, achieving area under the receiver operating characteristic curve (AUC) values of 0.767 ~ 0.852 across mutations. This noninvasive approach could enable curative treatment for millions with undiagnosed PA, advancing precision management of endocrine hypertension through sEV-based liquid biopsy.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aeb4949","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T18:00:21Z","timestamp":1776448821000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["High-gradient magnetic separation chip\u2013based small extracellular vesicle isolation for noninvasive subtyping of primary aldosteronism"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-8572","authenticated-orcid":true,"given":"Dong","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8588-7913","authenticated-orcid":true,"given":"Jun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Core Instrument Facility, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5984-0563","authenticated-orcid":true,"given":"Zhixin","family":"Chen","sequence":"additional","affiliation":[{"name":"Core Instrument Facility, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2823-4365","authenticated-orcid":true,"given":"Junyuan","family":"Yang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Technology, Beijing 100081, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4918-7676","authenticated-orcid":true,"given":"Yingjie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4370-0552","authenticated-orcid":true,"given":"Shiwei","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8764-6821","authenticated-orcid":true,"given":"Dongxu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5115-5407","authenticated-orcid":true,"given":"Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8058-9702","authenticated-orcid":true,"given":"Yushi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, 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