ObjectiveTo detecte the expressions of phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene and protein in peripheral blood mononuclear cells (PBMC) of patients with sepsis and to explore its role in the pathogenesis of acute obstructive suppurative cholangitis (AOSC). MethodsThe PBMC and serum were separated from AOSC patients (n=25) before treatment and in 1 week after recure, and healthy volunteers (normal control group, n=15). The serum levels of lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α) and interleukin 10 (IL-10) were detected by enzyme linked immunosorbent assay (ELISA) methods. The mRNA and protein expression levels of PTEN, nuclear fator κB P65 (NF-κB), and inhibitor of NF-κB (IκB) were detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, respectively. ResultsThe levels of LPS, TNF-α, and IL-10 before treatment were significantly higher than those of normal control group (P < 0.05), the indicators were significantly decreased and close to normal levels in 1 week after recure. The mRNA and protein expression levels of PTEN and IκB before treatment were lower than those of normal control group (P < 0.05), NF-κB P65 was higher than those of normal control group (P < 0.05), while the phosphorylation levels of PTEN and IκB were higher than those normal control group (P < 0.05), and in 1 week after recure, the above indicators returned to normal levels. ConclusionsSepsis shift may be associated with the occurrence of intestinal LPS, and caused the imbalance between proinflammatory and anti-inflammatory cytokines in the body. PTEN for phosphorylation activation of IκB or directly activation of NF-κB participate the originating process of sepsis, hinting a therapeutic potentialities in the early stage of sepsis.
Objective To retrospectively analyze the clinical characteristics of different lactate trajectories in sepsis patients receiving mechanical ventilation (MV) and to investigate their associations with acute kidney injury (AKI) and in-hospital death risk, aiming to provide references for early renal protection in critically ill sepsis patients. Methods Data from sepsis patients receiving MV were extracted from the Medical Information Mart for Intensive Care Ⅳ (MIMIC-Ⅳ) database. The daily mean lactate values over the first 10 days were calculated. The latent class trajectory model (LCTM) was used to identify lactate trajectories over time and group the patients accordingly. AKI was the primary outcome measure, while in-hospital death was the secondary outcome measure. Logistic regression and Cox regression analyses were used to explore the associations between different lactate trajectories and these outcomes. Kaplan-Meier curves were drawn to compare in-hospital death risks among different lactate trajectory groups. Results A total of 2 062 MV-treated sepsis patients were included. After LCTM analysis, 1 396 patients were classified into the low lactate trajectory group, 451 into the moderate lactate trajectory group, and 215 into the high lactate trajectory group. After adjusting for confounding factors, the high lactate trajectory group was associated with an increased risk of AKI and in-hospital death (P<0.05). Conclusions In sepsis patients receiving MV, those with high lactate trajectories have a higher risk of AKI. Lactate trajectory changes can serve as an early assessment indicator for AKI and mortality risk in critically ill sepsis patients.
Objective To explore the expression differences of procalcitonin (PCT) in different infection sites and bacterial strains, and to provide the evidence for early differential diagnosis of infectious diseases with PCT as a biomarker. Methods The patients with various kinds of infections diagnosed in West China Hospital of Sichuan University between January 2012 and June 2016 were retrospectively included. The expression differences of PCT in various infection sites and bacterial strains were analyzed. Results A total of 1 005 patients were include in this study, including 259 with systemic infection and 746 with local infection. The median PCT level in the systemic infection group was higher than that in the local infection group (8.57 vs. 0.10 ng/mL, P<0.05). In the 779 patients with pulmonary infection, the median PCT level of the patients with sepsis caused by pulmonary infection was higher than that of the ones without sepsis (4.61vs. 0.10 ng/mL, P<0.05), and the median PCT level of the patients with positive sputum culture was higher than that of the ones with negative sputum culture (0.28vs. 0.08 ng/mL, P<0.05). In the 48 patients with urinary tract infection, the median PCT level of the patients with sepsis caused by urinary tract infection was higher than that of the ones without sepsis (12.00vs. 0.42 ng/mL, P<0.05), and the median PCT level of the patients with complicated urinary tract infection was higher than that of the patients with simplex urinary tract infection (19.15vs. 5.02 ng/mL, P<0.05). In the 259 patients with systemic infection, the median PCT level of the patients with infective shock was higher than that of the ones without infective shock (40.26vs. 3.83 ng/mL, P<0.05); the mean PCT level of patients with infection of Gram-negative bacteria, Gram-positive bacteria and fungi was 13.66, 0.99, and 3.30 ng/mL with a significant difference (P<0.05). Conclusion The PCT level has unique advantages in identifying different sites of the infection, early diagnosing complicated urinary tract infection, and evaluating the severity of infection, which could provide evidence in early identification for sepsis caused by various kinds of infectious pathogens.
Objective To investigate the effects of hypertonic saline (HTS) treatment on the function and susceptibility to sepsis of reticuloendothelial system (RES) in mice with hemorrhagic shock. Methods Forty percent of total blood volume of male Balb/c mice was withdrawn by cardiac puncture. Two hours later, the mice were treated with blood infusion and normal saline (10 ml/kg) or 7.5% NaCl (10 ml/kg).The survival rate of the mice was observed after cecal ligation and puncture (CLP). The phagocytosis function of the RES was measured by carbon clearance rate(α) and carbon amount ingested by the macrophages of liver and spleen. In vitro, the peritoneal phagocyte function in solutions of different osmotic pressor was measured by assaying neutral red amount taken in. Results The survival rate after CLP in HTS treated group was 70%, whereas all the mice in the normal saline group died. At the third hour after hemorrhagic shock, the RES carbon clearance rate(α) and carbon amount ingested by the macrophages of liver in the HTS treated mice were 5.61±0.42 and 0.59±0.19 respectively, significantly higher than those in the normal saline treated mice (4.15±0.62， 0.42±0.16). In vitro, hyperosmolarity below 40 mmol/L had no significant effects on the phagocytosis activity of peritoneal macrophages in mice. Conclusion Treating hemorrhagic shock with HTS can decrease the susceptibility to sepsis and improve the RES phagocytosis function indirectly.
ObjectiveTo investigate the risk factors affecting the 28-day neurological outcome after admission of patients with sepsis complicated with consciousness disorder, create a simple scoring system, and evaluate its predictive value for the poor neurological outcome.MethodsWe retrospectively collected and analyzed the demographic data, clinical data, 28-day survival status and neurologic outcome of patients with sepsis complicated with disturbance of consciousness admitted to the Emergency Department of West China Hospital of Sichuan University between June 1st, 2017 and May 31st, 2018. Independent risk factors for the 28-day neurologic outcome of patients with disturbance of consciousness were obtained through univariate analyses and multiple logistic regression analysis, and then the continuous variables of risk factors were converted to binary variables according to the cut-off values from receiver operating characteristic (ROC) curve analysis, a simple scoring system was established and it’s predictive value for 28-day neurological outcome of patients with sepsis complicated with consciousness disorder was assessed.ResultsA total of 149 patients with sepsis complicated with consciousness disorder were included in this study, including 103 males (69.1%) and 46 females (30.9%), with an average age of (58.2±18.6) years old. There were 72 patients (48.3%) with poor outcome of neurological function on Day 28 after admission. Multiple logistic regression analysis revealed that total bile acid [odds ratio (OR)=1.040, 95% confidence interval (CI) (1.004, 1.077), P=0.027], blood ammonia [OR=1.014, 95%CI (1.001, 1.027), P=0.030], pulmonary infection [OR=3.255, 95%CI (1.401, 7.566), P=0.006], and Glasgow Coma Score (GCS) [OR=0.837, 95%CI (0.739, 0.949), P=0.005] were independent influencing factors for the poor neurological function in patients with sepsis complicated with consciousness disorder on Day 28 after admission. The area under the ROC curve predicting the 28-day poor neurological function was 0.754 [95%CI (0.676, 0.832)], and the sensitivity and specificity were 79.2% and 63.6%, respectively.ConclusionFor emergency patients with sepsis complicated with consciousness disorder, a simple scoring system based on early GCS, pulmonary infection, serum ammonia, and total bile acid has a favorable predictive value for short-term neurological function.
Objective To investigate the role of long chain non coding ribonucleic acid (LNcRNA) small nucleolar RNA host gene 14 (SNHG14) in regulating microribonucleic acid 223-3p (miR-223-3p) in alleviating sepsis associated lung injury in rats. Methods Sepsis rat models were established and the rats were randomly divided into SNHG14 upregulation group, SNHG14 upregulated control group, SNHG14 downregulation group, SNHG14 downregulation control group, miR-223-3p upregulation group, miR-223-3p upregulation control group, miR-223-3p downregulation group, miR-223-3p downregulation control group, and model group. Sham operation group was set up simutalously. All of them were administered through the tail vein. After 48 hours, the lung tissues was euthanized to detect the expressions of LncRNA SNHG14 and miR-223-3p. Tumor necrosis factor α (TNF- α), interleukin-1β (IL-1β), interleukin-18 (IL-18), lung wet weight/dry weight ratio (W/D) and the alveolar fluid clearance rate (AFC) were detected. Pathological changes in lung tissues were observed. Human NOD like receptor family protein 3 (NLPR3), cysteine-requiring aspartate protease 1 (caspase-1), and 1-aminocyclopropane-1-carboxylate synthase (ACS) genes and proteins expressions in lung tissues were detected. The dual luciferase reporter gene experiment was used to verify the targeted regulatory effect of LncRNA SNHG14 on miR-223-3p. Results Compared with the sham operation group, the model group showed increase in lung tissue LncRNA SNHG14 expression, serum inflammatory factor levels, W/D, pathological change quantification score, and lung tissue NLPR3, caspase-1 and ACS expressions (P<0.05), decrease in miR-223-3p expression and AFC (P<0.05). Compared with the model group and corresponding control groups, the SNHG14 upregulation group showed increase in LncRNA SNHG14 expression (P<0.05), and the SNHG14 upregulation group and the miR-223-3p downregulation group showed decrease in miR-223-3p expression and AFC (P<0.05), and increase in the levels of serum inflammatory factors, W/D, quantitative scores of pathological changes, and the expressions of NLPR3, caspase-1 and ACS in lung tissues (P<0.05). Compared with the model group and corresponding control groups, the expression of LncRNA SNHG14 in the SNHG14 downregulation group decreased (P<0.05), while the expression of miR-223-3p and AFC in the SNHG14 downregulation group and miR-223-3p upregulation group increased (P<0.05), which showed decrease in the levels of serum inflammatory factors, W/D, quantitative scores of pathological changes, and the expressions of NLPR3, caspase-1 and ACS in lung tissues (P<0.05). There were binding sites between LncRNA SNHG14 and miR-223-3p, and the former could negatively feedback targeted to regulate the latter. Conclusion Downregulation of LncRNA SNHG14 targets an increase in miR-223-3p expression and inhibit the NLRP3 pathway to alleviate sepsis related lung injury, which is related to the inhibition of inflammatory response, while upregulation of LncRNA SNHG14 negatively feedback targeting miR-223-3p and activated the NLRP3 pathway to exacerbate sepsis related lung injury.
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 changes of platelet-leukocyte aggregates (PLA) level in patients with sepsis and its diagnostic value in sepsis complicated with acute respiratory distress syndrome (ARDS).MethodsA prospective study was carried in adult sepsis patients admitted to our hospital from January 2015 to November 2016. According to the 2012 " Berlin definition” diagnostic criteria, 58 cases of sepsis with ARDS were allocated to an experimental group and 139 cases of sepsis non-ARDS patients were allocated to a control group. Immediately after the diagnosis of sepsis, elbow vein blood samples were collected for flow cytometry assay of PLA. The acute physiology and chronic health assessment II (APACHE II score) of each group was performed and the receiver operating characteristic (ROC) curve was drawn.ResultsPlatelet-neutrophil aggregates (PNA) and platelet-lymphocyte aggregates (PLyA) in the experimental group were higher than those in the control group, but there were no significant differences (both P>0.05). The platelet-monocyte aggregates (PMA) of the experimental group was significantly higher than that of the control group (P<0.05). Peripheral blood PMA was positively correlated with APACHE II score (r=0.671, P<0.001). When PMA was used as the test variable, the area under the curve (AUC) was 0.945 with significant diagnostic value (P<0.001), and optimal cutoff value of PMA was 8.25%, with diagnostic sensitivity of 0.806 and diagnostic specificity of 0.951. When APACHE II was used as the test variable, AUC was 0.930, with significant diagnostic value (P<0.001), and optimal threshold of APACHE II was 16.500 with diagnostic sensitivity of 0.871 and diagnostic specificity of 0.852.ConclusionPMA is of great value in the diagnosis of sepsis with ARDS.
Objective To investigate the expression of oncostatin M (OSM) in patients with sepsis and its role in early recognition of sepsis. Methods Thirty-four patients with sepsis admitted in Shanxi Bethune Hospital fromJune 3, 2021 to January 18, 2022 were selected as a sepsis group, 15 patients with community acquired pneumonia (CAP) as a case control group, and 16 adults who underwent physical examination in the same period were selected as a healthy control group. The patients in the sepsis group were followed up for 28 days and divided into a survival group and a death group. The serum OSM level and its correlation with clinical indexes (white blood cell, neutrophil, lymphocyte, sequential organ failure assessment score and acute physiology and chronic health evaluation Ⅱ) were analyzed, and the diagnostic value of OSM expression level in the early identification of sepsis was analyzed. Results Compared with the case control group and the healthy control group, the expression level of OSM in the sepsis group was significantly higher [(502.07±209.93)pg/mL vs. (368.22±65.95)pg/mL and (382.09±73.04)pg/mL, P<0.05]. However, the high expression of OSM had no significant correlation with white blood cell, neutrophil, lymphocyte or disease severity score (P>0.05), and there was no significant difference in serum OSM level between the sepsis survival group and the death group. Compared with white blood cell count, the high expression of OSM has certain diagnostic value in the early identification of sepsis. The area under the receiver operator characteristic curve of OSM in predicting sepsis was 0.794 (95% confidence interval 0.666 - 0.922, P<0.05), with the sensitivity of 79.4% and the specificity of 73.3%. Conclusion The expression of OSM in patients with sepsis is significantly increased, and the high expression of OSM has a certain diagnostic value in the early identification of sepsis.
經過數十年全球的共同努力，膿毒血癥（Sepsis）在臨床治療以及在病因、病理生理、診斷與治療策略上都取得了令人鼓舞的成績，但在ICU的重癥患者中，其發病率與死亡率居高不下，仍然是引發臟器功能不全及死亡的高風險因素。在美國，Sepsis是前十位的死亡原因，年死亡約為23萬6千人。中國的一項調查顯示，在大型醫院外科ICU中嚴重膿毒血癥（Severe Sepsis）的發病率為8.68%，死亡率為48.7%，與發達國家的調查相近。在對Sepsis調查及干預研究中，與其相關的綜合征的定義及命名仍然主要采用1991年美國胸科醫師協會/危重病醫學會芝加哥聯席會議的建議，包括了從全身炎性反應綜合征（systemic inflammatory response syndrome, SIRS）、Sepsis、嚴重膿毒血癥（Severe Sepsis）、感染性休克（Septic Shock）直至多器官功能不全綜合征（multiple organ dysfunction syndrome, MODS）的概念與定義，這些概念雖未得到完全的認可，但在建立統一和規范的臨床診斷及研究基線和標準上仍然發揮了很大的作用。經過10年的不斷改進，2001美國及歐洲的重癥醫學會，提出了改進的Sepsis診斷標準。