---
title: "NLRP3-linked ASTRA transcriptomic score associates with lower 28-day mortality in ICU sepsis cohor"
id: "pubmed-42700257"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42700257"
content_type: "clinical_feed_article"
specialty: "Critical Care"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42700257/"
doi: "10.1007/s00011-026-02352-0"
published_at: "2026-09-05T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# NLRP3-linked ASTRA transcriptomic score associates with lower 28-day mortality in ICU sepsis cohor
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42700257
- **Specialty:** [Critical Care](https://medichelpline.com/clinical-feed/critical-care.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42700257/)
- **DOI:** [10.1007/s00011-026-02352-0](https://doi.org/10.1007%2Fs00011-026-02352-0)
- **Published At:** 2026-09-05T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The authors developed ASTRA, an author-defined, literature-informed **Astragalus** mechanistic prior to generate mechanism-guided whole-blood transcriptomic scores in sepsis. - Primary analysis used 479 adult sepsis patients from GSE65682; an exploratory directional cross-cohort assessment used 51 Day‑1 septic shock patients from GSE95233. - Mean‑Z integrated ASTRA score showed a nominal inverse association with 28‑day mortality but did not survive false‑discovery‑rate (FDR) correction. - A three‑gene **NLRP3**-related node-level score had the strongest association in GSE65682 (OR per 1‑SD increase 0.70; 95% CI 0.57–0.86; q = 0.0072) and was directionally stable in leave‑one‑gene‑out analyses. - The NLRP3 score correlated positively with IL1B and IL6 mRNA and with MCP-counter monocytic-lineage and neutrophil scores, indicating overlap with inflammatory transcription and estimated myeloid cell abundance. - Adjustment for estimated cell composition showed method-sensitive effects: joint MCP-counter adjustment attenuated the NLRP3 association (OR 0.79; 95% CI 0.58–1.06), while xCell neutrophil adjustment strengthened it (OR 0.64; 95% CI 0.50–0.83). - In the smaller GSE95233 cohort the age‑adjusted NLRP3 point estimate was directionally concordant but imprecise (OR 0.68; 95% CI 0.37–1.23). - Sensitivity analyses included singscore, restricted cubic splines, label permutation, leave‑one‑gene‑out, correlation checks with IL1B/IL6, and adjustment for transcriptome-derived myeloid composition. - Authors emphasize ASTRA as a reproducible framework for mechanism-guided transcriptomic scoring but note that findings do not establish protective inflammasome activity, Astragalus efficacy, or pharmacological target engagement. - The study was a secondary analysis of publicly available de-identified datasets; authors declared no competing interests.
## Clinical Analysis & Structured Key Points
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Affiliations Expand ### Affiliations * 1 Department of Clinical Nutrition, Shanghai Jing'an District Zhabei Central Hospital, Shanghai, 200070, China. * 2 Naval Medicine Center of PLA, Naval Medical University, Shanghai, 200433, China. * 3 Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China. * 4 Department of Clinical Nutrition, Shanghai Jing'an District Zhabei Central Hospital, Shanghai, 200070, China. yuanwei6975@163.com. * 5 Teaching and Research Support Center, Naval Medical University, Shanghai, 200433, China. gbdata@163.com. # Contributed equally. * PMID: **42700257** * DOI: [ 10.1007/s00011-026-02352-0 ](https://doi.org/10.1007/s00011-026-02352-0) Item in Clipboard # An NLRP3 inflammasome-anchored Astragalus mechanistic prior yields a mortality-associated transcriptomic signal in ICU sepsis: a secondary analysis with exploratory cross-cohort assessment Xiaojuan Yang et al. Inflamm Res. 2026. Show details Display options Display options Format Abstract PubMed PMID Inflamm Res Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Inflamm+Res%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Inflamm+Res%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700257/) . 2026 Sep 5;75(1):201. doi: 10.1007/s00011-026-02352-0. ### Authors [Xiaojuan Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+X&cauthor_id=42700257)[#](https://pubmed.ncbi.nlm.nih.gov/42700257/#short-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42700257/#short-view-affiliation-1 "Department of Clinical Nutrition, Shanghai Jing'an District Zhabei Central Hospital, Shanghai, 200070, China."), [Tiantian Hu](https://pubmed.ncbi.nlm.nih.gov/?term=Hu+T&cauthor_id=42700257)[#](https://pubmed.ncbi.nlm.nih.gov/42700257/#short-view-equal-contrib-explanation "Contributed equally")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42700257/#short-view-affiliation-2 "Naval Medicine Center of PLA, Naval Medical University, Shanghai, 200433, China."), [Jiali Wang](https://pubmed.ncbi.nlm.nih.gov/?term=Wang+J&cauthor_id=42700257)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42700257/#short-view-affiliation-1 "Department of Clinical Nutrition, Shanghai Jing'an District Zhabei Central Hospital, Shanghai, 200070, China."), [Zhiyuan Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+Z&cauthor_id=42700257)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42700257/#short-view-affiliation-3 "Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China."), [Wei Yuan](https://pubmed.ncbi.nlm.nih.gov/?term=Yuan+W&cauthor_id=42700257)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42700257/#short-view-affiliation-4 "Department of Clinical Nutrition, Shanghai Jing'an District Zhabei Central Hospital, Shanghai, 200070, China. yuanwei6975@163.com."), [Biao Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+B&cauthor_id=42700257)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42700257/#short-view-affiliation-5 "Teaching and Research Support Center, Naval Medical University, Shanghai, 200433, China. gbdata@163.com.") ### Affiliations * 1 Department of Clinical Nutrition, Shanghai Jing'an District Zhabei Central Hospital, Shanghai, 200070, China. * 2 Naval Medicine Center of PLA, Naval Medical University, Shanghai, 200433, China. * 3 Clinical Laboratory Medicine Center, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China. * 4 Department of Clinical Nutrition, Shanghai Jing'an District Zhabei Central Hospital, Shanghai, 200070, China. yuanwei6975@163.com. * 5 Teaching and Research Support Center, Naval Medical University, Shanghai, 200433, China. gbdata@163.com. # Contributed equally. * PMID: **42700257** * DOI: [ 10.1007/s00011-026-02352-0 ](https://doi.org/10.1007/s00011-026-02352-0) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract **Objective and design:** We developed ASTRA, a literature-informed, author-defined Astragalus mechanistic prior, and examined whether integrated and node-level whole-blood transcriptomic scores were associated with 28-day mortality in ICU sepsis. **Methods:** The primary analysis included 479 adults with sepsis from GSE65682; an exploratory cross-cohort directional assessment included 51 Day-1 patients with septic shock from GSE95233. Mean-Z scores were evaluated using age-adjusted logistic regression with false-discovery-rate correction. Sensitivity analyses included singscore, restricted cubic splines, label permutation, leave-one-gene-out analysis, correlations with IL1B and IL6 mRNA, and adjustment for transcriptome-derived myeloid-cell composition. **Results:** The integrated ASTRA score showed a nominal inverse association with mortality but did not survive false-discovery-rate correction. The NLRP3-related three-gene score showed the strongest association in GSE65682 (OR per 1-SD increase, 0.70; 95% CI 0.57-0.86; q = 0.0072) and remained directionally stable in leave-one-gene-out analyses. It correlated positively with IL1B and IL6 mRNA and with MCP-counter monocytic-lineage and neutrophil scores. Joint MCP-counter adjustment attenuated the association to an OR of 0.79 (95% CI 0.58-1.06), whereas xCell neutrophil adjustment strengthened it to an OR of 0.64 (95% CI 0.50-0.83), indicating method-sensitive dependence on estimated cell composition. In GSE95233, the age-adjusted NLRP3 estimate was directionally concordant but imprecise (OR 0.68; 95% CI 0.37-1.23). **Conclusions:** ASTRA provides a reproducible framework for mechanism-guided transcriptomic scoring in sepsis. The NLRP3-linked signal represents an observational whole-blood transcriptomic state that partly tracks estimated myeloid-cell composition and concurrent inflammatory transcription. It does not establish protective inflammasome activity, Astragalus efficacy, or pharmacological target engagement. **Keywords:** Astragalus; Mechanistic prior; Mortality; NLRP3 inflammasome; Sepsis; Transcriptomics. © 2026. The Author(s). [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Declarations. Conflict of interest: The authors declare no competing interests. Ethical approval and consent to participate: This study involved a secondary analysis of publicly available, de-identified transcriptomic and clinical data from the NCBI Gene Expression Omnibus datasets GSE65682 and GSE95233. No new participants were recruited, and no identifiable personal information was accessed. Therefore, additional ethics approval and consent to participate were not required for the present study. The original studies were conducted in accordance with the ethical approvals and informed-consent procedures reported by the respective investigators. Consent for publication: Not applicable. The manuscript contains no identifiable individual-level information, images, or clinical case details. ## References 1. 1. Lira Chavez FM, Gartzke LP, van Beuningen FE, Wink SE, Henning RH, Krenning G, et al. Restoring the infected powerhouse: Mitochondrial quality control in sepsis. Redox Biol. 2023;68:102968. - [DOI](https://doi.org/10.1016/j.redox.2023.102968) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/38039825/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/10711241/) 2. 1. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA. 2016;315:801–10. - [DOI](https://doi.org/10.1001/jama.2016.0287) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/26903338/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/4968574/) 3. 1. van der Poll T, Shankar-Hari M, Wiersinga WJ. The immunology of sepsis. Immunity. 2021;54:2450–64. - [DOI](https://doi.org/10.1016/j.immuni.2021.10.012) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/34758337/) 4. 1. Davenport EE, Burnham KL, Radhakrishnan J, Humburg P, Hutton P, Mills TC, et al. Genomic landscape of the individual host response and outcomes in sepsis: a prospective cohort study. Lancet Respir Med. 2016;4:259–71. - [DOI](https://doi.org/10.1016/s2213-2600\(16\)00046-1) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/26917434/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/4820667/) 5. 1. Scicluna BP, van Vught LA, Zwinderman AH, Wiewel MA, Davenport EE, Burnham KL, et al. Classification of patients with sepsis according to blood genomic endotype: a prospective cohort study. Lancet Respir Med. 2017;5:816–26. - [DOI](https://doi.org/10.1016/s2213-2600\(17\)30294-1) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/28864056/) Show all 36 references ## MeSH terms * Aged Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Aged%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Aged) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700257/) * Cohort Studies Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Cohort+Studies%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Cohort+Studies) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700257/) * Female Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Female%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Female) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700257/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700257/) * Inflammasomes* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Inflammasomes%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Inflammasomes) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700257/) * Intensive Care Units Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Intensive+Care+Units%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Intensive+Care+Units) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700257/) * Interleukin-1beta / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Interleukin-1beta%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Interleukin-1beta) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700257/) * Male Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Male%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Male) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700257/) * Middle Aged Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Middle+Aged%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Middle+Aged) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42700257/) * NLR Family, Pyrin Domain-Containing 3 Protein* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22NLR+Family%
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