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.
ObjectiveTo explore the expression of programmed death-1 ligand (PD-L1) on peripheral blood monocytes in septic mice, and analyze the difference between the mild and severe septic mice.
MethodsFirstly, thirty C57 mice were randomly divided into a sham group, a mild sepsis group and a severe sepsis group. Sepsis model was induced by cecal ligation and puncture (CLP). The severity of sepsis was distinguished by length of cecum ligated. Survival rate was recorded after CLP and compared between three groups. Then sixty C57 mice were randomly divided into a sham group, a mild sepsis group and a severe sepsis group. Peripheral blood was obtained at 6 h and 24 h to detect PD-L1 expression on monocytes in peripheral blood by flow cytometry. Tumor necrosis factor-α(TNF-α) and interleukin-10 (IL-10) in serum were detected by enzyme-linked immunosorbent assay.
ResultsThe survival rate in the mild sepsis group was higher than that in the severe sepsis group. TNF-αand IL-10 levels in the mild and severe sepsis groups were higher than those in the sham group at 6 h and 24 h (P < 0.01). PD-L1 expression on monocytes in the mild and severe sepsis groups was higher than that in the sham group at 6 h and 24 h (P < 0.05). The expression of PD-L1 in the severe sepsis group was higher than that in the mild sepsis group, however, there was no statistical difference between two groups (P > 0.05).
ConclusionsPD-L1 expression on monocytes is increased in septic mice. PD-L1 expression tended to increase in severe sepsis compared with the mild sepsis.
ObjectiveTo explore the effect of continuous renal replacement therapy (CRRT) to treat sepsis associated acute kidney injury (AKI) in patients aged over 80.MethodsForty-one patients diagnosed with sepsis and AKI were enrolled in geriatric RICU department of Huadong Hospital from January 2013 to July 2018, 38 patients were male and 3 were female. All patients were treated with anti-infection and fluid resuscitation therapy. After comprehensive judgment of the indication of renal replacement, they were divided into two groups by the choices of using CRRT. There were 20 patients in CRRT group and 21 in control group. Clinical data such as age, body mass index, previous diseases, 28-day mortality rate, blood cells, APACHEⅡ as well as SOFA scores were compared between two groups. Blood renal function and inflammatory markers at the first day were also compared to those after 3-day treatment of initial time.ResultsNo statistical difference was observed in sex ratio, age, body mass index and previous diseases between two groups (all P>0.05). There was also no difference in APACHEⅡ score, SOFA score, blood cells, hemoglobin and survival time. The 28-day mortality rate in CRRT group was lower than that in control group (P<0.05). The levels of serum UA and C reactive protein (CRP) in CRRT group decreased after 3-day treatment compared with those at the onset, and the differences were statistically significant (all P<0.05). The level of serum blood urea nitrogen (BUN), creatinine (Cr), uric acid (UA) and cystain C in control group increased after 3 days compared with those at the onset, and the difference were statistically significant (all P<0.05). There was no significant difference in serum BUN, Cr, UA, cystain C, CRP and procalcitonin (PCT) between two groups at the onset (all P>0.05). After 3 days of CRRT, the levels of serum PCT, BUN, Cr and UA in CRRT group were lower than those in the control group (all P<0.05).ConclusionCRRT can improve hyperuricemia, control deterioration of renal function, reduce early systemic inflammatory response and 28-day mortality rate in aged patients with sepsis and AKI.
ObjectiveTo systematically review the efficacy and safety of acupuncture as adjuvant treatment on sepsis related gastrointestinal dysfunction. MethodsThe PubMed, Web of Science, Cochrane Library, WanFang Data, CNKI, VIP and SinoMed databases were electronically searched to collect randomized controlled trials (RCTs) related to the objectives from inception to July, 2024. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.3 software. ResultsA total of 20 RCTs involving 1 384 patients were included. The results of meta-analysis showed that the bowel sound frequency per minute on the 7th day (MD=0.82, 95%CI 0.57 to 1.07, P<0.01), the effective rate of improvement in sepsis-related gastrointestinal dysfunction on the 7th day (RR=1.38, 95%CI 1.25 to 1.54, P<0.01), intra-abdominal pressure at 7th day (MD=?1.52, 95%CI ?2.21 to ?0.83, P<0.01), gastric residential volume on the 7th day (MD=?14.94, 95%CI ?24.72 to ?5.16, P<0.01), APACHE-Ⅱ score at 7th day (MD=?2.40, 95%CI ?3.56 to ?1.24, P<0.01), concentrations of procalcitonin on the 7th day (MD=?1.82, 95%CI ?2.68 to ?0.97, P<0.01) in the acupuncture group were all superior to the conventional treatment group. However, there was no significant difference between the two groups concerning the 28-day mortality. ConclusionCurrent evidence shows that acupuncture adjuvant treatment can promote the recovery of bowel sounds, reduce intra-abdominal pressure, and decrease gastric residual volume in patients with sepsis and gastrointestinal dysfunction, with good safety. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
ObjectiveTo evaluate the clinical efficacy of fish oil containing lipid emulsion (FO) in sepsis.
MethodsRandomized controlled trials about fish oil containing lipid emulsion in sepsis,which were published from 1980,were searched from the following electronic databases:PubMed,Embase,Foreign Medical Journal Service,Cochrane Library,CNKI,Wanfang Database,and VIP Database. The articles screening,quality assessment and data extraction were conducted by two reviewers independently. The methodological quality of trials was assessed by Jadad's scale. All data was analyzed by Review Manager 5.2 software.
ResultsFifteen studies involving 794 participants met the inclusion criteria. The meta-analysis results were as follows:compared with the control group,①FO could shorten the length of ICU stay[WMD=-5.59,95%CI(-7.65,-3.53)] and the length of hospital stay[WMD=-10.48,95%CI(-14.67,-6.29)],and also decrease the 28-day mortality[RR=0.69,95%CI(0.52,0.93)]. ②FO could reduce the concentration of TNF-α[WMD=31.78,95%CI(5.63,57.92)] and improve oxygenation index[WMD=41.95,95%CI(30.80,53.11)] in septic patients. ③There was no statistical significance in the decrease of C-reactive protein (CRP) between two groups(P>0.05).
ConclusionThe administration of FO in septic patients can significantly shorten the length of ICU stay and hospital stay,decrease the 28-day mortality,reduce the concentration of TNF-α and improve oxygenation index. However,it shows no significant difference in the decrease of CRP compared with the administration of traditional lipid emulsion. All of the above results show that the septic patients can benefit from the administration of fish oil containing lipid emulsion.
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.
Objective To investigate the changes in osteoprotegerin (OPG) / receptor activator of nuclear factor-κB ligand (RANKL) ratio in sepsis-associated acute lung injury (SA-ALI) and the role of regulation of this ratio on the inflammatory response in SA-ALI. Methods Eighteen C57BL/6 male mice were randomly divided into sham operation group, cecal ligation and perforation (CLP) group and RANKL group, with 6 mice in each group. Before the experiment, the RANKL group was intraperitoneally injected with 5 μg (0.2 mL) of recombinant RANKL antibody, whereas both the sham operation group and the CLP group were intraperitoneally injected with a volume-matched normal saline. One hour later, the sham operation group underwent only abdominal exploration and repositioning, while the other groups underwent the CLP surgery to induce the SA-ALI model. After 24 h of modelling, all mice were sacrificed and samples were collected. Pathological evaluation of lung tissues was performed by haematoxylin-eosin staining; enzyme-linked immunosorbent assay was used to detect serum concentrations of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β; while the mRNA and protein expression of OPG and RANKL, along with their ratio values, were detected by real-time polymerase chain reaction for quantitative analysis and protein immunoblotting. Results The SA-ALI mouse model was successfully established. Compared with the sham operation group, mice in the CLP group showed disturbed alveolar structure, obvious alveolar and interstitial haemorrhage and inflammatory cell infiltration, elevated serum levels of IL-6, TNF-α and IL-1β (P<0.05), significantly increased mRNA and protein expression of OPG and elevated OPG/RANKL ratio in lung tissue (P<0.05), whereas RANKL mRNA and protein expression was significantly decreased (P<0.05). Compared with the CLP group, the pathological damage of lung tissue in the RANKL group was reduced, the infiltration of alveolar and interstitial inflammatory cells was significantly improved, and the alveolar structure and morphology were more regular, with lower serum levels of IL-6, TNF-α and IL-1β (P<0.05), significantly lower mRNA and protein expression of OPG and OPG/RANKL ratio in lung tissue (P<0.05), and significantly higher mRNA and protein expression of RANKL in lung tissue (P<0.05). Conclusion The alteration of OPG/RANKL ratio may be related to the pathophysiological process of SA-ALI, and the decrease in its level may reflect the attenuation of the inflammatory response in SA-ALI.
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 explore the value of inferior vena cava inspiratory collapsibility (ΔIVC) in guiding septic shock resuscitation with early goal-directed therapy (EGDT).MethodsA single center, randomized controlled trial was conducted at an 812-bed hospital in Mianyang, Sichuan. Adult patients with early septic shock in the intensive care unit were assessed and treated at defined intervals over 6 h using an ΔIVC-guided resuscitation protocol or an EGDT protocol. Feasibility outcomes were fluid balance and norepinephrine administration. The primary clinical outcomes were in-hospital mortality rate, 90-day survival rate. Secondary outcomes included incidence of acute kidney injury and consumption of health resources.ResultsSixty-eight patients with septic shock were enrolled in this study. Baseline characteristics were similar between the two groups. The ΔIVC-guided septic shock resuscitation group was lower than the EGDT group in the ICU 24 h fluid replacement (L): 3.8 (4.0, 5.3) vs. 4.7 (4.0, 6.6), 72 h liquid positive balance (L): 0.2 (–0.65, 1.2) vs. 2.5 (0.0, 4.1), intensive care unit length of stay (d): 7.5 (5.0, 14.0) vs. 15.0 (7.0, 21.5), mechanical ventilation cumulative time (d): 3.0 (0.0, 7.0) vs. 7.5 (2.2, 12.0), ICU costs (ten thousand yuan): 3.4 (2.1, 5.9) vs. 8.6 (4.2, 16.5), bedside blood purification treatment costs (ten thousand yuan): 2.3 (1.1, 3.3) vs. 6.8 (2.1, 10.0) (P<0.05). No difference was observed in the incidence of acute kidney injury (P > 0.05), in-hospital mortality and 90-day survival between the two groups (log-rank χ2=0.35, P>0.05).ConclusionsAmong patients with septic shock, a ΔIVC-guided septic shock resuscitation, compared with EGDT, did not reduce in-hospital mortality. It might prevent the risk of over resuscitation, shorten the duration of mechanical ventilation, and lead to a better utilization of intensive care unit resources.
Objective To investigate the expression and clinical significance of soluble triggering receptor expression on myeloid cells-1（sTREM-1） in sepsis patients.Methods Serum concentrations of sTREM-1，procalcitonin（PCT），tumor necrosis factor alpha（TNF-α） and interleukin-10（IL-10） were measured by enzyme-linked immunosorbent assay，while high sensitivity C-reactive protein （hsCRP） level was detected by immunoturbidimetry in 68 patients with sepsis，40 patients with no-infective SIRS，and 20 normal individuals. The diagnostic and prognostic value of sTREM-1 and its comparison with PCT and hsCRP were analyzed. The sequential organ failure assessment （SOFA） score system was used to evaluate the severity of sepsis. The relationship between sTREM-1, PCT , hsCRP , SOFA score，TNF-α ,and IL-10 of the sepsis patients was analyzed，respectively. Results The differences in the serum concentrations of sTREM-1，PCT，hsCRP，IL-10 and IL-10/TNF-α ratio had statistical significance among three groups（Plt;0.05）. The differences in the serum concentration of TNF-α had no statistical significance among three groups （Pgt;0.05）. However，the serum levels of sTREM-1，PCT and hsCRP in the sepsis group were significantly higher than those in the SIRS group （Plt;0.05）. The receiver operating characteristic curve （ROC） analysis showed the area under the curve （AUC） for sTREM-1，PCT and hsCRP were 0.772 （95%CI 0.674-0.871），0.718 （95%CI 0.601-0.835） and 0.664 （95%CI 0.532-0.797），respectively. The serum levels of sTREM-1 and PCT in the non-survivors were significantly higher than the survivors in the sepsis group （Plt;0.01），but the differences in the serum concentration of hsCRP had no statistical significance between the non-survivors and the survivors in the sepsis group （Pgt;0.05）. There were significantly positive correlations between sTREM-1 and SOFA score，IL-10 or IL-10/TNF-α ratio（r value of 0.453，0.301，0.417，Plt;0.05），but no correlation between sTREM-1 and TNF-α（Pgt;0.05）. There was significantly positive correlation between PCT and SOFA score （r=0.436，Plt;0.05），while no relationship between hsCRP and SOFA score（Pgt;0.05）. Conclusions The serum level of sTREM-1 not only be valuable in the diagnosis of sepsis，but also may be used as a prognostic marker in sepsis，as it can reflect the severity of sepsis in certain degree. Furthermore，sTREM-1 or PCT may be superior to hsCRP in diagnosis，prognostic judgment and severity assessment of sepsis.
