Evidence mapPaperPMID 42345211Full record

ArticleAnnals of medicine2026

Progressive suppression of regulated cell death defines terminal macrophage states in liver cirrhosis.

Kepu Zheng, Leiyang Dai, Yanghui Wen, Haitao Jiang, Yang Gao, Feng Ren, Yu Tang, Xiang Huang, Jianghua Ran, Yunjie Chen

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Article in Annals of medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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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

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

10 authors.

Kepu ZhengDepartment of Hepato-Biliary-Pancreatic Surgery, Ningbo No.2 Hospital, Ningbo, China.
Leiyang DaiDepartment of Clinical Laboratory, the First Affiliated Hospital of Kunming Medical University, Kunming, China.
Yanghui WenDepartment of Hepato-Biliary-Pancreatic Surgery, Ningbo No.2 Hospital, Ningbo, China.
Haitao JiangDepartment of Hepato-Biliary-Pancreatic Surgery, Ningbo No.2 Hospital, Ningbo, China.
Yang GaoDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People's Hospital of Kunming, Kunming, China.
Feng RenDepartment of Hepato-Biliary-Pancreatic Surgery, Ningbo No.2 Hospital, Ningbo, China.
Yu TangDepartment of Genetics, Zunyi Medical University, Zunyi, China.
Xiang HuangDepartment of Medical Experiment, Ningbo No.2 Hospital, Ningbo, China.
Jianghua RanDepartment of Hepato-Biliary-Pancreatic Surgery, The Affiliated Calmette Hospital of Kunming Medical University, The First People's Hospital of Kunming, Kunming, China.
Yunjie ChenDepartment of Hepato-Biliary-Pancreatic Surgery, Ningbo No.2 Hospital, Ningbo, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMacrophages are central regulators of liver immunity and fibrosis; Recent single-cell studies have characterized macrophage heterogeneity in cirrhosis; however, how regulated cell death programs shape their functional transitions across disease progression in human liver remains poorly defined.

methodsWe integrated scRNA-seq data from 224,529 cells across 31 adult liver samples to define macrophage states and trajectories. Functional activities of regulated cell death pathways were assessed, and key programs were validated by dual immunofluorescence in human liver tissues.

resultsFour macrophage subsets with disease-biased distributions were identified. Cirrhotic macrophages exhibited progressive suppression of autophagy, necroptosis, apoptosis, and immunogenic cell death along differentiation, most prominently in terminal states, accompanied by transcriptional exhaustion and reduced immune regulator expression. A disease-associated transitional subpopulation displayed hybrid metabolic-immune features and yielded a six-gene diagnostic signature (LDHB, CD37, S100A10, RNASE1, CXCR4 and CORO1A) validated in bulk RNA-seq data (AUC = 0.936). Spatial analyses confirmed attenuation of autophagy and necroptosis and enrichment of CXCR4- and S100A10-positive macrophages in fibrotic niches.

conclusionHuman cirrhosis is characterized by progressive repression of regulated cell death programs in liver macrophages, providing mechanistic insight into disease progression and identifying macrophage-associated molecular signatures that may aid in patient stratification and serve as potential targets for future therapeutic intervention.

Indexed as

LiverLiver CirrhosisMacrophagesRegulated Cell DeathAdultApoptosisAutophagyCell DeathDisease ProgressionFemaleHumansMaleMiddle AgedNecroptosisReceptors, CXCR4Receptors, CXCR4diagnostic biomarkersLiver cirrhosismacrophagesmetabolic reprogrammingprogrammed cell deathsingle-cell RNA sequencing

Identifiers

PMID42345211
PMCPMC13307378

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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 Socratic graph.