S100β、IL-1β与IL-6联合检测对青壮年颅脑损伤诊断及预后评估的价值
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摘要
目的探讨血清和脑脊液中S100蛋白质β(S100β)、白细胞介素1β(IL-1β)、白细胞介素6(IL-6)联合检测对青壮年创伤性颅脑损伤(TBI)诊断和预后评估的价值。方法选取青岛市市立医院神经外科术后转入ICU治疗的青壮年TBI病人132例作为观察组(轻型35例,中型55例,重型42例),以同期需行脑脊液穿刺检查的非TBI住院青壮年病人50例作为对照组。采用电化学发光法检测两组病人血清和脑脊液中S100β、IL-1β、IL-6的含量。应用受试者工作特征曲线(ROC曲线)分析S100β、IL-1β、IL-6联合检测对TBI的诊断价值,分析血清S100β、IL-1β、IL-6水平与TBI病人预后的相关性。结果观察组重型病人血清和脑脊液中S100β、IL-1β、IL-6含量均显著高于对照组(F=8.351～8.967,P<0.05)。观察组血清中S100β、IL-1β、IL-6的含量与脑脊液中的含量均呈正相关关系(r=0.83～0.89,P<0.05)。血清S100β、IL-1β、IL-6检测及三者联合检测诊断TBI的ROC曲线下面积分别为0.810、0.758、0.703和0.922。观察组血清和脑脊液中S100β、IL-1β、IL-6的表达水平与青壮年TBI预后呈负相关关系(F=8.671～9.371,P<0.05)。结论血清和脑脊液中S100β、IL-1β、IL-6水平与青壮年TBI病人病情严重程度和预后密切相关,且三者联合检测诊断效率高于单独检测。
Objective To investigate the value of combined measurement of S100β, interleukin-1β(IL-1β), and interleukin-6(IL-6) in serum and cerebrospinal fluid in the diagnosis and prognostic evaluation of young adults with traumatic brain injury(TBI). Methods A total of 132 young adult patients with TBI who underwent surgery and were then transferred to the intensive care unit in Department of Neurosurgery in Qingdao Municipal Hospital were enrolled as observation group, among whom 35 had mild TBI, 55 had moderate TBI, and 42 had severe TBI; 50 young adult patients without TBI who were hospitalized and underwent cerebrospinal fluid puncture were enrolled as control group. Electrochemical luminescence was used to measure the levels of S100β, IL-1β, and IL-6 in serum and cerebrospinal fluid. The receiver operating characteristic(ROC) curve was used to observe the value of combined measurement of S100β, IL-1β, and IL-6 in the diagnosis of TBI, and the correlation of serum S100β, IL-1β, and IL-6 with the prognosis of TBI patients was analyzed. Results The patients with severe TBI had significantly higher levels of S100β, IL-1β, and IL-6 in serum and cerebrospinal fluid than those in the control group(F=8.351-8.967,P<0.05). In the observation group, the levels of S100β, IL-1β, and IL-6 in serum were positively correlated with their levels in cerebrospinal fluid(r=0.83-0.89,P<0.05). The measurement of serum S100β, IL-1β, or IL-6 alone had an area under the ROC curve of 0.810, 0.758, and 0.703, respectively, while combined measurement of serum S100β, IL-1β, and IL-6 had an area of 0.922. In the observation group, the expression levels of S100β, IL-1β, and IL-6 in serum and cerebrospinal fluid were negatively correlated with the prognosis of young adults with TBI(F=8.671-9.371,P<0.05). Conclusion The levels of S100β, IL-1β, and IL-6 in serum and cerebrospinal fluid are closely associated with disease severity and prognosis of young adult patients with TBI, and combined measurement of S100β, IL-1β, and IL-6 has a higher diagnostic efficiency than the measurement of S100β, IL-1β, or IL-6 alone.
Objective To investigate the value of combined measurement of S100β, interleukin-1β(IL-1β), and interleukin-6(IL-6) in serum and cerebrospinal fluid in the diagnosis and prognostic evaluation of young adults with traumatic brain injury(TBI). Methods A total of 132 young adult patients with TBI who underwent surgery and were then transferred to the intensive care unit in Department of Neurosurgery in Qingdao Municipal Hospital were enrolled as observation group, among whom 35 had mild TBI, 55 had moderate TBI, and 42 had severe TBI; 50 young adult patients without TBI who were hospitalized and underwent cerebrospinal fluid puncture were enrolled as control group. Electrochemical luminescence was used to measure the levels of S100β, IL-1β, and IL-6 in serum and cerebrospinal fluid. The receiver operating characteristic(ROC) curve was used to observe the value of combined measurement of S100β, IL-1β, and IL-6 in the diagnosis of TBI, and the correlation of serum S100β, IL-1β, and IL-6 with the prognosis of TBI patients was analyzed. Results The patients with severe TBI had significantly higher levels of S100β, IL-1β, and IL-6 in serum and cerebrospinal fluid than those in the control group(F=8.351-8.967,P<0.05). In the observation group, the levels of S100β, IL-1β, and IL-6 in serum were positively correlated with their levels in cerebrospinal fluid(r=0.83-0.89,P<0.05). The measurement of serum S100β, IL-1β, or IL-6 alone had an area under the ROC curve of 0.810, 0.758, and 0.703, respectively, while combined measurement of serum S100β, IL-1β, and IL-6 had an area of 0.922. In the observation group, the expression levels of S100β, IL-1β, and IL-6 in serum and cerebrospinal fluid were negatively correlated with the prognosis of young adults with TBI(F=8.671-9.371,P<0.05). Conclusion The levels of S100β, IL-1β, and IL-6 in serum and cerebrospinal fluid are closely associated with disease severity and prognosis of young adult patients with TBI, and combined measurement of S100β, IL-1β, and IL-6 has a higher diagnostic efficiency than the measurement of S100β, IL-1β, or IL-6 alone.
引文
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[16] BOGOSLOVSKY T,GILL J,JEROMIN A,et al.Fluid biomarkers of traumatic brain injury and intended context of use[J].Diagnostics,2016,6(4):37.
[17] AGOSTON D V,SHUTES-DAVID A,PESKIND E R.Bio-fluid biomarkers of traumatic brain injury[J].Brain Injury,2017,31(9):1195-1203.
[18] WANG K K,YANG Z H,ZHU T,et al.An update on diagnostic and prognostic biomarkers for traumatic brain injury[J].Expert Review of Molecular Diagnostics,2018,18(2):165-180.
[19] PARK S H,HWANG S K.Prognostic value of serum levels of S100 calcium-binding protein B,neuron-specific enolase,and interleukin-6 in pediatric patients with traumatic brain injury[J].World Neurosurgery,2018,118:e534-e542.
[20] HEIZMANN C W.S100 proteins:diagnostic and prognostic biomarkers in laboratory medicine[J].Biochimica et Biophysica Acta-Molecular Cell Research,2019,1866(7):1197-1206.
[21] MICHETTI F,D’AMBROSI N,TOESCA A,et al.The S100B story:from biomarker to active factor in neural injury[J].Journal of Neurochemistry,2019,148(2):168-187.
[22] WELCH R D,AYAZ S I,LEWIS L M,et al.Ability of se-rum glial fibrillary acidic protein,ubiquitin C-terminal hydrolase-L1,and S100B to differentiate normal and abnormal head computed tomography findings in patients with suspected mild or moderate traumatic brain injury[J].Journal of Neurotrauma,2016,33(2):203-214.
[23] HELMY A,GUILFOYLE M R,CARPENTER K L,et al.Recombinant human interleukin-1 receptor antagonist promotes M1 microglia biased cytokines and chemokines following human traumatic brain injury[J].Journal of Cerebral Blood Flow and Metabolism,2016,36(8):1434-1448.
[24] WEBSTER K M,SUN M J,CRACK P,et al.Inflammation in epileptogenesis after traumatic brain injury[J].Journal of Neuroinflammation,2017,14(1):10-12.
[25] HELMY A,CARPENTER K L,MENON D K,et al.The cytokine response to human traumatic brain injury:temporal profiles and evidence for cerebral parenchymal production[J].Journal of Cerebral Blood Flow and Metabolism,2011,31(2):658-670.
[2] LASKOWSKI R A,CREED J A,RAGHUPATHI R.Pathophysiology of mild TBI:implications for altered signaling pathways[J].Journal of Neuroinflammation,2015,12(1):120-122.
[3] GRIFFIN G D.The injured brain:TBI,mTBI,the immune system,and infection:connecting the dots[J].Military Medicine,2011,176(4):364-368.
[4] HUIE J R,DIAZ-ARRASTIA R,YUE J K,et al.Testing a multivariate proteomic panel for traumatic brain injury biomarker discovery:a TRACK-TBI pilot study[J].Journal of Neurotrauma,2019,36(1):100-110.
[5] HASHIZAKI T,NISHIMURA Y,TERAMURA K A,et al.Differences in serum IL-6 response after 1 degrees C rise in core body temperature in individuals with spinal cord injury and cervical spinal cord injury during local heat stress[J].International Journal of Hyperthermia,2019,35(1):541-547.
[6] ORIS C,PEREIRA B,DURIF J,et al.The biomarker S100B and mild traumatic brain injury:a meta-analysis[J].Pediatrics,2018,141(6):e20180037.
[7] HOOSHMAND M,SOROUSHMEHR S M R,WILLIAMSON C,et al.Automatic midline shift detection in traumatic brain injury [J].Conference Proceedings,2018,2018:131-134.
[8] 邹莉玲,余小金,闵捷,等.ROC曲线在医学诊断中的应用与进展[J].东南大学学报(医学版),2003,22(1):67-70.
[9] CARNEY N,TOTTEN A M,O’REILLY C,et al.Guidelines for the management of severe traumatic brain injury,fourth edition[J].Neurosurgery,2016,80(1):6-15.
[10] WANG Xiaogang,GAO Ding,LI Tao,et al.The correlation analysis of prehospital GCS score of brain injury patients and prognosis[J].Chinese Journal for Clinicians,2015,87(1):23-25.
[11] DEKOSKY S T,ASKEN B M.Injury cascades in TBI-related neurodegeneration[J].Brain Injury,2017,31(9):1177-1182.
[12] IORIO-MORIN C,FORTIN D,BLANCHARD J.TBI prognosis calculator:a mobile application to estimate mortality and morbidity following traumatic brain injury[J].Clinical Neuro-logy and Neurosurgery,2016,142:48-53.
[13] CROKE L.Mild TBI in children:guidance from the CDC for diagnosis and treatment[J].American Family Physician,2019,99(7):462-464.
[14] PIKSTRA A R A,METTING Z,FOCK J M,et al.The juvenile head trauma syndrome-deterioration after mild TBI:diagnosis and clinical presentation at the Emergency Department[J].European Journal of Paediatric Neurology,2017,21(2):344-349.
[15] THOMPSON W H,THELIN E P,LILJA A A,et al.Functional resting-state fMRI connectivity correlates with serum levels of the S100B protein in the acute phase of traumatic brain injury[J].NeuroImage Clinical,2016,12:1004-1012.
[16] BOGOSLOVSKY T,GILL J,JEROMIN A,et al.Fluid biomarkers of traumatic brain injury and intended context of use[J].Diagnostics,2016,6(4):37.
[17] AGOSTON D V,SHUTES-DAVID A,PESKIND E R.Bio-fluid biomarkers of traumatic brain injury[J].Brain Injury,2017,31(9):1195-1203.
[18] WANG K K,YANG Z H,ZHU T,et al.An update on diagnostic and prognostic biomarkers for traumatic brain injury[J].Expert Review of Molecular Diagnostics,2018,18(2):165-180.
[19] PARK S H,HWANG S K.Prognostic value of serum levels of S100 calcium-binding protein B,neuron-specific enolase,and interleukin-6 in pediatric patients with traumatic brain injury[J].World Neurosurgery,2018,118:e534-e542.
[20] HEIZMANN C W.S100 proteins:diagnostic and prognostic biomarkers in laboratory medicine[J].Biochimica et Biophysica Acta-Molecular Cell Research,2019,1866(7):1197-1206.
[21] MICHETTI F,D’AMBROSI N,TOESCA A,et al.The S100B story:from biomarker to active factor in neural injury[J].Journal of Neurochemistry,2019,148(2):168-187.
[22] WELCH R D,AYAZ S I,LEWIS L M,et al.Ability of se-rum glial fibrillary acidic protein,ubiquitin C-terminal hydrolase-L1,and S100B to differentiate normal and abnormal head computed tomography findings in patients with suspected mild or moderate traumatic brain injury[J].Journal of Neurotrauma,2016,33(2):203-214.
[23] HELMY A,GUILFOYLE M R,CARPENTER K L,et al.Recombinant human interleukin-1 receptor antagonist promotes M1 microglia biased cytokines and chemokines following human traumatic brain injury[J].Journal of Cerebral Blood Flow and Metabolism,2016,36(8):1434-1448.
[24] WEBSTER K M,SUN M J,CRACK P,et al.Inflammation in epileptogenesis after traumatic brain injury[J].Journal of Neuroinflammation,2017,14(1):10-12.
[25] HELMY A,CARPENTER K L,MENON D K,et al.The cytokine response to human traumatic brain injury:temporal profiles and evidence for cerebral parenchymal production[J].Journal of Cerebral Blood Flow and Metabolism,2011,31(2):658-670.