共刺激分子程序性细胞死亡受体-1/程序性细胞死亡受体配体-1调控树突状细胞对脓毒症患者免疫功能的影响

来源 :中华危重病急救医学 | 被引量 : 0次 | 上传用户:baohuse
下载到本地 , 更方便阅读
声明 : 本文档内容版权归属内容提供方 , 如果您对本文有版权争议 , 可与客服联系进行内容授权或下架
论文部分内容阅读
目的:观察程序性细胞死亡受体-1/程序性细胞死亡受体配体-1(PD-1/PD-L1)调控树突状细胞(DC)对脓毒症患者免疫状态的影响,分析PD-1/PD-L1对脓毒症患者预后的预测价值。方法:从2018年10月至2019年9月住遵义医科大学附属医院综合重症监护病房(ICU)病区的脓毒症患者中采用随机数表法抽选25例,根据28 d预后将患者分为存活组(10例)和死亡组(15例);同时随机抽取本院健康体检者20例作为健康对照组。脓毒症患者于确诊后24 h内、健康对照组于入组时取患者外周血,分离血清,采用流式细胞仪(FCM)检测CD4n +T、CD8n +T细胞比值,T细胞亚群比值(CD4/CD8),CD4n +T、CD8n +T细胞PD-1的表达,DC表面PD-L1、CD86的表达情况;采用酶联免疫吸附试验(ELISA)检测血清白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)的分泌水平;采用Spearman相关性分析法分析CD11cn +PD-L1与CD4n +PD-1、CD8n +PD-1、TNF-α、DC、CD11cn +CD86、T细胞亚群比值、CD4n +T细胞、CD8n +T细胞、IL-10的相关性;采用二元Logistic回归分析影响脓毒症患者死亡的危险因素,并绘制受试者工作特征曲线(ROC曲线),评价独立危险因素对患者预后的预测价值。n 结果:死亡组序贯器官衰竭评分(SOFA)、急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)均明显高于存活组〔SOFA评分(分):15.1±4.1比10.7±2.7,APACHEⅡ评分(分):27.0±7.3比17.0±3.9,均n P<0.05〕。存活组和死亡组T细胞亚群比值均<1,且死亡组CD4/CD8明显低于存活组(0.54±0.15比0.79±0.09,n P1。与健康对照组比较,存活组和死亡组CD4n +T细胞、CD8n +T细胞、CD11cn +DC、CD11cn +CD86、IL-10、TNF-α水平均明显降低,CD4n +PD-1、CD8n +PD-1、CD11cn +PD-L1水平均明显升高,且死亡组上述指标的变化较存活组更显著〔CD4n +T细胞:0.14±0.07比0.22±0.08,CD8n +T细胞:0.24±0.07比0.28±0.10,CD11cn +DC:0.84±0.14比0.93±0.03,CD11cn +CD86:(58.83±20.77)%比(78.24± 9.39)%,IL-10(ng/L):34.22±13.98比18.49±5.55,TNF-α(ng/L):95.30±29.33比67.00±20.16,CD4n +PD-1:(39.58±10.08)%比(27.03±6.35)%,CD8n +PD-1:(38.77±11.91)%比(29.15±8.37)%,CD11cn +PD-L1:(21.13±11.54)%比(12.11±8.34)%,均n P<0.05〕。Spearman相关性分析显示,CD11cn +PD-L1与CD4n +PD-1、CD8n +PD-1、IL-10呈正相关(n r值分别为0.748、0.713、0.898,均n P<0.05),与DC、CD11cn +CD86、T细胞亚群比值、CD4n +T细胞、CD8n +T细胞、TNF-α呈负相关(n r值分别为-0.587、-0.906、-0.840、-0.706、-0.513、-0.820,均n P<0.05)。多因素二元Logistic回归分析显示,CD4n +PD-1是影响脓素症患者预后的独立危险因素〔优势比(n OR)=1.463,95%可信区间(95%n CI)为1.032~2.074,n P=0.033〕;ROC曲线分析显示,CD4n +PD-1对脓毒症患者预后有一定预测价值〔ROC曲线下面积(AUC)=0.857,95%n CI为0.709~1.000,n P<0.01〕;当最佳预测值为34.48%时,其敏感度为66.7%,特异度为90.0%,准确度85.7%。n 结论:外周血PD-1/PD-L1的上调会抑制DC的活化及增殖,影响T细胞活化,诱导脓毒症患者进入免疫抑制状态;PD-1/PD-L1可反映脓毒症患者的免疫状况,其中,CD4n +TPD-1对患者预后评估有一定价值。n “,”Objective:To study the effect of programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) regulating dendritic cells (DC) on the immune status of sepsis, and analyze the effect of PD-1/PD-L1 on prognosis.Methods:Twenty-five patients with sepsis in the intensive care unit (ICU) of the Affiliated Hospital of Zunyi Medical University from October 2018 to September 2019 were collected and followed up for 28 days. According to the 28-day survival of patients, patients were divided into survival group and death group. Among them, 10 cases were in the survival group and 15 cases were in the death group. Simultaneously, 20 healthy subjects in our hospital during the same period served as the healthy control group. Peripheral blood of patients with sepsis was taken within 24 hours after diagnosis, and the healthy control group was taken at the time of enrollment. Flow cytometry was used to detect the proportion of CD4n +T and CD8n +T cells, the ratio of T cell subsets (CD4/CD8), the expression of PD-1 on CD4n +T and CD8n +T cells, and the expression of PD-L1 and CD86 in DC. Enzyme linked immunosorbent assay (ELISA) was used to detect the levels of interleukin-10 (IL-10) and tumor necrosis factor-α(TNF-α) in serum. Spearman correlation analysis was used to analyze the correlation between CD11cn +PD-L1 and CD4n +PD-1, CD8n +PD-1, TNF-α, DC, CD11cn +CD86, T cell subpopulation ratio, CD4n +T cells, CD8n +T cells, and IL-10. Binary Logistic regression was used to analyze the risk factors affecting the death of patients with sepsis, and receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of independent risk factors on the prognosis of patients.n Results:The scores of acute physiology and chronic health evaluationⅡ (APACHEⅡ) and sequential organ failure assessment (SOFA) in the death group were higher than that in the survival group (APACHEⅡ score: 27.0±7.3 vs. 17.0±3.9, SOFA score: 15.1±4.1 vs. 10.7±2.7, both n P < 0.05). The ratio of T cell subsets in the survival group and the death group was less than 1, the death group was lower than that in the survival group (CD4/CD8: 0.54±0.15 vs. 0.79±0.09, n P < 0.05), and the ratio of T cell subsets in the healthy control group was greater than 1. Compared with healthy control group, the levels of CD4 n +T cells, CD8n +T cells, CD11cn +DC, CD11cn +CD86, IL-10 and TNF-α in survival group and death group were significantly decreased, the level of CD4n +PD-1, CD8n +PD-1, CD11cn +PD-L1 were significantly increased, and the changes in the above indicators in the death group were significant compared with the survival group [CD4n +T cells: 0.14±0.07 vs. 0.22±0.08, CD8n +T cells: 0.24±0.07 vs. 0.28±0.10, CD11cn +DC: 0.84±0.14 vs. 0.93±0.03, CD11cn +CD86: (58.83±20.77)% vs. (78.24±9.39)%, IL-10 (ng/L): 34.22±13.98 vs. 18.49±5.55, TNF-α(ng/L): 95.30±29.33 vs. 67.00±20.16, CD4n +PD-1: (39.58±10.08)% vs. (27.03±6.35)%, CD8n +PD-1: (38.77±11.91)% vs. (29.15±8.37)%, CD11cn +PD-L1: (21.13±11.54)% vs. (12.11± 8.34)%, all n P < 0.05]. Spearman correlation analysis showed that CD11c n +PD-L1 was positively correlated with CD4n +PD-1, CD8n +PD-1, and IL-10 (n r values were 0.748, 0.713, 0.898, all n P < 0.05), while was negatively correlated with DC, CD11c n +CD86, T cell subpopulation ratio, CD4n +T cells, CD8n +T cells, and TNF-α(n r values were -0.587, -0.906, -0.840, -0.706, -0.513, -0.820, all n P < 0.05). Multivariate binary Logistic regression analysis showed that CD4 n +T PD-1 was an independent risk factor for the prognosis of sepsis patients [odds ratio (n OR) = 1.463, 95% confidence interval (95%n CI) = 1.032-2.074, n P = 0.033]. ROC curve analysis showed that CD4n +TPD-1 had certain predictive value for the prognosis of patients with sepsis [area under ROC curve (AUC) = 0.857, 95%n CI was 0.709-1.000, n P < 0.01). When the best predictive value was 34.48%, the sensitivity, specificity, and accuracy were 66.7%, 90.0%, and 85.7% respectively.n Conclusions:Up-regulation of PD-1/PD-L1 in peripheral blood could inhibit the activation and proliferation of DC, affect the activation of T cells, and induce immunosuppressive state. PD-1/PD-L1 can reflect the immune status of patients with sepsis. The expression of PD-1 on CD4n +T cells may have important significance for the evaluation of prognosis.n
其他文献
凌晨的急诊科,最让人心惊的是急救中心的电话铃声,伴随它而来的急救对象大多是喝得不省人事的醉汉,他们或是躺在马路上或草丛上,或是哪个小酒馆的厕所或餐桌底下,或是学生宿舍的底板或楼道里.rn这天连续处理完醉酒的急救任务后,时间已是凌晨三点多,值班房里的鼾声深沉,人困马乏的我恨不得立马加入.在躺下之前,我要再次确认手机处于电量充足以及铃声开启状态.
期刊
笔者所在地的邻县区曾出现新冠肺炎本土疫情,当地政府立即按照相关应急预案要求开展疫情防控工作.其中,医疗行业主管部门立即启动视频会议,传达相关防控信息和工作要求.会议中,一个话题引发了笔者深思.那就是卫生健康部门的一位领导讲到在接种新冠病毒疫苗时,提醒我们应当增加人文关怀.
期刊
“脾为后天之本,气血生化之源”.脾位于中焦,五行属土,与胃相表里,一升一降,是三焦运行的枢纽,主运化、统血、升清、开窍于口等,脾胃功能的强健是人体健康的重要标志.rn顾护脾胃由来已久rn自古以来,众多医家临证用药时都注重顾护脾胃.如金元四大家之一的李东垣是补土派的创始人,首创脾胃学说,著有《脾胃论》《内外伤辨惑论》等,他所创的补中益气汤更为后世所广泛使用.
期刊
目前,关于安宁疗护护士的素质要求存在着两种观点,一种是患者及家属对医疗护理没有更高的期待,所以对安宁护士的要求不高,只要做好基础护理和生活护理就行了;另一种则认为,安宁疗护的患者病情复杂,涉及的护理操作多,还有精神和心理方面的工作,绝不是一个普通护士就可以胜任的.然而,事情真的是这样子吗?
期刊
2020年是我国消除绝对贫困、打赢脱贫攻坚战役的收官之年,实施健康扶贫工程是打赢脱贫攻坚战役的关键之举.我院在实施健康扶贫工程中,尤其是在建档立卡贫困患者住院诊疗管理过程中,把医学人文理念贯穿始终,全面提升了健康扶贫工程的内涵质量,对全面打赢脱贫攻坚战役贡献健康扶贫力量具有明显的现实意义与历史价值.
期刊
在医疗纠纷解决过程中,难免遇上僵局.僵局是指医患双方由于某种原因相持不下,使协调陷入进退两难的境地.在医疗纠纷调解中,僵局产生的原因主要有:rn1.情感争执.在纠纷调解中,由于一方言行不慎,伤害对方的感情或者使对方丢了面子,形成了僵局.一些有经验的谈判专家认为,有不少谈判人员维护个人的面子甚于维护团体的利益.如果在医疗纠纷解决中,他们感到丢了面子,就会奋起反击,极力挽回面子,甚至不惜退出协商、调解.
期刊
一、阴虚有什么表现?rn阴虚的人主要表现为:rn一是“干”.表现为阴津不足,身体呈缺水状态,如口干咽燥、两目干涩、干咳痰少、毛发干枯、皮肤干燥、大便干结、体型干瘦等.rn二是“热”.体内阴液亏少而无以制阳,滋润、濡养等作用减退,出现燥热不安、骨蒸潮热、面部烘热、盗汗、五心烦热(指两手两足心发热,并自觉心胸烦热)、脉细数等.rn不管“干”也好,“热”也好,两者都离不开“火”,正所谓阴虚火旺,这也就是大家所说的虚火、阴火,跟实火有本质的区别,大家要区别对待.
期刊
作为一名安宁疗护的医务人员,我深知安宁疗护起步难,运营难,生存难,大医院不愿意做,小医院做不好的现状.想要改变这种现状,必须要依靠提高群众对生命的理解,减少和消除对死亡的恐惧,这也是在百姓中普及安宁疗护理念的意义所在.然而这些事情都无法一蹴而就,我们还有很长的一段路要走,路上也会面临很多的阻碍.不过近日我中心的一位患者及其家属的选择与态度让我明白,安宁疗护必须要坚定地走下去,因为它正获得越来越多人的支持和理解,只要我们坚守,就会有更多人参与进来.
期刊
抗磷脂综合征为一种以反复动脉或者静脉血栓、流产,同时伴有抗心磷脂或者狼疮抗凝物实验持续阳性的疾患,可继发于系统性红斑狼疮或者其他自身免疫病,但也可单独出现.rn临床病例rn一诊:患者女,39岁,主诉后肩背处多发红点,于休息不好或情绪紧张焦虑后加重.2011年发现血小板降低,经检查未能确诊病因,后经中医解毒化瘀、凉血活血法调治后康复出院,自此月经数月不潮,排卵试纸监测2~3个月排卵1次.此次因“后背红疹”就诊时发现:抗心磷脂IgG抗体180.8CU(参考值0~20CU),抗心磷脂IgA抗体126.3CU(参
期刊
最近门诊骨科医生老赵被患者投诉了,他觉得自己很冤枉,因为患者的投诉理由是他的态度不好.rn回想那天的场景,骨科门诊外面传来叫唤:“这破医院,这医生的态度真不好,我要投诉!”rn“去去去,告院长去.”医生老赵的声音接着传来.rn10多分钟后,医务科科长赶来,详细询问,原来事情是这样的:rn一患者的腿部关节有问题,需要做核磁共振,他问老赵:“今天能排上么?”rn老赵说:“这我哪知道啊!”rn医务科科长向患者解释,医生确实无法左右检查的排序和进程.但是患者觉得,不管能不能排上检查,医生也不能用这种态度来回应,自
期刊