ObjectiveTo investigate the potential role and mechanism of hydrogen sulfide (H2S) in regulating arterial baroreflex (ABR) in septic rats. MethodsThe rat model of cecal ligation and puncture (CLP) induced sepsis was established. Fortyseven male SpargueDawley rats were randomly divided into 9 groups: ① Sham operation (SO)+0.9% NaCl (NS) intravenous injection (i.v.) group; ② SO+NaHS i.v. group; ③ CLP+NaHS i.v. group; ④ SO+artificial cerebrospinal fluid (aCSF) bilater nucleus tractus solitarii (NTS) microinjection group; ⑤ SO+NaHS bilater NTS microinjection group; ⑥ SO+vehicle (DMSO)+NaHS group; ⑦ SO+Gli+NaHS group; ⑧ CLP+vehicle (DMSO) group; ⑨ CLP+Gli group. The ABR function was measured before administration and 5 min and 30 min after administration. Results① The ABR value of rats at different time in the same group: Compared with the ABR value before administration in the SO+NaHS i.v. group, CLP+NaHS i.v. group, SO+NaHS bilater NTS microinjection group, and SO+vehicle+NaHS group, the ABR values of rats significantly decreased at 5 min and 30 min after administration (Plt;0.05, Plt;0.01), which significantly increased in the CLP+Gli group at 5 min and 30 min after administration (Plt;0.05). ② The ABR value of rats at the same time in the different groups: Before administration, the ABR value of rat in the CLP+NaHS i.v. group was significantly lower than that in the SO+NS i.v. group or SO+NaHS i.v.group (Plt;0.05). At 5 min and 30 min after adminis tration, the ABR value of rat in the CLP+NaHS i.v. group was significantly lower than that in the SO+NS i.v. group or SO+NaHS i.v. group (Plt;0.05), which in the SO+NaHS i.v. group or SO+NaHS bilater NTS microinjection group was significantly lower than that in the SO+NS i.v. group or SO+aCSF bilater NTS microinjection group, respectively (Plt;0.05, Plt;0.01), in the SO+Gli+NaHS group or CLP+Gli group was significantly higher than that in the SO+vehicle+NaHS group or CLP+vehicle group, respectively (Plt;0.05). ConclusionsH2S plays an adverse role in septic ABR function, and opening KATP channel located at the pathway of ABR, may be the mechanism involved in the downregulation of ABR function in septic rat. Notably, the NTS may be also responsible for reduction of ABR value.
Objective To explore independent risk factors for 30-day mortality in critical patients with pulmonary infection and sepsis, and build a prediction model. Methods Patients diagnosed with pulmonary infection and sepsis in the MIMIC-Ⅲ database were analyzed. The CareVue database was the training cohort (n=934), and the Metavision database was the external validation cohort (n=687). A COX proportional hazards regression model was established to screen independent risk factors and draw a nomogram. We conducted internal cross-validation and external validation of the model. Using the receiver operator characteristic (ROC) curve, Calibration chart, and decision curve analysis, we detected the discrimination, calibration, and benefit of the model respectively, comparing with the SOFA scoring model. Results Age, SOFA score, white blood cell count≤4×109/L, neutrophilic granulocyte percentage (NEU%)>85%, platelet count (PLT)≤100×109/L, PLT>300×109/L, red cell distribution width >15%, blood urea nitrogen, and lactate dehydrogenase were independent risk factors. The areas under the ROC curve of the model were 0.747 (training cohort) and 0.708 (external validation cohort), respectively, which was superior to the SOFA scoring model in terms of discrimination, calibration, and benefit. Conclusion The model established in this study can accurately and effectively predict the risk of the disease mortality, and provide a visual assessment method for early identification of high-risk patients.
Objective To investigate the clinical value of peripheral serum cell-free DNA/neutrophil extracellular traps (cf-DNA/NETs) level in diagnosis and severity assessment of sepsis patients. Methods Forty patients with sepsis and 40 patients with non-infectious systemic inflammatory response syndrome (nf-SIRS) were enrolled in this study. The cf-DNA/NETs level in serum of all subjects were measured. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic ability of the cf-DNA/NETs, white blood cell count (WBC), procalcitonin (PCT) and interleukin-6 (IL-6). The sepsis patients were stratified into a survival group and a death group according to the prognosis. Sequential organ failure (SOFA) score were recorded in the sepsis patients, and the correlations between SOFA and cf-DNA/NETs, PCT, WBC, IL-6 were analyzed. Results Compared with the nf-SIRS group, cf-DNA/NETs and PCT levels were significantly higher in the sepsis group (both P<0.05). WBC and IL-6 showed no significant differences between the two groups (bothP>0.05). The area under the ROC curve (AUC) of cf-DNA/NETs was 0.884 for diagnosis of sepsis, and it was higher than the AUC of PCT (0.803). The cf-DNA/NETs showed better sensitivity (81.2% and 79.2%) and specificity (81.0% and 82.4%) than PCT. cf-DNA/NETs and PCT were significantly higher in the death group than those in the survival group. Bivariate collection analysis revealed positive correlations between SOFA score and the two biomarkers of cf-DNA/NETs and PCT (r1=0.573, r2=0.518; both P<0.01). Conclusions cf-DNA/NETs and PCT have certain value in early diagnosis of sepsis, and cf-DNA/NETs shows better diagnostic value in distinguishing sepsis from nf-SIRS than PCT. cf-DNA/NETs can be used as a routine monitoring index to help assess disease severity in sepsis.
Objective To evaluate the predicting effect of quick Sequential Organ Failure Assessment (qSOFA) on septic shock, and investigate the probability of improving the predicting effect. Methods Patients with sepsis diagnosed in Emergency Department from July 2015 to June 2016 were enrolled. They were divided into shock group and non-shock group based on whether or not they had septic shock during 72 hours after admission. The multivariate logistic regression analysis was used to find out the independent risk factors affecting the incidence of septic shock. Receiver operating characteristic (ROC) curve was used to analyze those risk factors. Modified Early Warning Score (MEWS), Mortality in Emergency Department Sepsis Score (MEDS), Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic HealthEvaluation (APACHE)Ⅱ and qSOFA were also compared with ROC curve analysis. The possibility of improvement of qSOFA predicting effect was discussed. Results A total of 821 patients were enrolled, with 108 in septic shock group and 713 in non-septic shock. The result of multivariate logistic regression analysis indicated that respiratory rate, systolic blood pressure, pH value, oxygenation index, lactate, albumin, Glasgow Coma Score and procalcitonin were the independent risk factors (P<0.05). The result of ROC analysis showed that the area under curve (AUC) of pH value, lactate and procalcitonin was 0.695, 0.678 and 0.694, respectively. Lactate had the highest value of specificity (0.868), positive predictive value (0.356) and positive likelihood ratio (3.644), while the sensitivity (0.889) and negative predictive value (0.961) of procalcitonin were the highest. MEWS, MEDS, SOFA, APACHEⅡ and qSOFA were compared with ROC. SOFA had the best predicting effect with the statistical results of AUC (0.833), sensitivity (0.835), specificity (0.435), positive predictive value (0.971), negative predictive value (0.971), and positive likelihood ratio (5.048); and MEWS had the highest negative likelihood ratio (0.581). qSOFA did not show a best predicting value. Conclusion qSOFA is not the best choice to predict the possibility of septic shock, but its predicting value might be improved when combined with pH value, lactate and procalcitonin.
Objective To explore the possible anti-inflammatory mechanism of intensive insulin therapy （IIT） by studying the effect of IIT on the levels of TNF-α, IL-6, C-reactive protein （CRP） and APACHE Ⅱ score in biliary pyemia. Methods Twenty eight patients with biliary pyemia who were admitted by our department and given an operation within 24 h form Jan. 2005 to Dec. 2008 were randomly divided into two groups by using random number table numbers: one group treated with IIT （IIT group, n=14） and another group treated with routine insulin therapy （RIT group, n=14）. The inflammatory factors, such as TNF-α, IL-6 and CRP were detected dynamically and the APACHEⅡ score was calculated. ResultsThe level of CRP and APACHEⅡ score on day 5 and 7 and the levels of TNF-α and IL-6 on day 3, 5 and 7 after operation in IIT group were significantly lower than those in RIT group （P＜0.05, P＜0.0１）. Compared with preoperative levels, the IL-6 and APACHEⅡ score in IIT group commenced to decrease on day 3 after operation （P＜0.05）, that was earlier than control group. Conclusion The treatment with IIT can suppress the composition of TNF-α, IL-6 and CRP, protect impaired hepatic cells, and reduce APACHEⅡ score, the degree of systemic inflammation and incidence of MODS.
Objective To observe the effects of δ-opioid receptor agonists D-Ala2-D-Leu5-enkephali （DADLE） on hepatocyte apoptosis and expressions of bcl-2 and caspase-3 in septic rat, and to investigate the possible mechanism by which DADLE protects the liver in sepsis. Methods Sepsis was reproduced in rats by cecum ligation and puncture (CLP). Fifty-four SD rats (either male or female) were randomly divided into CLP group (n=18), DADLE group (n=18) and sham operation (SO) group (n=18). The rats were respectively killed at different time (2 h, 4 h and 6 h after operation). Hepatocyte apoptosis was detected by TdT-mediated dUTP Nick End Labeling (TUNEL). The expressions of bcl-2 and caspase-3 protein were detected by immunohistochemistry. And the changes of pathology in hepatic tissue were detected by light microscope. Results The hepatic pathological lesion of rats in CLP group was obviously serious compared with SO group, while it was obviously improved in DADLE group. The apoptosis index of rat hepatocytes in CLP group significantly increased compared with SO group, and further it was prominent at 4 h （P＜0.01). The apoptosis index of rat hepatocytes at each time of DADLE group was significantly decreased compared with CLP group （P＜0.01）. Expression of caspase-3 protein in liver tissues of CLP group significantly increased compared with SO group （P＜0.01）, while the expression of bcl-2 protein significantly decreased （P＜0.05）. Expression of caspase-3 protein in liver tissues of DADLE group significantly decreased compared with the CLP group （P＜0.01）, while the expression of bcl-2 protein significantly increased （P＜0.05）. There was positive correlation between expression of caspase-3 in liver tissues and apoptosis index of hepatocyte (r=0.83, P＜0.01) and negative correlation between expression of bcl-2 in liver tissues and apoptosis index of hepatocyte (r=-0.65, P＜0.01). Conclusions The findings indicate that δ-opioid receptor agonists DADLE can obviously improve hepatic pathological changes of septic rats. And its protective mechanism contains down regulation of caspase-3 expression, upregulation of bcl-2 expression and thus the apoptosis of hepatocyte is repressed.
Objective To systematically review the efficacy of enteral nutrition with eicosapentaenoic acid ( EPA) , gamma-linolenicacid ( GLA) , and anti-oxidants for patients with sepsis. Methods We searched the PubMed, EMbase, Cochrane Library, Wanfang Database, CNKI and VIP for all randomized controlled trials about the efficacy of an enteral diet enriched with EPA, GLA, and anti-oxidants for patients with sepsis. The quality of the studies was evaluated by the method recommended by Cochrane Collaboration. Meta-analysis was conducted using the Cochrane Collaboration’s RevMan 5.0 software.Results Three RCTs involving 350 patients were included in our systematic review. The results showed a significant reduction in the length of ICU stay ( MD =6.21, 95% CI: 4.61-8.19; P lt;0.00001) and hospital stay ( P lt;0.0001) , a fewer development of neworgan dysfunctions in the patients fed with the study diet and no more adverse events were observed. However, no significant difference in 28-day mortality of all cause was revealed( RR=0.83, 95% CI: 0.60-1.16, P = 0.27) . There were controversial results about the duration of mechanical ventilation.Conclusion A diet enriched with EPA, GLA, and elevated antioxidants is safe and beneficial for the clinical outcome in patients with sepsis.
ObjectiveTo systematically review the diagnostic value of Presepsin for sepsis. MethodsWe searched databases including PubMed, EMbase, Web of Science, WanFang, VIP and CNKI from inception to June 2015 to collect diagnostic tests related to Presepsin for spesis. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies by QUADAS-2 tool. Then, meta-analysis was performed by Stata 13.0 software. ResultsA total of 19 studies involving 4140 samples were included. The results of meta-analysis showed that:the pooled sensitivity (Sen) and specificity (Spe) were 0.85 (95%CI 0.79 to 0.90) and 0.83 (95%CI 0.76 to 0.87), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.91 (95%CI 0.88 to 0.93). ConclusionPresepsin shows high diagnostic value for sepsis as a novel biomarker. Due to the limited quality of the included studies, more high quality studies are needed to verify the above conclusion.