PLD2 deficiency alleviates endothelial glycocalyx degradation in LPS-induced ARDS/ALI.

- Acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) is a life-threatening condition marked by severe lung inflammation and increased lung endothelial barrier permeability. Endothelial glycocalyx deterioration is the primary factor of vascular permeability changes in ARDS/ALI. Although previous studies have shown that phospholipase D2 (PLD2) is closely related to the onset and progression of ARDS/ALI, its role and mechanism in the damage of endothelial cell glycocalyx remains unclear. We used LPS-induced ARDS/ALI mice (in vivo) and LPS-stimulated injury models of EA.hy926 endothelial cells (in vitro). We employed C57BL/6 mice, including wild-type and PLD2 knockout (PLD2-/-) mice, to establish the ARDS/ALI model. We applied immunofluorescence and ELISA to examine changes in syndecan-1 (SDC-1), matrix metalloproteinase-9 (MMP9), inflammatory cytokines (TNF-α, IL-6, and IL-1ß) levels and the effect of external factors, such as phosphatidic acid (PA), 1-butanol (a PLD inhibitor), on SDC-1 and MMP9 expression levels. We found that PLD2 deficiency inhibits SDC-1 degradation and MMP9 expression in LPS-induced ARDS/ALI. Externally added PA decreases SDC-1 levels and increases MMP9 in endothelial cells, hence underlining PA's role in SDC-1 degradation. Additionally, PLD2 deficiency decreases the production of inflammatory cytokines (TNF-α, IL-6, and IL-1ß) in LPS-induced ARDS/ALI. In summary, these findings suggest that PLD2 deficiency plays a role in inhibiting the inflammatory process and protecting against endothelial glycocalyx injury in LPS-induced ARDS/ALI.

NETs induce ferroptosis of endothelial cells in LPS-ALI through SDC-1/HS and downstream pathways.

BACKGROUND: Extracellular neutrophil extracellular traps (NETs) play an important role in acute lung injury (ALI), but their mechanisms are still unclear. The aim of this study is to explore the effects of NETs on endothelial glycocalyx/HGF/cMET pathway and ferroptosis in ALI and elucidate their potential mechanisms. METHODS: Plasma was collected from healthy and sepsis patients to test for differences in neutrophil elastase (NE) expression of NETs components. In addition, LPS-ALI mice and endothelial cell injury models were established, and NETs were disrupted by siPAD4 (a driver gene for NETs) and sivelestat (an inhibitor of the NETs component) in the mice and by sivelestat in the endothelial cell injury models, and the effects of NETs on the SDC-1/HS/HGF/cMET pathway were studied. To verify the relationship between NETs and ferroptosis, Fer1, a ferroptosis inhibitor, was added as a positive control to observe the effect of NETs on ferroptosis indicators. RESULTS: The expression level of NE was significantly higher in the plasma of sepsis patients. In ALI mice, intervention in the generation of NETs reduced pulmonary vascular permeability, protected the integrity of SDC-1/HS and promoted the downstream HGF/cMET pathway. In addition, sivelestat also improved the survival rate of mice, decreased the serious degree of ferroptosis. In the endothelial cells, the results were consistent with those of the ALI mice. CONCLUSION: The study indicates that inhibiting the production of NETs can protect the normal conduction of the SDC-1/HS/HGF/cMET signalling pathway and reduce the severity of ferroptosis.

[Effect of proprotein convertase subtilisin/kexin type 9 on platelet activation associated with sepsis].

OBJECTIVE: To investigate the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) on platelet activation in sepsis. METHODS: (1) Clinical trial: a prospective study was conducted. Patients with sepsis and septic shock aged ≥ 18 years old who met the diagnostic criteria of Sepsis-3 admitted to the department of intensive care medicine of the Affiliated Hospital of Binzhou Medical College from January to October in 2021 were selected as subjects. Healthy subjects in the same period were taken as healthy control group. Platelet count (PLT) in the first routine blood test after admission was recorded. Venous blood was taken 1 day after diagnosis, and serum PCSK9 level was determined by enzyme-linked immunosorbent assay (ELISA). The differences of PCSK9 level and PLT between the two groups were compared, and subgroup analysis was conducted based on PLT for patients with sepsis. The correlation between PCSK9 level and PLT in septic patients was analyzed by Pearson correlation method. (2) Animal experiment: 80 male C57BL/6 mice were randomly divided into control group, sepsis model group [lipopolysaccharide (LPS) group], PCSK9 inhibitor pretreatment group (PCSK9 inhibitor+LPS group) and PCSK9 inhibitor control group (PCSK9 inhibitor group), with 20 mice in each group. The mouse model of sepsis was reproduced by intraperitoneal injection of LPS 12 mg/kg, and the control group and PCSK9 inhibitor group were intraperitoneally injected with the same amount of sterile normal saline. PCSK9 inhibitor+LPS group and PCSK9 inhibitor group were pretreated with PCSK9 inhibitor 5 mg/kg intraperitoneal injection for 7 days before injection of LPS or normal saline, respectively, and the control group and LPS group were injected with an equal amount of sterile normal saline. The lung tissues were taken for pathological and immunohistochemical observation 24 hours after modeling. Blood was taken from the heart for determining PLT. Platelet activation was detected by flow cytometry. The expression level of platelet-activation marker CD40L was detected by Western blotting. RESULTS: (1) Clinical trial: there were 57 cases in the sepsis group and 27 cases in the healthy control group. Serum PCSK9 level in the sepsis group was significantly higher than that in the healthy control group (µg/L: 232.25±72.21 vs. 191.72±54.92, P < 0.05), and PLT was significantly lower than that in the healthy control group [×109/L: 146.00 (75.50, 204.50) vs. 224.00 (194.00, 247.00), P < 0.01]. Subgroup analysis showed that the serum PCSK9 level in the thrombocytopenia patients (n = 20) was significantly higher than that in the non-thrombocytopenia patients (n = 37; µg/L: 264.04±60.40 vs. 215.06±72.95, P < 0.01). Correlation analysis showed a significant negative correlation between serum PCSK9 levels and PLT in septic patients (r = -0.340, P = 0.010). (2) Animal experiment: there were no significant pathological changes in lung tissue in the control group and PCSK9 inhibitor group under light microscope, and no significant differences in PLT, platelet activation and plasma CD40L protein expression was found between the two groups. In the LPS group, a large number of inflammatory cells were infiltrated in the pulmonary interstitium, the alveolar structure was damaged obviously, the alveolar septum was widened, the alveolar cavity was extensively bleeding, the capillary dilatation with bleeding and platelet aggregation were found, the PLT was significantly decreased, the platelet activation and the expression level of CD40L protein in plasma were significantly increased. The infiltration of inflammatory cells in lung tissue of mice in the PCSK9 inhibitor+LPS group was reduced to a certain extent, the thickening of alveolar septa was reduced, the platelet aggregation in lung tissue was decreased as compared with the LPS group, the PLT was significantly increased (×109/L: 515.83±46.60 vs. 324.83±46.31, P < 0.05), the platelet activation and the expression level of CD40L protein in plasma were significantly decreased [positive expression rate of platelet activation dependent granule surface facial mask protein CD62P: (12.15±1.39)% vs. (18.33±2.74)%, CD40L protein (CD40L/ß-actin): 0.77±0.08 vs. 1.18±0.10, both P < 0.05]. CONCLUSIONS: PCSK9 level has a certain effect on promoting platelet activation in sepsis, and inhibition of PCSK9 level may have potential research value in improving adverse outcomes caused by sepsis thrombocytopenia.

Genetic differentiation and species diversification of the Adoxophyes orana complex (Lepidoptera: Tortricidae) in East Asia.

The Adoxophyes tea tortrix (Lepidoptera: Tortricidae) is a group of leaf rollers that cause enormous economic losses on tea and apple crops. In East Asia, taxonomic ambiguity of the Adoxophyes orana complex (AOC), which consists of A. orana, A. dubia, A. honmai, and A. paraorana, has persisted for decades because of vague diagnostic characters. In this study, differences in the AOC were examined to improve species identification, determine genetic variations, and develop control strategies. Analyses revealed that A. orana comprised 2 lineages, a widely distributed Palearctic lineage and an East Asian lineage that was nested with other Asian species. Genetic divergence of >3% is proposed to confirm the AOC species that would benefit subsequent taxonomic revision. The monophyletic Taiwanese A. sp. with 2.8-4% from other AOC species appeared to suggest it as an independent taxon, and low interspecific divergence between A. honmai and A. dubia of 0.3% indicated possibility of recent divergence or intraspecific variations. Our result further suggested that the Z9-14:Ac ratio of semiochemicals could be a reference for the reblending of pheromone attractants in Taiwanese tea plantations. Moreover, the AOC species appeared to have a tendency of specific geographic distributions, with A. dubia and A. honmai in Japan and China, A. paraorana in Korea, and A. sp. in Taiwan. Maintaining the unique genetic composition of Adoxophyes species in each geographic region and preventing the possible invasions into those AOC-free countries through the transportation of host plants are essential in managing the AOC in East Asia.

[Effect of continuous blood purification on immunity and endothelial cell function in patients with sepsis].

OBJECTIVE: To explore the effect of continuous blood purification (CBP) on the immunity and endothelial cell function of patients with sepsis. METHODS: A prospective study was conducted. The patients aged ≥ 18 years old and meeting the diagnostic criteria of sepsis admitted to the department of critical care medicine of Binzhou Medical University Hospital from March 2019 to October 2020 were selected as the research subjects, and the patients were divided into standard treatment group and CBP treatment group according to random number table method. Both groups were given standard treatment including initial fluid resuscitation, infection source control and antibiotics according to the 2016 international guidelines for the management of sepsis and septic shock. CBP treatment group was additionally given continuous veno-venous hemofiltration (CVVH) at a dose of 25-30 mL×kg-1×h-1 and blood flow rate of 150-200 mL/min for more than 20 hours a day for 3 days. The clinical data of patients including blood lactic acid (Lac), procalcitonin (PCT), lymphocyte count (LYM), acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score were recorded before treatment and 1 day and 3 days after treatment. At the same time, the venous blood was collected, and the immune function related indexes [interleukins (IL-4, IL-7), programmed death receptor-1 (PD-1), programmed death ligand-1 (PD-L1), interferon-γ (IFN-γ)] and endothelial cell injury related markers [soluble thrombomodulin (sTM), angiopoietin-2 (Ang-2), von Willebrand factor (vWF), heparan sulfate (HS), syndecan-1 (SDC-1)] levels in serum were determined by enzyme-linked immunosorbent assay (ELISA). The length of intensive care unit (ICU) stay of patients in the two groups was recorded, and the outcomes of patients in the two groups were followed up for 28 days. RESULTS: Finally, 20 patients were enrolled in the standard treatment group, and 19 patients were enrolled in the CBP treatment group. There were no significant differences in gender, age and infection site between the two groups. The length of ICU stay in the standard treatment group was (10±5) days, and 5 patients died and 15 patients survived after 28 days. The length of ICU stay in the CBP treatment group was (9±4) days, and 8 patients died and 11 patients survived after 28 days. There were no significant differences in the length of ICU stay and number of patients who died within 28 days between the two groups (both P > 0.05). There were no significant differences in the Lac, PCT, LYM, APACHE II score, SOFA score and immune function and endothelial cell injury related indexes before treatment and 1 day after treatment between the two groups. After 3 days of treatment, the Lac, PCT, APACHE II score and SOFA score of the CBP treatment group were significantly lower than those before treatment, and pro-inflammatory and anti-inflammatory cytokines such as IFN-γ and IL-4, apoptosis-related indicators such as PD-1 and IL-7, and endothelial injury related factors such as sTM, SDC-1 and HS were significantly improved compared with the pre-treatment, the improvement degree of the above indicators was more obvious than that of the standard treatment group, and LYM was significantly higher than that of the standard treatment group (×109/L: 1.3±0.3 vs. 0.9±0.4, P < 0.05), IL-4, IFN-γ, IFN-γ/IL-4 ratio, IL-7, PD-1, sTM, SDC-1, HS, and Ang-2 were significantly lower than those of the standard treatment group [IL-4 (ng/L): 2.8 (1.5, 3.2) vs. 3.3 (2.7, 5.2), IFN-γ (ng/L): 6.3 (5.4, 106.5) vs. 217.9 (71.4, 517.1), IFN-γ/IL-4 ratio: 3.7 (1.8, 70.3) vs. 59.1 (18.3, 124.9), IL-7 (ng/L): 4.6 (3.2, 5.1) vs. 6.3 (5.2, 8.0), PD-1 (µg/L): 0.04 (0.03, 0.06) vs. 0.08 (0.05, 0.12), sTM (µg/L): 4.9 (4.3, 7.4) vs. 8.7 (6.0, 10.8), SDC-1 (µg/L): 0.6 (0.3, 1.1) vs. 0.9 (0.8, 2.5), HS (ng/L): 434.8 (256.2, 805.0) vs. 887.9 (620.1, 957.3), Ang-2 (ng/L): 934.0 (673.3, 1 502.1) vs. 2 233.9 (1 472.5, 3 808.4)], the differences were statistically significant (all P < 0.05). CONCLUSIONS: CBP treatment can eliminate the patient's immunosuppressive state, reduce a variety of endothelial injury markers and the degradation of glycocalyx, but cannot decrease the 28-day death risk or shorten the length of ICU stay.

Association between plasma glycocalyx component levels and poor prognosis in severe influenza type A (H1N1).

Influenza A virus infection causes a series of diseases, but the factors associated with disease severity are not fully understood. Disruption of the endothelial glycocalyx contributes to acute lung injury in sepsis, but has not been well studied in H1N1 influenza. We aim to determine whether the plasma glycocalyx components levels are predictive of disease severity in H1N1 influenza. This prospective observational study included 53 patients with influenza A (H1N1) during the influenza season, and 30 healthy controls in our hospital. Patients were grouped by severity and survival. We collected clinical data and blood samples at admission. Inflammatory factors (tumor necrosis factor-α, interleukin-6, interleukin-10) and endothelial glycocalyx components (syndecan-1, hyaluronan, heparan sulfate) were measured. The plasma levels of syndecan-1, hyaluronan, and heparan sulfate were significantly higher in patients with severe influenza A (H1N1) than in mild cases. Syndecan-1 and hyaluronan were positively correlated with disease severity, which was indicated by the APACHE II and SOFA scores and lactate levels, and negatively correlated with albumin levels. At a cutoff point ≥ 173.9 ng/mL, syndecan-1 had a 81.3% sensitivity and 70.3% specificity for predicting of 28-day mortality. Kaplan-Meier analysis demonstrated a strong association between syndecan-1 levels and 28-day mortality (log-rank 11.04, P = 0.001). Elevated plasma levels of syndecan-1 has a potential role in systemic organ dysfunction and may be indicative of disease severity in patients with influenza A (H1N1).

[Assistant role of manifestations under tracheoscopy in the diagnosis of invasive pulmonary aspergillosis in severe patients].

OBJECTIVE: To evaluate the assistant role of manifestations under tracheoscopy in the diagnosis of invasive pulmonary aspergillosis (IPA) in severe patients. METHODS: A retrospective study was conducted. The patients with suspected IPA admitted to intensive care unit (ICU) of Affiliated Hospital of Binzhou Medical College from January 2015 to December 2019 were enrolled. The diagnosis, clinical diagnosis and suspected diagnosis were made according to the grading criteria of Guidelines for the diagnosis and treatment of invasive fungal infection in severe patients (2007). Those who met the criteria were enrolled in the IPA group, and those who did not meet the criteria or other pathogens were enrolled in the non-IPA group. The general data of the patients were collected, and the changes of tracheal and bronchial mucosa under tracheal microscope before and after treatment were recorded, as well as the results of galactomannan (GM) test and aetiology culture of bronchoalveolar lavage fluid (BALF). The baseline, bronchoscopy and pulmonary CT manifestations and their dynamic changes were compared in each group. RESULTS: A total of 142 patients with suspected IPA were finally enrolled. Among them, 12 were pathologically proven IPA, 77 were probable IPA, 22 were possible IPA, and 31 were undefined IPA. Of the 142 patients, 60 had typical manifestations of mucosal injury under bronchoscopy, including 7 proven IPA patients (58.3%), 52 probable IPA patients (67.5%), and 1 possible IPA patient (4.5%), but none undefined IPA patient. The patients undergoing lung CT scan were 12 proven IPA patients (100%), 73 probable IPA patients (94.8%), and 21 possible IPA patients (95.5%), respectively. Most of the Chest CT showed patchy or strip density increasing and other non-specific manifestations. There were 3 proven IPA patients (25.0%), 7 probable IPA patients (9.0%), and 0 possible IPA patient (0%) who had typical IPA CT manifestations (halo sign and cavity or crescent sign). Among the patients of proven IPA and probable IPA (89 cases), there were a total of 35 cases with endoscopic airway mucosal injury and tracheoscopy reexamination ≥ 3 times. All the 35 patients received anti-aspergillus treatment, among which 16 survived and 19 died. Among the 16 patients who survived, the microscopic appearance of mucosal injury was gradually reduced and the clinical manifestations were gradually improved. Of the 19 patients who died, 16 had deteriorated endoscopic airway mucosal injury. CONCLUSIONS: The specific manifestations of severe patients with bronchial mucosal injury are of great significance in the diagnosis of IPA. In the case of severe patients who cannot receive pathological examination or chest CT in time, dynamic observation of the changes of airway mucosal injury is a simple auxiliary method to discover the changes of patients' condition in time, evaluate the effect of antifungal therapy and the prognosis of IPA.

[Significance of high mobility group box 1, von Willebrand factor and other cytokines in the evaluation of severity and prognosis of sepsis patients].

OBJECTIVE: To explore the value of high mobility group box 1 (HMGB1), von Willebrand factor (vWF) and other cytokines in predicting the severity and prognosis of sepsis patients. METHODS: Patients with sepsis and septic shock who ≥ 18 years old and met the Sepsis-3 diagnostic criteria admitted to the department of critical care medicine of Binzhou Medical University Hospital from January to June 2019 were taken as the research objects. The healthy individuals for regular health examination in the same period were taken as the control. The basic information, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) scores were recorded. The venous blood was taken within 24 hours after the patients were diagnosed. The levels of HMGB1, vWF, tumour necrosis factor-α (TNF-α), interleukin-10 (IL-10), soluble thrombomodulin (sTM), vascular endothelial growth factor receptor 2 (VEGFR-2), angiopoetin-2 (Ang-2) and other cytokines in serum were determined by enzyme linked immunosorbent assay (ELISA). Differences among patients with sepsis, septic shock, healthy physical examinees, and patients who died in 28-day and those who survived, were compared. Spearman rank correlation method was used to analyze the correlation among each cytokine and APACHE II, SOFA scores. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of cytokines on the prognosis of patients with sepsis/septic shock. Logistic regression was used to analyze the risk factors of 28-day death. RESULTS: Eleven patients with sepsis, 25 patients with septic shock and 30 healthy individuals were enrolled. Among the patients with sepsis/septic shock, 15 died in 28-day and 21 survived. The serum levels of TNF-α, IL-10, HMGB1, vWF, sTM and VEGFR-2 in patients with sepsis were significantly higher than those in the healthy control group. The levels of TNF-α, IL-10, HMGB1, vWF, sTM in septic shock group were higher than those in the sepsis group, while the Ang-2 level decreased significantly. The serum levels of TNF-α, IL-10, HMGB1, vWF and sTM in the death group were higher than those in the survival group, while Ang-2 was lower than the survival group. Spearman correlation analysis showed that HMGB1, TNF-α, sTM, IL-10, vWF were positively correlated with APACHE II score when patients with sepsis/septic shock were enrolled (r values were 0.652, 0.666, 0.445, 0.430 and 0.355, respectively, all P < 0.05), and HMGB1, TNF-α also positively correlated with SOFA score (r values were 0.433, 0.479, both P < 0.05). Ang-2 was negatively correlated with APACHE II and SOFA scores (r values were -0.519, -0.440, both P < 0.05). ROC curve analysis showed that the predictive value of HMGB1, vWF, IL-10, sTM for 28-day death in patients with sepsis/septic shock were higher than the APACHE II score [the area under ROC curve (AUC) and 95% confidence interval (95%CI): 0.946 (0.870-1.000), 0.902 (0.790-1.000), 0.877 (0.745-1.000), 0.868 (0.734-1.000) vs. 0.846 (0.700-0.991)]. Logistic regression analysis showed that APACHE II score, vWF, sTM, and IL-10 were independent risk factors for 28-day death in patients with sepsis/septic shock (ß values were 4.731, 0.407, -7.058, -0.887, all P < 0.05). CONCLUSIONS: HMGB1, vWF, IL-10, sTM and other cytokines all can be used to evaluate the severity and prognosis of sepsis patients.

Low molecular weight heparin may prevent acute lung injury induced by sepsis in rats.

The purpose of this study was to assess the protective effect of low molecular weight heparin (LMWH) on acute lung injury (ALI) in rats induced by sepsis. Rat ALI model was reproduced by cecal ligation and puncture (CLP). All rats were randomly divided into three groups (n=50): control group (A), ALI group (B), and LMWH-treated group (C). Group A received a sham operation and the other groups underwent CLP operation. Groups A and B accepted intraperitoneal injection (i.p.) of normal saline (NS) at a dose of 2.0 ml kg(-1) and ceftriaxone (30 mg kg(-1)), group C was intraperitoneally injected with additional LMWH (150 U kg(-1)) except saline and ceftriaxone. Blood was collected and lung tissue was harvested at the designated time points for analysis. The lung specimens were harvested for morphological studies, immunohistochemistry examination. Lung tissue edema was evaluated by tissue water content. The levels of lung tissue myeloperoxidase (MPO) were determined. Meanwhile, the nuclear factor-kappa B (NF-κB) activation, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) levels, high mobility group box 1 (HMGB1) and intercellular adhesion molecule-1 (ICAM-1) protein levels in the lung were studied. There was a significant difference in each index between groups A and B (P<0.05). Treatment with LMWH significantly decreased the expression of TNF-α, IL-1ß, HMGB1 and ICAM-1 in the lungs of ALI rats. Similarly, treatment with LMWH dramatically diminished sepsis-induced neutrophil sequestration and markedly reduced the enhanced lung permeability. In the present study, LMWH administration inhibited the nuclear translocation of NF-κB in the lungs. These data suggest that LMWH attenuates inflammation and ameliorates lung pathology in CLP-induced sepsis in a rat model.

[Comparison of the effects of BiPAP ventilation combined with lung recruitment maneuvers and low tidal volume A/C ventilation in patients with acute respiratory distress syndrome].

OBJECTIVE: To compare the effects of BiPAP ventilation combined with lung recruitment maneuvers (LRM) with low tidal volume A/C ventilation in patients with acute respiratory distress syndrome (ARDS). METHODS: A prospective, randomized comparison of BiPAP mechanical ventilation combined with lung recruitment maneuvers (test group) with low tidal volume A/C ventilation (control group) was conducted in 28 patients with ARDS. FiO2/PaO2 ratio, respiratory system compliance (Cs), central venous pressure (CVP), duration of ventilation support were recorded at 0 h, 48 h and 72 h separately. The ventilation associated lung injury and mortality at 28 d were also recorded. RESULTS: The FiO2/PaO2 ratio were (298+/-16) and (309+/-16) cm H2O, Cs were (38.4+/-2.2) and (42.0+/-1.3) ml/cm H2O, CVP were (13.8+/-0.8) and (11.6+/-0.7) cm H2O in the test group at 48 h and 72 h separately. In the control group, FiO2/PaO2 ratio were (212+/-12) and (246+/-17) cm H2O, Cs were (29.5+/-1.3) and (29.0+/-1.0) ml/cm H2O, CVP were 18.6+/-1.1 and (16.8+/-1.0) cm H2O. The results were better in the test group as compared with the control group (t=10.03-29.68, all P<0.01). The duration of ventilation support in the test group was shorter than the control group [(14+/-3) d vs (19+/-3) d, t=4.80, P<0.01]. The mortality in 28 d and ventilation associated lung injury were similar in the two groups. CONCLUSION: The results show that combination of LRM with BiPAP mode ventilation, as compared with the control group, contributes to improved FiO2/PaO2 ratio, pulmonary compliance, stable hemodynamic and shorter duration of ventilation support in patients with ARDS.

[Efficacy of goal-directed therapy in the treatment of septic shock].

OBJECTIVE: To investigate the efficacy and effect on outcome of goal-directed therapy in patients with septic shock compared with conventional therapy. METHODS: Sixteen patients with septic shock were randomly assigned to receive goal-directed therapy, with central venous pressure (CVP) 8-12 mm Hg (1 mm Hg=0.133 kPa), mean arterial pressure (MAP) >or=65 mm Hg, venous oxygen saturation (SvO(2))>0.70 (superior vena cava saturation), and urine output >or=0.5 ml/min as therapeutic goals. Another 17 patients received conventional therapy as controls. The arterial oxygen saturation (SaO(2)), SvO(2), MAP, CVP, heart stroke volume cardiac index (CI), serum lactate, volume of fluid, amount of vasopressors, the numbers of organ injured and patients who needed continuity blood purification (CBP) and/or ventilation were recorded serially for 6-48 hours, and they were compared between the two groups. The mortality of the patients in two groups on 7 days and 14 days were also recorded. RESULTS: There were no significant differences between the groups with respect to base-line characteristics. During the interval from 24 to 48 hours, the patients assigned to goal-directed therapy had a significantly higher in SaO(2), SvO(2), MAP, CVP, CI (P<0.05 or P<0.01), a lower lactate concentration (P<0.01), significantly more fluid during 6-24 hours and less vasopressors (both P<0.01). Seven and 14 days in-hospital mortality were lower in goal-directed therapy group as compared with the control group(P<0.05). CONCLUSION: The efficacy of goal-directed therapy in patients with septic shock is significantly better than conventional therapy in ameliorating outcome of shock and can be easily used in intensive care unit (ICU).