[Hydrogen Sulfide Ameliorates Myocardial Injury Caused by Sepsis Through Suppressing ROS-Mediated Endoplasmic Reticulum Stress].

Objective: To investigate the effect of hydrogen sulfide (H 2S) on reactive oxygen species (ROS)-mediated endoplasmic reticulum stress in myocardial injury caused by sepsis. Methods: A sepsis model was induced in Sprague-Dawley (SD) rats by cecal ligation and puncture (CLP). The rats were randomly divided into sham operation (sham) group, sepsis (CLP) group, and sepsis+sodium hydrosulfide (NaHS) (CLP+NaHS) group. The left ventricular function of the rats was observed with echocardiography and their plasma H 2S levels were measured. Lactate dehydrogenase (LDH), malondialdehyde (MDA), glutathione (GSH) levels were measured and HE staining was done to evaluate the level of myocardial oxidative stress in rats. HE staining was done to observe the morphological changes of rat myocardium, and transmission electron microscope was used to observe the ultrastructure of myocardial mitochondria. Western blot was done to examine changes in the expression of two endogenous hydrogen sulfide synthases, cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfur transferase (3-MST), and changes in the expression of endoplasmic reticulum stress (ERS) marker proteins, including phosphorylated (p) protein kinase R-like endoplasmic reticulum kinase (p-PERK), p-eukaryotic translation initiation factor 2α (p-eIF2α), p-inositol requires enzyme 1α (IRE1α), recombinant activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP). TUNEL staining was performed to observe the changes of cardiomyocyte apoptosis in rats. Results: Left ventricular ejection fraction (LVEF), left ventricular shortening fraction (LVFS) and plasma H 2S decreased in septic rats ( P<0.05). Plasma H 2S exhibited linear correlation with LVEF and LVFS ( r 2=0.62 and r 2=0.64, all P<0.05). The ROS levels were significantly elevated in rats of the CLP group. In addition, these rats showed increased level of LDH ( P<0.05), increased expression of MDA ( P<0.05), and decreased expression of GSH ( P<0.05). Inflammatory cell infiltration and cardiomyocyte edema were observed in HE staining. Transmission electron microscopic observation revealed significant mitochondrial damage, observable mitochondrial edema, and cristae structure dissolution. The Western blot results showed that the expression levels of CSE and 3-MST decreased ( P<0.05), while the ERS marker proteins, including p-PERK, p-eIF2, IRE1α, ATF4, and CHOP, were expressed at increased levels ( P<0.05). TUNEL staining showed significant increase of apoptosis in cardiomyocytes ( P<0.05). After NaHS treatment, LVEF and LVFS increased ( P<0.05) and plasma H 2S increased in septic rats ( P<0.05). Myocardial oxidative stress levels decreased. HE staining and transmission electron microscopy showed improved myocardial morphology. Mitochondrial damage was reduced and CSE and 3-MST levels were significantly increased ( P<0.05). The expression of p-PERK, p-eIF2α, p-IRE1α, and CHOP proteins decreased ( P<0.05). A decrease in cardiomyocyte apoptosis levels was observed by TUNEL staining ( P<0.05). Conclusion: H 2S reduces septic cardiomyocyte apoptosis by inhibiting ROS-mediated ERS, thereby improving myocardial dysfunction in sepsis.

Elevated serum IL-37 concentrations in patients with sepsis.

To investigate the changes and significance of IL-37 in patients with sepsis.A total of 50 patients with sepsis between September 2016 and October 2017 at the intensive care unit (ICU) of the First Affiliated Hospital of Shihezi University School of Medicine were selected as the sepsis group, 30 age and sex-matched healthy controls were selected as the control group. The levels of IL-37 in serum were measured by enzyme-linked immunosorbent assay (ELISA) on day 1 and day 7 of the sepsis patients.The levels of serum IL-37 in the sepsis group on day 1 [(39.13 ±â€Š34.35)pg/mL] were significantly higher than that in the control group [(23.75 ±â€Š2.52)pg/mL] with significant difference (P <.05). The levels of IL-37 in the sepsis group after treatment [(30.57 ±â€Š11.01)pg/mL] on day 7 were obviously lower than that before treatment without statisticaly difference (P >.05). A correlation analysis showed that the levels of serum IL-37 and IL-1ß were positively correlated.The level of IL-37 observed in sepsis was found to correlate with the severity of the inflammatory reaction. IL-37 could be an important cytokine in the control of sepsis by suppressing the production of pro-inflammatory cytokines.

Effects of ABCDE Bundle on Hemodynamics in Patients on Mechanical Ventilation.

BACKGROUND Mechanical ventilation is an important part of advanced life support in the intensive care unit (ICU). This study aimed to investigate the effects of ABCDE bundle on hemodynamics in patients on mechanical ventilation (MV). MATERIAL AND METHODS This study used a cross-sectional overall controlled approach in which 143 patients on mechanical ventilation were divided into 2 groups. In the pre-ABCDE bundle group (n=70), conventional sedation and analgesia strategy were used. In the post-ABCDE bundle group (n=73), ABCDE bundle was used. Changes in hemodynamics parameters and related prognostic indicators were monitored at various time points before (T0) and at 1 d (T1), 3 d (T3), 5 d (T5), and 7 d (T7) after implementation of the 2 strategies. RESULTS Mean arterial blood pressure (MAP), central venous pressure (CVP), heart rate (HR), and oxygenation index (PaO2/FiO2) in the bundle group were improved more significantly than those in the pre-ABCDE bundle group (P<0.05). For comparison between various monitoring time points in the same group, compared with before intervention, MAP, CVP, HR, and PaO2/FiO2 changed significantly in the bundle group at 3 d, 5 d, and 7 d after intervention, and the difference was statistically significant (P<0.05). Compared with before intervention, differences in all hemodynamics indicators were statistically significant in the pre-ABCDE bundle group at 5 d and 7 d after intervention (P<0.05). Compared with the pre-ABCDE bundle group, differences in prognostic indicators in the post-ABCDE bundle were statistically significant (P<0.05). CONCLUSIONS ABCDE bundle is safe and effective for patients on mechanical ventilation, and can improve hemodynamics and enhance oxygenation index. ABCDE bundle might be helpful in reducing 28-d mortality and improving prognosis.

Effects of peritoneal macrophage autophagy on the immune function of sepsis mice.

OBJECTIVE: To investigate the effect of peritoneal macrophage autophagy on immune function in sepsis mice. METHODS: Seventy-two male BALB/C mice were intraperitoneally injected with LPS to induce sepsis. The mice were randomly divided into six groups: LPS+2 h, LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h. LPS with a dose of 10 mg/kg was intraperitoneally injected into the abdominal cavity of the sepsis mice, and the control group was injected with the same dose of saline. ELISA was used to detect the concentrations of inflammatory factors IL-2, IL-10 and TNF-α in the peripheral blood, and the CD4+T/CD8+T ratio in the peripheral blood was detected by flow cytometry. The expression levels of LC3II and Beclin-1/beta-action in the mouse macrophages were measured using Western blot to determine the level of autophagy. RESULTS: The expression levels of LC3II and Beclin-1 were significantly higher in the peritoneal macrophages of the mice from the LPS+2 h group than in those of the mice from the normal group (P<0.05). Meanwhile, these levels continuously declined in the LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups (P<0.05). The peripheral blood CD4+T/CD8+T cell ratio was significantly higher in the LPS+2 h and LPS+6 h groups than in the normal group (P<0.05). The ratio peaked at 6 h and then continuously declined (P<0.05). Furthermore, the concentrations of IL-2 and Tnf-α were significantly higher in the peripheral blood serum of the LPS+2 h, LPS+6 h and LPS+12 h groups than in those of the normal group (P<0.05). The peak was observed at 12 h followed by a continuous decline in the LPS+24 h and 3 LPS+6 h groups (P<0.05). The peripheral serum IL-10 concentration was significantly higher in the LPS+2 h, LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups than in the normal group (P<0.05). In the LPS+6 h, LPS+12 h, LPS+24 h and LPS+36 h groups, the peritoneal macrophages LC3II, Beclin-1 and peripheral serum CD+4T/CD+8T ratio correlation index R2=0.716 (P=0.043), R2=0.954 (P=0.023). CONCLUSION: Autophagy in peritoneal macrophages plays an important role in the immune function of sepsis mice. In addition, the autophagy of peritoneal macrophages and the immune function of sepsis mice are strongly correlated. Furthermore, macrophage autophagy plays an important role in the immune function changes in sepsis mice, and the underlying mechanism may be involved in inflammation and macrophage antigen presentation by regulating the secretion of inflammatory cytokines and lymphocyte apoptosis antagonism.

Endoplasmic reticulum stress-mediated apoptosis signal pathway is involved in sepsis-induced liver injury.

Endoplasmic reticulum (ER) stress has been increasingly recognized to have an important role in various liver diseases. Sepsis-induced multi-organ failure remains to have a high mortality rate, and the liver plays a central pathophysiological role. This study aims to explore whether ER stress is involved in liver injury in septic rats. Sepsis was induced via cecal ligation and puncture (CLP). Rats were randomly divided into five groups as follows: sham, CLP 2 h, CLP 6 h, CLP 12 h, and CLP 24 h. They were monitored to record body weight (BW) and liver weight changes for every time point after surgery. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected via colorimetric activity assays. In addition, the morphological changes of the liver tissue were evaluated by staining the sections with hematoxylin and eosin and observing under light microscopy. The levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and cleaved caspase-12 were detected via Western blot analysis. Apoptosis was detected via terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method. The results showed that septic rat serums ALT and AST were increased, with the increase being more obvious in the CLP 24 h group. In addition, septic rats appeared to have histopathological abnormalities in the liver. The liver weight and index increased after CLP. No differences were noted in the BW between septic groups. The level of GRP78, CHOP, and cleaved caspase-12 were upregulated after CLP. However, CHOP and caspase-12 were induced later than GRP78. The density of TUNEL-positive apoptotic hepatocytes was significantly increased after 12 h and 24 h CLP. It indicates that the unfolded protein response occurred in the early stage of sepsis-induced liver damage. The ER stress-mediated apoptosis signal pathway is among the mechanisms of septic liver injury and may be a target in clinical prevention and therapy of sepsis-induced liver injury.

Lung-protective Ventilation in Patients with Brain Injury: A Multicenter Cross-sectional Study and Questionnaire Survey in China.

BACKGROUND: Over the years, the mechanical ventilation (MV) strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation (LPV), among brain-injured patients in China. METHODS: This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units (ICUs) across China. Mechanically ventilated patients (18 years and older) with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. RESULTS: A total of 104 patients were enrolled in the present study, 87 (83.7%) of whom were identified with severe brain injury based on a Glasgow Coma Scale ≤8 points. Synchronized intermittent mandatory ventilation (SIMV) was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg (interquartile range [IQR], 7.0-8.9 ml/kg) of the predicted body weight; 50 (48.1%) patients received LPV. The median positive end-expiratory pressure (PEEP) was set to 5 cmH2O (IQR, 5-6 cmH2O). No PEEP values were higher than 10 cmH2O. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. CONCLUSIONS: Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV. TRIAL REGISTRATION: ClinicalTrials.org NCT02517073 https://clinicaltrials.gov/ct2/show/NCT02517073.