Article(id=1203036772180648072, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203036770628755576, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2023.04.0431, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1625760000000, receivedDateStr=2021-07-09, revisedDate=null, revisedDateStr=null, acceptedDate=1649001600000, acceptedDateStr=2022-04-04, onlineDate=1764755917830, onlineDateStr=2025-12-03, pubDate=1682611200000, pubDateStr=2023-04-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1764755917830, onlineIssueDateStr=2025-12-03, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1764755917830, creator=13701087609, updateTime=1764755917830, updator=13701087609, issue=Issue{id=1203036770628755576, tenantId=1146029695717560320, journalId=1189873630562394117, year='2023', volume='48', issue='4', pageStart='367', pageEnd='488', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1764755917460, creator=13701087609, updateTime=1764756108290, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1203037571086508742, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203036770628755576, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1203037571086508743, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1203036770628755576, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=431, endPage=436, ext={EN=ArticleExt(id=1203036772478443665, articleId=1203036772180648072, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=The early diagnosis value of neutrophil-side-fluorescence intensity on heat stroke complicated with disseminated intravascular coagulation, columnId=1190310109000602400, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Clinical Research, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the early diagnosis value of neutrophil-side-fluorescence intensity (NE-SFI) on heat stroke (HS)-related disseminated intravascular coagulation (DIC). Methods According to the International Society of Thrombosis and Haemostasis (ISTH) scoring criteria, thirty-four HS patients admitted to the General Hospital of Southern Theater Command from January 1, 2017 to December 31, 2018 were selected and divided into HS without DIC group (DIC score <5 points, n=23)and HS with DIC group (DIC score ≥5 points, n=11). The patient's general information, NE-SFI, and neutrophil extracellular traps (NETs)-related markers such as, dsDNA (double-stranded DNA), myeloperoxidase (MPO) and citrullinated histone (CitH3)were compared between the two groups. Receiver operating characteristic (ROC) curve was used to analyze the early diagnostic value of NE-SFI in HS with DIC. Results There was no significant difference in age, maximum body temperature, white blood cell count and neutrophil count between the two groups (P>0.05). The proportion of patients in the HS with DIC group whose core temperature dropped below 38.5 ℃ within 3 hours and the GCS (Glasgow Coma Scale) score were lower than those in the HS without DIC group, while the alanine aminotransferase (ALT), creatinine, ISTH (International Society of Thrombosis and Haemostasis) score, and the proportion of concurrent multiple organ dysfunction syndrome (MODS) in the HS with DIC group were higher than those in the HS without DIC group (P<0.05). On the 1st to 3rd day of onset, the NE-SFI values of the HS with DIC group were higher than those of the HS without DIC group (P<0.001). Compared with the serum dsDNA, MPO, and CitH3 in HS without DIC group [respectively (30.14±7.01) ng/ml, (56.39±34.64) pg/ml, (320.26±89.60) ng/μl], the serum dsDNA, MPO and CitH3 levels in HS with DIC group [respectively (372.93±135.77) ng/ml, (108.32±38.58) pg/ml, (600.18±183.74) ng/μl]are significantly increased (P<0.001). Spearman correlation analysis showed that the value of NE-SFI on day 1-3 were positively correlated with the levels of dsDNA, MPO and CitH3 on day 1 (P<0.05 or P<0.01). ROC curve analysis showed that NE-SFI on day 2 had a high value for the early diagnosis of HS complicated with DIC, and its AUC was 0.921 (95%CI 0.820-1.000, P<0.001). Conclusion NE-SFI can be used as an effective indicator for the early diagnosis in HS complicated with DIC.

, correspAuthors=Lei Su, authorNote=null, correspAuthorsNote=
E-mail:
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目的 探讨中性粒细胞侧向荧光(NE-SFI)强度对重症中暑(HS)合并弥散性血管内凝血(DIC)的早期诊断价值。方法 选取南部战区总医院2017年1月1日-2018年12月31日收治的HS患者34例,依据国际血栓与止血学会(ISTH)发布的显性DIC评分标准,将34例患者分为HS未合并DIC组(DIC评分<5分,n=23)与HS合并DIC组(DIC评分≥5分,n=11)。比较两组患者的一般资料,NE-SFI,以及血清中性粒细胞胞外诱捕网(NETs)相关标志物dsDNA、髓过氧化物酶(MPO)、瓜氨酸化组蛋白(CitH3)的水平。利用受试者工作特征(ROC)曲线分析NE-SFI对HS合并DIC的早期诊断价值。结果 两组患者年龄、发病最高核心体温、白细胞计数、中性粒细胞计数比较差异均无统计学意义(P>0.05)。HS合并DIC组3 h内核心温度降至38.5 ℃以下患者比例、GCS评分低于HS未合并DIC组,谷丙转氨酶(ALT)、肌酐、ISTH评分、并发多器官功能障碍综合征(MODS)比例高于HS未合并DIC组,差异均有统计学意义(P<0.05)。发病第1~3天,HS合并DIC组的NE-SFI值均高于HS未合并DIC组,差异有统计学意义(P<0.001)。HS合并DIC组患者的血清dsDNA、MPO、CitH3水平[分别为(372.93±135.77)ng/ml、(108.32±38.58)pg/ml、(600.18±183.74)ng/μl]明显高于HS未合并DIC组[分别为(30.14±7.01)ng/ml、(56.39±34.64)pg/ml、(320.26±89.60)ng/μl],差异有统计学意义(P<0.001)。Spearman相关分析显示:发病第1~3天的NE-SFI值与发病第1天的dsDNA、MPO、CitH3水平均呈正相关(P<0.05或P<0.01)。ROC曲线分析显示,发病第2天的NE-SFI值对HS合并DIC的诊断效能最高,其AUC为0.921(95%CI 0.820~1.000,P<0.001)。结论 NE-SFI可作为早期诊断HS并发DIC的有效指标。

, correspAuthors=苏磊, authorNote=null, correspAuthorsNote=
苏磊,E-mail:
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陈文达,医学硕士,主要从事重症中暑凝血机制方面的研究

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陈文达,医学硕士,主要从事重症中暑凝血机制方面的研究

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陈文达,医学硕士,主要从事重症中暑凝血机制方面的研究

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figureFileSmall=u5Q28Z3Ehi1nqZMtKgCZfA==, figureFileBig=D8OEPWSKG41P34PrQL8GwQ==, tableContent=null), ArticleFig(id=1203036777805210038, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036772180648072, language=CN, label=图1, caption=两组典型病例外周血NE-SFI变化

图中数据为日本东亚Sysmex XN-3000型全自动分析仪检测的NE-SFI值,单位AU,正常值为46.4 AU

, figureFileSmall=u5Q28Z3Ehi1nqZMtKgCZfA==, figureFileBig=D8OEPWSKG41P34PrQL8GwQ==, tableContent=null), ArticleFig(id=1203036777989759424, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036772180648072, language=EN, label=Fig. 2, caption=ROC of NE-SFI for early diagnosis of severe heat stroke complicated with DIC, figureFileSmall=QA9IoxJDdMgaOOyfiznV1w==, figureFileBig=KuzA6UOU+6cuan1iXUA5NQ==, tableContent=null), ArticleFig(id=1203036778094617026, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036772180648072, language=CN, label=图2, caption=NE-SFI早期诊断重症中暑患者合并DIC的ROC曲线

NE-SFI1、2、3分别代表第1、2、3天的中性粒细胞侧向荧光强度;ΔNE-SFI为第3天与第1天NE-SFI的差值;DIC. 弥散性血管内凝血

, figureFileSmall=QA9IoxJDdMgaOOyfiznV1w==, figureFileBig=KuzA6UOU+6cuan1iXUA5NQ==, tableContent=null), ArticleFig(id=1203036778199474631, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036772180648072, language=EN, label=Tab. 1, caption=

Comparison of general data of two groups of HS patients

, figureFileSmall=null, figureFileBig=null, tableContent=
指标未合并DIC组(n=23)合并DIC组(n=11)t/χ2/ZP
年龄(岁,$\bar{x}±s$)24.5±9.829.6±11.7-0.1040.195
发病最高核心体温(℃, $\bar{x}±s$)39.92±1.1040.22±1.08-0.3780.458
3 h内核心温度降至38.5 ℃以下[例(%)]20(87.0)2(18.2)5.360<0.001
白细胞计数(×109/L, $\bar{x}±s$)11.26±5.1411.79±3.450.0000.757
中性粒细胞计数(×109/L, $\bar{x}±s$)9.16±4.999.91±2.73-0.2640.647
GCS评分(分,$\bar{x}±s$)13.43±2.669.36±4.152.9720.010
ALT[mmol/L, M(Q1, Q3)]48(9, 145)780(57, 3206)-578.500<0.001
肌酐(μmol/L, $\bar{x}±s$)113.87±36.53163.73±79.06-9.6810.016
ISTH评分(分,$\bar{x}±s$)1.17±1.076.82±0.41-22.158<0.001
并发MODS[例(%)]5(21.7)11(100.0)-6.284<0.001
), ArticleFig(id=1203036778287555019, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036772180648072, language=CN, label=表1, caption=

两组HS患者一般资料比较

, figureFileSmall=null, figureFileBig=null, tableContent=
指标未合并DIC组(n=23)合并DIC组(n=11)t/χ2/ZP
年龄(岁,$\bar{x}±s$)24.5±9.829.6±11.7-0.1040.195
发病最高核心体温(℃, $\bar{x}±s$)39.92±1.1040.22±1.08-0.3780.458
3 h内核心温度降至38.5 ℃以下[例(%)]20(87.0)2(18.2)5.360<0.001
白细胞计数(×109/L, $\bar{x}±s$)11.26±5.1411.79±3.450.0000.757
中性粒细胞计数(×109/L, $\bar{x}±s$)9.16±4.999.91±2.73-0.2640.647
GCS评分(分,$\bar{x}±s$)13.43±2.669.36±4.152.9720.010
ALT[mmol/L, M(Q1, Q3)]48(9, 145)780(57, 3206)-578.500<0.001
肌酐(μmol/L, $\bar{x}±s$)113.87±36.53163.73±79.06-9.6810.016
ISTH评分(分,$\bar{x}±s$)1.17±1.076.82±0.41-22.158<0.001
并发MODS[例(%)]5(21.7)11(100.0)-6.284<0.001
), ArticleFig(id=1203036778375635408, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036772180648072, language=EN, label=Tab. 2, caption=

Changes of NE-SFI in peripheral blood of two groups of HS patients (AU, $\bar{x}±s$)

, figureFileSmall=null, figureFileBig=null, tableContent=
指标未合并DIC组(n=23)合并DIC组(n=11)tP
NE-SFI153.96±3.3158.55±4.14-3.4890.001
NE-SFI253.77±3.3359.90±3.59-4.899<0.001
NE-SFI352.76±4.9061.92±6.57-4.558<0.001
), ArticleFig(id=1203036778467910100, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036772180648072, language=CN, label=表2, caption=

两组HS患者外周血NE-SFI变化(AU,$\bar{x}±s$)

, figureFileSmall=null, figureFileBig=null, tableContent=
指标未合并DIC组(n=23)合并DIC组(n=11)tP
NE-SFI153.96±3.3158.55±4.14-3.4890.001
NE-SFI253.77±3.3359.90±3.59-4.899<0.001
NE-SFI352.76±4.9061.92±6.57-4.558<0.001
), ArticleFig(id=1203036778589544918, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036772180648072, language=EN, label=Tab. 3, caption=

Comparison of serum dsDNA, MPO and CitH3 between two groups of HS patients ($\bar{x}±s$)

, figureFileSmall=null, figureFileBig=null, tableContent=
指标未合并DIC组(n=23)合并DIC组(n=11)tP
MPO(pg/ml)56.39±34.64108.32±38.58-3.944<0.001
dsDNA(ng/ml)30.14±7.01372.93±135.77-6.024<0.001
CitH3(ng/μl)320.26±89.60600.18±183.74-5.927<0.001
), ArticleFig(id=1203036778702791129, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036772180648072, language=CN, label=表3, caption=

两组HS患者血清dsDNA、MPO、CitH3比较($\bar{x}±s$)

, figureFileSmall=null, figureFileBig=null, tableContent=
指标未合并DIC组(n=23)合并DIC组(n=11)tP
MPO(pg/ml)56.39±34.64108.32±38.58-3.944<0.001
dsDNA(ng/ml)30.14±7.01372.93±135.77-6.024<0.001
CitH3(ng/μl)320.26±89.60600.18±183.74-5.927<0.001
), ArticleFig(id=1203036778807648734, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036772180648072, language=EN, label=Tab. 4, caption=

Correlation between NE-SFI and dsDNA, MPO and CitH3 levels

, figureFileSmall=null, figureFileBig=null, tableContent=
指标MPOdsDNACitH3
NE-SFI10.346*0.508**0.509**
NE-SFI20.430*0.616**0.574**
NE-SFI30.492**0.539**0.583**
), ArticleFig(id=1203036778870563297, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036772180648072, language=CN, label=表4, caption=

NE-SFI与dsDNA、MPO、CitH3水平的相关性

, figureFileSmall=null, figureFileBig=null, tableContent=
指标MPOdsDNACitH3
NE-SFI10.346*0.508**0.509**
NE-SFI20.430*0.616**0.574**
NE-SFI30.492**0.539**0.583**
), ArticleFig(id=1203036778933477861, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036772180648072, language=EN, label=Tab. 5, caption=

Early diagnostic value of NE-SFI in heat stroke complicated with DIC

, figureFileSmall=null, figureFileBig=null, tableContent=
指标最佳截断值(AU)特异度敏感度AUCAUC 95%CIP
NE-SFI157.60.910.550.7910.625~0.9560.007
NE-SFI256.20.910.910.9210.820~1.000<0.001
NE-SFI355.60.870.910.9210.820~1.000<0.001
ΔNE-SFI0.100.700.910.7770.595~0.9580.062
), ArticleFig(id=1203036779038335464, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1203036772180648072, language=CN, label=表5, caption=

NE-SFI对HS合并DIC的早期诊断价值

, figureFileSmall=null, figureFileBig=null, tableContent=
指标最佳截断值(AU)特异度敏感度AUCAUC 95%CIP
NE-SFI157.60.910.550.7910.625~0.9560.007
NE-SFI256.20.910.910.9210.820~1.000<0.001
NE-SFI355.60.870.910.9210.820~1.000<0.001
ΔNE-SFI0.100.700.910.7770.595~0.9580.062
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中性粒细胞侧向荧光强度对重症中暑合并弥散性血管内凝血的早期诊断价值
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陈文达 1, 2 , 彭娜 1, 3 , 刘帅 1 , 童华生 1 , 唐柚青 1 , 刘靖华 3 , 苏磊 2, 4, *
解放军医学杂志 | 临床研究 2023,48(4): 431-436
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解放军医学杂志 | 临床研究 2023, 48(4): 431-436
中性粒细胞侧向荧光强度对重症中暑合并弥散性血管内凝血的早期诊断价值
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陈文达1, 2, 彭娜1, 3, 刘帅1, 童华生1, 唐柚青1, 刘靖华3, 苏磊2, 4, *
作者信息
  • 1南部战区总医院急诊科,广东广州 510010
  • 2广东药科大学研究生院,广东广州 510080
  • 3南方医科大学基础医学院病理生理学教研室/广东省蛋白质组学重点实验室,广东广州 510515
  • 4南部战区总医院重症医学科/全军热区创伤救治与组织修复重点实验室,广东广州 510010
  • 陈文达,医学硕士,主要从事重症中暑凝血机制方面的研究

通讯作者:

苏磊,E-mail:
The early diagnosis value of neutrophil-side-fluorescence intensity on heat stroke complicated with disseminated intravascular coagulation
Wen-Da Chen1, 2, Na Peng1, 3, Shuai Liu1, Hua-Sheng Tong1, You-Qing Tang1, Jing-Hua Liu3, Lei Su2, 4, *
Affiliations
  • 1Department of Emergency, Guangzhou, Guangdong 510010, China
  • 2Graduate School, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510080, China
  • 3Department of Pathophysiology, Southern Medical University/Guangdong Provincial Key Laboratory of Proteomics, Guangzhou,Guangdong 510515, China
  • 4Department of Intensive Care Unit/Key Laboratory of Hot Zone Trauma Care and Tissue Repair of Chinese PLA, General Hospital of Southern Theater Command, Guangzhou, Guangdong 510010, China
出版时间: 2023-04-28 doi: 10.11855/j.issn.0577-7402.2023.04.0431
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目的 探讨中性粒细胞侧向荧光(NE-SFI)强度对重症中暑(HS)合并弥散性血管内凝血(DIC)的早期诊断价值。方法 选取南部战区总医院2017年1月1日-2018年12月31日收治的HS患者34例,依据国际血栓与止血学会(ISTH)发布的显性DIC评分标准,将34例患者分为HS未合并DIC组(DIC评分<5分,n=23)与HS合并DIC组(DIC评分≥5分,n=11)。比较两组患者的一般资料,NE-SFI,以及血清中性粒细胞胞外诱捕网(NETs)相关标志物dsDNA、髓过氧化物酶(MPO)、瓜氨酸化组蛋白(CitH3)的水平。利用受试者工作特征(ROC)曲线分析NE-SFI对HS合并DIC的早期诊断价值。结果 两组患者年龄、发病最高核心体温、白细胞计数、中性粒细胞计数比较差异均无统计学意义(P>0.05)。HS合并DIC组3 h内核心温度降至38.5 ℃以下患者比例、GCS评分低于HS未合并DIC组,谷丙转氨酶(ALT)、肌酐、ISTH评分、并发多器官功能障碍综合征(MODS)比例高于HS未合并DIC组,差异均有统计学意义(P<0.05)。发病第1~3天,HS合并DIC组的NE-SFI值均高于HS未合并DIC组,差异有统计学意义(P<0.001)。HS合并DIC组患者的血清dsDNA、MPO、CitH3水平[分别为(372.93±135.77)ng/ml、(108.32±38.58)pg/ml、(600.18±183.74)ng/μl]明显高于HS未合并DIC组[分别为(30.14±7.01)ng/ml、(56.39±34.64)pg/ml、(320.26±89.60)ng/μl],差异有统计学意义(P<0.001)。Spearman相关分析显示:发病第1~3天的NE-SFI值与发病第1天的dsDNA、MPO、CitH3水平均呈正相关(P<0.05或P<0.01)。ROC曲线分析显示,发病第2天的NE-SFI值对HS合并DIC的诊断效能最高,其AUC为0.921(95%CI 0.820~1.000,P<0.001)。结论 NE-SFI可作为早期诊断HS并发DIC的有效指标。

重症中暑  /  弥散性血管内凝血  /  中性粒细胞侧向荧光  /  多器官功能障碍综合征

Objective To investigate the early diagnosis value of neutrophil-side-fluorescence intensity (NE-SFI) on heat stroke (HS)-related disseminated intravascular coagulation (DIC). Methods According to the International Society of Thrombosis and Haemostasis (ISTH) scoring criteria, thirty-four HS patients admitted to the General Hospital of Southern Theater Command from January 1, 2017 to December 31, 2018 were selected and divided into HS without DIC group (DIC score <5 points, n=23)and HS with DIC group (DIC score ≥5 points, n=11). The patient's general information, NE-SFI, and neutrophil extracellular traps (NETs)-related markers such as, dsDNA (double-stranded DNA), myeloperoxidase (MPO) and citrullinated histone (CitH3)were compared between the two groups. Receiver operating characteristic (ROC) curve was used to analyze the early diagnostic value of NE-SFI in HS with DIC. Results There was no significant difference in age, maximum body temperature, white blood cell count and neutrophil count between the two groups (P>0.05). The proportion of patients in the HS with DIC group whose core temperature dropped below 38.5 ℃ within 3 hours and the GCS (Glasgow Coma Scale) score were lower than those in the HS without DIC group, while the alanine aminotransferase (ALT), creatinine, ISTH (International Society of Thrombosis and Haemostasis) score, and the proportion of concurrent multiple organ dysfunction syndrome (MODS) in the HS with DIC group were higher than those in the HS without DIC group (P<0.05). On the 1st to 3rd day of onset, the NE-SFI values of the HS with DIC group were higher than those of the HS without DIC group (P<0.001). Compared with the serum dsDNA, MPO, and CitH3 in HS without DIC group [respectively (30.14±7.01) ng/ml, (56.39±34.64) pg/ml, (320.26±89.60) ng/μl], the serum dsDNA, MPO and CitH3 levels in HS with DIC group [respectively (372.93±135.77) ng/ml, (108.32±38.58) pg/ml, (600.18±183.74) ng/μl]are significantly increased (P<0.001). Spearman correlation analysis showed that the value of NE-SFI on day 1-3 were positively correlated with the levels of dsDNA, MPO and CitH3 on day 1 (P<0.05 or P<0.01). ROC curve analysis showed that NE-SFI on day 2 had a high value for the early diagnosis of HS complicated with DIC, and its AUC was 0.921 (95%CI 0.820-1.000, P<0.001). Conclusion NE-SFI can be used as an effective indicator for the early diagnosis in HS complicated with DIC.

heat stroke  /  disseminated intravascular coagulation  /  neutrophil-side-fluorescence intensity  /  multiple organ dysfunction syndrome
陈文达, 彭娜, 刘帅, 童华生, 唐柚青, 刘靖华, 苏磊. 中性粒细胞侧向荧光强度对重症中暑合并弥散性血管内凝血的早期诊断价值. 解放军医学杂志, 2023 , 48 (4) : 431 -436 . DOI: 10.11855/j.issn.0577-7402.2023.04.0431
Wen-Da Chen, Na Peng, Shuai Liu, Hua-Sheng Tong, You-Qing Tang, Jing-Hua Liu, Lei Su. The early diagnosis value of neutrophil-side-fluorescence intensity on heat stroke complicated with disseminated intravascular coagulation[J]. Medical Journal of Chinese People’s Liberation Army, 2023 , 48 (4) : 431 -436 . DOI: 10.11855/j.issn.0577-7402.2023.04.0431
重症中暑(heat stroke,HS)是在高温高湿环境伴或不伴高强度体力劳动下,机体热平衡失调及水电解质代谢紊乱造成的以高热、中枢神经系统功能受损为主要表现的急性热损伤相关疾病,常导致多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)[1]。弥散性血管内凝血(disseminated intravascular coagulation,DIC)是HS早期常见的并发症之一,发生率为30%~60%,病死率为31%~86%[2]
目前研究认为,HS导致凝血激活的机制包括以系统性内皮病为核心的全身炎症反应以及免疫性血栓启动等[3],其中中性粒细胞释放的中性粒细胞胞外诱捕网(neutrophil extracellular traps,NETs)在免疫性血栓形成中起重要作用[4]。NETs以DNA为主要骨架,由组蛋白、细胞质的颗粒酶如髓过氧化物酶(myeloperoxidase,MPO)及弹性蛋白酶等蛋白组成,呈网状、丝状结构,是血栓形成的基本支架[5-6]。因此,NETs水平可反映机体血栓生成早期的生理变化。已有研究通过测定血浆中双链DNA(dsDNA)水平及其他NETs相关成分来监测凝血紊乱及DIC的发生[7]。但是,前述标志物的检测目前仍停留在实验室阶段,尚无法在临床中推广应用。中性粒细胞侧向荧光(neutrophil-side-fluorescence light,NE-SFI)是利用血细胞分析仪及流式细胞技术获取的中性粒细胞分类参数,反映了中性粒细胞核酸的含量[8]。有研究报道,脓毒症合并DIC患者的NE-SFI明显升高,且与中性粒细胞激活呈正相关[9],提示NE-SFI的变化可能反映早期NETs形成及继发的严重凝血紊乱。基于中性粒细胞释放NETs在HS相关DIC的病理生理过程中发挥着重要作用,早期诊断及治疗DIC是遏制HS转化为MODS的关键环节。而目前公认的DIC诊断标准采用的传统凝血指标往往滞后于临床变化,常导致早期诊断及治疗延迟。探寻DIC早期诊断敏感的生化指标一直是临床医师关注的热点,但大部分早期凝血标志物仍局限在实验室阶段。NE-SFI作为临床常规检测指标,可能从病理生理机制层面反映了中性粒细胞激活在凝血启动中的作用,但是否可为早期诊断HS患者的凝血紊乱提供有效参考尚未见报道。本研究旨在观察NE-SFI在HS相关DIC早期的变化,并探讨其对HS相关DIC的诊断价值。
选取南部战区总医院2017年1月1日-2018年12月31日收治的HS患者34例,均为男性,所有患者发病至入院时间<12 h,符合《职业性中暑诊断标准(GBZ41-2002)》。以国际血栓与止血学会(International Society on Thrombosis and Haemostasis,ISTH)评分≥5分(72 h内)作为显性DIC的诊断标准,将34例患者分为HS合并DIC组(n=11)与HS未合并DIC组(n=23)。收集患者临床数据,包括年龄、性别、发病时间、发病最高核心体温、发病2 h内体温是否下降至38.5 ℃以下、入院格拉斯哥昏迷评分(Glasgow coma scale,GCS)。MODS的诊断采用1997年修正的Fry-MODS诊断标准。本研究经广州军区广州总医院临床试验伦理委员会审批(20180726025),中国临床试验注册中心注册号ChiCTR1800018495。
采用日本东亚Sysmex XN-3000型全自动血液分析仪检测血常规指标(白细胞计数、血小板计数及白细胞分类计数);采用法国Stago公司的自动出凝血检测仪检测凝血酶原时间、部分活化凝血酶原时间、纤维蛋白原、国际标准化比值及D-二聚体水平;采用日本日立H7600型全自动生化分析仪检测肌酐、谷丙转氨酶(ALT)水平。采用日本东亚Sysmex XN-3000型全自动分析仪检测患者入院后第1、2、3天的NE-SFI值。具体原理和步骤如下:利用半导体激光流式细胞术、核酸荧光染色技术,采用稳定的红色二极管激光器,产生波长为633 nm的光束,用溶血剂完全溶解红细胞和血小板,白细胞膜仅部分溶解。用特异性裂解试剂处理进行细胞透化,核酸荧光染料进入白细胞内,使DNA及RNA着色。记录白细胞差分通道散点图中显示的3种不同信号,分别为反映细胞大小的NE-FSC,反映内部细胞结构和粒度的NE-SSC,以及反映DNA/RNA含量的NE-SFI。NE-SFI的正常值是46.4 AU。
采用真空法采血制备人外周血血清。分别用干燥管、枸橼酸抗凝管采集患者入院后第1天的血液标本,室温静置1 h后,3000 r/min室温离心15 min,吸取上层黄色液体即血清。采用ELISA试剂盒测定MPO(上海西唐生物科技公司)、瓜氨酸化组蛋白(citrullinated histones,CitH3)(美国Epigentek公司)水平;Quant-iT PicoGreen dsDNA分析试剂盒(美国Invitrogen公司)检测dsDNA水平,具体操作按照说明书要求进行。
比较合并或未合并DIC的两组HS患者的一般资料;分析NE-SFI与NETs主要标志物的相关性;采用受试者工作特征(receiver operator characteristic,ROC)曲线计算NE-SFI、ΔNE-SFI诊断DIC的最佳截断值、敏感度、特异度、ROC曲线下面积(area under the curve,AUC)及95%置信区间(confidence interval,CI)等。
数据采用SPSS 20.0统计学软件进行分析。正态分布的计量资料以$\bar{x}±s$表示,两组比较采用独立样本t检验;非正态分布的计量资料以MQ1Q3)表示,两组比较采用秩和检验;计数资料用例(%)表示,两组间比较采用χ2检验。相关性分析采用Spearman秩相关。P<0.05为差异有统计学意义。
两组患者年龄、发病最高核心体温、白细胞计数、中性粒细胞计数比较差异均无统计学意义(P>0.05)。HS合并DIC组3 h内核心温度降至38.5 ℃以下患者比例及GCS评分低于HS未合并DIC组,谷丙转氨酶、肌酐、ISTH评分、并发MODS比例高于HS未合并DIC组,差异均有统计学意义(P<0.05,表1)。
发病第1~3天,HS合并DIC组的NE-SFI值均高于HS未合并DIC组,差异有统计学意义(P<0.001,表2)。HS合并DIC组患者NE-SFI随复苏时间延长呈递增趋势,而HS未合并DIC组第1~3天的NE-SFI值无明显变化。典型病例NE-SFI检测见图1
HS合并DIC组的血清dsDNA、MPO及CitH3水平均高于HS未合并DIC组,差异有统计学意义(P<0.001,表3)。
Spearman秩相关分析结果显示,NE-SFI1、2、3均与MPO、dsDNA及CitH3呈正相关(P<0.05或P<0.01,表4),提示NE-SFI水平与NETs的形成相关。
ROC曲线分析结果显示,第2天的NE-SFI值对HS合并DIC的诊断效能最高,其诊断特异度和敏感度均为0.91,AUC为0.921(95%CI 0.820~1.000,P<0.001)(表5图2)。
HS是高发病率和高病死率的热相关疾病,以全身炎症反应、系统性内皮细胞损害为核心病理生理机制,最终可能导致MODS及死亡[1,10-12]。凝血功能障碍及DIC是HS早期常见的临床表现,也是驱动HS进展为MODS的重要因素。al-Mashhadani等[13]报道的132例中暑患者中,30%诊断为DIC且合并轻至重度出血,直接导致其中半数患者死亡。来自日本的一项纳入705例中暑患者的研究显示,DIC是HS患者住院病死率增高的独立危险因素[14]。本研究发现,与未合并DIC组比较,合并DIC组患者的ISTH评分、肌酐、谷丙转氨酶水平更高,GCS评分更低,提示HS合并DIC患者的中枢神经系统损伤及多脏器功能障碍更严重。因此,早期诊断并改善凝血紊乱是遏制HS病情进展及死亡的可控且有效的途径之一。
HS合并DIC尚无特异性诊断指标,目前仍采用ISTH、日本卫生福利部、日本急救医学协会等的评分系统,上述标准均采用传统的凝血指标,但是以凝血结局为检测终点的传统凝血指标对HS合并DIC的早期诊断欠敏感。近年研究表明,HS导致凝血紊乱的病理生理机制是以内皮细胞损害为核心环节的多种血细胞与免疫细胞激活及相互作用[15-16]。中性粒细胞激活是HS的重要特征[5],激活的中性粒细胞与损伤的内皮细胞黏附并释放NETs是血栓形成的基本支架,与多种血栓性疾病密切相关[6,17-18]。因此,从中性粒细胞激活释放NETs促进血栓形成的角度探寻早期DIC的诊断标志物,有利于HS合并DIC的早期诊断和治疗。Sysmex XN-3000型全自动血液分析仪通过对白细胞的参数进行分析,获取前向散射光(NE-forward-scattered light,NE-FSC)、侧向散射光(NE-side-scattered light,NE-SSC)及中性粒细胞侧向荧光(NE-SFI)等参数,分别反映中性粒细胞的大小、内部结构及细胞内核酸含量,其中NE-SFI主要反映中性粒细胞内DNA及RNA的含量变化[8]。既往研究显示,脓毒症合并DIC患者的NE-SFI较未合并DIC患者明显升高,与中性粒细胞激活呈正相关,NE-SFI对早期诊断脓毒症合并DIC的敏感度及特异度均高[9]。本研究发现,HS合并DIC患者在发病早期(72 h内)的NE-SFI值及血清NETs标志物dsDNA、MPO、CitH3均较HS未合并DIC患者明显升高,相关分析提示NE-SFI与NETs的形成具有密切联系,表明NETs的释放可能参与了HS相关DIC的生理及病理机制[19]。本研究通过ROC曲线评估NE-SFI对HS相关DIC的早期诊断价值,结果显示,第2天的NE-SFI值对HS相关DIC的诊断效能最高(特异度及敏感度高达91%),提示连续监测NE-SFI可反映HS的发展,提高早期诊断的敏感度。
综上所述,NE-SFI反映了HS激活的中性粒细胞内核酸的变化,可作为早期诊断HS相关DIC及预后评估的辅助指标,且该指标可通过自动化血液分析仪在血常规检测结果中获取,具有快速、价廉的优势,有望成为临床有效的生物标志物。
  • 国家自然科学基金青年基金(81701892)
  • 中国博士后科学基金面上项目(2017M622737)
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2023年第48卷第4期
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doi: 10.11855/j.issn.0577-7402.2023.04.0431
  • 接收时间:2021-07-09
  • 首发时间:2025-12-03
  • 出版时间:2023-04-28
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  • 收稿日期:2021-07-09
  • 录用日期:2022-04-04
基金
National Natural Science Foundation of China Youth Found(81701892)
国家自然科学基金青年基金(81701892)
General Program of China Postdoctoral Foundation(2017M622737)
中国博士后科学基金面上项目(2017M622737)
作者信息
    1南部战区总医院急诊科,广东广州 510010
    2广东药科大学研究生院,广东广州 510080
    3南方医科大学基础医学院病理生理学教研室/广东省蛋白质组学重点实验室,广东广州 510515
    4南部战区总医院重症医学科/全军热区创伤救治与组织修复重点实验室,广东广州 510010

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2种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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