ABSTRACT
OBJECTIVE@#To investigate the diagnostic value of Hepcidin as a sepsis biomarker in critically ill adults.@*METHODS@#An observational study was conducted. The patients with suspected or proven infection admitted to intensive care unit (ICU) of Zhoupu Hospital Affiliated to Shanghai University of Medicine and Health Sciences from March 2016 to November 2017 were enrolled. According to the third international consensus definitions for sepsis and septic shock (Sepsis-3), the patients were divided into non-sepsis group and sepsis group, and the septic patients were subdivided into general sepsis subgroup and septic shock subgroup according to the severity of disease. The differences in serum Hepcidin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), C-reactive protein (CRP), white blood cell (WBC), neutrophil granulocytes (NEUT) and lactic acid (Lac) within 1 hour after ICU admission between non-sepsis and sepsis groups and among the sepsis subgroups were compared. The acute physiology and chronic health evaluation II (APACHE II) within 24 hours after ICU admission and sequential organ failure score (SOFA) were recorded, and the mortality rate was followed up for 28 days. Receiver operation characteristic curve (ROC) was used to evaluate and compare the diagnostic value of Hepcidin and PCT, CRP, WBC for sepsis. Logistic regression model was used to estimate the association between Hepcidin and sepsis. Spearman correlation analysis was used to analyze the correlation between Hepcidin and other parameters of sepsis patients.@*RESULTS@#A total of 183 patients were enrolled, 93 in the non-sepsis group and 90 in the sepsis group (48 with general sepsis and 42 with septic shock). (1) The levels of Hepcidin, IL-6, TNF-α, PCT, Lac in serum, and APACHE II and SOFA scores in the sepsis group were significantly higher than those in the non-sepsis group. ROC analysis showed that the area under the ROC curve (AUC) of Hepcidin and PCT for sepsis diagnosis were 0.865 [95% confidence interval (95%CI) = 0.807-0.911] and 0.848 (95%CI = 0.788-0.897), respectively, without statistical significance (Z = 0.443, P = 0.657). Furthermore, the AUC of Hepcidin for sepsis diagnosis was significantly higher than that of the conventional biomarkers CRP and WBC [AUC was 0.530 (95%CI = 0.455-0.604) and 0.527 (95%CI = 0.452-0.601), respectively] with statistical significance (both P < 0.01). When Hepcidin > 54.00 μg/L, its sensitivity for sepsis diagnosis was 95.56%, specificity was 66.67%, positive and negative predictive value was 73.51% and 93.94%, respectively. Parallel test was conducted for combination of Hepcidin and PCT, which showed that the AUC was 0.885, and the sensitivity and negative predictive value was significantly improved to 98.96% and 98.36%, respectively. Logistic regression analysis demonstrated that after adjusted for PCT, Hepcidin > 54.00 μg/L was also associated with sepsis independently, with odds ratio (OR) of 1.011 (95%CI = 1.008-1.015, P < 0.001), indicating that Hepcidin and PCT were not completely overlapped in the diagnosis of sepsis. (2) With the increase in infection severity, serum Hepcidin, PCT, IL-6, TNF-α, Lac, APACHE II, SOFA score and 28-day mortality all showed an increasing trend in patients. There was a significantly positive correlation between Hepcidin and IL-6, TNF-α, PCT, APACHE II, and SOFA in the sepsis patients (r value was 0.526, 0.449, 0.591, 0.359, and 0.374, respectively, all P < 0.01), but no correlation was found between Hepcidin and Lac (r = 1.104, P > 0.05).@*CONCLUSIONS@#Serum Hepcidin is a useful biomarker for the diagnosis of sepsis, and it is correlated to the severity of the sepsis. The combination of Hepcidin and PCT can improve the accuracy of diagnosis of sepsis.@*CLINICAL TRIAL REGISTRATION@#China Clinical Trial Registration Center, ChiCTR-DDD-16008522.
Subject(s)
Adult , Humans , Biomarkers , C-Reactive Protein , Calcitonin , Calcitonin Gene-Related Peptide , China , Critical Illness , Hepcidins , Prognosis , Protein Precursors , ROC Curve , SepsisABSTRACT
Objective@#To investigate the diagnostic value of Hepcidin as a sepsis biomarker in critically ill adults.@*Methods@#An observational study was conducted. The patients with suspected or proven infection admitted to intensive care unit (ICU) of Zhoupu Hospital Affiliated to Shanghai University of Medicine & Health Sciences from March 2016 to November 2017 were enrolled. According to the third international consensus definitions for sepsis and septic shock (Sepsis-3), the patients were divided into non-sepsis group and sepsis group, and the septic patients were subdivided into general sepsis subgroup and septic shock subgroup according to the severity of disease. The differences in serum Hepcidin, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), procalcitonin (PCT), C-reactive protein (CRP), white blood cell (WBC), neutrophil granulocytes (NEUT) and lactic acid (Lac) within 1 hour after ICU admission between non-sepsis and sepsis groups and among the sepsis subgroups were compared. The acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) within 24 hours after ICU admission and sequential organ failure score (SOFA) were recorded, and the mortality rate was followed up for 28 days. Receiver operation characteristic curve (ROC) was used to evaluate and compare the diagnostic value of Hepcidin and PCT, CRP, WBC for sepsis. Logistic regression model was used to estimate the association between Hepcidin and sepsis. Spearman correlation analysis was used to analyze the correlation between Hepcidin and other parameters of sepsis patients.@*Results@#A total of 183 patients were enrolled, 93 in the non-sepsis group and 90 in the sepsis group (48 with general sepsis and 42 with septic shock).① The levels of Hepcidin, IL-6, TNF-α, PCT, Lac in serum, and APACHEⅡand SOFA scores in the sepsis group were significantly higher than those in the non-sepsis group. ROC analysis showed that the area under the ROC curve (AUC) of Hepcidin and PCT for sepsis diagnosis were 0.865 [95% confidence interval (95%CI) = 0.807-0.911] and 0.848 (95%CI = 0.788-0.897), respectively, without statistical significance (Z = 0.443, P = 0.657). Furthermore, the AUC of Hepcidin for sepsis diagnosis was significantly higher than that of the conventional biomarkers CRP and WBC [AUC was 0.530 (95%CI = 0.455-0.604) and 0.527 (95%CI = 0.452-0.601), respectively] with statistical significance (both P < 0.01). When Hepcidin > 54.00 μg/L, its sensitivity for sepsis diagnosis was 95.56%, specificity was 66.67%, positive and negative predictive value was 73.51% and 93.94%, respectively. Parallel test was conducted for combination of Hepcidin and PCT, which showed that the AUC was 0.885, and the sensitivity and negative predictive value was significantly improved to 98.96% and 98.36%, respectively. Logistic regression analysis demonstrated that after adjusted for PCT, Hepcidin > 54.00 μg/L was also associated with sepsis independently, with odds ratio (OR) of 1.011 (95%CI = 1.008-1.015, P < 0.001), indicating that Hepcidin and PCT were not completely overlapped in the diagnosis of sepsis. ② With the increase in infection severity, serum Hepcidin, PCT, IL-6, TNF-α, Lac, APACHEⅡ, SOFA score and 28-day mortality all showed an increasing trend in patients. There was a significantly positive correlation between Hepcidin and IL-6, TNF-α, PCT, APACHEⅡ, and SOFA in the sepsis patients (r value was 0.526, 0.449, 0.591, 0.359, and 0.374, respectively, all P < 0.01), but no correlation was found between Hepcidin and Lac (r = 1.104, P > 0.05).@*Conclusions@#Serum Hepcidin is a useful biomarker for the diagnosis of sepsis, and it is correlated to the severity of the sepsis. The combination of Hepcidin and PCT can improve the accuracy of diagnosis of sepsis.@*Clinical trial registration@#China Clinical Trial Registration Center, ChiCTR-DDD-16008522.
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OBJECTIVE:To optimize the ultrasonic extraction and purification technology of total saponins from Marsdenia te-nacissima,and to prepare purified total saponins from M. tenacissima. METHODS:Using the extraction rate of total saponins from M. tenacissima as index,ethanol volume fraction,solvent-solid ratio and extraction temperature as factors,ultrasonic extraction technology of total saponins from M. tenacissima was optimized by single factor test and Box-Behnken response surface design. Us-ing the content of total saponins in elution,the effects of ethanol elution volume fraction on purification technology of total sapo-nins by D101 type macroporous adsorption resin was investigated. RESULTS:The optimal ultrasonic extraction technology was as follows as ethanol volume fraction of 85%,solvent-solid ratio of 18.5∶1 (ml/g),extraction temperature of 80 ℃. In verification test,the average extraction rate of total saponins from M. tenacissima was 4.80%(RSD=1.06%,n=3);it was close to predicted value 4.89%,and the deviation was 1.84%. The optimal purification technology was as follows as 45% ethanol as eluant,90%ethanol for purification. Verification test showed that the average content of total saponins from M. tenacissima was 62.45%(RSD=0.88%,n=3). CONCLUSIONS:The optimized technology can be used for the extraction and purification of total saponins from M. tenacissima. The technology is stable and reliable.
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Objective To master the serum nickel change rule of acute nickel carbonyl poisoning in rats,and to provide laboratory support for clinical treatment of acute nickel carbonyl poisoning patients.Methods SPF rats were given nickel carbonyl (250mg/m3,500mg/m3) in static inhalation for 30min.Rats were anesthetized by ether for 15 seconds after exposure for 30min,2h,4h,8h,12h,24h,48h,72h and 7d respectively.Anatomized rats,kept blood collection 2-3mL,and separated serum 0.5-1mL.Serum nickel was detected by AA800 (American PE company).Results The average serum nickel levels of 250mg/m3 dose group at 30min,2h,4h,8h,12h,24h,48h,72h,7d were (33.69 ±2.59),(24.61 ±3.03),(27.83 ±5.69),(21.36 ±4.14),(20.39 ±4.14),(18.80 ±7.02),(14.51 ±8.21),(13.58 ± 5.78) and (12.83 ± 4.41)μg/L.30 minutes reached the peak,and was 5.30-fold of those in normal controls.There had significant differences compared with normal control(t =5.959,5.958,5.990,5.998,5.997,5.994,5.990,4.317,4.347,all P ＜ 0.01).The average serum nickel levels of 500mg/m3 dose group at 30min,2h,4h,8h,12h,24h,48h,72h,7d were (72.22 ± 1.62),(57.78 ± 12.99),(42.25 ± 7.25),(103.77 ± 11.11),(79.04 ±12.26),(26.35 ±6.56),(18.58 ±4.92),(17.22 ±9.73),(14.59 ±5.27) μg/L.8h reached the peak,and was 16.33-fold of normal controls.The differences were significant (t =5.960,5.947,5.978,5.927,5.948,5.959,3.143,2.447,2.440,all P ＜ 0.05).Meanwhile,there were significant differences between two groups of 30min,2h,4h,8h,12h(t =5.208,2.447,2.449,5.959,5.959,P =0.001,0.049,0.042,0.000,0.000),but there was no significant difference after 24h.Conclusion There was significant doses-effect relationship between serum nickel content of acute nickel carbonyl poisoning rats and the dosage.Nickel carbonyl or its metabolites were excreted mainly within 24h.