25-hydroxycholesterol promotes proliferation and metastasis of lung adenocarcinoma cells by regulating ERß/TNFRSF17 axis.

Lung adenocarcinoma is the main type of lung cancer in women. Our previous findings have evidenced that 25-hydroxycholesterol (25-HC) promotes migration and invasion of lung adenocarcinoma cells (LAC), during which LXR as a 25-HC receptor plays an important role. Estrogen receptor beta (ERß) is a receptor of 27-hydroxycholesterol that is structurally analogous to 25-HC, but its role in the functional actions of 25-HC remained largely unknown. In this study, we demonstrated that 25-HC treatment triggered ERß expression in LAC. Knockdown of ERß inhibited 25-HC-mediated proliferation, migration and invasion, and reduced 25-HC-induced LAC metastasis in vivo. Further investigation revealed that ERß knockdown restrained the expression of TNFRSF17 (BCMA). In vivo experiments also confirmed that ERß knockdown blocked 25-HC-induced TNFRSF17 expression. TNFRSF17 knockdown also restrained 25-HC-induced proliferation, migration and invasion. Bioinformatic analysis showed that the levels of ERß and TNFRSF17 were elevated in lung adenocarcinoma, and were closely related to tumor stages and nodal metastasis status. These results suggested that 25-HC promoted the proliferation and metastasis of LAC by regulating ERß/TNFRSF17 axis.

[Predictive effect of combined procalcitonin, interleukin-6 and antithrombin III on the severity and prognosis of patients with sepsis].

OBJECTIVE: To investigate the correlation of procalcitonin (PCT), interleukin-6 (IL-6) and antithrombin III (AT III) with the severity of sepsis, and to compare the predictive value of the above indicators alone or in combination. METHODS: A retrospective cohort study was conducted. Eighty-five patients with sepsis admitted to the department of intensive care medicine of Shandong Provincial Hospital Affiliated to Shandong First Medical University from April 2021 to September 2022 were enrolled. General information, sequential organ failure assessment (SOFA) score and acute physiology and chronic health evaluation II (APACHE II) score within 24 hours of admission, inflammatory indicators [PCT, IL-6, serum amyloid A (SAA), neutrophil to lymphocyte ratio (NLR), and C-reactive protein (CRP)] and coagulation indicators (D-dimer and AT III) levels at admission, and 28-day prognosis were collected. The differences of the above indicators were compared among patients with different prognosis at 28 days and different severity of sepsis. The correlation between PCT, IL-6, AT III and the severity of sepsis was analyzed by Spearman rank correlation method. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCT, IL-6 and AT III alone or in combination on the 28-day death of patients with sepsis. RESULTS: Eighty-five patients were enrolled finally, 67 cases survived and 18 cases died at 28 days. The mortality was 21.2%. There were no statistical significant differences in gender, age and other general data between the two groups. The patients in the death group were more serious than those in the survival group, and PCT, IL-6, and CRP levels were significantly higher than those in the survival group [PCT (µg/L): 4.34 (1.99, 14.42) vs. 1.17 (0.31, 3.94), IL-6 (ng/L): 332.40 (50.08, 590.18) vs. 61.95 (31.64, 194.20), CRP (mg/L): 149.28 (75.34, 218.60) vs. 83.23 (48.22, 174.96), all P < 0.05], and AT III activity was significantly lower than that in the survival group [(53.67±28.57)% vs. (80.96±24.18)%, P < 0.01]. However, there were no significant differences in D-dimer, NLR and SAA between the two groups. Among the 85 patients, 36 had sepsis with single organ dysfunction, 29 had sepsis with multiple organ dysfunction, and 20 had septic shock with multiple organ dysfunction. With the increase of the severity of sepsis, PCT and IL-6 levels gradually increased [PCT (µg/L): 0.36 (0.19, 1.10), 3.00 (1.22, 9.94), 4.34 (2.18, 8.86); IL-6 (ng/L): 43.99 (20.73, 111.13), 100.00 (45.37, 273.00), 332.40 (124.4, 693.65)], and the activity of AT III decreased gradually [(89.81±21.42)%, (71.97±24.88)%, and (53.50±25.41)%], all with statistically significant differences (all P < 0.01). Spearman rank correlation analysis showed that PCT and IL-6 levels in sepsis patients were significantly positively correlated with the severity of the disease (r values were 0.562 and 0.517, respectively, both P < 0.01), and AT III activity was significantly negatively correlated with the severity of the disease (r = -0.523, P < 0.01). ROC curve analysis showed that PCT, IL-6, and AT III alone or in combination had some predictive value for the death of sepsis patients at 28 days. The area under the ROC curve (AUC) of the above three indicators in combination was higher than that of the individual tests (0.818 vs. 0.722, 0.725, and 0.770), with a sensitivity of 83.3% and a specificity of 73.1%. CONCLUSIONS: PCT, IL-6, and AT III were significantly correlated with the severity of sepsis patients. The combined assay of the above three indicators can effectively improve the prediction of the prognosis of sepsis patients.

Research progress on the activation mechanism of NLRP3 inflammasome in septic cardiomyopathy.

Sepsis is an uncontrolled host response to infection, resulting in a clinical syndrome involving multiple organ dysfunctions. Cardiac damage is the most common organ damage in sepsis. Uncontrolled inflammatory response is an important mechanism in the pathogenesis of septic cardiomyopathy (SCM). NLRP3 inflammasome promotes inflammatory response by controlling the activation of caspase-1 and the release of pro-inflammatory cytokines interleukin IL-1ß and IL-18. The role of NLRP3 inflammasome has received increasing attention, but its activation mechanism and regulation of inflammation in SCM remain to be investigated.

Emerging roles of microRNAs in septic cardiomyopathy.

As one of the serious complications of sepsis, septic cardiomyopathy has gained more and more attention, because of its high morbidity and mortality. With the in-depth study of septic cardiomyopathy, several methods have been adopted clinically but have poor therapeutic effects due to failure to find precise therapeutic targets. In recent years, microRNAs have been found to be related to the pathogenesis, diagnosis, and treatment of septic cardiomyopathy via regulating immunity and programmed cell death. This paper reviews the role of microRNAs in septic cardiomyopathy, aiming to provide new targets for the diagnosis and treatment of septic cardiomyopathy.

Hyperuricaemia is an important risk factor of the erectile dysfunction: A systematic review and meta-analysis.

Serum uric acid can affect endothelial function, and hyperuricaemia-induced endothelial dysfunction is involved in the pathogenesis of cardiovascular diseases. As endothelial dysfunction is also a main pathogenic mechanism of erectile dysfunction (ED), the present study aims to evaluate the relationship between hyperuricaemia and ED via systemic review and meta-analysis. Five cohort studies and six cross-sectional studies on hyperuricaemia and ED, including a total of 454,510 participants, were recruited. Odds ratio (OR) and the 95% confidence intervals (CI) were adopted to estimate the relationship between hyperuricaemia and ED. Overall risk on effects of urate-lowering therapy (ULT) were analysed. In addition, subgroup analyses on study design, populations, age stratification and the object were conducted. In the patients with hyperuricaemia, the risk of ED was 1.59-fold higher than (pooled OR = 1.59, 95% CI [1.29, 1.97]) the non-hyperuricaemia counterparts. Urate-lowing therapy (ULT) in these hyperuricaemia patients reduced the risk of ED by 27% (OR = 1.27, 95% CI [1.14, 1.41]). After subgroup analysis, the association between hyperuricaemia and ED remained significant apart from the >60 years subgroup. Hyperuricaemia is an important risk factor of ED, while ULT can reduce the risk of ED in hyperuricaemia. This study suggests that hyperuricaemia-associated endothelial dysfunction may also underlie the pathogenesis of ED in these patients.

The role of the cholinergic anti-inflammatory pathway in septic cardiomyopathy.

Septic cardiomyopathy (SCM)is common in septic patients and results in cardiovascular failure. The pathogenesis of SCM is complicated, and patients with SCM have high mortality because current treatment methods are limited. The cholinergic anti-inflammatory pathway (CAP) modulates inflammatory responses through vagus nerve stimulation that leads to the release of acetylcholine (ACh), which binds to the alpha7 nicotinic acetylcholine receptor (α7nAChR). Moreover, α7nAChR activation by its agonists at the tissue level inhibits inflammatory mediators and regulates the function of immune cells in sepsis. Therefore, the α7nAChR can maintain balance of the inflammatory-immune response in sepsis. CAP has been elucidated as a critical regulator of anti-inflammation in many diseases, including rheumatoid arthritis, inflammatory boweldisease and SCM. Additionally, some clinical and preclinical trials show therapeutic potential via regulating CAP. There are excellent studies regarding the beneficial role of CAP activation, especially α7nAChR, in experimental SCM. This review aims to discuss the CAP in attenuating inflammation and the potential role of α7nAChR activation in regulating immune and reducing inflammation in SCM.

Role of pulmonary function and FeNO detection in early screening of patients with ACO.

Measurement of fractional exhaled nitric oxide (FeNO) is a quantitative and non-invasive approach to examine airway inflammation, which is a powerful aid in diagnosing chronic disorders of airways like asthma. Diagnostic value of FeNO and relevant indices on pulmonary function in the patients with asthma and chronic obstructive pulmonary disease (COPD) was evaluated. A total of 164 patients [58 asthma, 49 COPD and 57 asthma-COPD overlap (ACO)] were randomly recruited. FeNO, pulmonary ventilation function, and bronchial diastolic function were performed. Eight indicators including FeNO, vital capacity percentage (VC%), forced vital capacity percentage (FVC%), forced expiratory volume in one second percentage (FEV1%), forced expiratory volume in one second to forced vital capacity percentage (FEV1/FVC%), maximum independent ventilation volume percentage (MVV%), the increased percentage of FEV1 after bronchial diastolic test, the increased absolute value of FEV1 after bronchial diastolic test were examined. Significant difference in VC%, FVC%, FEV1%, FEV1/FVC%, MVV%, the increased absolute value of FEV1 after bronchial diastolic test and FeNO were significantly different between patients with asthma and patients with COPD (P<0.05). There were significant differences of VC%, FVC%, FEV1%, FEV1/FVC%, MVV% and the increased percentage of FEV1 after bronchial diastolic test in cases of patients with asthma compared to ACO patients (P<0.05). There was no statistical significance on VC%, FVC%, FEV1%, FEV1/FVC%, MVV% between COPD patients and ACO patients (P>0.05). However, more importantly, the increased percentage of FEV1 after bronchial diastolic test, the increased absolute value of FEV1 after bronchial diastolic test and the alterations on FeNO were found significantly different in ACO group compared with COPD alone (P<0.05). We compared the results from pulmonary ventilation function, bronchial diastolic function examination as well as FeNO detection among 3 groups of asthma, COPD and ACO. The examination of pulmonary ventilation function and bronchial diastolic function combined with FeNO detection is helpful in the early screening of ACO.

Extracorporeal Membrane Oxygenation (ECMO) in Critically Ill Patients with Coronavirus Disease 2019 (COVID-19) Pneumonia and Acute Respiratory Distress Syndrome (ARDS).

Traced back to December 2019, an unexpected outbreak of a highly contagious new coronavirus pneumonia (COVID-19) has rapidly swept around China and the globe. There have now been an estimated 2 580 000 infections and more than 170 000 fatal cases around the world. The World Health Organization (WHO) estimated that approximately 14% of infections developed into severe disease, 5% were critically ill, and the mortality rate of critically ill patients is reported to be over 50%. The shortage of specific anti-viral treatment and vaccines remains a huge challenge. In COVID-19, refractory hypoxemia is common among the critically ill with acute respiratory distress syndrome (ARDS) despite invasive mechanical ventilation, and is further complicated by respiratory and circulatory failure. This difficult situation calls for the use of extracorporeal membrane oxygenation (ECMO) for assisting respiration and circulation if necessary. This article reviews the pertinent clinical literature, technical guidance, and expert recommendations on use of ECMO in critically ill cases of COVID-19. Here, we present basic knowledge and opinions about COVID-19 and ECMO, review the evidence on ECMO use in Middle East Respiratory Syndrome (MERS) and H1N1 influenza, share the technical guidance and recommendations on use of ECMO in COVID-19, summarize the current use of ECMO against COVID-19 in China, and discuss the issues in use of ECMO in COVID-19.

Current Status of Septic Cardiomyopathy: Basic Science and Clinical Progress.

Septic cardiomyopathy (SCM) is a complication that is sepsis-associated cardiovascular failure. In the last few decades, there is progress in diagnosis and treatment despite the lack of consistent diagnostic criteria. According to current studies, several hypotheses about pathogenic mechanisms have been revealed to elucidate the pathophysiological characteristics of SCM. The objective of this manuscript is to review literature from the past 5 years to provide an overview of current knowledge on pathogenesis, diagnosis and treatment in SCM.

The Effects of High-volume Hemofiltration by Different Ultrasound Directing on Extra Vascular Lung Water Index in Patients with Septic Shock.

BACKGROUND: We explored the effects of high-volume hemofiltration(HVHF) by different ultrasound directing on the plasma N-terminal pro-B-type natriuretic peptide(NT-Pro-BNP), extra vascular lung water index (EVLWI), liquid net balance quantity and prognosis in patients with septic shock. METHODS: Overall, 107 intensive patients with septic shock were enrolled by retrospective analysis from Department of Intensive Care Unit (ICU) of the Shandong Provincial Hospital affiliated to Shandong University from 2014-2017. According to HVHF by different ultrasound directing, all the patients were divided into two groups ((ultrasonic cardiac output monitor (USCOM), group A, n=51cases)) and ((critical bedside ultrasound (CBU), group B, n=56cases)). RESULTS: The value of CI in group A had a significant positive correlation with the value of PCCI by the PiCCO2 monitoring (P<0.05). The lung ultrasound water B lines in group B also had a significant positive correlation with the value of EVLWI by the PiCCO2 monitoring. The cumulative liquid net balance quantity in group B had a more significant elevation than group A after treatment 7th d. The level of EVLWI after treatment 48 h and 72 h, the level of plasma NT-Pro-BNP, the levels of P(A-a)DO2,OI and blood lactic after treatment 72 h, and the APACHE II scores and SOFA scores after treatment 7thd were reduced more significantly in group B than group A (P<0.001). The mortality at 28th day had a more significant decrease in group B than group A. CONCLUSION: It could decrease the level of NT-Pro-BNP, EVLWI, P(A-a)DO2, which then improves pulmonary oxygenation. Consequently, it decreased the APACHE II and SOFA scores and improved the 28th survival rate of patients.

Red blood cell distribution width as a risk factor for inhospital mortality in obstetric patients admitted to an intensive care unit: a single centre retrospective cohort study.

BACKGROUND: Red blood cell distribution width (RDW) has been shown to predict mortality in critically ill patients. To our knowledge, whether or not RDW is associated with clinical outcomes of obstetric patients requiring critical care has not been evaluated. METHODS: This was a single centre, retrospective, observational study of obstetric patients admitted to the intensive care unit (ICU). Patients were excluded from the analysis if they had known haematological diseases or recently underwent blood transfusion. Patients who died or were discharged from the ICU within 24 hours of admission were also excluded. Patient clinical characteristics at ICU admission were retrieved from the medical charts. Multiple logistic regression was used to estimate OR and 95% CI for inhospital mortality associated with RDW. The receiver operating characteristic curve was used to examine the performance of RDW, alone or in combination with the Acute Physiology and Chronic Health Evaluation II score (APACHE II), in predicting inhospital mortality. RESULTS: A total of 376 patients were included in the study. The hospital mortality rate was 5.32%. A significant association was found between baseline RDW levels and hospital mortality (OR per per cent increase in RDW, 1.31; 95% CI 1.15 to 1.49). Further adjustment for haematocrit and other potential confounders did not appreciably alter the result (p<0.001). The area under the curve (AUC) for inhospital mortality based on RDW was similar to that based on the APACHE II score (0.752 vs 0.766). A combination of these two factors resulted in substantial improvement in risk prediction, with an AUC value of 0.872 (p<0.001). CONCLUSIONS: The study suggests that RDW is an independent predictor for inhospital mortality among ICU admitted obstetric patients. Combining RDW and APACHE II score could significantly improve inhospital prognostic prediction among these critically ill obstetric patients.

Effects of atorvastatin combined with low-molecular-weight heparin on plasma inflammatory cytokine level and pulmonary pathophysiology of rats with sepsis.

The aim of the present study was to investigate the effect of atorvastatin combined with low-molecular-weight heparin (LMWH) on plasma early inflammatory cytokine levels as well as pulmonary pathophysiology of rats with sepsis. A total of 122 rats were randomly divided into five groups including the sham operation group (n=10), CLP group (n=10), atorvastatin group (n=34, 20 mg/kg/day), LMWH group (n=34, 100 IU/kg/day), and atorvastatin combined with LMWH group (n=34). Blood samples from 6 rats in each group were collected to detect TNF-α, IL-1ß and HMGB1 concentration in plasma by linked immunosorbent assay at baseline and postoperatively at 4, 8, 12 and 24 h. Pulmonary pathophysiology was observed postoperatively at 24 h. The remaining 10 rats in each group were used to calculate the 7-day cumulative mortality rate. Compared to the sham operation group, the scores in CLP were greater than those of the sham operation group (P<0.05). Compared to the CLP group, the sepsis severity scores of the atorvastatin, LMWH, and atorvastatin combined with LMWH groups decreased gradually. Significant difference was detected in the four groups (P<0.05 0.01). Compared to the sham operation group, at 4, 8, 12 and 24 h, the TNF-α, IL-1ß and HMGB1 levels in plasma in CLP increased significantly (P<0.01). Compared to the CLP group, the TNF-α, IL-1ß and HMGB1 levels of plasma in other groups decreased gradually, and there was a significant difference in the four groups (P<0.01). At 24 h post operation, compared to the sham operation group, the damage of pulmonary pathophysiology in CLP was more severe. Compared to the CLP group, the damage of pulmonary pathophysiology in other groups was slight. Compared to the CLP group, the 7-day cumulative mortality rate in other groups decreased significantly (P<0.05). In conclusion, atorvastatin, combined with LMWH can decrease sepsis severity, plasma inflammatory cytokine levels, pulmonary pathophysiology, and the 7-day cumulative mortality rate. Atorvastatin, and LMWH may therefore be useful for the treatment of sepsis due to its ability to inhibit the release of TNF-α, IL-1ß and HMGB1 in septic rats.

Effect of probiotics on the incidence of ventilator-associated pneumonia in critically ill patients: a randomized controlled multicenter trial.

PURPOSE: To evaluate the potential preventive effect of probiotics on ventilator-associated pneumonia (VAP). METHODS: This was an open-label, randomized, controlled multicenter trial involving 235 critically ill adult patients who were expected to receive mechanical ventilation for ≥48 h. The patients were randomized to receive (1) a probiotics capsule containing live Bacillus subtilis and Enterococcus faecalis (Medilac-S) 0.5 g three times daily through a nasogastric feeding tube plus standard preventive strategies or (2) standard preventive strategies alone, for a maximum of 14 days. The development of VAP was evaluated daily, and throat swabs and gastric aspirate were cultured at baseline and once or twice weekly thereafter. RESULTS: The incidence of microbiologically confirmed VAP in the probiotics group was significantly lower than that in the control patients (36.4 vs. 50.4 %, respectively; P = 0.031). The mean time to develop VAP was significantly longer in the probiotics group than in the control group (10.4 vs. 7.5 days, respectively; P = 0.022). The proportion of patients with acquisition of gastric colonization of potentially pathogenic microorganisms (PPMOs) was lower in the probiotics group (24 %) than the control group (44 %) (P = 0.004). However, the proportion of patients with eradication PPMO colonization on both sites of the oropharynx and stomach were not significantly different between the two groups. The administration of probiotics did not result in any improvement in the incidence of clinically suspected VAP, antimicrobial consumption, duration of mechanical ventilation, mortality and length of hospital stay. CONCLUSION: Therapy with the probiotic bacteria B. Subtilis and E. faecalis are an effective and safe means for preventing VAP and the acquisition of PPMO colonization in the stomach.

[Protective effects of combined use of atorvastatin and low molecular weight heparin on the inflammatory reaction and pulmonary functions in rats with sepsis].

Objective: To investigate the influence of combined use of atorvastatin (ATO) and low molecular weight heparin (LMWH) on the inflammatory reaction and pulmonary protection functions in rats with sepsis. Methods: A total of 122 healthy male Sprague-Dawley (SD) rats were divided into five groups using a random number table: sham-operated group (sham group, n =10),sepsis group (n =10),ATO group (n =34),LMWH group (n =34),and ATO combined with LMWH group (ATO+LMWH group, n =34).The rat model of sepsis was reproduced by cecal ligation and puncture (CLP),while in sham group, rats were only subjected to laparotomy without cecum ligation and puncture. The rats of each pretreatment group received relevant therapies for 5 days, either gastric perfusion with ATO 20 mg/kg or subcutaneous injection with LMWH 100 U/kg or both before operation. The sepsis severities of the model animals were scored according to the modified sepsis severity assessment standards of experimental animals. Ten rats in each group were calculated the 7-day cumulative mortality rate. Blood samples from 6 rats in each group were collected to determine the levels of tumor necrosis factor-α (TNF-α),interleukin-1 ß (IL-1 ß) and high mobility group protein box-1 (HMGB1) contents in plasma using enzyme linked immunosorbent assay (ELISA)before operation (0 hour) and 4,8,12,and 24 hours post operation. The lung tissue was harvested 24 hours after operation, and the pulmonary pathology was assayed by hematoxylin and eosin (HE) staining using optical microscope. Results: ① The sepsis severity grades of sepsis group were significantly higher than those of sham group at 4 hours after operation (score:12.2 ± 2.0 vs.7.2 ± 0.5,P ＜ 0.05).Furthermore, they displayed a gradually increasing tendency, with the 7-day cumulative mortality rate being 90％ (9/10).The sepsis severity grades in ATO group, LMWH group, and ATO+LMWH group showed a significant decrease compared with sepsis group at 8 hours after operation (12.2± 2.0,11.2±2.2,10.0± 1.7 vs.16.6±2.5,all P ＜ 0.05).The 7-day cumulative mortality rates in ATO group, LMWH group, and ATO+LMWH group were 60％ (6/10),60％ (6/10),and 40％ (4/10),respectively, all of which was significantly lower than that of sepsis group (all P ＜ 0.05).② The levels of TNF-α,IL-1 ß and HMGB1 have not shown much variations in the sham group after operation; the levels of pro-inflammatory cytokines in other 4 groups were significantly increased after operation compared with those before operation; the levels of TNF-α,IL-1ß,and HMGB 1 reached peak at 4,8,and 24 hours, respectively. The levels of pro-inflammatory cytokines in sepsis group were significantly higher than those in the sham group. However, the levels of pro-inflammatory cytokines in ATO group, LMWH group, and ATO+LMWH group were significantly lower than those in sepsis group [4-hour TNF-α (ng/L):668.3 ± 124.6,536.5 ± 118.5,496.5 ± 108.5 vs.783.8 ± 134.7;8-hour IL-1 ß (ng/L):2 476.7 ± 137.8,2 460.4± 171.2,2 090.0 ± 151.2 vs.2 873.9 ± 295.6;24-hour HMGB1 (µg/L):654.4± 154.4,659.0± 134.6,609.4±90.5 vs.859.3 ± 167.5,P ＜ 0.05 or P ＜ 0.01].③ It was showed by optical microscopy that the pulmonary tissue morphology was normal in sham group and that the damage of pulmonary pathology was relatively severe in sepsis group. Compared with sepsis group, the damage of pulmonary pathology in ATO group, LMWH group, and ATO + LMWH group was alleviated obviously, and the most obvious improvements were found in ATO + LMWH group. Conclusions: Either ATO or LMWH could decrease sepsis severity, suppress the release of plasma pro-inflammatory cytokines at the early and late stages, alleviate the damage of pulmonary pathology, and reduce the 7-day cumulative mortality rate. Therefore, the combined treatment of sepsis using both ATO and LMWH resulted in better outcomes than implemented individually.

[Study of the effects of high volume hemofiltration on extra vascular lung water and alveolar-arterial oxygen exchange in patients with septic shock].

OBJECTIVE: To explore the effects of high volume hemofiltration (HVHF) on inflammatory factors, extra vascular lung water and alveolar-arterial oxygen exchange in patients with septic shock. METHODS: The data of 87 patients with septic shock underwent fluid resuscitation admitted to intensive care unit (ICU) of Shandong Provincial Hospital Affiliated to Shandong University were retrospectively analyzed. According to whether HVHF was used or not, all the patients were divided into fluid resuscitation group (n=41) and HVHF group (n=46). The patients in HVHF group received bedside high volume continuous vein-vein hemofiltration for at least 3 days on the basis of fluid resuscitation. The inflammatory factors, indexes of heart function, hemodynamics monitored by pulse-indicated continuous cardiac output (PiCCO), oxygen exchange, the severity of the disease before and after treatment, and 28-day mortality were compared between the two groups. The relationship between extra-vascular lung water index (EVLWI) and alveolar-arterial oxygen pressure difference (P(A-a)DO2) was analyzed. RESULTS: (1) After treatment, the serum levels of interleukin-6 (IL-6), procalcitonin (PCT), and N-terminal pro-B-type natriuretic peptide (NT(-pro)BNP) in both group were gradually decreased. The IL-6, PCT, and NT(-pro)BNP on the 3rd day after treatment in HVHF group were significantly lower than those in fluid resuscitation group [IL-6 (µg/L): 34.8 ± 15.8 vs. 63.3 ± 21.2, PCT (µg/L): 7.5 ± 6.4 vs. 17.3 ± 11.2, NT(-pro)BNP (µg/L): 561.8 ± 23.7 vs. 584.3 ± 56.7, P<0.05 or P<0.01]. (2) The hemodynamics indexes were improved after treatment in both groups. The levels of intrathoracic blood volume index (ITBVI), EVLWI and pulmonary vascular permeability index (PVPI) on the 3rd day after treatment in HVHF group were significantly lower than those in fluid resuscitation group [ITBVI (mL/m²): 634.2 ± 125.8 vs. 963.8 ± 321.0, EVLWI (mL/kg): 7.5 ± 2.4 vs. 12.3 ± 4.2, PVPI: 2.2 ± 1.2 vs. 4.2 ± 2.0, all P<0.01]. (3) The levels of PA-aDO2and arterial blood lactic (Lac) were gradually decreased, and oxygenation index (PaO2/FiO2) was gradually increased in both groups. Compared with fluid resuscitation group, the P(A-a)DO2and Lac on the 3rd and the 7th day were significantly declined[P(A-a)DO2(mmHg, 1 mmHg=0.133 kPa) on the 3rd day: 252.37 ± 29.45 vs. 270.82 ± 38.07, on the 7th day: 181.08 ± 21.81 vs. 221.02 ± 29.13; Lac (mmol/L) on the 3rd day: 3.17 ± 2.03 vs. 4.07 ± 2.43, on the 7th day: 1.95 ± 0.97 vs. 2.45 ± 1.07, P<0.05 or P<0.01], and the PaO2/FiO2on the 7th day was significantly elevated (mmHg: 258 ± 41 vs. 178 ± 34, P<0.01). (4) A significant positive correlation was found between EVLWI and P(A-a)DO2(r=0.693, P=0.001), with the 95% confident interval (95% CI) 0.617-0.773. (5) The condition was improved after treatment in the two groups. The acute physiology and chronic health evaluationII (APACHEII) scores and sepsis-related organ failure assessment (SOFA) scores on the 7th day after treatment in HVHF group were significantly reduced compared with those in fluid resuscitation group (APACHEII score on the 3rd day: 18.2 ± 7.7 vs. 22.4 ± 8.6, on the 7th day: 8.2 ± 3.8 vs. 17.2 ± 6.8; SOFA score on the 3rd day: 13.6 ± 3.4 vs. 15.8 ± 5.0, on the 7th day: 7.6 ± 3.3 vs. 12.8 ± 3.9, P<0.05 or P<0.01). The 28-day mortality in HVHF group was significantly lower than that in fluid resuscitation group [15.22% (7/46) vs. 34.15% (14/41), χ² = 4.242, P=0.038]. CONCLUSIONS: HVHF could decrease blood inflammatory factors, and reduce the vaso-permeability and extra vascular lung water with a result of the improvement of the levels of alveolar- arterial oxygen exchange in patients with septic shock and the prognosis at the same time.

[Effect of continuous high-volume hemofiltration in patients with severe acute respiratory distress syndrome].

OBJECTIVE: To investigate the effect of continuous high-volume hemofiltration (CHVHF) in patients with severe acute respiratory distress syndrome (ARDS). METHODS: A prospective randomized controlled trial was conducted. Sixty-five patients with severe ARDS admitted to intensive care unit (ICU) from June 2007 to June 2011 were divided into control group (n=28) and treatment group (n=37). Patients in treatment group were treated with CHVHF and other routine treatments. Patients in control group received routine treatments only. The oxygenation index (PaO2/FiO2), extravascular lung water index (EVLWI), arterial partial pressure of carbon dioxide (PaCO2), heart rate (HR), mean arterial pressure (MAP) were compared between control group and treatment group before and 6, 24, 48, 72 hours after treatment. The duration of mechanical ventilation (MV), ICU stay time, percentage of weaning from MV, and 28-day survival rate were also compared. RESULTS: The indexes of pulmonary function were improved after treatment in both groups. With prolonged time of treatment, PaO2/FiO2 was elevated, and EVLWI, PaCO2 were lowered, and the improvements were more marked in treatment group compared with control group (6-hour PaO2/FiO2: 92.6±7.2 mm Hg vs. 83.8±11.4 mm Hg, 24-hour EVLWI: 10.8±3.7 ml/kg vs. 12.6±4.5 ml/kg, 24-hour PaCO2: 47.2±8.5 mm Hg vs. 51.4±4.8 mm Hg, all P<0.05). HR and MAP were improved after the treatment in both groups, and there was no significant difference between groups. Compared with control group, the duration of MV and ICU stay were shortened in treatment group (duration of MV: 12±4 days vs. 19±6 days, ICU stay time: 21±4 days vs. 33±8 days, both P<0.05), and percentage of successful weaning from MV and 28-day survival rate were higher in treatment group (percentage of successful weaning from MV: 81.1% vs. 64.3%, 28-day survival rate: 86.5% vs. 71.4%, both P<0.05). CONCLUSIONS: CHVHF is an effective adjuvant treatment for severe ARDS. It can improve the lung function, shorten the duration of MV, improve the percentage of successful weaning from MV, and the survival rate, and it lowers the mortality, but it imparts no obvious influence to hemodynamics in patients.

Effectiveness of combining plasma exchange with continuous hemodiafiltration on acute Fatty liver of pregnancy complicated by multiple organ dysfunction.

Acute fatty liver of pregnancy (AFLP) is a rare disease of progressive hepatic insufficiency and secondary systemic complications that induce significant maternal risk. The application of combining plasma exchange (PE) and continuous hemodiafiltration (CHDF) is a novel concept for patients with AFLP. Since 2002, we have utilized the combination of PE with CHDF as adjunctive medical therapy for 11 AFLP patients with multiple organ dysfunction. Before PE and CHDF initiation, four patients had signs and symptoms of encephalopathy, four required ventilatory support, and all 11 were developing liver failure, significant renal compromise, and coagulopathy. PE combined with CHDF for patients was initiated a mean of 2 days postpartum (range, days 0-3). Daily or every other day PE combined with CHDF was undertaken on two to eight occasions for each of the 11 patients. Ten patients responded with composite clinical and laboratory improvement and were discharged to the ward, then cured and discharged from hospital; one patient died of septic shock. Average duration of hospitalization was 17 days (range, days 9-38) from time of admission to discharge; the average duration of intensive care unit was 10 days (range, days 4-23). No significant PE- and CHDF-related complications occurred. These results indicate that combing PE and CHDF in a series-parallel circuit is an effective and safe treatment for patients with severe AFLP. This finding may have important implications for the development of an effective treatment for patients with AFLP suffering multiple organ dysfunction.

[The effects of joint administration of 6% hydroxyethyl starch 130/0.4 and high-volume hemofiltration on patients with acute lung injury and acute kidney injury].

OBJECTIVE: To evaluate the effects of administration of 6% hydroxyethyl starch (6% HES 130/0.4, voluven) in combination with high volume hemofiltration (HVHF) in patients with ALI and AKI. METHODS: One hundred and eight patients with acute lung injury (ALI) and acute kidney injury (AKI) were enrolled from Department of Intensive Care Unit (ICU) of the provincial Hospital Affiliated to Shandong University between August 2006 and May 2011. The patients were randomly divided into two groups A (n = 68) and B (n = 40) to receive voluven (i.v., for volume resuscitation) and voluven+HVHF for 72 hours. The arterial blood lactate concentration (Lac), high sensitivity C-reactive protein (hs-CRP) serum concentration, pulmonary function index alveolar-arterial oxygen pressure difference [P(A-a)DO2] and oxygenation index (OI), as well as kidney function index serum cystatin C (Cyst C) and serum creatinine clearance rate (CCr) were measured at the time of admission and 72 hours after the treatment for statistical analysis. RESULTS: In comparison with group A, group B had significantly (all P < 0.01) lower mean value in the level of arterial Lac (mmol/L: 1.7 ± 0.7 vs. 2.7 ± 1.5), serum hs-CRP (mg/L: 35.8 ± 18.8 vs. 99.5 ± 20.4), P(A-a)DO2 (mm Hg, 1 mm Hg=0.133 kPa: 115.5 ± 23.1 vs. 155.4 ± 27.4), Cyst C (mg/L: 2.06 ± 1.12 vs. 3.95 ± 2.06) and significantly higher (both P < 0.01) mean value of OI (mm Hg: 295.2 ± 38.8 vs. 239.5 ± 32.7) and CCr (ml/min: 108.71 ± 31.33 vs. 90.21 ± 30.35) 72 hours after treatment. The mortality rate of group B was significantly lower than group A [10.00%(4/40) vs. 29.41%(20/68), P < 0.05] 7 days after the admission. CONCLUSION: 6% HES 130/0.4 in combination with HVHF could improve the lung and kidney function of the patients with ALI and AKI, prevent the development of multiple organ dysfunction syndrome (MODS), therefore improve the survival rate of these patients.

Effects of high-volume hemofiltration on alveolar-arterial oxygen exchange in patients with refractory septic shock.

BACKGROUND: High-volume hemofiltration (HVHF) is technically possible in severe acute pancreatitis (SAP) patients complicated with multiple organ dysfunction syndrome (MODS). Continuous HVHF is expected to become a beneficial adjunct therapy for SAP complicated with MODS. In this study, we aimed to explore the effects of fluid resuscitation and HVHF on alveolar-arterial oxygen exchange, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with refractory septic shock. METHODS: A total of 89 refractory septic shock patients, who were admitted to ICU, the Provincial Hospital affiliated to Shandong University from August 2006 to December 2009, were enrolled in this retrospective study. The patients were randomly divided into two groups: fluid resuscitation (group A, n=41), and fluid resuscitation plus high-volume hemofiltration (group B, n=48). The levels of O2 content of central venous blood (CcvO2), arterial oxygen content (CaO2), alveolar-arterial oxygen pressure difference P(A-a)DO2, ratio of arterial oxygen pressure/alveolar oxygen pressure (PaO2/PaO2), respiratory index (RI) and oxygenation index (OI) were determined. The oxygen exchange levels of the two groups were examined based on the arterial blood gas analysis at different times (0, 24, 72 hours and 7 days of treatment) in the two groups. The APACHE II score was calculated before and after 7-day treatment in the two groups. RESULTS: The levels of CcvO2, CaO2 on day 7 in group A were significantly lower than those in group B (CcvO2: 0.60±0.24 vs. 0.72±0.28, P<0.05; CaO2: 0.84±0.43 vs. 0.94±0.46, P<0.05). The level of oxygen extraction rate (O2ER) in group A on the 7th day was significantly higher than that in group B (28.7±2.4 vs. 21.7±3.4, P<0.01). The levels of P(A-a)DO2 and RI in group B on the 7th day were significantly lower than those in group A. The levels of PaO2/PaO2 and OI in group B on 7th day were significantly higher than those in group A (P<0.05 or P<0.01). The APACHE II score in the two groups reduced gradually after 7-day treatment, and the APACHE II score on the 7th day in group B was significantly lower than that in group A (8.2±3.8 vs. 17.2±6.8, P<0.01). CONCLUSION: HVHF combined with fluid resuscitation can improve alveolar-arterial-oxygen exchange, decrease the APACHE II score in patients with refractory septic shock, and thus it increases the survival rate of patients.

[The role of p38 mitogen-activated protein kinase in interleukin-6 induction by lipopolysaccharide in vascular smooth muscle cells].

OBJECTIVE: To investigate the regulation mechanism of p38 mitogen-activated protein kinase (p38MAPK) in interleukin-6 (IL-6) expression of vascular smooth muscle cell (VSMC) induced by lipopolysaccharide (LPS). METHODS: Rat VSMCs were divided into LPS group, SB203580+LPS group, SB203580 group and control group. LPS group was treated with 100 microg/L LPS for 0, 3, 6, 12, 24 hours, SB203580+LPS group was first treated with 10 micromol/L SB203580 for 2 hours and then exposed to 100 microg/L LPS for 0, 3, 6, 12, 24 hours, SB203580 group was pretreated with 10 micromol/L SB203580 for 2 hours. The level of IL-6 mRNA was determined by real-time polymerase chain reaction (PCR) and IL-6 secretion in the culture medium was measured by enzyme linked immunosorbent assay (ELISA) at different time points. RESULTS: The expression of IL-6 mRNA and the release of IL-6 were increased significantly in VSMC as early as 3 hours after being treated with LPS [mRNA: (21.3+/-3.2)x10(4), protein: (296.2+/-19.6) ng/L], peaked in 12 hours [mRNA: (131.4+/-11.2)x10(4), protein: (897.7+/-34.0) ng/L], and the elevation persisted up to 24 hours after treatment [mRNA: (15.3+/-4.7)x10(4), protein: (194.3+/-24.0) ng/L] compared with control group [mRNA: (9.4+/-1.9)x10(4), protein: (29.4+/-4.4) ng/L, all P<0.05]. On the other hand, the expression of IL-6 was significantly suppressed by p38MAPK inhibitor SB203580 at 3, 6, 12 hours [mRNA: (15.4+/-3.6)x10(4), (43.2+/-6.6)x10(4), (56.2+/-5.5)x10(4), protein: (180.3+/-23.6), (432.2+/-56.8), (546.2+/-57.9) ng/L, all P<0.05]. CONCLUSION: The release of IL-6 and the expression of IL-6 mRNA was increased significantly in LPS-challenged VSMC; however, the induction of IL-6 was significantly suppressed by p38MAPK inhibitor. p38MAPK may play an important role in the release of IL-6 induced by LPS.