Objective To investigate the effects of simvastatin on lung tissue in septic rats by observing the protein expression of nuclear factor kappa B ( NF-κB) and pathologic changes in lung tissue at different time points. Methods 90 healthy male Sprague-Dawley rats were randomly divided into three groups ( n =30 in each group) . All the rats received administration by caudal vein and capacity volume is 2 mL. The rats in the control group were treated with saline ( 2 mL) . The rats in the LPS group were treated with LPS ( 5 mg/kg ) . The rats in the simvastatin group were treated with LPS ( 5 mg/kg) and simvastatin ( 20 mg/kg) . Six rats in each group were killed randomly at 2, 4, 6, and 12 hours after the injection, and the right middle lobe of lung was taken out. Pathological changes of lung tissue wee investigated under light microscope. The expression of NF-κB in lung tissue was determined by immunohistochemistry ( IHC) method. Results Microscopic studies showed that there were not pathological changes in the lung tissue of rats in the control group. While in the LPS group, the alveolar spaces were narrowed and the alveolar wall were thickened. Furthermore, severe interstitial edema of lung and proliferation of epithelial cells were observed. In the simvastatin group, the degree of the infiltration of leukocytes and the lung interstitial edema were less severe than those in the simvastatin group. In the control group, the expression of NF-κB protein in most of lung tissue was negative. In the LPS group, the expression of NF-κB protein was detected at 2h, andreached the peak at 6h, then decreased at 12h. In the Simvastatin group, the NF-κB expression was significantly lower than that in the LPS group at all time points ( P lt; 0. 01) . Conclusion Simvastatin can ameliorate pathological lesions and decrease expression of NF-κB in lung tissue of septic rats.
Sepsis is not only a common critical disease , but also a common complication and cause of death of patients in intensive care unit. It has the characteristics of dangerous condition, rapid development and high mortality. How to treat sepsis to improve the prognosis and quality of life of patients is very important. Timely and reasonable anti-infection is a vatal part in the treatment of sepsis. This article will review the progress of anti-infective therapy in adult patients with sepsis, starting from empirical anti-infection, procalcitonin-guided anti-infection, bacterial culture combined drug sensitivity test-guided anti-infection and anti-infection with antimicrobial peptides, aiming to provide a certain basis and reference for the anti-infective treatment of adult sepsis.
Objective To compare the vasoactive effects of norepinephrine( NE) and dopamine of different doses on isolated rabbit pulmonary and systemic arteries in septic shock. Methods Six paired pulmonary and systemic arterial rings were prepared fromsix rabbits, and matched randomly assigned into a normal group and a LPS group. The assigned groups were intervened by different doses of NE. Another six paired pulmonary and systemic arterial rings were prepared from another six rabbits. They were assigned to different groups as above and intervened by different doses of dopamine. The LPS groups were pre-incubated in RPMI mediumsupplemented with4 μg/mL LPS to simulate septic shock. The tension of arterial rings was measured and its response to NE and dopamine were studied. Results ( 1) In the normal groups, the contraction of the systemic arteries was ber than the pulmonary arteries in response to low,middle dose of NE, and high dose of dopamine ( all P lt; 0. 05) , and which was weaker in response to middle dose of dopamine and similar in response to high dose of NE( P gt;0. 05) . Both the pulmonary and systemic arteriesrelaxed in response to low dose of dopamine. ( 2) After LPS pre-incubation, the contraction of the systemic arteries was weaker than the pulmonary arteries in response to low dose of dopamine ( P lt;0. 05) , and which was similar in response to low,middle and high dose of NE, and middle, high dose of dopamine. ( 3) Comparing the LPS groups with the normal groups, the contraction in response to middle dose of dopamine increased in the systemic arteries and dreased in the pulmonary arteries ( P lt;0. 05) . Conclusions In septic shock, the vasoactive effect of different doses of NE is not different between pulmonary and systemic arteries. But middle dose of dopamine can increase the contraction of systemic arteries and decrease the contraction of pulmonary arteries.
Objective To investigate the changes of microRNA-150 ( miR-150) in peripheral blood leukocytes in sepsis patients, and their relationship with expression of immune cytokines and sepsis severity. Methods The level of mature miR-150 was quantified by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and normalized to that of control miRNA, U6, in peripheral blood leukocytes of 40 patients with sepsis, 20 patients with systemic inflammatory response syndrome ( SIRS) , and 20 normal individuals. Serum concentrations of tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) were measured by enzyme-linked immunoabsorbent assay in all subjects. The sequential organ failure assessment ( SOFA) score systemwas used to evaluate the severity of sepsis. The relationships between miR-150 and the white blood cell count ( WBC) , TNF-α, IL-10 and SOFA score of the sepsis patients were analyzed. Results MiR-150 was stable for at least 5 days when specimen stored at 4 ℃ and the determination of miR-150 had a broad linear detecting range ( 6. 97-6. 97 ×104 pg/ μL RNA, the lowest detecting limit: 6. 97 pg/μL RNA,r=0.999) .MiR-150 expression in the peripheral blood leukocytes in the sepsis group was significantly lower than that in the healthy control group ( Plt;0.01) , while WBC, IL-10 and IL-10/TNF-α ratio were significantly higher ( Plt;0.05) . There was no significant difference in levels of miR-150, IL-10, IL-10/TNF-α ratio, and WBC between the sepsis group and the SIRS group (Pgt;0.05) . There was no significant difference in serum concentrations of TNF-α among three groups ( Pgt;0.05) . MiR-150 expression in non-survivor sepsis patients was significantly lower than that in survivor sepsis patients (Plt;0.05) , while serum IL-10 and IL-10/TNF-αratio were significantly higher (Plt;0.01) , but there was no significant difference in serum TNF-α between the non-survivor group and the survivor group ( Pgt;0.05) . There was significantly negative correlation between miR-150 and SOFA score, TNF-α and IL-10( r=-0. 619, - 0.457, -0. 431, Plt;0.05, respectively) , but no correlation between miR-150 and WBC ( r =-0. 184, Pgt;0.05) . There was no relationship between serum TNF-α, IL-10, IL-10 /TNF-α ratio or SOFA score ( Pgt;0.05) . Conclusions MiR-150 expression in the peripheral blood specimens is significantly decreased in sepsis patients. The expression level of miR-150 not only reflect the situation of inflammatory response, but also may be used as a prognostic marker in sepsis, as it can reflect the severity of sepsis in certain degree.
ObjectiveTo investigate the protective effects of diisopropylamini dichlorocacetas on impairment of hepatic function in patients with sepsis.
MethodsThe 60 inpatients with liver dysfunction and sepsis treated in our hospital between June 2010 and December 2012 were randomly divided into two groups: treatment group (n=30) and control group (n=30). In the treatment group, patients were treated with intravenous diisopropylamini dichlorocacetas for 7 days, while patients in the control group were treated with Vitamin C for the same period. The venous blood sample of each patient of the two groups was collected and examined for the content of alanine aminotransferase, aspartate aminotransferase, glutamyl transpeptidase, alkaline phosphatase, total bilirubin, and direct bilirubin before and after treatment, and the effective rates of the two groups were determined.
ResultsLiver function indicators after treatment of both the two groups were reduced. Compared with the control group, the liver function indicators were significantly decreased and the total effective rate was significantly higher in the treatment group (P<0.05).
ConclusionDiisopropylamini dichlorocacetas is effective in the treatment of impairment of hepatic function in patients with sepsis.
ObjectivesTo systematically review the prognostic value of plasma soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) level in predicting 28-day mortality in sepsis.MethodsPubMed, The Cochrane Library, EMbase, Web of Science, CBM, CNKI, VIP and WanFang Data databases were electronically searched to collect studies about the prognostic value of plasma sTREM-1 in early 28-day mortality in sepsis from inception to April 16th, 2018. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies, then, meta-analysis was performed by using Stata 14.0 software.ResultsA total of 13 studies involving 1 115 patients were included. The results of meta-analysis showed that the sensitivity and specificity were 79% and 77%, respectively. The positive likelihood ratio and the negative likelihood ratio were 3.4 and 0.28, respectively. The diagnostic ratio was 12. The overall area under the summary receiver operator characteristic (SROC) curve was 0.80.ConclusionsCurrent evidence shows that plasma sTREM-1, as a single index, may play a prognostic role in the early 28-day mortality of sepsis in patients. Due to limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
Sepsis, a serious clinical syndrome known as organs dysfunction caused by an unbalanced host inflammatory response to infection, is of great concern in emergency medicine. Over the past two decades, the definition of sepsis has changed from systemic inflammatory response syndrome lead by infection to organs damage caused by infection. Under the new diagnostic criterion, septic patients are too serious to be treated in Emergency Department, and need intensive treatment of Intensive Care Unit. In this paper, by analyzing the development process from infection to sepsis and expounding the role of cytokines in the development of sepsis, we think that measures should be taken at the early stage of infection in order to prevent and block the occurrence of sepsis.
ObjectiveTo evaluate the diagnostic value of various severity assessment scoring systems for sepsis after cardiac surgery and the predictive value for long-term prognosis.MethodsThe clinical data of patients who underwent cardiac sugeries including coronary artery bypass grafting (CABG) and (or) valve reconstruction/valve replacement were extracted from Medical Information Mark for Intensive Care-Ⅲ (MIMIC-Ⅲ). A total of 6 638 patients were enrolled in this study, including 4 558 males and 2 080 females, with an average age of 67.0±12.2 years. Discriminatory power was determined by comparing the area under the receiver operating characteristic (ROC) curve (AUC) for each scoring system individually using the method of DeLong. An X-tile analysis was used to determine the optimal cut-off point for each scoring system, and the patients were grouped by the cut-off point, and Kaplan-Meier curves and log-rank test were applied to analyze their long-term survival.ResultsCompared with the sequential organ failure assessment (SOFA) score, acute physiology score-Ⅲ (APS-Ⅲ, P<0.001), the simplified acute physiology score-Ⅱ (SAPS-Ⅱ, P<0.001) and logistic organ dysfunction score (LODS, P<0.001) were more accurate in distinguishing sepsis. Compared with the non-septic group, the 10-year overall survival rate of the septic group was lower (P<0.001). Except for the systemic inflammation response score (SIRS) system, the 10-year overall survival rates of patients in the high risk layers of SOFA (HR=2.50, 95%CI 2.23-2.80, P<0.001), SAPS (HR=2.93, 95%CI 2.64-3.26, P<0.001), SAPS-Ⅱ (HR=2.77, 95%CI 2.51-3.04, P<0.001), APS-Ⅲ (HR=2.90, 95%CI 2.63-3.20, P<0.001), LODS (HR=2.17, 95%CI 1.97-2.38, P<0.001), modified logistic organ dysfunction score (MLODS, HR=2.04, 95%CI 1.86-2.25, P<0.001) and the Oxford acute severity of illness score (OASIS, HR=2.37, 95%CI 2.16-2.60, P<0.001) systems were lower than those in the low risk layers.ConclusionCompared with SOFA score, APS-Ⅲ score may have higher value in the diagnosis of sepsis in patients who undergo isolated CABG, a valve procedure or a combination of both. Except for SIRS scoring system, SOFA, APS-Ⅲ, SAPS, SAPS-Ⅱ, LODS, MLODS and OASIS scoring systems can be applied to predict the long-term outcome of patients after cardiac surgery.
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 study the effect and mechanism of Xuebijing injection on sepsis-induced acute lung injury (ALI) in mice by regulating autophagy. Methods A total of 80 BALB/c male mice were randomly divided into control group, model group, Xuebijing group and Xuebijing+3-methyladenosine (3-MA) group, with 20 mice in each group. The control group received sham operation, while sepsis-induced ALI model was established in the later three groups by cecal ligation and puncture, on that basis, the Xuebijing group was given 10 mL/kg Xuebijing by intraperitoneal injection and the Xuebijing+3-MA group was given 10 mL/kg Xuebijing and 10 mg/kg autophagy inhibitor 3-mA by intraperitoneal injection. The cumulative survival rates of the four groups were observed 72 h after modeling, and the pathological changes of lung tissues, lung wet weight /dry weight ratios, inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin (IL)-1 β, and IL-18] contents, numbers of autophagosome, and the protein expression levels of autophagy genes [microtubule-associated protein light chain3 (LC3)-Ⅱ/LC3-Ⅰand Beclin-1] were detected. Results In the control group, the 72-hour cumulative survival rate was 100%, the lung wet weight /dry weight ratio was 3.89±0.85, the TNF-α, IL-1β, and IL-18 contents were (0.83±0.14) ng/mg, (0.74±0.15) ng/mg, and (84.51±13.25) pg/mg, respectively, the number of autophagosome was (0.41±0.09)/field, and the expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 were 0.20±0.04 and 0.17±0.03, respectively. In the model group, the lung tissue showed typical ALI pathological changes, the 72-hour cumulative survival rate (50%) was lower than that in the control group, and the lung wet weight /dry weight ratio (6.77±0.94), contents of TNF-α, IL-1β, and IL-18 [(3.15±0.76) ng/mg, (2.88±0.62) ng/mg, (274.62±45.58) pg/mg], autophagosome number [(3.14±0.55)/field], and expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 (0.69±0.09, 0.35±0.06) were higher than those in the control group (P<0.05). In the Xuebijing group, the ALI pathological changes alleviated, the 72-hour cumulative survival rate (75%), autophagosome number [(5.77±0.75)/field], and expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 (0.98±0.13, 0.62±0.08) were higher than those in the model group (P<0.05), and the lung wet weight /dry weight ratio (4.23±0.76) and contents of TNF-α, IL-1β, and IL-18 [(1.52±0.32) ng/mg, (1.29±0.30) ng/mg, (121.36±26.51) pg/mg] were lower than those in the model group (P<0.05). In the Xuebijing+3MA group, the ALI pathological changes aggravated, the 72-hour cumulative survival rate (55%), autophagosome number [(0.78±0.16)/field], and expression levels of LC3-Ⅱ/LC3-Ⅰ and Beclin-1 (0.37±0.05, 0.32±0.05) were lower than those in the Xuebijing group (P<0.05), and the lung wet weight /dry weight ratio (6.31±0.91) and contents of TNF-α, IL-1β, and IL-18 [(2.88±0.56) ng/mg, (2.41±0.58) ng/mg, (252.35±37.65) pg/mg] were higher than those in the Xuebijing group (P<0.05). Conclusion Xuebijing injection can reduce ALI induced by sepsis in mice, and activation of autophagy is the molecular mechanism.
