miR-186-5p improves alveolar epithelial barrier function by targeting the wnt5a/ß-catenin signaling pathway in sepsis-acute lung injury.

BACKGROUND: Alveolar epithelial barrier dysfunction is one of the pathological features of sepsis-acute lung injury(ALI). However, the molecular mechanisms that regulate the function of alveolar epithelial barrier remain unclear. This study aimed to determine the regulatory role of miR-186-5p in alveolar epithelial barrier function in sepsis-ALI and its underlying molecular mechanism. METHODS: We established sepsis-ALI models in vivo and in vitro, detected the miR-186-5p and wnt5a/ß-catenin expressions, and observed the functional changes of the alveolar epithelial barrier by miR-186-5p overexpression. We used rescue experiments to clarify whether miR-186-5p works through wnt5a/ß-catenin. RESULTS: miR-186-5p expression was decreased, wnt5a expression was increased, and the wnt5a/ß-catenin signaling pathway was activated in mouse lung tissues and A549 cells after inflammatory stimulation. miR-186-5p overexpression resulted in wnt5a/ß-catenin signaling pathway inhibition, decreased apoptosis in A549 cells, improved alveolar epithelial barrier function, reduced lung tissue injury in ALI mice, decreased IL-6 and TNF-α levels, and increased claudin4 and ZO-1 expression. Using miRNA-related database prediction and dual-luciferase reporter gene analysis, the targeting relationship between miR-186-5p and wnt5a was determined. The protective effect produced by miR-186-5p overexpression on the alveolar barrier was reversed after the application of the wnt5a/ß-catenin activator Licl. CONCLUSION: Our experimental data suggest miR-186-5p targets the wnt5a/ß-catenin pathway, thereby regulating alveolar epithelial barrier function. Furthermore, both miR-186-5p and wnt5a/ß-catenin are potential therapeutic targets that could impact sepsis-ALI.

Silencing long non-coding RNA SNHG3 repairs the dysfunction of pulmonary microvascular endothelial barrier by regulating miR-186-5p/Wnt axis.

Barrier permeability changes of human pulmonary microvascular endothelial cells (HPMVECs) are important in sepsis-related acute lung injury (ALI) pathogenesis. Long non-coding small nucleolar RNA host gene 3 (SNHG3) mediates the cell-biological phenotype of lung cancer cells and affects the progression of lung cancer, but its role in regulating functions of lung non-malignant cells is still rarely reported. Therefore, we evaluated the regulatory effect of SNHG3 on the function of PMVECs in sepsis-related ALI. Small interference RNA (siRNA)-mediated deletion of SNHG3 promoted the proliferation of PMVECs, reduced apoptosis and barrier permeability, and increased the expression of tight junction proteins claudin-5 and ZO-1. Knockdown of SNHG3 increased the miR-186-5p expression, while overexpression of SNHG3 upregulated the level of wnt5a. Through a dual luciferase reporter assay, we confirmed the binding between SNHG3 and miR-186-5p, miR-186-5p and wnt5a. We further found that knockout of miR-186-5p could inhibit cell proliferation, increase apoptosis and barrier permeability, and down-regulate claudin-5 and ZO-1. Importantly, silencing miR-186-5p and activating Wnt signal pathway could eliminate the barrier repair effect caused by down-regulation of SNHG3. To sum up, our results suggested that knockdown of long non-coding RNA SNHG3 repaired the dysfunction of pulmonary microvascular endothelial barrier through the miR-186-5p/Wnt axis.

[Clinical value of renal artery resistance index and urinary angiotensinogen in early diagnosis of acute kidney injury in patients with sepsis].

OBJECTIVE: To investigate the value of renal artery resistance index (RRI) and urinary angiotensinogen (UAGT) in the early diagnosis of acute kidney injury (AKI) in patients with sepsis. METHODS: A prospective study was conducted. Seventy-eight patients with sepsis admitted to the department of critical care medicine of General Hospital of Ningxia Medical University from January to September 2021 were enrolled. Patients were observed for the development of AKI within 1 week. General data [gender, age, body mass index (BMI), major infection sites and critical illness related scores], laboratory indicators [mean arterial pressure (MAP), central venous pressure (CVP), procalcitonin (PCT), arterial blood lactic acid (Lac), etc.], duration of mechanical ventilation and length of intensive care unit (ICU) stay were recorded. After hemodynamic stabilization of the patients, renal ultrasound was performed to measure the RRI within 24 hours after ICU admission. Urine samples were taken immediately after diagnosis, and the level of UAGT was detected by enzyme-linked immunosorbent assay (ELISA). The above parameters were compared between the two groups. Multivariate Logistic regression was used to analyze the risk factors of AKI in patients with sepsis. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of related indicators for AKI in sepsis. RESULTS: A total of 78 patients were finally enrolled, of which 45 developed AKI and 33 did not. Compared with the non-AKI group, the rates of vasoactive drugs use, 28-day mortality, sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, PCT, Lac, RRI and UAGT were significantly higher in the AKI group [rates of vasoactive drugs use: 68.9% vs. 39.4%, 28-day mortality: 48.9% vs. 24.2%, SOFA score: 12.0 (10.5, 14.0) vs. 8.0 (7.0, 10.0), APACHE II score: 22.0 (18.0, 27.5) vs. 16.0 (15.0, 18.5), PCT (µg/L): 12.5±2.6 vs. 10.9±2.8, Lac (mmol/L): 2.6 (1.9, 3.4) vs. 1.9 (1.3, 2.6), RRI: 0.74±0.03 vs. 0.72±0.02, UAGT (µg/L): 75.16±19.99 vs. 46.28±20.75, all P < 0.05], the duration of mechanical ventilation and the length of ICU stay were significantly prolonged [duration of mechanical ventilation (days): 8.0 (7.0, 12.0) vs. 5.0 (4.0, 6.0), length of ICU stay (days): 14.0 (10.0, 16.0) vs. 9.0 (8.0, 11.5), both P < 0.01], and MAP was significantly lowered [mmHg (1 mmHg ≈ 0.133 kPa): 68.5±11.2 vs. 74.2±12.8, P < 0.05]. There was no significant difference in other parameters between the two groups. Multivariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 2.088, 95% confidence interval (95%CI) was 1.322-3.299], APACHE II score (OR = 1.447, 95%CI was 1.134-1.845), RRI (OR = 1.432, 95%CI was 1.103-1.859), and UAGT (OR = 1.077, 95%CI was 1.035-1.121) were independent risk factors for sepsis complicated with AKI (all P < 0.01). ROC curve analysis showed that SOFA score, APACHE II score, RRI and UAGT had certain predictive value for AKI in septic patients, the area under the ROC curve (AUC) were 0.814 (95%CI was 0.716-0.912), 0.804 (95%CI was 0.708-0.901), 0.789 (95%CI was 0.690-0.888), and 0.840 (95%CI was 0.747-0.934), respectively, and the AUC of RRI combined with UAGT was 0.912 (95%CI was 0.849-0.974), which was better than the above single index (all P < 0.05). CONCLUSIONS: RRI combined with UAGT has a high early predictive value for septic AKI.

[Effect of dexmedetomidine on expression of tight junction protein ZO-1 in kidney tissue of rats with acute kidney injury induced by sepsis].

OBJECTIVE: To observe the effect of dexmedetomidine (DEX) on the expression of tight junction protein ZO-1 in kidney tissues of rats with acute kidney injury (AKI) induced by sepsis. METHODS: Sixty healthy male Sprague-Dawley rats were selected and divided into four groups: sham operation group (Sham group), DEX + Sham group, cecal ligation and puncture (CLP) group and DEX + CLP group according to a random number table, with 15 rats in each group. Each group was then divided into 3 subgroups at 6, 12, and 24 hours after the operation, with 5 rats in each subgroup. Modified CLP was used to establish a sepsis model. In Sham group and DEX + Sham group, only laparotomy and abdominal closure were performed. Each group was given pretreatment 1 hour before modeling. DEX + Sham group and DEX + CLP group were pumped into DEX at a rate of 5 µg×kg-1×h-1 through the caudal vein; Sham group and CLP group were pumped with the equal amount of normal saline through the caudal vein. Rats in each group were sacrificed at 6, 12, and 24 hours after operation to obtain kidney tissue. After hematoxylin-eosin (HE) staining, the pathological changes were observed under a light microscope, and the pathological score of renal injury was calculated. The positive expression level of ZO-1 in kidney tissue was detected by immunohistochemistry. RESULTS: The pathological changes of rat kidney tissue could be seen at 6 hours after CLP. With the prolongation of postoperative time, the degree of renal injury showed a tendency to aggravate, with 24 hours being more significant. Semi-quantitative analysis showed that compared with the Sham group, the CLP group had significantly higher renal injury pathology scores at each time point (1.98±0.37 vs. 0.36±0.25 at 6 hours, 2.62±0.34 vs. 0.39±0.18 at 12 hours, 3.52±0.34 vs. 0.42±0.20 at 24 hours,all P < 0.01); the positive expression level of ZO-1 in kidney tissue was significantly reduced [percentage of positive area: (3.17±0.74)% vs. (10.83±0.83)% at 6 hours, (2.56±0.76)% vs. (9.02±0.88)% at 12 hours, (1.75±0.66)% vs. (8.25±0.94)% at 24 hours, all P < 0.01]. Compared with the CLP group, the pathological score of renal injury in the DEX + CLP group was significantly reduced at each time point (0.66±0.27 vs. 1.98±0.37 at 6 hours, 1.34±0.26 vs. 2.62±0.34 at 12 hours, 2.08±0.38 vs. 3.52±0.34 at 24 hours, all P < 0.01); the positive expression level of ZO-1 in kidney tissue was significantly increased [percentage of positive area: (8.58±0.86)% vs. (3.17±0.74)% at 6 hours, (7.44±1.05)% vs. (2.56±0.76)% at 12 hours, (6.60±0.87)% vs. (1.75±0.66)% at 24 hours, all P < 0.01]. There was no significant difference in renal injury pathology score and ZO-1 positive expression between the DEX+Sham group and the Sham group. CONCLUSIONS: DEX may reduce sepsis-induced AKI in rats by up-regulating the expression of tight junction protein ZO-1 in kidney tissue.

TEG in the monitoring of coagulation changes in patients with sepsis and the clinical significance.

Application values of thromboelastography (TEG) in dynamic monitoring of coagulation parameters of sepsis patients were investigated. Eighty-one patients with sepsis who were admitted to the ICU department of the General Hospital of Ningxia Medical University from April 1, 2015 to December 31, 2015 were collected. Clinical data of the patients were collected. Data were compared using 5 grouping methods: i) the 81 patients were divided into the sepsis group (n=45) and sepsis shock group (n=36); ii) patients were divided into two groups: group A (APACHE II score ≤13, n=51); group B (APACHE II score >13, n=30); iii) according to Disseminated Intravascular Coagulation Diagnosis Integral System (CDSS), patients were divided into non-disseminated intravascular coagulation (DIC) group (CDSS <7 points) and DIC group (CDSS ≥7 points); TEG indexes were compared between the two groups; iv) correlation between TEG indexes and Sequential Organ Failure Assessment (SOFA) scores was analyzed; v) patients were divided into survival group and non-survival group and correlations between TEG indicators and prognosis were analyzed. At 6 h after ICU entry, compared with sepsis group, R value and K time were significantly increased, LY30 was also increased, while MA value, coagulation index (CI), and α angle were significantly decreased in the septic shock group (P<0.05). At 6 h after ICU entry, compared with sepsis group, R value and K time were significantly increased, while MA value, CI, and α angle were significantly decreased in the septic shock group (P<0.05). Compared with the non-DIC group, the DIC group had prolonged K time, decreased α angle, increased R value, and decreased CI and MA value (P<0.05). With increase of SOFA scores, R value and K value increased significantly, and α angle, MA value, and CI decreased significantly (P<0.05). According to TEG, platelet function and fibrinogen function of DIC patients were significantly reduced, and the body showed hypocoagulability.

Colquhounia Root Tablet Protects Rat Pulmonary Microvascular Endothelial Cells against TNF-α-Induced Injury by Upregulating the Expression of Tight Junction Proteins Claudin-5 and ZO-1.

BACKGROUND: There are currently limited effective pharmacotherapy agents for acute lung injury (ALI). Inflammatory response in the lungs is the main pathophysiological process of ALI. Our preliminary data have shown that colquhounia root tablet (CRT), a natural herbal medicine, alleviates the pulmonary inflammatory responses and edema in a rat model with oleic acid-induced ALI. However, the potential molecular action mechanisms underlining its protective effects against ALI are poorly understood. This study aimed to investigate the effects and mechanism of CRT in rat pulmonary microvascular endothelial cells (PMEC) with TNF-α-induced injury. METHODS: PMECs were divided into 6 groups: normal control, TNF-α (10 ng/mL TNF-α), Dex (1×10-6 M Dex + 10 ng/mL TNF-α), CRT high (1000 ng/mL CRT + 10 ng/mL TNF-α), CRT medium (500 ng/mL CRT + 10 ng/mL TNF-α), and CRT low group (250 ng/mL CRT + 10 ng/mL TNF-α). Cell proliferation and apoptosis were detected by MTT assay and flow cytometry. Cell micromorphology was observed under transmission electron microscope. The localization and expression of tight junction proteins Claudin-5 and ZO-1 were analyzed by immunofluorescence staining and Western blot, respectively. RESULTS: TNF-a had successfully induced an acute endothelial cell injury model. Dex and CRT treatments had significantly stimulated the growth and reduced the apoptosis of PMECs (all p < 0.05 or 0.01) and alleviated the TNF-α-induced cell injury. The expression of Claudin-5 and ZO-1 in Dex and all 3 CRT groups was markedly increased compared with TNF-a group (all p < 0.05 or 0.01). CONCLUSION: CRT effectively protects PMECs from TNF-α-induced injury, which might be mediated via stabilizing the structure of tight junction. CRT might be a promising, effective, and safe therapeutic agent for the treatment of ALI.

[Effects of keratinocyte growth factor-2 on expressions of chemokine FKN and tight junction protein claudin-5 in lung of rats with acute lung injury].

OBJECTIVE: To observe the effects of keratinocyte growth factor-2 (KGF-2) on the expressions of chemokine FKN and tight junction protein claudin-5 in lung tissue of rats with acute lung injury (ALI). METHODS: Healthy male Sprague-Dawley (SD) rats were randomly divided into normal saline (NS) control group, ALI model group and KGF-2 pretreatment group, with 10 rats in each group. The rat ALI model was reproduced by injection of 0.01 mL/kg oleic acid into the tail vein, and the rats in NS control group were injected with the same amount of NS. The rats in KGF-2 pretreatment group were instilled with 5 mg/kg KGF-2 in the airway at 72 hours before the model reproduction, and the rats in the NS control group and the ALI model group were instilled with the same amount of NS. The abdominal aortic blood of rats was collected at 8 hours after model reproduction, and then the rats were sacrificed, bronchoalveolar in left lung was lavage, and the bronchoalveolar lavage fluid (BALF) was collected for determination of protein levels in plasma and BALF, and the lung permeability index (LPI) was calculated. The lung tissues were harvested, after hematoxylin-eosin (HE) staining, the histopathological changes were observed under light microscope, and the ALI pathology score (LIS) was calculated. The lung wet/dry weight (W/D) ratio was determined. Immunohistochemistry and Western Blot were used to qualitatively and quantitatively analyze the expressions of FKN and claudin-5 in the lung tissue. The correlation between two variables was analyzed by linear or curve fitting correlation analysis. RESULTS: In the ALI model group, the lung tissue was severely damaged, and obvious pathological changes were observed, including thickened alveolar space and inflammatory cell infiltration, and LIS score, lung W/D ratio and LPI were significantly higher than those of the NS control group (LIS: 3.56±0.28 vs. 0.62±0.36, lung W/D ratio: 6.37±0.29 vs. 4.39±0.33, LPI: 3.46±0.69 vs. 0.98±0.17, all P < 0.01). Compared with the NS control group, the positive expression of FKN in the lung tissue of the ALI model group was significantly increased, and the expression level was significantly increased (FKN/GAPDH: 0.97±0.18 vs. 0.62±0.04, P < 0.01); the positive expression of claudin-5 was significantly decreased, and the expression level was significantly decreased (claudin-5/GAPDH: 0.56±0.11 vs. 1.06±0.13, P < 0.01). There was a significant negative correlation between FKN and claudin-5 protein expression (r = -0.817, P = 0.025). After pretreatment with KGF-2, the degree of lung tissue damage was significantly reduced, and the pathological changes were significantly improved, and the LIS score, lung W/D ratio and LPI were significantly lower than those of the ALI model group (LIS: 2.41±0.17 vs. 3.56±0.28, lung W/D ratio: 5.45±0.55 vs. 6.37±0.29, LPI: 2.42±0.19 vs. 3.46±0.69, all P < 0.01). Compared with the ALI model group, the positive expression of FKN in the lung tissue of KGF-2 pretreatment group was significantly decreased, and the expression level was significantly decreased (FKN/GAPDH: 0.79±0.03 vs. 0.97±0.18, P < 0.01); the positive expression of claudin-5 was significantly increased, and the expression level was significantly increased (claudin-5/GAPDH: 0.80±0.05 vs. 0.56±0.11, P < 0.01). There was still a significant negative correlation between FKN and claudin-5 protein expression (r = -0.847, P = 0.012). CONCLUSIONS: KGF-2 may restore the expression of tight junction protein claudin-5 by down-regulating the expression of chemokine FKN, thereby reducing the damage of blood barrier in ALI.

[Consistency study of indirect calorimetry and HB equation for measuring energy expenditure of patients with multiple injury receiving mechanical ventilation].

OBJECTIVE: To evaluate the difference and correlation of 24-hour energy expenditure in patients with multiple trauma receiving mechanical ventilation predicted by indirect calorimetry (IC) and HB formula. METHODS: 140 patients with multiple trauma receiving mechanical ventilation admitted to intensive care unit (ICU) of the General Hospital of Ningxia Medical University from December 1st, 2016 to August 31st, 2017 were enrolled. The 24-hour energy expenditure of patients was repeatedly measured at 1, 3, 5, and 7 days after ICU admission by IC method, and the 24-hour energy expenditure measured by IC method was used as the "gold standard" to calculate the 24-hour kilogram body weight energy expenditure. The 24-hour energy expenditure value measured by IC method was compared with the 24-hour energy expenditure predicted value calculated by HB formula method, the consistency of the two measurement methods was detected by Bland-Altman method, and the correlation between the two measurement methods was analyzed by Pearson method and the linear equation was fitted. RESULTS: The 24-hour energy expenditure of patients at 1, 3, 5 and 7 days after ICU was repeatedly measured by IC method for 501 times, and there was no significant difference in 24-hour energy expenditure (kJ/d: 8 163.1±1 599.4, 8 221.1±1 694.7, 8 445.8±1 756.4, 8 707.0±1 820.7, respectively, F = 2.451, P = 0.063) and 24-hour kilogram body weight energy expenditure (kJ×kg-1×d-1: 120.5±18.9, 121.4±19.7, 122.7±19.3, 121.4±19.3, respectively, F = 0.252, P = 0.860) at each time point, indicating that the first week of multi-injury patients had no significant changes in energy metabolism. The consistency between the 24-hour energy expenditure measured by IC method on the first day [(8 163.1±1 599.4) kJ/d] and that predicted by HB formula method [(6 568.8±782.0) kJ/d] was analyzed. The results showed that there was significant bias between the two methods, with an average bias of -(1 591.8±121.4) kJ/d, but the correlation analysis showed that there was a linear correlation between them (r = 0.439, P = 0.000), using one-way regression, the fitted linear equation was Y = 2 270.5+0.897X (X was 24-hour energy expenditure predicted by the HB formula). CONCLUSIONS: The energy metabolism of patients with multiple trauma receiving mechanical ventilation is not obvious within 1 week. The HB formula method underestimates the 24-hour energy expenditure of patients. The prediction formula can be used to correct the HB formula and further to improve the accuracy of predicting the 24-hour energy consumption of patients.

[Correlation of severity classification of acute respiratory distress syndrome by the Berlin definition with extra vascular lung water index and pulmonary vascular permeability index].

OBJECTIVE: To explore the correlation of severity classification of acute respiratory distress syndrome (ARDS) by the Berlin definition with extra vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI). METHODS: A total of 70 cases with ARDS at intensive care unit of our hospital from July 2012 to July 2014 were divided into three groups of mild (n = 20), moderate (n = 30) and severe (n = 20) according to the Berlin definition. The scores of acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) within 24 h of admission were recorded. And the values of EVLWI and PVPI of three groups from Day 1-4 were monitored by pulse indicator continuous cardiac output (PiCCO). Receiver operating characteristic (ROC) curve was drawn for these parameters and the area under curve was compared. Meanwhile blood gas was analyzed and oxygenation index (OI) calculated. And the correlations of EVLWI and PVPI with OI were analyzed. RESULTS: Comparisons of EVLWI, PVPI and OI were made for three groups at different timepoints: As the severity of ARDS aggravated, EVLWI and PVPI of three groups increased significantly at any timepoint while OI decreased sharply (P < 0.05). EVLWI and PVPI declined gradually from Day 1-4 in mild ARDS group (P < 0.05), PVPI declined dramatically (P < 0.05) while EVLWI showed no obvious change in moderate ARDS group (P > 0.05). There was no sharp decline of EVLWI or PVPI in severe ARDS group (P > 0.05). And OI increased significantly from Day 1-4 in three groups (P < 0.01). The area under ROC curve (AUC) for PVPI in evaluating the prognosis of three groups was 0.594, 0.643, 0.723 and 0.816 respectively. PVPI > 2.95 at Day 4 of admission was used as the best threshold value for judging prognosis. And the sensitivity was 70% and specificity 92%. OI had negative correlation with EVLWI and PVPI in three groups from Day 1-4 [(r = -0.685, P = 0.000) and (r = -0.631, P = 0.000)]. CONCLUSION: Both EVLWI and PVPI reflect adequately the severity of ARDS by the Berlin definition. And the dynamic trend of PVPI is superior to that of EVLWI.

[Investigation on the predictive value of the dynamic changes of EVLWI and PVPI on the prognosis of ARDS patients].

OBJECTIVE: To investigate the dynamic changes of extra vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI) on the prognosis of acute respiratory distress syndrome (ARDS), and predict the risk factors affecting prognosis of ARDS. METHODS: 70 patients meeting ARDS Berlin definition, who were admitted to the ICU from July 2012 to July 2014, were analyzed with a prospective method. The patients were divided into a survival group and a death group according to their survival situation in 28 days. EVLWI (EVLWI1-EVLWI4), PVPI (PVPI1-PVPI4), DeltaEVLWI (subtracting EVLWI day 4 from day 1), and DeltaPVPI (subtracting PVPI day 4 from day 1) of the two groups of patients from the 1st day to the 4th day were monitored by the pulse indicator continuous cardiac output (PiCCO). Parameters including the acute physiology and chronic health evaluation (APACHE II) score, sequential organ failure assessment (SOFA) score, EVLWI, PVPI, DeltaEVLWI, DeltaPVPI, oxygenation index (OI), CVP, the number of organ dysfunction were compared between the two groups. Univariate analysis and multivariate logistic regression were used to analyze the independent risk factors associated with prognosis. Receiver operating characteristic curve (ROC curve) was drawn to evaluate the prediction performance of those risk factors in the prognosis of ARDS. RESULTS: Comparison of EVLWI and PVPI between the survival group and the death group of ARDS patients at different time points: EVLWI and PVPI showed no statistical difference from the 1st day to the 2nd day after admission, but those two parameters in the death group were higher than those in the survival group form the 3rd day to the 4th day after admission (P<0.01). The comparison of the dynamic changes of EVLWI and PVPI within the two groups: the EVLWI and PVPI in the survival group declined gradually from 1st day to 4th day after treatment, but that changing trend in the death group showed no statistical difference. DeltaEVLWI and DeltaPVPI changes in the survival group were higher than in the death group (P<0.01). They were independent risk factors of patients 28-day prognosis (P<0.05). ROC curve and 28-day survival curve showed that the area under ROC curve of DeltaPVPI predicting prognosis of patients with ARDS was 0.812, when the optimal cut off value was 1.2, and the median survival period in DeltaPVPI>1.2 group was longer than that in the Delta PVPI≤1.2 group. CONCLUSIONS: The continuous dynamic observation of EVLWI and PVPI changes is better than that of a single detection. DeltaEVLWI and DeltaPVPI are independent risk factors and can be used as an auxiliary indicator for the prognosis of patients with ARDS.

Endothelial cell injury with inflammatory cytokine and coagulation in patients with sepsis.

BACKGROUND: Current studies on CD62P have focused mainly on cardiovascular diseases, while only few studies have evaluated the effects of CD62P on the development of sepsis and the association between endothelial cell injury with inflammation and coagulation. This study attended to explore the association between endothelial cell injury with inflammation and coagulation by evaluating the expression of soluble CD62P (s-CD62P) in plasma and its mechanism in patients with sepsis, thus to provide the evidence of effective treatment of sepsis with anti-adhesion therapy targeted CD62P. METHODS: A total of 70 critically ill patients with systemic inflammatory response syndrome (SIRS) admitted to intensive care unit (ICU) between September 2009 and February 2010 were enrolled for a prospective and control study. According to the diagnostic criteria of sepsis/SIRS, the patients were divided into two groups: a sepsis group (n=38) and a SIRS group (n=32). Another 20 healthy volunteers served as a control group. Patients in the sepsis group and SIRS group were matched by clinical signs of high blood pressure, diabetes and its complications. The demographics of the patients including age, sex, body mass index (BMI), smoking and alcohol addict were compared among the groups. Six mL peripheral blood samples were collected within 24-hour admission in ICU for enzymelinked immunosorbent assay (ELISA) to detect the plasma levels of s-CD62P, TNF-α, and hs-CRP. And variables of coagulation function such as platelet (PLT), prothrombin (PT), activated partial thromboplastin time (APTT), D-dimer and antithrombin-III (AT-III) were analyzed during 24 hours after admission to ICU. Meanwhile sequential organ failure assessment (SOFA) score of critically ill patients was evaluated. Data were expressed as mean±standard deviation and were statistically analyzed by using SPSS 17.0 statistical software. The differences in plasma levels of s-CD62P of patients in each group were analyzed by ANOVA and the Kruskal-Wallis test. The relations between s-CD62P and inflammatory cytokines as well as with coagulation were determined by Pearson's product moment correlation coefficient analysis. Changes were considered as statistically significant if P value was less than 0.05. RESULTS: Compared with the control group and SIRS group, the sepsis group demonstrated significantly higher levels of s-CD62P, TNF-α and highly sensitive C-reactive protein (hs-CRP) (P<0.05). The plasma levels of D-dimer, PT, and APTT in the sepsis and SIRS groups were significantly higher than those in the control group, while the platelet count and the activity of AT-III were obviously lower (P<0.05). In the sepsis group, the plasma levels of hs-CRP and TNF-α were positively correlated with PT, APTT, and D-dimer, and negatively correlated with AT-III and PLT (P<0.05). The plasma levels of s-CD62P were significantly correlated with the plasma levels of TNF-α, hs-CRP, D-dimer, PT, and APTT, whereas they were correlated negatively well with PLT and AT-III (P<0.05). CONCLUSIONS: The concentration of plasma s-CD62P is elevated as a early biomarker in patients with sepsis, and it serves as one of the pathogenic factors responsible for endothelial cell damage. Coagulation and mediators of inflammation promote each other, aggravating the severity of sepsis. Plasma s-CD62P may be an important factor for the development of coagulation and inflammatory reaction.

[Comparison of computer-driven weaning and physician-directed weaning from mechanical ventilation: a randomized prospective study].

OBJECTIVE: To evaluate if the computer-driven weaning (CDW) with a closed-loop knowledge-based system introduced in a ventilator is superior to physician-directed weaning (PDW) in difficult-to-wean patients in the intensive care unit (ICU). METHODS: Sixty-two difficult-to-wean patients were randomized into 2 groups: weaning with Smart Care/PS (SC group, n = 32) or with synchronize intermittent mandatory ventilation add positive support ventilation (SP group, n = 30). In the SC group, the automated system titrated pressure support, conducted a spontaneous breathing trial and provided notification of success (separation potential). In the SP group, weaning from ventilators was carried out by gradually decreasing respiratory support. The length of mechanical ventilation and stay in ICU, the rate of ventilator-associated pneumonia (VAP), the retubing rate in 48 h, manual ventilator setting changes before extubation were compared between the 2 groups. RESULTS: In the SC group, the weaning time was (49 +/- 13) h, (67 +/- 37) h, and (254 +/- 96) h, respectively in patients with neuromuscular diseases, for post-operative respiratory support and patients with respiratory diseases; while in the SP group, the weaning time was (223 +/- 38) h, (106 +/- 34) h and (502 +/- 91) h, respectively; the difference between the 2 groups being statistically significant (chi(2) = 8.33, 4.77, 4.43, all P < 0.05). The time of stay in ICU was (9.0 +/- 1.7) d and (7.3 +/- 1.9) d in the SC group for patients with neuromuscular diseases and patients with post-operative respiratory support, respectively, while that was (20.8 +/- 5.1) d and (14.6 +/- 1.7) d in the SP group, respectively. Time of stay in ICU was significantly shorter in the SC group (chi2 = 6.74, 7.68, both P < 0.05). The number of manual ventilator setting changes was (5 +/- 1) times in the SC group, significantly less than that of the SP group (13 +/- 3, t = 2.73, P < 0.05). There were no significant differences between the SC and the SP groups in the rate of re-intubation, the rate of tracheotomy, the incidence of pneumothorax, the incidence of VAP and the incidence of subcutaneous emphysema. CONCLUSION: The CDW method used in patients with difficult weaning from ventilators was shown to shorten the weaning time, reduce stay in ICU, and decrease the need for manual adjustment of ventilators.

[Study of relationship between stress hyperglycemia and insulin-resistance related factors].

OBJECTIVE: To observe related factors in the stress hyperglycemia (SHG) of critical illness and to investigate possible pathogenesis of insulin-resistance (IR). METHODS: Blood glucose (BG), insulin (INS), C-peptide (C-P), cortisol (Cor), somatostatin (SS), glucagon (Gluc), tumor necrosis factor-alpha (TNF-alpha),soluble tumor necrosis factor receptor I (sTNFRI) and sTNFRII were determined respectively by radioimmunoassay (RIA) or enzyme linked immunoadsorbent assay (ELISA) in 47 SHG patients with critical illness and 15 healthy volunteers serving as normal controls. Their insulin sensitivity index (ISI) was calculated. RESULTS: (1)Eleven of 47 patients died, while 36 cases survived. Mean acute pathology and chronic health evaluation II (APACHEII) was (13.89+/-6.29) scores within 24 hours after admission to intensive care unit (ICU), mean days of stay in ICU was (5.5+/-6.3) days,and mean duration of mechanical ventilation (MV) was (51.49+/-66.01) hours. (2)The concentrations of INS, ISI, C-P, Cor, Gluc, TNF-alpha, sTNFRI and sTNFRII in 47 SHG patients with critical illness were significantly higher than those in normal controls, except for SS, the differences among groups were significant (P<0.05 or P<0.01). (3)The results of analysis of severity of SHG showed that the more severe SHG was, the higher C-P and INS were, and the less prominent ISI was. (4)Analysis of scores of APACHEII in 47 cases of SHG showed that BG was not increased, but duration of MV, Cor, Gluc, SS, TNF-alpha, sTNFRI and sTNFRII were significantly increased with higher scores of APACHEII. (5)The effect of SHG was significant on MV (F=10.438,P<0.01), but not significant for outcome and days of stay in ICU. (6)The main correlative factors of BG were respectively concentrations of INS (r=0.674, P<0.01), C-P(r=0.552,P<0.01), ISI (r=-0.787, P<0.01), APACHE II(r=0.267,P<0.05) and sTNFRI(r=0.465, P<0.01). CONCLUSION: These results show that main reason of SHG in critical illness is IR. There is no strong significant correlation between acute stress hormones and the level of SHG. sTNFRI has an influence on SHG. However, the over release of TNF-alpha and sTNFRII could be the results of seriousness of the critical illness. There is closely correlation between BG and MV, but not with the age, outcome and days of stay in ICU. The strategy of control and therapy of SHG should be alleviation of stress and improve the utilization of BG in the tissue, and increase sensitivity of INS in the tissue.