Evidence mapPaperPMID 39738868Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Mild Hyperthermia Accelerates Bone Repair by Dynamically Regulating iNOS/Arg1 Balance in the Early Stage.

Jinhui Zhao, Yiping Luo, Lei Zhang, Yunfeng Chen, Yixing Chen, Xinhui Wu, Aihemaitijiang Aierken, Dilixiati Duolikun, Tianlong Wang, Zifei Zhou and 2 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Jinhui ZhaoDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Yiping LuoDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Lei ZhangDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Yunfeng ChenDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Yixing ChenDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Xinhui WuDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Aihemaitijiang AierkenDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Dilixiati DuolikunDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Tianlong WangDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Zifei ZhouDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Zhiqing LiuDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.
Longpo ZhengDepartment of Orthopedics, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, 200072, China.ORCID https://orcid.org/0000-0002-1749-2449

Funding

National Key Research and Development Program of China 2022YFE0123500National Natural Science Foundation of China 82372395Natural Science Foundation of Shanghai Municipality 21ZR1450000Natural Science Foundation of Shanghai Municipality 22S31903300Shanghai Science and Technology Development Foundation 23S31905700
6 · The paper itself

Abstract

Mild hyperthermia therapy has garnered interest as an adjunctive treatment for bone repair. However, its optimal timing, duration, and underlying mechanisms remain unclear. In this study, how mild hyperthermia supports bone repair during the early stages is assesed. These findings reveal that mild hyperthermia accelerates bone regeneration by dynamically regulating inducible nitric oxide synthase/arginase 1 (iNOS/Arg1) balance. This process involves macrophage polarization to the M1 phenotype through iNOS activation, followed by a rapid transition to the M2 phenotype through Arg1 activation after 3 days of sustained mild hyperthermia. RNA-Seq reveals that a single day of mild hyperthermia induced immune alterations aligned with the early inflammatory phase of bone repair, characterized by osteoclast activation, cell recruitment, and neovascularization, thereby preparing for the transition to the repair phase. Experiments involving subcutaneous abscesses, subcutaneous embedding, and critical cranial bone defects further confirm that early mild hyperthermia treatment dynamically regulates macrophage phenotypes. This regulation enhances early antibacterial activity, promotes angiogenesis, and facilitates the transition from inflammation to repair, ultimately accelerating bone-defect repair. This study is the first to elucidate the dual temporal effects of early mild hyperthermia on immune regulation, offering insights into the optimal timing and duration of photothermal therapy following bone repair surgery.

Indexed as

ArginaseBone RegenerationHyperthermia, InducedNitric Oxide Synthase Type IIAnimalsMacrophagesMaleMiceMice, Inbred C57BLArg1 protein, mouseArginaseNitric Oxide Synthase Type IINos2 protein, mousebone repairiNOS/Arg1 balancemacrophagemild hyperthermia

Identifiers

PMID39738868
PMCPMC11848644

What Socratic holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.