{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:26:42Z","timestamp":1792805202617,"version":"4.5.0"},"reference-count":52,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology (Taiwan)","award":["MOST 109-2628-B-006-034"],"award-info":[{"award-number":["MOST 109-2628-B-006-034"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Science and Technology (Taiwan)","award":["MOST 109-2311-B-006-007"],"award-info":[{"award-number":["MOST 109-2311-B-006-007"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Cheng Kung University Hospital (Taiwan)","award":["NCKUH-10909047"],"award-info":[{"award-number":["NCKUH-10909047"]}],"id":[{"id":"https:\/\/ror.org\/04zx3rq17","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peripheral compressive neuropathy causes significant neuropathic pain, muscle weakness and prolong neuroinflammation. Surgical decompression remains the gold standard of treatment but the outcome is suboptimal with a high recurrence rate. From mechanical compression to chemical propagation of the local inflammatory signals, little is known about the distinct neuropathologic patterns and the genetic signatures after nerve decompression. In this study, controllable mechanical constriction forces over rat sciatic nerve induces irreversible sensorimotor dysfunction with sustained local neuroinflammation, even 4 weeks after nerve release. Significant gene upregulations are found in the dorsal root ganglia, regarding inflammatory, proapoptotic and neuropathic pain signals. Genetic profiling of neuroinflammation at the local injured nerve reveals persistent upregulation of multiple genes involving oxysterol metabolism, neuronal apoptosis, and proliferation after nerve release. Further validation of the independent roles of each signal pathway will contribute to molecular therapies for compressive neuropathy in the future.<\/jats:p>","DOI":"10.3390\/ijms22094746","type":"journal-article","created":{"date-parts":[[2021,4,30]],"date-time":"2021-04-30T05:10:55Z","timestamp":1619759455000},"page":"4746","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Investigation of Neuropathology after Nerve Release in Chronic Constriction Injury of Rat Sciatic Nerve"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1688-3026","authenticated-orcid":false,"given":"Szu-Han","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Center of Cell Therapy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"International Research Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Ching","family":"Wu","sequence":"additional","affiliation":[{"name":"International Research Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-Che","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery, Tainan Municipal An-Nan Hospital, China Medical University, Tainan 709, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Ling","family":"Tseng","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Center of Cell Therapy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tzu-Chieh","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali","family":"Yadav","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Anatomy, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2401-7360","authenticated-orcid":false,"given":"Fu-I","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Bioindustry Science, College of Bioscience and Biotechnology, National Cheng-Kung University, Tainan 701, Taiwan"},{"name":"The iEGG and Animal Biotechnology Center, National Chung Hsing University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Hsin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3423-991X","authenticated-orcid":false,"given":"Shau-Ping","family":"Lin","sequence":"additional","affiliation":[{"name":"Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8968-694X","authenticated-orcid":false,"given":"Yuan-Yu","family":"Hsueh","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"Center of Cell Therapy, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan"},{"name":"International Research Center for Wound Repair and Regeneration, National Cheng Kung University, Tainan 701, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/j.hcl.2013.04.002","article-title":"Nerve physiology: Mechanisms of injury and recovery","volume":"29","author":"Menorca","year":"2013","journal-title":"Hand Clin."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s11552-012-9391-7","article-title":"Surgical options for recalcitrant carpal tunnel syndrome with perineural fibrosis","volume":"7","author":"Abzug","year":"2012","journal-title":"Hand"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/B978-0-12-802973-2.00015-X","article-title":"Peripheral neuropathies","volume":"138","author":"Hanewinckel","year":"2016","journal-title":"Handb. Clin. Neurol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1055\/s-0031-1271800","article-title":"Cubital tunnel syndrome\u2013A review and management guidelines","volume":"72","author":"Assmus","year":"2011","journal-title":"Cent. Eur. Neurosurg."},{"key":"ref_5","first-page":"315","article-title":"Neuropathic pain as a process: Reversal of chronification in an animal model","volume":"4","author":"Dableh","year":"2011","journal-title":"J. Pain Res."},{"key":"ref_6","first-page":"e37","article-title":"Early versus late spinal decompression surgery in treatment of traumatic spinal cord injuries; a systematic review and meta-analysis","volume":"5","author":"Yousefifard","year":"2017","journal-title":"Emergency"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.2106\/00004623-199911000-00013","article-title":"Pathophysiology of nerve compression syndromes: Response of peripheral nerves to loading","volume":"81","author":"Rempel","year":"1999","journal-title":"J. Bone Jt. Surg. Am."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/S0749-0712(01)00012-9","article-title":"Pathophysiology of nerve compression","volume":"18","author":"Mackinnon","year":"2002","journal-title":"Hand Clin."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2151","DOI":"10.1016\/j.jhsa.2013.06.034","article-title":"Perforator-based radial forearm fascial flap for management of recurrent carpal tunnel syndrome","volume":"38","author":"Mahmoud","year":"2013","journal-title":"J. Hand Surg. Am."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1097\/PRS.0b013e318290faba","article-title":"A systematic review of the literature on the outcomes of treatment for recurrent and persistent carpal tunnel syndrome","volume":"132","author":"Soltani","year":"2013","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1007\/s00402-007-0451-3","article-title":"Subjective and functional outcome after revision surgery in carpal tunnel syndrome","volume":"128","author":"Unglaub","year":"2008","journal-title":"Arch. Orthop. Trauma Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.jor.2020.09.003","article-title":"Recurrent and persistent carpal tunnel syndrome: \u201cTriple-therapy approach\u201d","volume":"22","author":"Spielman","year":"2020","journal-title":"J. Orthop."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"847","DOI":"10.3171\/2018.11.JNS182598","article-title":"Recurrent and persistent carpal tunnel syndrome: Predicting clinical outcome of revision surgery","volume":"132","author":"Sun","year":"2019","journal-title":"J. Neurosurg."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.aanat.2011.02.011","article-title":"Wallerian degeneration and peripheral nerve conditions for both axonal regeneration and neuropathic pain induction","volume":"193","year":"2011","journal-title":"Ann. Anat."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1097\/NEN.0b013e318298de5b","article-title":"Local and remote immune-mediated inflammation after mild peripheral nerve compression in rats","volume":"72","author":"Schmid","year":"2013","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/1742-2094-7-27","article-title":"TNF-alpha and neuropathic pain\u2013A review","volume":"7","author":"Leung","year":"2010","journal-title":"J. Neuroinflamm."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"108615","DOI":"10.1016\/j.jneumeth.2020.108615","article-title":"Controllable forces for reproducible chronic constriction injury mimicking compressive neuropathy in rat sciatic nerve","volume":"335","author":"Chen","year":"2020","journal-title":"J. Neurosci. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/0304-3959(88)90209-6","article-title":"A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man","volume":"33","author":"Bennett","year":"1988","journal-title":"Pain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/S0165-0270(99)00174-0","article-title":"Methods to evaluate functional nerve recovery in adult rats: Walking track analysis, video analysis and the withdrawal reflex","volume":"96","author":"Dijkstra","year":"2000","journal-title":"J. Neurosci. Methods"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/jor.1100100508","article-title":"The functional recovery of peripheral nerves following defined acute crush injuries","volume":"10","author":"Chen","year":"1992","journal-title":"J. Orthop. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"321","DOI":"10.3109\/2000656X.2016.1168742","article-title":"Altered behavioural responses and functional recovery in rats following sciatic nerve compression and early vs late decompression","volume":"50","author":"Pettersson","year":"2016","journal-title":"J. Plast. Surg. Hand Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1097\/SAP.0000000000001646","article-title":"Alteration of sciatic nerve histology and electrical function after compression and after neurolysis in a diabetic rat model","volume":"81","author":"Hu","year":"2018","journal-title":"Ann. Plast. Surg."},{"key":"ref_23","first-page":"288","article-title":"Comparison of the Effects of Curcumin, Tramadol and Surgical Treatments on Neuropathic Pain Induced by Chronic Constriction Injury in Rats","volume":"28","author":"Ceyhan","year":"2018","journal-title":"Turk. Neurosurg."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S0304-3959(00)00333-X","article-title":"Thalidomide treatment in chronic constrictive neuropathy decreases endoneurial tumor necrosis factor-alpha, increases interleukin-10 and has long-term effects on spinal cord dorsal horn met-enkephalin","volume":"88","author":"George","year":"2000","journal-title":"Pain"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.neulet.2010.06.039","article-title":"Antihyperalgesic and antiallodynic effect of sirolimus in neuropathic pain and the role of cytokines in this effect","volume":"481","author":"Orhan","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1002\/ejp.618","article-title":"Hyperbaric oxygenation treatment alleviates CCI-induced neuropathic pain and decreases spinal apoptosis","volume":"19","author":"Hu","year":"2015","journal-title":"Eur. J. Pain"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1186\/1742-2094-8-110","article-title":"Wallerian degeneration: Gaining perspective on inflammatory events after peripheral nerve injury","volume":"8","author":"Gaudet","year":"2011","journal-title":"J. Neuroinflamm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1002\/1098-2752(2000)20:5<255::AID-MICR6>3.0.CO;2-A","article-title":"Cellular activity of resident macrophages during Wallerian degeneration","volume":"20","author":"Shen","year":"2000","journal-title":"Microsurgery"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1097\/01.LAB.0000056993.28149.BF","article-title":"Macrophage response to peripheral nerve injury: The quantitative contribution of resident and hematogenous macrophages","volume":"83","author":"Mueller","year":"2003","journal-title":"Lab. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1097\/00005072-199311000-00001","article-title":"Macrophage systems in peripheral nerves. A review","volume":"52","author":"Griffin","year":"1993","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5269","DOI":"10.3390\/ijms20215269","article-title":"Differential Expression of Neuroinflammatory mRNAs in the Rat Sciatic Nerve Following Chronic Constriction Injury and Pain-Relieving Nanoemulsion NSAID Delivery to Infiltrating Macrophages","volume":"20","author":"Stevens","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1016\/S0014-4886(03)00182-1","article-title":"Four PGE2 EP receptors are up-regulated in injured nerve following partial sciatic nerve ligation","volume":"183","author":"Ma","year":"2003","journal-title":"Exp. Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"939","DOI":"10.4103\/1673-5374.250566","article-title":"Gene expression changes in dorsal root ganglia following peripheral nerve injury: Roles in inflammation, cell death and nociception","volume":"14","author":"Martin","year":"2019","journal-title":"Neural Regen. Res."},{"key":"ref_34","first-page":"2259","article-title":"Role of inflammatory cytokines in peripheral nerve injury","volume":"7","author":"Fregnan","year":"2012","journal-title":"Neural Regen. Res."},{"key":"ref_35","first-page":"212","article-title":"Caspase-mediated apoptosis in sensory neurons of cultured dorsal root Ganglia in adult mouse","volume":"15","author":"Momeni","year":"2013","journal-title":"Cell J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1097\/WNR.0000000000001031","article-title":"Evaluation of apoptotic pathways in dorsal root ganglion neurons following peripheral nerve injury","volume":"29","author":"Wiberg","year":"2018","journal-title":"Neuroreport"},{"key":"ref_37","first-page":"3124","article-title":"Substance P and calcitonin gene-related peptide expression in dorsal root ganglia in sciatic nerve injury rats","volume":"8","author":"Fu","year":"2013","journal-title":"Neural Regen. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1016\/S0306-4522(98)00068-2","article-title":"Partial and complete sciatic nerve injuries induce similar increases of neuropeptide Y and vasoactive intestinal peptide immunoreactivities in primary sensory neurons and their central projections","volume":"86","author":"Ma","year":"1998","journal-title":"Neuroscience"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/nrd1107","article-title":"Neurotrophic factors as novel therapeutics for neuropathic pain","volume":"2","author":"Sah","year":"2003","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1194\/jlr.M700301-JLR200","article-title":"Biosynthesis of the regulatory oxysterol, 5-cholesten-3beta,25-diol 3-sulfate, in hepatocytes","volume":"48","author":"Li","year":"2007","journal-title":"J. Lipid Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1186\/s12974-018-1114-8","article-title":"Oxysterol levels and metabolism in the course of neuroinflammation: Insights from in vitro and in vivo models","volume":"15","author":"Mutemberezi","year":"2018","journal-title":"J. Neuroinflamm."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.biochi.2018.04.014","article-title":"EBI2\u2013Sensor for dihydroxycholesterol gradients in neuroinflammation","volume":"153","author":"Kurschus","year":"2018","journal-title":"Biochimie"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.redox.2016.09.001","article-title":"Changes in brain oxysterols at different stages of Alzheimer\u2019s disease: Their involvement in neuroinflammation","volume":"10","author":"Testa","year":"2016","journal-title":"Redox Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.21037\/atm-20-2746","article-title":"Cerebrotendinous xanthomatosis with peripheral neuropathy: A clinical and neurophysiological study in Chinese population","volume":"8","author":"Zhang","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1007\/s00415-012-6630-3","article-title":"Polyneuropathy in cerebrotendinous xanthomatosis and response to treatment with chenodeoxycholic acid","volume":"260","author":"Ginanneschi","year":"2013","journal-title":"J. Neurol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1080\/15384101.2019.1710916","article-title":"microRNA-192-5p is involved in nerve repair in rats with peripheral nerve injury by regulating XIAP","volume":"19","author":"Liu","year":"2020","journal-title":"Cell Cycle"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1080\/15287394.2019.1684028","article-title":"The protective mechanisms underlying Ginsenoside Rg1 effects on rat sciatic nerve injury","volume":"82","author":"Huo","year":"2019","journal-title":"J. Toxicol. Environ. Health A"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"10043","DOI":"10.1200\/jco.2010.28.15_suppl.10043","article-title":"BRAF V600E mutations in benign and malignant peripheral nerve sheath tumors","volume":"28","author":"Serrano","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"967","DOI":"10.6004\/jnccn.2018.7033","article-title":"Genomic Profiling in Patients with Malignant Peripheral Nerve Sheath Tumors Reveals Multiple Pathways with Targetable Mutations","volume":"16","author":"Kaplan","year":"2018","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1224","DOI":"10.3389\/fphar.2019.01224","article-title":"FGF10 Enhances Peripheral Nerve Regeneration via the Preactivation of the PI3K\/Akt Signaling-Mediated Antioxidant Response","volume":"10","author":"Dong","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1080\/14737159.2019.1623672","article-title":"Application of NanoString technologies in companion diagnostic development","volume":"19","author":"Eastel","year":"2019","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1186\/s12974-018-1219-0","article-title":"Temporal changes in macrophage phenotype after peripheral nerve injury","volume":"15","author":"Tomlinson","year":"2018","journal-title":"J. Neuroinflamm."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4746\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:55:42Z","timestamp":1760162142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/9\/4746"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,4,29]]},"references-count":52,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["ijms22094746"],"URL":"https:\/\/doi.org\/10.3390\/ijms22094746","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,4,29]]}}}