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中华脑科疾病与康复杂志(电子版) ›› 2024, Vol. 14 ›› Issue (04) : 201 -207. doi: 10.3877/cma.j.issn.2095-123X.2024.04.002

临床研究

血清sTIM-3及其配体Gal-9、CEACAM-1与创伤性颅脑损伤患者脑损伤程度及预后的关系
胡志恒1, 任洪波1, 宋志远1, 张运刚2, 韩晓正1,†()   
  1. 1.056000 河北邯郸，邯郸市中心医院神经外三科
    2.056000 河北邯郸，邯郸市中心医院检验科
  • 收稿日期:2024-03-09 出版日期:2024-08-15
  • 通信作者: 韩晓正
  • 基金资助:
    国家卫生健康委医药卫生科技发展研究中心课题项目（W2022ZT629）

Relationship between serum sTIM-3 and its ligand Gal-9, CEACAM-1 and the degree of brain injury and prognosis in patients with traumatic brain injury

Zhiheng Hu1, Hongbo Ren1, Zhiyuan Song1, Yungang Zhao2, Xiaozheng Han1,†()   

  1. 1.Third Department of Neurosurgery, Handan Central Hospital, Handan 056000, China
    2.Department of Clinical Laboratory, Handan Central Hospital, Handan 056000, China
  • Received:2024-03-09 Published:2024-08-15
  • Corresponding author: Xiaozheng Han
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引用本文：

胡志恒, 任洪波, 宋志远, 张运刚, 韩晓正. 血清sTIM-3及其配体Gal-9、CEACAM-1与创伤性颅脑损伤患者脑损伤程度及预后的关系[J]. 中华脑科疾病与康复杂志(电子版), 2024, 14(04): 201-207.

Zhiheng Hu, Hongbo Ren, Zhiyuan Song, Yungang Zhao, Xiaozheng Han. Relationship between serum sTIM-3 and its ligand Gal-9, CEACAM-1 and the degree of brain injury and prognosis in patients with traumatic brain injury[J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2024, 14(04): 201-207.

目的

探讨创伤性颅脑损伤（TBI）患者血清可溶性T 细胞免疫球蛋白黏蛋白分子-3（sTIM-3）及其配体半乳糖凝集素-9（Gal-9）、癌胚抗原相关细胞黏附分子-1（CEACAM-1）水平与脑损伤程度和预后的关系。

方法

选取邯郸市中心医院神经外三科自2022 年2 月至2023 年2 月收治的120 例TBI 患者作为观察组，选取同期进行体检的120 例健康受试者作为对照组，比较2 组受试者的sTIM-3、Gal-9 和CEACAM-1 水平差异。按照术前GCS 评分对TBI 患者进行病情分级（即重型、中型和轻型），探究不同TBI程度患者的血清sTIM-3、Gal-9和CEACAM-1水平差异。治疗1个月后，按照GOS 评分评估TBI 患者预后，采用单因素分析和多因素Logistic 回归分析筛选TBI 患者预后不良的影响因素，受试者工作特征曲线（ROC）分析影响因素指标对TBI 患者预后的预测价值。

结果

观察组患者中重型36例，中型42例，轻型42例。与对照组相比，观察组患者的sTIM-3、Gal-9和CEACAM-1水平升高，且表达水平随TBI程度增高而升高，差异均有统计学意义（P＜0.05）。治疗1个月后，预后良好者76例，预后不良者44例。单因素分析显示，预后不良患者血清sTIM-3、Gal-9、CEACAM-1 水平及GCS 评分高于预后良好患者，差异有统计学意义（P＜0.05）；多因素Logistic 回归分析显示，sTIM-3、Gal-9、CEACAM-1 及GCS 评分是TBI 患者预后的独立影响因素（P＜0.05）。ROC分析结果显示，血清sTIM-3、Gal-9、CEACAM-1 及GCS 评分单独及联合应用时的曲线下面积（95%CI）分别为0.744、0.706、0.697、0.739、0.823（0.724～0.921），联合应用的诊断效能高于各指标单独应用（P＜0.05）。

结论

血清sTIM-3 及其配体Gal-9、CEACAM-1 可作为评估TBI 患者严重程度和预后的新的有意义的分子标志物。

关键词: 创伤性颅脑损伤, 可溶性T 细胞免疫球蛋白黏蛋白分子-3, 半乳糖凝集素-9, 癌胚抗原相关细胞黏附分子-1, 脑损伤程度, 预后

Objective

To explore the relationship between serum levels of soluble T cell immunoglobulin and mucin domain-3 (sTIM-3), and its ligand Galectin-9 (Gal-9) and carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM-1) in patients with traumatic brain injury (TBI) and the degree of brain injury and prognosis.

Methods

A total of 120 patients with TBI admitted to the Third Department of Neurosurgery of Handan Central Hospital from February 2022 to February 2023 were selected as the observation group, and 120 healthy subjects who underwent physical examination during the same period were selected as the control group.The levels of sTIM-3, Gal-9 and CEACAM-1 were compared between the two groups.The TBI patients were graded according to the preoperative GCS score (severe type, moderate type and mild type), and the differences of serum sTIM-3, Gal-9 and CEACAM-1 levels in patients with different TBI degrees were explored.After 1 month of treatment, the prognosis of TBI patients was evaluated according to the GOS score.Univariate and multivariate Logistic regression analysis was used to analyze the influencing factors of poor prognosis in TBI patients.The receiver operating characteristic (ROC) curve was used to analyze the predictive value of the influencing factors on the prognosis of TBI patients.

Results

In the observation group, there were 36 cases of severe type, 42 cases of moderate type and 42 cases of mild type.Compared with the control group, the levels of sTIM-3, Gal-9 and CEACAM-1 in the observation group increased, and the expression level increased with the increase of TBI degree, the differences were statistically significant (P＜0.05).After 1 month of treatment, 76 cases had good prognosis and 44 cases had poor prognosis.Univariate analysis showed that the levels of serum sTIM-3,Gal-9,CEACAM-1 and GCS score in patients with poor prognosis were higher than those in patients with good prognosis (P＜0.05).Multivariate Logistic regression analysis showed that sTIM-3, Gal-9, CEACAM-1 and GCS score were independent factors affecting the prognosis of TBI patients (P＜0.05).ROC analysis showed that the area under the curve (95%CI) of serum sTIM-3,Gal-9, CEACAM-1 and GCS score alone and in combination were 0.744, 0.706, 0.697, 0.739 and 0.823(0.724-0.921), respectively, the diagnostic efficiency of combined application was higher than that of each index alone (P＜0.05).

Conclusion

Serum sTIM-3 and its ligands Gal-9 and CEACAM-1 can be used as new and meaningful molecular markers to evaluate the severity and prognosis of TBI patients.

Key words: Traumatic brain injury, Soluble T - cell immunoglobulin and mucin - domain containing-3, Galectin-9, Carcinoembryonic antigen-related cell adhesion molecule-1, Degree of brain injury; Prognosis
表1 观察组与对照组血清sTIM-3、Gal-9和CEACAM-1水平比较[ng/mL，M（Q1，Q3）]
Tab.1 Comparison of serum sTIM-3,Gal-9 and CEACAM-1 levels between the observation group and the control group[ng/mL，M(Q1,Q3)]
组别 例数 sTIM-3 Gal-9 CEACAM-1
观察组 120 2.62（1.65，3.89） 2.28（1.14，3.02） 20.53（15.42，25.38）
对照组 120 1.68（1.20，3.18） 1.50（1.15，2.87） 18.96（15.32，21.94）
U值 4.227 3.935 2.346
P值 ＜0.001 ＜0.001 0.019
表2 不同脑损伤程度TBI患者血清sTIM-3、Gal-9和CEACAM-1水平比较[ng/mL，M（Q1，Q3）]
Tab.2 Comparison of serum sTIM-3,Gal-9 and CEACAM-1 levels in TBI patients with different degrees of brain injury[ng/mL,M(Q1，Q3)]
脑损伤程度 例数 sTIM-3 Gal-9 CEACAM-1
轻型 42 2.53（1.65，2.61） 1.98（1.14，2.46） 18.47（14.31，23.04）
中型 42 2.71（1.67，3.26） 2.19（1.18，2.65） 19.94（14.56，22.31）
重型 36 2.83（1.70，3.89） 2.31（1.30，3.02） 22.08（15.73，25.38）
差异检验 H值 7.907 9.976 6.607
P值 0.019 0.007 0.037
趋势检验 χ 2值 6.229 6.350 7.477
P值 0.044 0.042 0.024
表3 影响TBI患者预后的单因素分析
Tab.3 Univariate analysis of prognosis in TBI patients
因素 预后良好（n=76） 预后不良（n=44） χ 2/t/U值 P值 OR值 95%CI
性别[例（%）] 0.186 0.666 0.785 0.463～1.315
女 25（48.08） 27（51.92）
男 30（48.11） 38（55.88）
年龄[例（%）] 0.011 0.916 1.152 0.723～1.826
40～47岁 23（63.64） 35（59.15）
48～53岁 24（36.36） 38（40.85）
损伤类型[例（%）] 0.072 0.965 0.854 0.490～1.476
软组织损伤 17（48.57） 18（51.43）
颅骨损伤 22（45.83） 26（54.17）
颅内组织损伤 17（45.95） 20（54.05）
损伤原因[例（%）] 0.062 0.969 0.907 0.568～1.426
交通事故 31（48.44） 33（51.56）
高空坠落 16（47.06） 18（52.94）
打击伤 10（45.45） 12（54.55）
GCS评分（分，Mean±SD） 12.65±2.18 7.06±2.34 13.176 ＜0.001 0.422 0.311～0.573
sTIM-3[ng/mL，M（Q1，Q3）] 2.61（1.65，3.39） 2.79（1.68，3.88） 2.652 0.008 0.948 0.516～1.714
Gal-9[ng/mL，M（Q1，Q3）] 2.01（1.14，2.78） 2.30（1.22，2.89） 2.241 0.025 0.875 0.489～1.550
CEACAM-1[ng/mL，M（Q1，Q3）] 21.09（14.62，25.17） 23.06（15.21，27.12） 2.097 0.036 0.911 0.423～1.960
表4 影响TBI患者预后的多因素Logistic回归分析
Tab.4 Multivariate Logistic regression analysis of prognosis in patients with TBI
因素 偏回归系数 标准误 Waldχ2值 P值 OR值 95%CI
常数 -0.149 0.069 4.636 0.031
sTIM-3 0.793 0.283 7.851 0.005 2.210 1.269～3.848
Gal-9 0.711 0.186 14.569 ＜0.001 2.036 1.414～2.932
CEACAM-1 0.486 0.192 6.440 0.011 1.625 1.116～2.369
GCS评分 -0.904 0.255 12.572 ＜0.001 0.405 0.246～0.668
图1 血清sTIM-3、Gal-9、CEACAM-1水平及GCS评分预测TBI患者预后的ROC曲线 sTIM-3：可溶性T 细胞免疫球蛋白及黏蛋白分子-3；Gal-9：半乳糖凝集素-9；CEACAM-1：癌胚抗原相关细胞黏附分子-1；ROC：受试者工作特征曲线
Fig.1 ROC curve of serum sTIM-3,Gal-9,CEACAM-1 levels and GCS score in predicting the prognosis of TBI patients
表5 ROC曲线分析血清sTIM-3、Gal-9、CEACAM-1水平及GCS评分对预后的预测价值
Tab.5 ROC curve analysis of the predictive value of serum sTIM-3,Gal-9,CEACAM-1 levels and GCS score for prognosis
指标 AUC（95%CI） 阈值（实值） 灵敏度 特异度 约登指数 准确度
sTIM-3 0.744 1（2.62ng/mL） 0.750 0.737 0.487 0.742
Gal-9 0.706 1（2.28ng/mL） 0.727 0.684 0.411 0.700
CEACAM-1 0.697 1（20.53ng/mL） 0.682 0.711 0.393 0.700
GCS评分 0.739 1（11分） 0.727 0.750 0.477 0.742
联合应用 0.823（0.724～0.921） 0.54 0.864 0.789 0.653 0.817
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