血清可溶性程序性细胞死亡蛋白1、可溶性B7同源体5和三叶因子2评估急性胰腺炎患者病情程度和死亡风险的价值研究

Evaluation value of serum soluble programmed cell death protein 1,soluble B7 homolog 5 molecules combined with trefoil factor 2 on disease severity and death risk in patients with acute pancreatitis

目的探讨血清可溶性程序性细胞死亡蛋白1(sPD-1)、可溶性B7同源体5(sB7-H5)和三叶因子2(TFF2)对急性胰腺炎(AP)患者病情程度和死亡风险的评估价值。方法采用前瞻性研究的方法,选取襄阳市中心医院2020年2月至2021年2月AP患者328例(AP组),其中轻症AP(MAP)124例,中度重症AP(MSAP)106例,重症AP(SAP)98例。应用酶联免疫吸附实验法检测血清sPD-1、sB7-H5和TFF2水平,并与60例健康体检者(健康对照组)进行比较。AP患者随访90 d,生存284例,死亡44例;比较两者的淀粉酶、C-反应蛋白(CRP)、降钙素原(PCT)、急性生理学与慢性健康状况评分Ⅱ(APACHEⅡ)、序贯器官衰竭评分(SOFA)、改良CT严重指数(MCTSI)、sPD-1、sB7-H5和TFF2等。采用Pearson法进行相关性分析;采用多因素Logistic回归分析影响AP患者死亡的独立危险因素;采用受试者工作特征(ROC)曲线评估sPD-1、sB7-H5和TFF2预测AP患者死亡的效能。结果AP组sPD-1、sB7-H5和TFF2明显高于健康对照组[(177.99±17.81)ng/L比(50.20±10.81)ng/L、(2.69±0.72)μg/L比(1.40±0.35)μg/L和(569.97±38.91)μg/L比(94.59±11.98)μg/L],差异有统计学意义(P<0.01)。MSAP和SAP患者淀粉酶、sPD-1、sB7-H5和TFF2明显高于MAP患者[(639.36±91.67)和(835.24±109.30)U/L比(575.24±89.78)U/L、(180.13±20.61)和(221.17±15.70)ng/L比(142.03±16.76)ng/L、(2.85±0.74)和(3.34±0.82)μg/L比(2.05±0.52)μg/L、(539.66±36.58)和(763.55±40.08)μg/L比(442.90±35.79)μg/L],SAP患者明显高于MSAP患者,差异均有统计学意义(P<0.01)。Pearson相关分析结果显示,AP患者sPD-1与sB7-H5、TFF2呈正相关(r=0.552和0.641,P<0.01),sB7-H5与TFF2呈正相关(r=0.610,P<0.01)。死亡患者淀粉酶、CRP、PCT、APACHEⅡ、SOFA、MCTSI、sPD-1、sB7-H5和TFF2明显高于生存患者[(1098±105)U/L比(641±93)U/L、(235.60±40.17)mg/L比(118.04±32.90)mg/L、(4.32±0.52)μg/L比(3.14±0.44)μg/L、(19.39±3.14)分比(11.18±2.53)分、(12.13±2.78)分比(7.40±2.15)分、(7.12±1.73)分比(4.31±1.52)分、(222.23±22.30)ng/L比(171.14±18.50)ng/L、(3.37±0.89)μg/L比(2.59±0.59)μg/L和(629.27±39.63)μg/L比(560.78±30.45)μg/L],差异有统计学意义(P<0.01)。多因素Logistic回归分析结果显示,CRP、PCT、APACHEⅡ、SOFA、sPD-1、sB7-H5和TFF2是影响AP患者死亡的独立危险因素(OR=1.339、1.416、1.285、1.327、1.092、1.171和1.080,95%CI 1.145~1.566、1.146~1.751、1.132~1.460、1.150~1.531、1.024~1.164、1.072~1.280和1.031~1.131,P<0.01)。ROC曲线分析结果显示,sPD-1、sB7-H5、TFF2联合检测预测AP患者死亡的曲线下面积明显大于sPD-1、sB7-H5和TFF2单独检测(0.870比0.771、0.734和0.685)。结论AP患者血清sPD-1、sB7-H5和TFF2水平明显升高,且与患者病情程度有关,三者联合检测能够辅助评估AP患者的死亡风险。

Objective To investigate the value of serum soluble programmed cell death protein 1(sPD-1),soluble B7 homolog 5(sB7-H5)and trefoil factor 2(TFF2)in evaluating the severity of disease and the risk of death in patients with acute pancreatitis(AP).Methods A prospective research method was adopted.Three hundred and twenty-eight patients with AP(AP group)from February 2020 to February 2021 in Xiangyang Central Hospital were selected,including 124 patients with mild AP(MAP),106 patients with moderately severe AP(MSAP)and 98 patients with severe AP(SAP).The serum levels of sPD-1,sB7-H5 and TFF2 were measured by enzyme-linked immunosorbent assay and compared with 60 healthy people(healthy control group).The patients with AP were followed up for 90 d,284 patients survived and 44 died.The amylase,C-reactive protein(CRP),procalcitonin(PCT),acute physiology and chronic health evaluationⅡ(APACHEⅡ),sequential organ failure assessment(SOFA),modified CT severity index(MCTSI),sPD-1,sB7-H5 and TFF2 were compared between the two groups.Pearson method was used for correlation analysis.Multivariate Logistic regression was used to analyze the independent risk factors of death in patients with AP.The efficacy of sPD-1,sB7-H5 and TFF2 in predicting the death in patients with AP was evaluated using the receiver operating characteristics(ROC)curve.Results The sPD-1,sB7-H5 and TFF2 in AP group were significantly higher than those in healthy control group:(177.99±17.81)ng/L vs.(50.20±10.81)ng/L,(2.69±0.72)μg/L vs.(1.40±0.35)μg/L and(569.97±38.91)μg/L vs.(94.59±11.98)μg/L,and there were statistical differences(P<0.01).The amylase,sPD-1,sB7-H5 and TFF2 in patients with MSAP and SAP were significantly higher than those in patients with MAP:(639.36±91.67)and(835.24±109.30)U/L vs.(575.24±89.78)U/L,(180.13±20.61)and(221.17±15.70)ng/L vs.(142.03±16.76)ng/L,(2.85±0.74)and(3.34±0.82)μg/L vs.(2.05±0.52)μg/L,(539.66±36.58)and(763.55±40.08)μg/L vs.(442.90±35.79)μg/L,the indexes in patients with SAP were significantly higher than those in patients with MSAP,and there were statistical differences(P<0.01).Pearson correlation analysis result showed that sPD-1 was positively correlated with sB7-H5 and TFF2 in patients with AP(r=0.552 and 0.641,P<0.01),and the sB7-H5 was positively correlated with TFF2(r=0.610,P<0.01).The amylase,CRP,PCT,APACHEⅡ,SOFA,MCTSI,sPD-1,sB7-H5 and TFF2 in the dead patients were significantly higher than those in the living patients:(1098±105)U/L vs.(641±93)U/L,(235.60±40.17)mg/L vs.(118.04±32.90)mg/L,(4.32±0.52)μg/L vs.(3.14±0.44)μg/L,(19.39±3.14)scores vs.(11.18±2.53)scores,(12.13±2.78)scores vs.(7.40±2.15)scores,(7.12±1.73)scores vs.(4.31±1.52)scores,(222.23±22.30)ng/L vs.(171.14±18.50)ng/L,(3.37±0.89)μg/L vs.(2.59±0.59)μg/L and(629.27±39.63)μg/L vs.(560.78±30.45)μg/L,and there were statistical differences(P<0.01).Multivariate Logistic regression analysis result showed that CRP,PCT,APACHEⅡ,SOFA,sPD-1,sB7-H5 and TFF2 were independent risk factors death of in patients with AP(OR=1.339,1.416,1.285,1.327,1.092,1.171 and 1.080;95%CI 1.145 to 1.566,1.146 to 1.751,1.132 to 1.460,1.150 to 1.531,1.024 to 1.164,1.072 to 1.280 and 1.031 to 1.131;P<0.01).The ROC curve analysis result showed that the area under the curve of sPD-1,sB7-H5 and TFF2 combined detection to predict the death in patients with AP was larger than that of sPD-1,sB7-H5,and TFF2 alone detection(0.870 vs.0.771,0.734 and 0.685).Conclusions The increase of serum sPD-1,sB7-H5 and TFF2 levels in patients with AP is related to the severity of disease of patients with AP.The combined detection of the indexes can assist in evaluating the risk of death in patients with AP.