中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (23): 6062-6070.doi: 10.12307/2026.357

• 组织工程相关大数据分析 Big data analysis in tissue engineering • 上一篇    下一篇

烧伤与多组学生物标志物：41种炎症因子和35种血液尿液指标的因果关系

高敏怡1，刘平洪1，林海雄2，3   

  1. 1广州市中西医结合医院烧伤与创面修复科，广东省广州市   510800；宁夏医科大学，2中医学院，3中医燥证教育部重点实验室，宁夏回族自治区银川市   750004


  • 收稿日期:2025-07-29 接受日期:2025-09-11 出版日期:2026-08-18 发布日期:2026-01-04
  • 通讯作者: 林海雄，博士，博士后，副研究员，硕士生导师，宁夏医科大学，中医学院，中医燥证教育部重点实验室，宁夏回族自治区银川市 750004
  • 作者简介:高敏怡，女，1992年生，广东省广州市人，汉族，2016年广州中医药大学毕业，主治医师，主要从事烧伤与创面修复。
  • 基金资助:
    宁夏医科大学校级科研项目资助(4005250001)，项目负责人：林海雄

Burn and multi-omic biomarkers: causal relationships with 41 inflammatory factors and 35 blood and urine markers

Gao Minyi1, Liu Pinghong1, Lin Haixiong2, 3   

  1. 1Department of Burns and Wound Repair, Guangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou 510800, Guangdong Province, China; 2School of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; 3Key Laboratory of Dryness Syndrome in Chinese Medicine, Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • Received:2025-07-29 Accepted:2025-09-11 Online:2026-08-18 Published:2026-01-04
  • Contact: Lin Haixiong, PhD, Associate researcher, Master’s supervisor, School of Traditional Chinese Medicine, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China; Key Laboratory of Dryness Syndrome in Chinese Medicine, Ministry of Education, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
  • About author:Gao Minyi, Attending physician, Department of Burns and Wound Repair, Guangzhou Hospital of Integrated Traditional Chinese and Western Medicine, Guangzhou 510800, Guangdong Province, China
  • Supported by:
    the Scientific Research Project of Ningxia Medical University, No. 4005250001 (to LHX)

PDF

10

摘要：



文题释义：
孟德尔随机化：凭借遗传变异作为工具变量模拟随机对照试验的优势，成为解析复杂疾病因果关联的重要工具。
生物标志物(Biomarker)：是指可以标记系统、器官、组织、细胞及亚细胞结构或功能的改变或可能发生改变的生化指标，具有非常广泛的用途。生物标志物可用于疾病诊断、判断疾病分期或者评价新药和新疗法在目标人群中的安全性及有效性。

背景：传统观察性研究难以揭露烧伤与生物标志物间的潜在因果关系，孟德尔随机化凭借遗传变异作为工具变量模拟随机对照试验的优势，成为解析复杂疾病因果关联的重要工具。
目的：基于孟德尔随机化方法探讨烧伤与41种炎症因子和35种血液和尿液标志物的关系。
方法：①烧伤的完整全基因组关联研究数据在IEU open gwas project数据库(由英国The University of Bristol构建)中获取，该数据包括了218 131例样本，16 380 465个单核苷酸多态性；②41种炎症因子数据来源于芬兰青年心血管风险研究数据库(由图尔库大学应用和预防心血管医学研究中心构建)一项8 293人的研究数据；③35种血液和尿液生物标志物数据来源于英国生物样本库(由英国政府、惠康基金会和英国医学研究理事会共同发起的大型生物医学数据库项目)(n=363 228人)。以单核苷酸多态性作为工具变量，利用逆方差加权、MR Egger、加权中位数和加权模式的方法进行分析。采用 Cochrane’s Q 检验来识别结果的异质性，MR Egger截距检验和MR-PRESSO检验及“留一法”检验等评估暴露-结局关联的可靠性。
结果与结论：烧伤降低了白细胞介素9(OR=0.97；95%CI，0.949 to 0.997；P=0.030)和睾酮 (OR=0.997；95%CI，0.995 to 0.999；P=0.025)水平，且不存在异质性和水平多效性，证明了结果的稳健性。研究通过孟德尔随机化分析表明，烧伤后白细胞介素9和睾酮水平降低，提示提高白细胞介素9和睾酮水平可能有助于烧伤后组织修复和改善蛋白质分解速率。

http://orcid.org/0009-0009-4721-5889 (高敏怡)；https://orcid.org/0000-0002-9939-7698 (林海雄)


中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 烧伤, 炎症因子, 生物标志物, 孟德尔随机化, 白细胞介素9, 睾酮

Abstract: BACKGROUND: Conventional observational studies are inadequate to reveal the potential causal relationship of biomarkers in burns patients. Mendelian randomization, leveraging genetic variation as an instrumental variable to mimic the advantages of randomized controlled trials, has emerged as a crucial tool for dissecting causal associations in complex diseases.
OBJECTIVE: To explore the relationship of burn injury with 41 inflammatory cytokines and 35 blood and urinary biomarkers using Mendelian Randomization. 
METHODS: (1) Burn-related data of genome-wide association studies were obtained from the IEU open GWAS project database, constructed by The University of Bristol, UK, including 218 131 samples and 16 380 465 single nucleotide polymorphisms were included in the study. (2) Data for 41 types of inflammatory cytokines were derived from a study involving 8 293 participants in the Finnish Young Cardiovascular Risk Study database, which is constructed by the Research Centre for Applied and Preventive Cardiovascular Medicine, University of Turku. (3) Data for 35 types of blood and urinary biomarkers were derived from a study involving 363 228 participants from the UK Biobank, which is a large biomedical database project jointly initiated by the UK government, the Wellcome Trust, and the Medical Research Council of the UK. Single nucleotide polymorphisms were employed as instrumental variables, and analyses were conducted using inverse variance weighted, Mendelian Randomization-Egger, weighted median, and weighted mode methods. Heterogeneity of results was assessed via Cochrane’s Q test. The reliability of exposure-outcome associations was evaluated using Mendelian Randomization-Egger intercept tests, Mendelian Randomization-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and leave-one-out sensitivity analyses. 
RESULTS AND CONCLUSION: The levels of interleukin-9 (odds ratio=0.97; 95% confidence interval, 0.949 to 0.997; P=0.030) and testosterone (odds ratio=0.997; 95% confidence interval, 0.995 to 0.999; P=0.025) were reduced in burn patients. No heterogeneity or horizontal pleiotropy demonstrated the robustness of the results. Through Mendelian randomization analysis, the study revealed the reduced interleukin-9 and testosterone levels following burns, suggesting that elevating these could potentially facilitate tissue repair and mitigate protein catabolism.

Key words: burn, inflammatory factors, biomarkers, Mendelian randomization, interleukin-9, testosterone

中图分类号: