Evidence map›Paper›PMID 41221556›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Inhibiting Liver-Derived C3 Protein Rescues Anesthesia/Surgery-Induced Cognitive Impairment, Synaptic Disorders, and Microglial Phagocytosis.

Qianqian Wu, Peilin Cong, Zhouxiang Li, Yuxin Zhang, Huanghui Wu, Qian Zhang, Yawei Li, Li Tian, Qingyuan Miao, Yinggang Zheng and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. A Neutrophil Membrane-Encapsulated Pd/hCeOAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
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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

18 authors.

Qianqian WuShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Peilin CongShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Zhouxiang LiShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Yuxin ZhangShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Huanghui WuShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Qian ZhangShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Yawei LiDepartment of Anesthesiology, Peking University First Hospital, Beijing, 100034, China.
Li TianShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Qingyuan MiaoShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Yinggang ZhengShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Hui ZhangShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Qian ChenShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Enduo FengShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Xinyang LiShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Zheping ChenShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.
Dong-Xin WangDepartment of Anesthesiology, Peking University First Hospital, Beijing, 100034, China.
Xinwei HuangShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.ORCID https://orcid.org/0000-0002-8568-6261
Lize XiongShanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Department of Anesthesiology and Perioperative Medicine, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, 200434, China.

Funding

Major Program of National Natural Science Foundation of China 82293640Major Program of National Natural Science Foundation of China 82293643Major Program of National Natural Science Foundation of China 82293644National Natural Science Foundation of China 82101256National Natural Science Foundation of China 82301370Natural Science Foundation of Shanghai 24ZR1457700Scientific Research Founds of Shanghai Fourth People's Hospital sykyqd07401Scientific Research Founds of Shanghai Fourth People's Hospital sykyqd08701Scientific Research Founds of Shanghai Fourth People's Hospital SY-XKZT-2023-1005Scientific Research Founds of Shanghai Fourth People's Hospital SY-XKZT-2023-1007
6 · The paper itself

Abstract

Identifying peripheral proteins having therapeutic effects on cognitive impairment could provide beneficial insights into the prevention and treatment of cognition-related disorders, including postoperative cognitive dysfunction (POCD) that is a common postoperative cognitive impairment mainly caused by anesthesia/surgery. Here, proteomic and transcriptomic analyses in multiple organs from humans and POCD mice are conducted to identify potential peripheral targets for anesthesia/surgery-induced cognitive impairment. The results show that anesthesia/surgery can disrupt the blood-brain barrier (BBB) and promote the release of hepatogenous C3 protein into the blood. This surgical dual factors ultimately drove C3 to cross the damaged BBB and selectively colocalize with C3aR in the hippocampus. Anesthesia/surgery-induced C3 upregulation in the liver is associated with hypomethylation of C3 promoter. Inhibiting hepatogenous C3 is demonstrated to salvage the anesthesia/surgery-induced cognitive impairment, structural and functional injury of synapse, and C3aR-mediated microglial phagocytosis. Perioperative alterations in serum C3 protein in surgical patients are related to POCD, showing potential for predicting this disorder. This study emphasizes that peripheral C3 is a promising target for the prevention and therapy, and a potential biomarker for predicting cognitive impairment, and confirms that the liver mediates anesthesia/surgery-induced cognitive impairment.

Indexed as

AnesthesiaCognitive DysfunctionComplement C3LiverMicrogliaPhagocytosisPostoperative Cognitive ComplicationsAnimalsBlood-Brain BarrierFemaleHumansMaleMiceMice, Inbred C57BLSynapsesComplement C3blood proteincognitive impairmentcomplement C3postoperative cognitive dysfunctionsurgery

Identifiers

PMID41221556
PMCPMC12786287

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Registered trials

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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 OpenQuestion graph.