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Objective:To explore the predictive value and prognosis effect of calprotectin on acute kidney injury (AKI) in patients with sepsis.Methods:A prospective observational study was conducted. From December 2018 to November 2020, patients with sepsis admitted to the Emergency Department of China Rehabilitation Research Center were enrolled. General clinical data of patients were collected continuously, and the acute physiology and chronic health evaluationⅡ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score and calprotectin were evaluated in 24 h after admission. The patients were divided into the AKI group and non-AKI group according to the occurrence of AKI within 7 days after admission. Calprotectin level and other clinical data were compared between the two groups. Logistic regression was used to analyze the risk factors for AKI in patients with sepsis, and receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of calprotectin for AKI in patients with sepsis. The patients with AKI were further divided into the survival group and death group according to the 28-day outcome, and the calprotectin levels between the two groups were compared.Results:A total of 207 patients with sepsis were enrolled, and the incidence of AKI was 68.12% (141/207). The level of calprotectin in patients with AKI was higher than that in patients without AKI [4.65 (3.25, 5.61) μg/mL vs. 3.42 (2.29, 4.09) μg/mL, P < 0.001]. Multivariable Logistic regression analysis showed that APACHEⅡ score ( OR=1.090, 95% CI: 1.043-1.139), C-reactive protein ( OR=1.004, 95% CI: 1.001-1.008) and calprotectin ( OR=1.590, 95% CI: 1.269-1.991) were independent risk factors for AKI in patients with sepsis. The area under ROC curve (AUC) of calprotectin for predicting AKI was 0.716 (95% CI: 0.643-0.788). The cutoff value of prediction was 4.63 μg/mL with the Yoden index of 0.405, which yielded a sensitivity of 0.511 and a specificity of 0.894. When calprotectin was combined with APACHE II score and SOFA score respectively, the predictive ability was significantly improved with the AUC of 0.768 (95% CI: 0.701-0.834) and 0.769 (95% CI: 0.701-0.837), respectively. We further divided patients with AKI into the survival group and non-survival group according to the 28-day outcome and there was no significant difference in calprotectin between the two groups [4.80 (3.40, 5.76) μg/mL vs. 4.19 (2.89, 5.29) μg/mL, P < 0.05]. Conclusions:The level of calprotectin in the AKI group is higher than that in the non-AKI group. Calprotectin can be regarded as an effective predictor of AKI in patients with sepsis, and the combination with APACHEⅡ score or SOFA score will improve its predictive efficacy. However, there is no significant difference in the concentration of calprotectin for patients with sepsis associated AKI with different prognosis.
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AIM:To investigate the inhibitory effect of PDE4 inhibitor rolipram on the releases of inflammatory cytokines in mouse macrophages (RAW264.7 cells) induced by myeloid-related protein 8/14 (MRP8/14), and to explore the role of nuclear factor-κB (NF-κB) in this process.METHODS:RAW264.7 cells were treated with MRP8/14.The inflammatory cytokines TNF-α and IL-6 were determined by LiquiChip and qPCR.In contrast, RAW264.7 cells were pretreated with rolipram prior to MRP8/14 exposure.After MRP8/14 challenge, the inflammatory cytokines TNF-α and IL-6 were determined by LiquiChip and qPCR.Moreover, the phosphorylation level of NF-κB P65 was determined by Western blot.The nuclear translocation of NF-κB P65 in RAW264.7 cells was detected by indirect immunofluorescence.RESULTS:The results of LiquiChip and qPCR showed that MRP8/14 enhanced the expression of TNF-α and IL-6 (P<0.01),while pretreatment with rolipram markedly down-regulated the level of inflammatory cytokines induced by MRP8/14 (P<0.05).Meanwhile, MRP8/14 significantly activated the phosphorylation of NF-κB P65, and the protein expression of p65 in the nucleus was increased,while pretreatment with rolipram suppressed the phosphorylation of NF-κB P65 induced by MRP8/14.CONCLUSION:Rolipram may significantly reduce the releases of the inflammatory cytokines induced by MRP8/14 through the NF-κB signaling.
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Objective To compare the MRP8/14 level in Normal people,benign prostatic hyperplasia(BPH) patient and prostate cancer patient,and explore the relationgship between MRP8/14 and prostate cancer.Methods 150 cases of normal people,150 cases of BPH patients and 150 cases of prostate cancer patients were chose from December 2012 to December 2014 in our hospital.ELISA method was used to detect the MRP8/14 level in each group.ROC cure was used to analyse the prediction value of MRP8/14 for prostate cancer.According to the cut off value of MRP8/14,prostate cancer patients were divided into MRP8/14 low value group (MRP8/14 ＜ cut off value) and MRP8/14 high value group (MRP8/14 ≥cut off value),and the difference of patient's clinical characteristics and survival function between high value group and low value group were explored.Results The MRP8/14 level of normal people was (966.7 ± 152.8) ng/ml,while the BPH patient was (1 207.0 ± 190.6) ng/ml,and the prostate cancer patient was (2 833.3 ± 1 101.5) ng/ml,the difference is statistically significant.ROC analysis result showed that the AUC for the prediction of prostate cancer was O.887 (95％ CI 0.841-0.934),with a high statistical significance,indicating that MRP8/14 may possess high prediction value for prostate cancer.In addition,the cut off value was 2 845.682 ng/ml,with the specifity of 76.4％ and sensitivity of 85.1％.According to the cut off value of MRP8/14,prostate cancer patients were divided into the low MRP8/14 group (＜ 2 845.682 ng/ml) and the high MRP8/14 group (≥2 845.682 ng/ml).Among the 150 prostate cancer patients,88 cases were in the low MRP8/14 group and 62 cases were in the high MRP8/14 group.Comparations of the baseline characteristics of the two groups showed that amount of patients belong to ECOG PS =1,Gleason score =8-10,organ involvement ＞ 2 and tumour stage ＞ Ⅲ were much more in MRP8/14 high value group.PSA level,LDH level,AKP level,CRP level and Alkaline Phosphatase level were also significantly increased in MRP8/14 high value group.Besides,prostate cancer patient with an average follow-up of 2 years,a total of 32 cases of patients died,12 cases in the MRP8/14 low value group with mortality of 13.6％,20 cases in MRP8/14 high value group with mortality of 32.3％.Kaplan Meier survival function curve shows 2 years survival rate of patients in high value group was significantly reduced.Cox regression analysis showed that MRP8/14 was possible risk factors associated with mortality,and the independent predictors for all-cause mortality during follow-up.Conclusion MRP8/14 was significantly increased in prostate cancer patients,and it was an independent predictor of 2-year mortality in prostate cancer patients.
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AIM:To investigate the effects of myeloid-related protein 8/14 ( MRP8/14 ) on the survival and apoptosis of human alveolar epithelial cell line A549, and to explore the role of nuclear factor-κB (NF-κB) in this process. METHODS:A549 cells were treated with different doses of MRP8/14 or stimulated with MRP8/14 for different time.The effect of MRP8/14 on the viability of A549 cells was determined by CCK-8 assay.The apoptotic rates were tested by flow cytometry.The nuclear translocation of NF-κB p65 was detected by Western blot and indirect immunofluorescence.Be-sides, the phosphorylation level of NF-κB p65 was determined by Western blot.NF-κB-specific inhibitor Bay 11-7082 was used to further analyze the role of NF-κB in the apoptosis induced by MRP8/14.RESULTS:The viability of the A549 cells was affected by MRP8/14 in a dose-and time-dependent manner.Flow cytometric analysis showed that the apoptotic rates were increased in the cells treated with MRP8/14 (P<0.01).In A549 cells administered with MRP8/14, NF-κB p65 was significantly phosphorylated and translocated into the nuclei, suggesting the activation of NF-κB signaling pathway. However, NF-κB-specific inhibitor Bay 11-7082 significantly attenuated the cell apoptosis induced by MRP8/14 ( P <0.01).CONCLUSION:NF-κB plays an important role in regulating the apoptosis of human alveolar epithelial cells in-duced by MRP8/14.
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Objective To investigate the expression changes of myeloid-related protein-8 (MRP-8) and myeloid-related protein-14 (MRP-14) in children with Kawasaki disease (KD) and to obtain laboratory diagnostic serum markers and new targets for its drug therapy.Methods A total of 46 patients with KD(KD group) were enrolled from Jul.2009 to Dec.2010 and divided into the coronary artery dilatation(CAD) group(n =15) and the normal coronary artery group(n =31) ;Meanwhile,25 febrile patients with acute respiratory tract infection but without disease in the circulatory,blood,immune systems formed the non-KD febrile group.Twenty healthy children from the out-patient department formed the healthy control group.Peripheral venous blood was collected in the acute and subacute stage of KD.Levels of MRP-8/MRP-14 were detected with enzyme-linked immunosorbnent assay (ELISA).Gene expressions of MRP-8,MRP-14 in leukocytes were analyzed by semi-quantitative reverse transcription-polymerase chain reaction(RTPCR).Results The serum levels of MRP-8/MRP-14 along with mRNA expressions of MRP-8 and MRP-14 in the leukocytes in the out-patient acute and subacute stage of KD were significantly higher than those in the non-KD febrile group and the healthy control group(all P ＜ 0.05) ;There was no significant difference between non-KD febrile group and healthy control group (P ＞ 0.05).The serum levels of MRP-8/MRP-14 along with mRNA expressions of MRP-8 and MRP-14 in leukocyte in actue stage of KD were significantly higher than those in subacute stage(all P ＜ 0.001).The serum levels of MRP-8/MRP-14 as well as mRNA expressions of MRP-8 and MRP-14 in the acute and the subacute stage of CAD group were significantly higher than those in the normal coronary artery group(P ＜ 0.05).Conclusions MRP-8/MRP-14 may probably play a role in the pathogenesis of KD and can be used as a diagnostic indicator for KD;MRP-8/MRP-14 may be involved in the formation of coronary artery lesion and can be used as an effective predictor for the coronary artery lesion.