首页|中性粒细胞游离脂肪酸受体3对重症急性胰腺炎患者继发感染的预测价值

中性粒细胞游离脂肪酸受体3对重症急性胰腺炎患者继发感染的预测价值

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目的 评价中性粒细胞游离脂肪酸受体3(FFAR3)对重症急性胰腺炎(SAP)患者继发感染的预测价值。方法 ①生物信息学分析:在基因表达数据库(GEO)中获取急性胰腺炎患者外周血相关公共微阵列数据集(GSE194331),该数据集包含32例健康成人、52例轻症急性胰腺炎患者、20例中重症急性胰腺炎患者和10例SAP患者数据。下载GSE194331数据集原始数据,并进行质量控制、修剪、定量、注释和差异性分析,获取差异性基因。②临床研究:采用前瞻性观察性研究方法,选择2022年1月至11月中国人民解放军东部战区总医院重症医学科收治的45例SAP患者,根据重症监护病房(ICU)住院期间是否出现继发感染分为感染组与非感染组;同时选择同期体检的10例健康成人志愿者作为对照。取各组受试者外周血,分离中性粒细胞,采用实时荧光定量反转录-聚合酶链反应(RT-PCR)检测FFAR3 mRNA表达量。采用Spearman相关法分析SAP患者中性粒细胞FFAR3 mRNA表达量与继发感染的相关性;采用多因素Logistic回归分析评价中性粒细胞FFAR3 mRNA表达量是否为SAP患者继发感染的危险因素;绘制受试者工作特征曲线(ROC曲线),评价中性粒细胞FFAR3 mRNA表达量对SAP患者继发感染的预测价值。结果 ①生物信息学分析结果:对GSE194331数据集的分析结果显示,在健康对照者与胰腺炎患者外周血细胞中呈差异性表达的基因共有301个;生物功能分析获得8个涉及免疫反应的生物功能,且这8个生物功能共富集了44个差异表达基因;细胞分布分析结果显示,有21个差异表达基因在中性粒细胞的表达量显著高于其他免疫细胞,其中与脂代谢相关的基因是FFAR3。说明FFAR3表达与SAP的发生发展密切相关。②临床研究结果:45例SAP患者中,有24例在ICU住院期间继发感染,21例未继发感染;感染组SAP患者中性粒细胞FFAR3 mRNA表达量显著高于非感染组SAP患者和健康对照者[2-ΔΔCt:3。8(3。0,4。2)比1。4(1。1,2。7)、1。0(0。8,1。1),均P<0。05]。Spearman相关分析显示,SAP患者中性粒细胞FFAR3 mRNA表达量与继发感染呈显著正相关(r=0。799,P<0。001)。多因素Logistic回归分析显示,FFAR3 mRNA表达量增加是SAP患者继发感染的独立危险因素[优势比(OR)=17。212,95%可信区间(95%CI)为3。004~98。613,P=0。001]。ROC曲线分析显示,中性粒细胞FFAR3 mRNA表达量预测SAP患者继发感染的ROC曲线下面积(AUC)为0。856(95%CI为0。750~0。981,P<0。001);当最佳截断值为2。37时,敏感度为95。83%,特异度为76。19%。根据ROC曲线分析得出的中性粒细胞FFAR3 mRNA表达量最佳截断值2。37,将45例SAP患者分为两组进行亚组分析,结果显示,FFAR3 mRNA表达量≥2。37的SAP患者继发感染率显著高于FFAR3 mRNA表达量<2。37的患者[82。14%(23/28)比5。88%(1/17)],差异具有统计学意义(P<0。01)。结论 中性粒细胞FFAR3 mRNA表达量与SAP患者继发感染密切相关,监测其水平能够有效预测SAP患者继发感染情况。
Predictive value of neutrophil free fatty acid receptor 3 for secondary infection in patients with severe acute pancreatitis
Objective To evaluate the predictive value of neutrophil free fatty acid receptor 3 (FFAR3) for secondary infection in patients with severe acute pancreatitis (SAP). Methods ① Biological information analysis:peripheral blood microarray data sets related to acute pancreatitis (GSE194331) were obtained from the Gene Expression Omnibus (GEO),including data from 32 healthy adults,52 patients with mild acute pancreatitis,20 patients with moderate-to-severe acute pancreatitis,and 10 patients with SAP. The original data of GSE194331 dataset were downloaded for quality control,pruning,quantification,annotation and difference analysis,and the different genes were obtained. ② Clinical study:a prospective observational study was conducted. Forty-five SAP patients admitted to the critical care medicine department of the Eastern Theater Command General Hospital of the Chinese People's Liberation Army from January to November 2022 were enrolled,and they were divided into infected group and non-infected group according to whether secondary infection occurred during intensive care unit (ICU) stay. At the same time,10 healthy adult volunteers were enrolled as control. Peripheral blood of subjects in each group was collected,neutrophils were isolated,and FFAR3 mRNA expression was detected by real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-PCR). Spearman correlation method was used to analyze the correlation between neutrophil FFAR3 mRNA expression and secondary infection in SAP patients. Multivariate Logistic regression analysis was used to evaluate whether neutrophil FFAR3 mRNA expression was a risk factor for secondary infection in SAP patients. Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive value of neutrophil FFAR3 mRNA expression on secondary infection in SAP patients. Results ① Results of biological information analysis:the analysis of GSE194331 dataset showed that 301 genes were differentially expressed in peripheral blood cells between healthy controls and patients with pancreatitis. By biological function analysis,8 biological functions involved in immune response were obtained,and 44 differential expressed genes were enriched in these 8 biological functions. The results of cell distribution analysis showed that there were 21 differential expressed genes expressions on neutrophils significantly higher than other immune cells,and the gene related to lipid metabolism was FFAR3. These results indicated that FFAR3 expression was closely related to the occurrence and development of SAP. ② Clinical study results:out of the 45 SAP patients,24 developed into secondary infection during ICU stay,21 did not develop into secondary infection. The expression of neutrophil FFAR3 mRNA in SAP patients with secondary infection was significantly higher than that in SAP patients without secondary infection and healthy controls[2-ΔΔCt:3.8 (3.0,4.2) vs. 1.4 (1.1,2.7),1.0 (0.8,1.1),both P<0.05]. Spearman correlation analysis showed that neutrophil FFAR3 mRNA expression was positively correlated with secondary infection in SAP patients (r=0.799,P<0.001). Multivariate Logistic regression analysis showed that increased FFAR3 mRNA expression was an independent risk factor for secondary infection in SAP patients[odds ratio (OR)=17.212,95% confidence interval (95%CI) was 3.004-98.613,P=0.001]. ROC curve analysis showed that the area under the ROC curve (AUC) of neutrophil FFAR3 mRNA expression for predicting secondary infection in SAP patients was 0.856 (95%CI was 0.750-0.981,P<0.001). When the optimal cut-off value was 2.37,the sensitivity was 95.83% and the specificity was 76.19%. According to the optimal cut-off value of neutrophil FFAR3 mRNA expression (2.37) for predicting secondary infection in SAP patients obtained by ROC curve analysis,45 SAP patients were divided into two groups for subgroup analysis. It suggested that the incidence of secondary infection in SAP patients with FFAR3 mRNA expression level ≥2.37 was significantly higher than that in SAP patients with FFAR3 mRNA expression level<2.37[82.14% (23/28) vs. 5.88% (1/17)],and the difference was statistically significant (P<0.01). Conclusion The expression of FFAR3 mRNA in neutrophils is closely related to the secondary infection in SAP patients,and monitoring its level can effectively predict the secondary infection in SAP patients.

Severe acute pancreatitisInfectionNeutrophilFree fatty acid receptor 3

肖敏、汪鹏、李百强、李维勤、刘大东

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中国人民解放军东部战区总医院(南京医科大学附属金陵医院)重症医学科,江苏南京 212001

重症急性胰腺炎 感染 中性粒细胞 游离脂肪酸受体3

2024

中华危重病急救医学
中华医学会

中华危重病急救医学

CSTPCD北大核心
影响因子:3.049
ISSN:2095-4352
年,卷(期):2024.36(10)