Clinical Value Of Apolipoproteins And Their Receptors In Gram-negative Sepsis

Objective:To investigate the diagnostic,disease severity and prognostic value of the proprotein convertase chymotrypsin 9(PCSK9),apolipoprotein E(apoE),low-density protein receptor(LDLR),low-density lipoprotein receptor-related protein(LRP),class B type 1 scavenger receptor(SR-BI),apolipoprotein M(apoM)and apolipoprotein C(apoC)in the diagnosis of Gram-negative(G-)sepsis.and prognosis of Gram-negative(G-)sepsis.Methods:One hundred and twenty-eight patients with sepsis(sepsis group),40 patients with simple systemic inflammatory response syndrome(SIRS)(SIRS group),and 40 healthy individuals(healthy control group)admitted to Hunan Provincial Brain Hospital from September 2019 to September 2020 were selected for the study.The sepsis group was divided into 90 patients with G-epsis(G-epsis group)and 38 patients with Gram-positive(G+)sepsis(G+sepsis group)according to blood culture and Gram staining results;the G-epsis group was divided into 2 groups,general G-epsis group(53 cases)and G-epsis shock group(37 cases),according to the severity of the disease;the G-epsis group was divided into the survival group according to the 28-day disease regression(69 cases)and the death group(21 cases).Fasting venous blood was collected on days 1,3 and 5 after admission to the ICU,and the clinical data and common clinical observation indexes were recorded.The differences in levels between the groups were analyzed,and the correlation between apolipoproteins and their receptors,as well as the correlation between apolipoproteins and their receptors and sepsis-related sequential organ failure score(SOFA),acute physiological and chronic health score Ⅱ(APACHE Ⅱ),and the working curve(ROC curve)and area under the curve(AUC)of the subjects were plotted to analyze the effect of apolipoproteins and their receptors on G-sepsis diagnostic,severity of disease and prognostic assessment value.Results:1.Early diagnosis:comparing the levels of different disease groups,the serum apoC,apoM,SR-BI,LRP and LDLR levels of patients in the SIRS group,G+sepsis group and G-sepsis group were significantly lower compared with healthy controls,while apoE and PCSK9 levels were significantly higher(P<0.05),and further results using ROC curve analysis showed that SR-BI,LDLR,PCSK9,LRP,apoE,apoM and apoC had cut-off values of 122.100 pg/mL,1.05 mmol/L,287.8 ng/mL,9.046 ng/mL,3.918 mg/mL,102.400ug/mL and 17.55 mg/mL,respectively,for the diagnosis of G-psoriasis,with a sensitivity was 97.78%,84.44%,77.78%,96.09%,78.95%,93.33%and 73.03%,and the specificity was 82.50%,95.00%,90.24%,87.18%,78.05%,61.54%and 82.50%,respectively.2.Correlation analysis:there were positive correlations between serum apoM,apoC and SR-BI in patients in the G-sepsis group,and the correlation coefficients between apoM and apoC,apoM and SR-BI,and apoC and SR-BI were(r=0.622,r=0.727,r=0.825),and the differences were statistically significant(P<0.05);serum There were positive correlations between apoE and its receptors(LDLR,LRP),and the correlation coefficients between apoE and LDR,apoE and LRP,and LDLR and LRP were(r=0.595,r=0.435,r=0.535),respectively,and negative correlations between PCSK9 and apoE,LDLR,and LRP,with correlation coefficients of(r=-0.485,r=-0.435,r=-0.535),and further analysis of the relationship between apolipoproteins and their receptors and SOFA scores and APACHE II scores showed that apoE,LDLR,LRP,SR-BI,apoC,apoM and SOFA scores(r=-0.409,r=-0.518,r=-0.491,r=-0.624,r=-0.343,r=-0.457),APACHE II scores(r=-0.632,r=-0.584,r=-0.594,r=-0.720,r=-0.595,r=-0.379)were negatively correlated,while PCSK9 was negatively correlated with SOFA scores(r=0.323),APACHE II scores(r=0.311)were positively correlated.3.Dynamic observation:detection of apolipoprotein and its receptor levels in G-sepsis patients on days 1,3 and 5 after admission to ICU,the results suggested that serum apoE levels in patients showed a continuous decreasing trend,while SR-BI and apoC levels showed an increasing trend,with significant differences at each time point(P<0.05);serum PCSK9 levels peaked on day 3 and then showed a decreasing trend,while LRP,apoM levels reached the lowest value after the 3rd day of ICU admission and then showed an increasing trend,with significant differences at each time point(P<0.05).LDLR levels did not change significantly at different time periods(P>0.05),and apoE,SR-BI,and apoC levels changed to a 2-9-fold degree.4.To determine the severity of the disease:serum apoC,apoM,SR-BI,LDLR and LRP levels were significantly lower in the G-sepsis shock group compared with the general G-sepsis group,and apoE.PCSK9,APACHE II score and SOFA score were significantly higher(P<0.05);further results of ROC curve analysis were used to show that PCSK9,apoE,LDLR and LRP had the best threshold values of 448.3Ong/mL,8.66ug/mL,0.38mmol/L,7.03ng/mL for the diagnosis of G-epsis shock,with sensitivities of 83.78%,70.27%,75.68%,83.56%,and specificities of 77.36%,77.36%,77.36%,58.49%,64.15%,and the optimal threshold values of apoM,apoC and SR-BI for the diagnosis of G-sepsis septic shock were 153.54pg/mL,41.73ug/mL,5.33mg/mL,respectively,with sensitivities of 72.97%,60.00%,43.24%,and specificities of 81.13%,73.58%,and 86.79%.5.Prognostic assessment:serum PCSK9,apoE,APACHE II score and SOFA score were significantly higher(P<0.05),while SR-BI,LDLR,LRP,apoM and apoC levels were significantly lower(P<0.05)in the death group compared with the surviving patients;serum apoE,LRP,SR-BI and The results of ROC curves showed that SR-BI had the best predictive efficacy(AUC>0.9),LRP,apoE and apoM had the second best predictive efficacy(0.7<AUC<0.9),and the AUC,sensitivity and specificity of apoM combined with SR-BI were 0.977,95.24%,89.88%,respectively.89.88%,higher than apoM(0.887,87.71%,85.50%)and SR-BI(0.923,86.36%,89.86%);the AUC,sensitivity and specificity of apoE combined with LRP were 0.97,95.24%,89.88%higher than apoE(0.71,66.18%,65.86%),LRP(0.78,66.67%,78.26%).Conclusions:1.Apolipoprotein and its receptor are related to the types of bacterial infections.The serum levels of PCSK9,SR-BI,apoE,apoM,LRP and LDLR can be used as potential biomarkers for early diagnosis of G-sepsis.2.The changes of apolipoprotein and its receptor can indicate the progress of G-sepsis.The patient’s serum PCSK9 and apoE levels increase,and apoC,apoM,SR-BI,LDLR,and LRP levels decrease,indicating that the condition is getting worse.In particular,the monitoring of PCSK9,apoC,and apoM is conducive to timely detection of changes in the disease.3.The combined application of apoM and SR-BI,apoE and LRP improves the sensitivity and specificity of prognostic evaluation.