血浆焦孔素D C-末端片段在脓毒症早期诊断中的价值

doi:10.3969/j.issn.1006-5725.2025.12.019

Abstract

Abstract:

Objective To assess the effectiveness of the Gasdermin D C-terminal fragment （GSDMD-CT） as a novel plasma biomarker for the clinical diagnosis of sepsis. Methods Between July 2021 and November 2024， 245 patients from Tangshan Gongren Hospital were enrolled in this study. In accordance with the diagnostic criteria for sepsis and the systemic inflammatory response syndrome （SIRS）， patient samples were classified into the sepsis group and the SIRS group. Meanwhile， healthy individuals were selected as the healthy control （HC） group. Sepsis patients were further categorized into the Gram-positive bacterial group， the Gram-negative bacterial group， and the fungal group based on the type of pathogen infection. The levels of GSDMD-CT， C-reactive protein （CRP）， and procalcitonin （PCT） were measured in all subjects. Nonparametric tests were employed to compare the differences in various indices among different groups. The diagnostic value of GSDMD-CT in sepsis was evaluated by constructing the receiver operating characteristic （ROC） curve. Spearman's correlation analysis was used to examine the relationships among GSDMD-CT， CRP， and PCT. Results The plasma GSDMD-CT levels in the sepsis group 23.02（16.71， 33.01） pg/mL and in the SIRS group 16.52（11.26， 22.22） pg/mL were significantly higher than those in the healthy control group 7.02（4.42， 11.43） pg/mL （U = -10.175， -7.890， P < 0.001）. Moreover， the plasma GSDMD-CT levels in the sepsis group were significantly higher than those in the SIRS group （U = -2.941， P < 0.05）. In the Gram-positive bacterial group， the Gram-negative bacterial group， and the fungal group， the GSDMD-CT levels were 23.01（17.16，27.51）pg/mL， 23.41（16.78，35.50） pg/mL， and 16.29 （14.53，56.27） pg/mL， respectively. When compared with the healthy control group， the GSDMD-CT levels in these three groups were all significantly higher （P < 0.05）. However， there were no significant differences in GSDMD-CT levels among these three groups （P > 0.05）. The area under the curve （AUC） of plasma GSDMD-CT for diagnosing sepsis was 0.881 （95％ confidence interval： 0.833 ~ 0.929）， with a Youden index （YI） of 0.695， a sensitivity of 85.0％， and a specificity of 84.5％. Spearman correlation analysis indicated a weak correlation between GSDMD-CT and C-reactive protein （CRP）（r = 0.32， P < 0.001） and a positive correlation between GSDMD-CT and procalcitonin （PCT）（r = 0.65， P < 0.001）. Conclusion GSDMD-CT exhibits significant clinical value in the diagnosis of sepsis and holds great potential as a biomarker in the diagnostic process of sepsis.

Key words: sepsis, biomarkers, GSDMD-CT, diagnose, correlation

CLC Number:

R446

Yuexian LYU,Xiu BI,Ying LIU,Shujing CUI,Lixin ZHAO,Ge GAO,Jianxia WANG,Juan LI,Jun LI. The efficacy of plasma gasdermin D C⁃terminal fragment in the early diagnosis of sepsis[J]. The Journal of Practical Medicine, 2025, 41(12): 1899-1906.

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References 29

1	EVANS L， RHODES A， ALHAZZANI W， et al. Executive Summary： Surviving Sepsis Campaign： International Guidelines for the Management of Sepsis and Septic Shock［J］.Crit Care Med， 2021， 49（11）： 1974-1982.
2	蔡兴，马兴龙，周长健，等. 巨噬细胞糖酵解在脓毒症中的研究进展［J］. 实用医学杂志， 2024， 40（19）： 2783-2788.
3	RUDD K E， JOHNSON S C， AGESA K M， et al. Global， regional， and national sepsis incidence and mortality， 1990-2017： Analysis for the Global Burden of Disease Study［J］. Lancet. 2020， 395（10219）： 200-211. doi:10.1016/s0140-6736(19)32989-7 doi: 10.1016/s0140-6736(19)32989-7
4	SRZIC I， NESEK ADAM V， TUNJIC PEJAK D. Sepsis defnition： What′s new in the treatment guidelines［J］. Acta Clin Croat， 2022， 61（）：67-72. doi:10.20471/acc.2022.61.s1.11 doi: 10.20471/acc.2022.61.s1.11
5	王仙琦，张斌，张琪，等.基于单细胞测序分析脓毒症早期血小板数量和功能变化［J］.实用医学杂志， 2024， 40（9）： 1218-1224.
6	EVANS L， RHODES A， ALHAZZANI W， et al.Surviving sepsis campaign： international guidelines for management of sepsis and septic shock 2021［J］. Intensive Care Med， 2021， 47（11）： 1181-1247.
7	HE R R， YUE G L， DONG M L， et al. SepsisBiomarkers： Advancements and Clinical Applications-A Narrative Review［J］. Int J Mol Sci， 2024， 25（16）： 9010. doi:10.3390/ijms25169010 doi: 10.3390/ijms25169010
8	PIERRAKOS C， VELISSARIS D， BISDORF M， et al. Biomarkers of Sepsis： Time for a Reappraisal［J］. Crit Care， 2020， 24（1）： 287. doi:10.1186/s13054-020-02993-5 doi: 10.1186/s13054-020-02993-5
9	MEIER M A， BRANCHE A， NEESER O L， et al. Procalcitonin-guided antibiotic treatment in patients with positive blood cultures： A patient-level meta-analysis of randomized trials［J］. Clin Infect Dis， 2019， 69（3）：388-396. doi:10.1093/cid/ciy917 doi: 10.1093/cid/ciy917
10	PÓVOA P， COELHO L， DAL-PIZZOL F， et al. How to use biomarkers of infection or sepsis at the bedside： Guide to clinicians［J］. Intensive Care Med， 2023， 49（2）： 142-153. doi:10.1007/s00134-022-06956-y doi: 10.1007/s00134-022-06956-y
11	HENNING D J， HALL M K， WATSJOLD B K， et al. Interleukin-6 improves infection identification when added to physician judgment during evaluation of potentially septic patients［J］. Am J Emerg Med， 2020， 38（5）： 947-952. doi:10.1016/j.ajem.2019.158361 doi: 10.1016/j.ajem.2019.158361
12	谭扬扬，杨旭凯，蔡高平，等.血清淀粉样蛋白A对成人脓毒症诊断价值的Meta分析［J］.中国急救医学， 2022，40（1）：35-40.
13	RAO Z， ZHU Y， YANG P， et al. Pyroptosis in inflammatory diseases and cancer［J］. Theranostics， 2022， 12（9）： 4310-4329. doi:10.7150/thno.71086 doi: 10.7150/thno.71086
14	QI X， LUO Y， XIAO M， et al. Mechanisms of alveolar type 2 epithelial cell death during acute lung injury［J］. Stem Cells， 2023， 41（12）： 1113-1132. doi:10.1093/stmcls/sxad074 doi: 10.1093/stmcls/sxad074
15	SHAO R， LOU X， XUE J， et al. Review： The role of GSDMD in sepsis［J］. Inflamm Res， 2022， 71（10-11）： 1191-1202. doi:10.1007/s00011-022-01624-9 doi: 10.1007/s00011-022-01624-9
16	NONG Y， WEI X， YU D. Infammatory mechanisms and intervention strategies for sepsis-induced myocardial dysfunction［J］. Immun Infamm Dis， 2023， 11（5）： e860. doi:10.1002/iid3.860 doi: 10.1002/iid3.860
17	LEVY M M， FINK M P， MARSHALL J C， et al.2001SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference［J］. Intensive Care Med， 2003， 31（4）： 1250-1256. doi:10.1097/01.ccm.0000050454.01978.3b doi: 10.1097/01.ccm.0000050454.01978.3b
18	曹钰，柴艳芬，邓颖，等. 中国脓毒症/脓毒性休克急诊治疗指南（2018）［J］. 感染、炎症、修复， 2019， 20（1）： 3-22.
19	XU D， JIANG J， LIU Y， et al.TIMP2 protects against sepsis-associated acute kidney injury by cAMP/NLRP3 axis-mediated pyroptosis［J］. Am J Physiol Cell Physiol， 2024， 326（5）： C1353-C1366. doi:10.1152/ajpcell.00577.2023 doi: 10.1152/ajpcell.00577.2023
20	周旻，杨磊，卓玉珍，等. 凉血活血方对脓毒症急性肾损伤小鼠肠道菌群及 NLRP3/caspase-1/GSDMD 焦亡通路的影响［J］. 中华危重病急救医学， 2023， 35（3）： 250-255.
21	QUIRANT-SÁNCHEZ B， PLANS-GALVÁN O， LUCAS E， et al. HLA-DR Expression on Monocytes and Sepsis Index Are Useful in Predicting Sepsis［J］. Biomedicines， 2023， 11（7）： 1836. doi:10.3390/biomedicines11071836 doi: 10.3390/biomedicines11071836
22	ZAKI H A， BENSLIMAN S， BASHIR K， et al. Accuracy of Procalcitonin for Diagnosing Sepsis in Adult Patients Admitted to the Emergency Department： A Systematic Review and Meta-Analysis［J］. Syst Rev， 2024， 13（1）： 37. doi:10.1186/s13643-023-02432-w doi: 10.1186/s13643-023-02432-w
23	SPROSTON N R， ASHWORTH J J. Role of C-reactive protein at sites of infammation and infection［J］. Front Immunol， 2018， 13（9）：754.
24	VON DACH E， ALBRICH W C， BRUNEL A S， et al. Efect of Creactive protein-guided antibiotic treatment duration， 7-daytreatment， or 14-day treatment on 30-day clinical failure rate in patients with uncomplicated gram-negative bacteremia： A randomized clinical trial［J］. JAMA， 2020， 323（21）：2160-2169. doi:10.1001/jama.2020.6348 doi: 10.1001/jama.2020.6348
25	TAN M， LU Y， JIANG H， et al. The diagnostic accuracy of procalcitonin and C-reactive protein for sepsis：A systematic review and meta-analysis［J］. J Cell Biochem， 2019， 120（4）： 5852-5859. doi:10.1002/jcb.27870 doi: 10.1002/jcb.27870
26	LI Z， HE L， LI S， et al. Combination of Procalcitonin and C-reactive Protein Levels in the Early Diagnosis of Bacterial Co-infections in Children with H1N1 Influenza［J］. Influenza Other Respir Viruses， 2019， 13（2）： 184-190. doi:10.1111/irv.12621 doi: 10.1111/irv.12621
27	PARLATO M， PHILIPPART F， ROUQUETTE A， et al. Circulating Biomarkers May Be Unable to Detect Infection at the Early Phase of Sepsis in ICU Patients： TheCAPTAIN Prospective Multicenter Cohort Study［J］. Intensive Care Med， 2018， 44（7）： 1061-1070. doi:10.1007/s00134-018-5228-3 doi: 10.1007/s00134-018-5228-3
28	XIA S， ZHANG Z， MAGUPALLI V G， et al. Gasdermin D Pore Structure Reveals Preferential Release of Mature Interleukin-1［J］. Nature， 2021， 593（7860）：607-611. doi:10.1038/s41586-021-03478-3 doi: 10.1038/s41586-021-03478-3
29	DAI Z， LIU W C， CHEN X Y， et al. Gasdermin D-Mediated Pyroptosis： Mechanisms， Diseases， and Inhibitor［J］. Front Immunol， 2023，14：1178662. doi:10.3389/fimmu.2023.1178662 doi: 10.3389/fimmu.2023.1178662

组别	样本量	年龄/岁	男性/［例（％）］	糖尿病 /［例（％）］	呼吸系统疾病 /［例（％）］	消化系统疾病 /［例（％）］	神经系统 /［例（％）］
HC组	200	65.0（55.0，72.0）	133（66.50）
SIRS组	145	66.5（56.0，75.0）	94（64.80）	4（2.80）	52（35.90）	18（12.40）	32（22.10）
Sepsis组	100	69.0（59.5，74.5）	70（70.00）	7（7.00）	25（25.00）	16（16.00）	31（31.00）
H/χ2值		4.768	0.723	1.592	3.240	0.637	2.471
P值		0.092	0.697	0.207	0.072	0.425	0.116

组别	样本量	年龄/岁	男性 /［例（％）］	糖尿病 /［例（％）］	呼吸系统疾病 /［例（％）］	消化系统疾病 /［例（％）］	神经系统疾病/［例（％）］
Gram-positive组	17	75.0（67.0，78.5）	12（70.60）	1（5.90）	6（35.30）	2（11.80）	6（35.30）
Gram-negative组	77	69.0（58.5，75.5）	53（68.80）	5（6.50）	18（23.40）	12（15.60）	24（31.20）
Fungal组	6	73.5（67.5，78.0）	5（83.30）	1（16.70）	1（16.70）	2（33.30）	1（16.70）
H/χ2值		4.000	-	-	-	-	-
P值		0.135	0.923	0.430	0.569	0.400	0.728

性能指标	结果
线性范围/（pg/mL）	1 ~ 3 000
检出限/（pg/mL）	≤ 1
准确度/％	85％ ~ 115％
批内变异系数/％	< 8％
批间变异系数/％	< 15％
各组分热稳定性/％	< 10％
校准品各点热稳定性/％	< 10％
质控品各点热稳定性/％	< 10％

组别	样本量	GSDMD-CT/（pg/mL）	CRP/（μg/mL）	PCT/（ng/mL）
HC 组	200	7.02（4.42，11.43）	2.56（0.88，4.60）	0.08（0.04，0.27）
SIRS组	145	16.52（11.26，22.22）	5.01（2.02，10.11）	0.19（0.08，0.75）
Sepsis组	100	23.02（16.71，33.01）	8.10（3.76，12.92）	0.43（0.12，2.67）
H值		125.37	54.92	41.15
P值		< 0.001	< 0.001	< 0.001

组别	样本量	GSDMD-CT
Gram-positive组	17	23.01（17.16，27.51）
Gram-negative组	77	23.41（16.78，35.50）
Fungal组	6	16.29（14.53，56.27）
H值		0.526
P值		0.769

The efficacy of plasma gasdermin D C⁃terminal fragment in the early diagnosis of sepsis

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影响因素	β	SE	Wald χ^２	P值	OR（95％CI）
GSDMD-CT	0.192	0.033	33.906	< 0.001	1.212（1.136 ~ 1.293）
CRP	0.178	0.049	13.214	< 0.001	1.195（1.085 ~ 1.315）
PCT	0.828	0.397	4.349	0.037	2.289（1.051 ~ 4.986）

指标	AUC	95％CI	敏感度/％	特异度/％	约登指数	P值
GSDMD-CT	0.881	0.833 ~ 0.929	85.0	84.5	0.695	< 0.001
CRP	0.782	0.719 ~ 0.844	75.0	76.7	0.517	< 0.001
PCT	0.733	0.666 ~ 0.799	69.0	70.7	0.397	< 0.001
GSDMD-CT+PCT+CRP	0.921	0.884 ~ 0.958	80.0	91.4	0.714	< 0.001
GSDMD-CT+CRP	0.920	0.882 ~ 0.957	87.0	83.6	0.706	< 0.001
GSDMD-CT+PCT	0.882	0.834 ~ 0.929	85.0	83.6	0.686	< 0.001
PCT+CRP	0.797	0.737 ~ 0.856	77.0	74.1	0.511	< 0.001

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