Sepsis is a life-threatening organ dysfunction caused by infection that lead to dysregulation of the host response. Sepsis and septic shock with a high mortality threaten human health at present, which are important medical and health problems. Early diagnosis and treatment decision-making for sepsis and septic shock still need to be improved. Exosomes are extracellular vesicles with a diameter of 30-150 nm formed by the fusion of multi-vesicle bodies and cell membranes. Exosomes can effectively transport a variety of bioactive substances such as proteins, lipids, RNA, DNA, and participate in the regulation of inflammatory response, immune response, infection and other pathophysiological processes. In recent years, exosomes have become one of the important methods for the diagnosis and treatment of systemic inflammatory diseases. This article will focus on the basic and clinical research of sepsis, and focus on the research progress of exosomes in the diagnosis and targeted therapy of sepsis.
Humans ; Shock, Septic/therapy* ; Exosomes/metabolism* ; Sepsis/therapy* ; Extracellular Vesicles/metabolism* ; RNA/metabolism*

OBJECTIVETo investigate the changes of proton transportation across the inner mitochondrial membrane (IMM) and H(+)-ATPase of hepatocytes in endotoxic shock rats.

METHODSEndotoxin from E. Coil of 5.0 mg/kg or saline of 1 ml/kg was injected into the femoral vein. The rats were sacrificed pre-injection and 1, 3, 5, 8 hours after injection, and plasma and liver tissue samples were collected respectively. The liver tissue samples were used for preparation of mitochondria and submitochondrial particles (SMPs). The proton-translocation of SMPs and H(+)-ATPase, phospholipase A(2) (PLA(2)) activities and malondialdehyde (MDA) content, membrane fluidities of different level of mitochondria membrane and plasma MDA content were assayed.

RESULTS(1) Five hours after E. Coli. O111B4 injection, the maximum fluorescence quenching ACMA after adding ATP, nicotinamide adenin dinucleoacid hydrogen (NADH), and the succinate were significantly decreased (P<0.05). The time of maximum fluorescent quenching and the half time of fluorescent quenching were significantly prolonged (P<0.01), especially when NADH was used as a substrate. (2) The mitochondrial H(+)-ATPase activity was significantly increased at early stage of endotoxic shock (P<0.05), and significantly decreased at late stage of endotoxic shock (P<0.01). (3) The mitochondrial membrane bound PLA(2) activity, plasmal and mitochondrial MDA content were significantly increased and succinate dehydrogenase (SDH) activity of mitochondria decreased markedly in endotoxic shock rats (P<0.05). (4) The mitochondrial membrane fluidity of different lipid regions was decreased, especially in the head of phospholipid.

CONCLUSIONSProton transportation across IMM and mitochondrial H(+)-ATPase activity are significantly decreased in endotoxic shock.

Animals ; Microscopy, Electron ; Mitochondria, Liver ; metabolism ; Proton-Translocating ATPases ; metabolism ; Rats ; Rats, Wistar ; Shock, Septic ; enzymology

The key to the treatment of septic shock is to provide adequate oxygen supply and improve tissue perfusion. Lactate and central venous oxygen saturation (ScvO) are commonly used as the indices of oxygen metabolism, but tissue hypoxia may still exist even when lactate and ScvOare within the normal range. Arteriovenous difference in carbon dioxide partial pressure (COgap) can accurately reflect oxygen delivery when ScvOis in the normal range. This article reviews the advantages and shortages of lactate, lactate clearance rate, ScvO, and COgap in evaluating tissue hypoxia, in order to provide a reference for treatment and severity evaluation of septic shock.
Carbon Dioxide ; blood ; Humans ; Lactic Acid ; metabolism ; Metabolic Clearance Rate ; Oxygen ; blood ; Shock, Septic ; metabolism

AIMTo observe the differences of hemodynamics and nitric oxide synthase(NOS) activity of ventricular cardiac muscle in two septic shock models and explore the possible mechanism.

METHODSTwo rat models of septic shock[lipopolysaccharide(LPS)-induced and cecal ligation and puncture (CLP)-induced septic shock] were used. The hemodynamic parameters and nitric oxide synthase activity of ventricular cardiac muscle were measured.

RESULTSThe hemodynamic parameters in CLP-induced model were increased in the early stage and decreased in the late stage while in LPS-induced model the parameters showed the same change of the CLP late stage. Both LPS model and CLP model (late stage) showed significant increase in NOS activity, but there was no difference between the two models. After treatment of the NOS inhibitor N-nitro-L-arginine methyl ester (L-NAME), the parameters of CLP-late stage and LPS model increased significantly. The NOS activity reached the highest level in the CLP-middle stage. The production of nitrite/nitrate decreased significantly in LPS model and CLP model(late stage) after treatment of L-NAME, but the nitrite/nitrate produced by constitutive NOS in LPS model was higher than CLP model(late stage).

CONCLUSIONThe increase of the NOS activity may be the main reason to lead to the depression of the hemodynamic parameters. Inducible NOS may play the leading role in the LPS model while cNOS and iNOS have the same effect in the CLP model.

Animals ; Hemodynamics ; Lipopolysaccharides ; Male ; Myocytes, Cardiac ; metabolism ; Nitric Oxide Synthase ; metabolism ; Rats ; Rats, Sprague-Dawley ; Shock, Septic ; classification ; metabolism

OBJECTIVETo explore the effect of Tongfu Jinghua Decoction (TJD) on hemodynamics and tissue oxygen metabolism in patients with post-traumatic sepsis shock.

METHODSTotally 60 patients were randomly assigned to the treatment group and the control group, 30 in each group. Patients in the treatment group took TJD or were administered with TJD by nasal feeding in combined with conventional Western medical treatment, while patients in the control group only received conventional Western medical treatment. Changes of each index in hemodynamics and tissue oxygen metabolism were observed before treatment, and at 6, 12, 24, and 48 h after treatment.

RESULTSCompared with before treatment in the same group, hemodynamic changes were significantly improved at each time point in the two groups. All indices of tissue oxygen metabolism at each time point of the two groups were significantly improved, except changes of O2 extraction ratio (ER) after treatment in the control group (P < 0.05, P < 0.01). Compared with the control group in the same period, heart rate (HR), systemic vascular resist- ance (SVR), and cardiac output (CO) were significantly improved with statistical difference (P < 0.05, P < 0.01). Mean arterial pressure (MAP), central venous pressure (CVP), and cardiac index (CI) were significantly improved at 6, 12, and 24 h after treatment with statistical difference (P < 0.05, P < 0.01). Each index of tissue oxygen metabolism in the treatment group were all improved at each time point with statistical difference (P < 0.05, P < 0.01).

CONCLUSIONTJD combined with conventional Western medical treatment could quickly improve hemodynamics and tissue oxygen metabolism disorder in patients with septic shock, and its curative effect was superior to that of conventional Western medical treatment alone.

Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Heart Rate ; Hemodynamics ; drug effects ; Humans ; Oxygen ; metabolism ; Sepsis ; Shock, Septic ; drug therapy ; metabolism

OBJECTIVE: To explore the expression levels and clinical significance of helper T cell 1/helper T cell 2 (Th1/Th2) cytokine and interleukin-6 (IL-6) in patients with acute leukemia (AL) complicated by infection. METHODS: 68 patients with AL complicated by infection admitted to Wuhan Fifth Hospital from May 2017 to January 2020 were enrolled as study group, 50 AL patients without infection were enrolled as AL group, and 30 healthy volunteers checked in physical examination center were enrolled as healthy control group. The levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10), and peripheral blood Th1/Th2 cells subsets were measured and compared among the three groups. The serum IL-6, IL-10, TNF-α and Th1/Th2 were compared between the patients with mild to moderate infection (n=52) and septic shock (n=16). The relationship between IL-6, IL-10, TNF-α, Th1/Th2 and AL infection was analyzed. RESULTS: The levels of IL-6, IL-10 , TNF-α, and the proportion of Th2 of the patients in study group and AL group were significantly higher than those in healthy control group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in healthy control group (P<0.001). The levels of IL-6, IL-10 and TNF-α, and the proportion of Th2 the patients in study group were significantly higher than those in AL group (P<0.001), while the proportion of Th1 and Th1/Th2 were significantly lower than those in AL group (P<0.001). The serum IL-6, IL-10 and TNF-α level of the patients in septic shock group were significantly higher than those in mild-to-moderate infection group (P<0.001), while Th1/Th2 was lower than those in mild-to-moderate infection group (P<0.001). The results of ROC curve analysis showed that the area under the ROC curve (AUC) values of IL-6, IL-10, TNF-α and Th1/Th2 alone for the diagnosis of septic shock were 0.779, 0.761, 0.724 and 0.718, which were lower than that their combination (0.910) (P<0.05). CONCLUSION The levels of serum IL-6, IL-10 and TNF-α are high in patients with AL complicated infection and septic shock, while Th1/Th2 cell subsets is low. The combined detection of serum IL-6, IL-10, TNF-α and Th1/Th2 is a good diagnostic value for predicting the occurrence of severe septic shock.
Cytokines/metabolism* ; Humans ; Interleukin-10 ; Interleukin-6/metabolism* ; Leukemia/metabolism* ; Shock, Septic/metabolism* ; Th1 Cells/metabolism* ; Th2 Cells/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

BACKGROUNDSevere sepsis and septic shock are the leading causes of morbidity and mortality in hospitalized patients. This study aimed to investigate the association of poly (ADP-ribose) polymerase-1 (PARP-1) activity in circulating mononuclear cells with myocardial dysfunction in patients with septic shock.

METHODSA total of 64 patients with septic shock were divided into the survival group (n = 41) and the nonsurvival group (n = 23) according to mortality at 28 days after enrollments. PARP-1 activity in circulating mononuclear cells, brain natriuretic peptide, Acute Physiology and Chronic Health Evaluation II score, the cardiac index (CI), the cardiac function index (CFI), global ejection fraction (GEF), and the left ventricular contractility index (dp/dt max) were measured after admission to the intensive care unit.

RESULTSPARP-1 activity in circulating mononuclear cells of nonsurvival patients with septic shock was significantly higher than that in survival patients. PARP-1 activity in circulating mononuclear cells was strongly, negatively correlated with the CI, the CFI, GEF, and dp/dt max. Multiple Logistic regression analysis showed that PARP-1 activity in circulating mononuclear cells was an independent risk factor of myocardial dysfunction. The optimal cutoff point of PARP-1 activity for predicting 28-day mortality was 942 nmol/L with a sensibility of 78.2% and specificity of 65.1%.

CONCLUSIONPARP-1 activity in circulating mononuclear cells is significantly associated with myocardial dysfunction and may have prognostic value in patients with septic shock.

Aged ; Aged, 80 and over ; Female ; Humans ; Leukocytes, Mononuclear ; enzymology ; Male ; Middle Aged ; Poly(ADP-ribose) Polymerases ; metabolism ; Shock, Septic ; enzymology

OBJECTIVETo identify the risk factors for death in children with septic shock.

METHODSClinical data of 53 children with septic shock admitted to the Yuying Children's Hospital between January 2006 and July 2008 were retrospectively studied. Risk factors for death were assessed using univariate analysis and logistic regression analysis.

RESULTSNineteen cases died out of 53 children with septic shock. Univariate analysis and logistic regression analysis showed that arterial blood pH value<7.0 (OR=89.66), hypotension (OR=84.00), the pediatric critical illness score<70 (OR=60.00), the number of organ dysfunction>or=3 (OR=38.98), incompletion of volume resuscitation within 6 hrs after shock (OR=26.41), and no administration of effective antibiotics within 1 hr after shock (OR=11.43) and of vasoactive drugs (OR=75.68) were risk factors for death in children with septic shock.

CONCLUSIONSA low arterial blood pH value (<7.0), hypotension, a pediatric critical illness score (<70) and the number of organ dysfunction>or=3 are related to a high mortality in children with septic shock. If the volume resuscitation can be completed within 6 hrs after shock, effective antibiotics can be administered within 1 hr after shock, and vasoactive drugs can be used properly, the outcome of children with septic shock may be improved.

Child ; Child, Preschool ; Female ; Humans ; Hydrogen-Ion Concentration ; Infant ; Logistic Models ; Male ; Risk Factors ; Shock, Septic ; metabolism ; mortality

BACKGROUND: Vibrio(V.) vulnificus is a pathogenic, marine, halophilic, gram-negative bacillus which causes fulminant septic shock. Shock can be complicated by occurrence of hypoglycemia, which is caused by an unbalance between glucose production and consumption. Metabolic changes, especially glucose metabolism, in septic shock caused by V. vulnificus are not well clarified yet. OBJECTIVE: Our purpose was to investigate the changes of blood sugar level after intravenous administration of V. vulnificus cytolysin which is known to be a major virulent factor for elucidating pathogenesis of septic shock. METHODS: After administration of the lethal dose(8 hemolytic units)of V. vulnificus cytolysin through mouse tail vein in non-fasting and fasting group, we obtained blood samples from heart according to time courses of every thirty minutes. We measured whole blood glucose level using commercially available blood glucose meter. RESULTS: The level of blood glucose increased until 90 minutes, began to decrease at 120 minutes, and fell to baseline at 360 minutes in non-fasting mouse group. In fasting group, although elevation of blood glucose level was not observed in early stage of toxemia, hypoglycemia was nearly concordant with non-fasting group in late stage of toxemia. CONCLUSION: Hypoglycemia should be checked in patients with V. vulnificus sepsis. Failure to recognize and treat the hypoglycemia may contribute to the prognosis of these patients.
Administration, Intravenous ; Animals ; Bacillus ; Blood Glucose* ; Fasting ; Glucose ; Heart ; Humans ; Hypoglycemia ; Metabolism ; Mice* ; Perforin* ; Prognosis ; Sepsis ; Shock ; Shock, Septic ; Toxemia ; Veins ; Vibrio vulnificus* ; Vibrio*

AIMTo study the protective role of endogenous carbon monoxide to lung and kidney tissues during septic shock and its mechanism.

METHODSA rat model of CLP was built by using the method of CLP. The malondialdehyde (MDA) content and the activity of superoxide dematase (SOD) in blood, lung and kidney were detected by immunohistochemical technique and light microscope.

RESULTSPathological changes of lung and kidney in CLP + Hemin group were lighter than CLP group, inflammatory reaction and lipid peroxidation were also lighter.

CONCLUSIONEndogenous CO can protect lung and kidney from the oxidative injury. It can suppress in flammation and the oxidative injury caused by activated inflammatory cells, it is probably an important mechanism of its protective effects.

Animals ; Carbon Monoxide ; physiology ; Hemin ; pharmacology ; Kidney ; metabolism ; pathology ; Lipid Peroxidation ; Lung ; metabolism ; pathology ; Male ; Malondialdehyde ; analysis ; Rats ; Rats, Sprague-Dawley ; Shock, Septic ; metabolism ; pathology ; Superoxide Dismutase ; metabolism