S-Allyl-L-cysteine (SAC) inhibits copper-induced apoptosis and cuproptosis to alleviate cardiomyocyte injury.

Cardiomyocyte injury is closely related to various myocardial diseases, and S-Allyl-L-cysteine (SAC) has been found to have myocardial protective effects, but its mechanism is currently unclear. Meanwhile, copper also has various physiological functions, and this study found that copper inhibited cell viability in a concentration and time-dependent manner, and was associated with multiple modes of death. Elesclomol plus CuCl2 (ES + Cu) significantly inhibited cell viability, and this effect could only be blocked by copper chelator TTM, indicating that "ES + Cu" induced cuproptosis in cardiomyocytes. SAC reduced the inhibitory effects of high concentration copper and "ES + Cu" on cell viability in a concentration and time-dependent manner, indicating that SAC plays a cardioprotective role under stress. Further mechanism study showed that high concentration of copper significantly induced cardiomyocyte apoptosis and increased the levels of LDH, MDA and ROS, while SAC inhibited the apoptosis and injury of cardiomyocytes induced by copper. "ES + Cu" significantly increased intracellular copper levels and decreased the expression of FDX1, LIAS, Lip-DLST and Lip-DLAT; FDX1 siRNA did not affect the expression of LIAS, but further reduced the expression of Lip-DLST and Lip-DLAT; SAC did not affect the expression of these genes, but enhanced the effect of "ES + Cu" in down-regulating these gene expression and restored intracellular copper levels. In addition, "ES + Cu" reduced ATP production, weakened the activity of mitochondrial complex I and III, inhibited cell viability, and increased the contents of injury markers LDH, MDA, CK-MB and cTnI, while SAC significantly improved mitochondrial function injury and cardiomyocyte injury induced by "ES + Cu". Therefore, SAC can inhibit apoptosis and cuproptosis to play a cardioprotective role.

Construction and evaluation of short-term and long-term mortality risk prediction model for patients with sepsis based on MIMIC-IV database. / 基于MIMIC-IVæž„å»ºåŠè¯„ä¼°è„“æ¯’ç—‡æ‚£è€ è¿‘æœŸå’Œè¿œæœŸæ­»äº¡é£Žé™©é¢„æµ‹æ¨¡åž‹.

OBJECTIVES: Given the high incidence and mortality rate of sepsis, early identification of high-risk patients and timely intervention are crucial. However, existing mortality risk prediction models still have shortcomings in terms of operation, applicability, and evaluation on long-term prognosis. This study aims to investigate the risk factors for death in patients with sepsis, and to construct the prediction model of short-term and long-term mortality risk. METHODS: Patients meeting sepsis 3.0 diagnostic criteria were selected from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and randomly divided into a modeling group and a validation group at a ratio of 7꞉3. Baseline data of patients were analyzed. Univariate Cox regression analysis and full subset regression were used to determine the risk factors of death in patients with sepsis and to screen out the variables to construct the prediction model. The time-dependent area under the curve (AUC), calibration curve, and decision curve were used to evaluate the differentiation, calibration, and clinical practicability of the model. RESULTS: A total of 14 240 patients with sepsis were included in our study. The 28-day and 1-year mortality were 21.45% (3 054 cases) and 36.50% (5 198 cases), respectively. Advanced age, female, high sepsis-related organ failure assessment (SOFA) score, high simplified acute physiology score II (SAPS II), rapid heart rate, rapid respiratory rate, septic shock, congestive heart failure, chronic obstructive pulmonary disease, liver disease, kidney disease, diabetes, malignant tumor, high white blood cell count (WBC), long prothrombin time (PT), and high serum creatinine (SCr) levels were all risk factors for sepsis death (all P<0.05). Eight variables, including PT, respiratory rate, body temperature, malignant tumor, liver disease, septic shock, SAPS II, and age were used to construct the model. The AUCs for 28-day and 1-year survival were 0.717 (95% CI 0.710 to 0.724) and 0.716 (95% CI 0.707 to 0.725), respectively. The calibration curve and decision curve showed that the model had good calibration degree and clinical application value. CONCLUSIONS: The short-term and long-term mortality risk prediction models of patients with sepsis based on the MIMIC-IV database have good recognition ability and certain clinical reference significance for prognostic risk assessment and intervention treatment of patients.

The therapeutic efficacy of plasmapheresis for sepsis with multiple organ failure: a propensity score-matched analysis based on the MIMIC-IV database.

BACKGROUND: Despite advancements in sepsis treatment, mortality remains high. Plasmapheresis (PE) targeting multiple pathways simultaneously appears to be a potential treatment option, but evidence is insufficient. We aimed to investigate the efficacy of PE for sepsis with multiple organ failure (MOF). METHOD: Septic patients with MOF were identified from the Medical Information Mart for Intensive Care IV database. Patients who received PE were matched with those receiving conventional therapy via propensity score matching (PSM). Regression analyses evaluated the association between PE and outcomes. The Kaplan-Meier (KM) method was utilized to analyze the survival probability. The generalized additive mixed model investigated early indexes changes' association with treatment modalities and 28-day mortality. RESULTS: 906 septic patients with MOF were enrolled. After PSM, PE and conventional groups consisted of 60 cases each. PE was associated with a reduced risk of 28-day mortality (hazard ratio [HR]: 0.50, 95% confidence interval [CI]: 0.27-0.94), 1-year mortality (HR: 0.44, 95%CI: 0.26-0.74), and in-hospital mortality (HR: 0.38, 95%CI: 0.20-0.71). KM curves demonstrated significant differences in survival probability between groups. Compared with the conventional group, the sequential organ failure assessment, norepinephrine dosage, prothrombin time, actate dehydrogenase, total bilirubin, white blood cells, and immature granulocytes in the PE group significantly decreased over time, while platelets, red blood cells, and hemoglobin significantly increased over time. CONCLUSIONS: Plasmapheresis demonstrated an association with reduced risks of 28-day, in-hospital and 1-year mortality in septic patients with MOF. Moreover, plasmapheresis might exhibit the potential to improve outcomes by improving organ function, hemodynamics and restoring several indicators such as coagulation, anemia, and inflammation.

Role of Quantitative EEG and EEG Reactivity in Traumatic Brain Injury.

OBJECTIVE: This study aimed to explore the effectiveness of quantitative electroencephalogram (EEG) and EEG reactivity (EEG-R) to predict the prognosis of patients with severe traumatic brain injury. METHODS: This was a prospective observational study on severe traumatic brain injury. Quantitative EEG monitoring was performed for 8 to 12 hours within 14 days of onset. The EEG-R was tested during the monitoring period. We then followed patients for 3 months to determine their level of consciousness. The Glasgow Outcome Scale (GOS) score was used. The score 3, 4, 5 of GOS were defined good prognosis, and score 1 and 2 as poor prognosis. Univariate and multivariate analyses were employed to assess the association of predictors with poor prognosis. RESULTS: A total of 56 patients were included in the study. Thirty-two patients (57.1%) awoke (good prognosis) in 3 months after the onset. Twenty-four patients (42.9%) did not awake (poor prognosis), including 11 cases deaths. Univariate analysis showed that Glasgow coma scale (GCS) score, the amplitude-integrated EEG (aEEG), the relative band power (RBP), the relative alpha variability (RAV), the spectral entropy (SE), and EEG-R reached significant difference between the poor-prognosis and good-prognosis groups. However, age, gender, and pupillary light reflex did not correlate significantly with poor prognosis. Furthermore, multivariate logistic regression analysis showed that only RAV and EEG-R were significant independent predictors of poor prognosis, and the prognostic model containing these 2 variables yielded a predictive performance with an area under the curve of 0.882. CONCLUSIONS: Quantitative EEG and EEG-R may be used to assess the prognosis of patients with severe traumatic brain injury early. RAV and EEG-R were the good predictive indicators of poor prognosis.

Lidocaine pretreatment up-regulates aquaporin-5 expression in primary alveolar epithelium type II cells injured by lipopolysaccharides.

Acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) is associated with decreased aquaporin-5 (AQP5) expression. Lipopolysaccharides (LPS) can decrease AQP5 expression. The effects and mechanisms of lidocaine pretreatment on primary alveolar epithelium type II (AEC II) cells injured by LPS were investigated. Primary AEC II cells were isolated from rats previously injured with LPS as an ALI model. The groups of cells were evaluated: 1) pretreated with lidocaine (2, 20, 200µg/ml) and/or Infliximab, an anti-TNF-α neutralizing antibody, 2) uninjured cells; 3) solvent pretreated injured cells and 4) untreated injured cells as controls. TNF-α levels were evaluated by ELISA. AQP5 expression was determined by mRNA and protein expression (q-PCR and western blot).The release of TNF-α was increased significantly in AEC II cells following LPS injury. The release of TNF-α was decreased by 33%-100% as a result of lidocaine pretreatment in a dose-dependent fashion. This decrease was accompanied by up-regulated AQP5 expression in LPS injured AEC II cells, and Infliximab can greatly block AQP5 expression in LPS injured AEC II cells pretreated with lidocaine. Lidocaine pretreatment (2-200µg/ml) of LPS injured AEC II cells results in a decrease in TNF-α release, then up-regulates AQP5 expression, which maybe involved in the mechanism of its effects on AEC II cells injured by LPS.

CUL5-Mediated Visfatin (NAMPT) Degradation Blocks Endothelial Proliferation and Angiogenesis via the MAPK/PI3K-AKT Signaling.

ABSTRACT: Endothelial dysfunction participates in the pathogenesis of various cardiovascular disorders, and dysregulated angiogenesis involves the vascular endothelial growth factor (VEGF)-matrix metalloproteinases (MMP) system. Nicotinamide phosphoribosyltransferase (NAMPT) is known to enhance endothelial function and angiogenesis. The study found that NAMPT overexpression protected human coronary artery endothelial cells (HCAECs) from H2O2-induced injury through promoting cell viability, inhibiting cell apoptosis, enhancing cell motility, and promoting tube formation. Through analyses based on 2 Protein-Protein Interaction databases, Mentha and BioGrid, we identified CUL5 as a protein that may interact with NAMPT, which was then validated by Co-IP experiments. Through interacting with NAMPT, CUL5 inhibited NAMPT expression. In contrast to NAMPT, CUL5 overexpression further aggravated H2O2-induced HCAEC dysfunction. In the meantime, CUL5 overexpression reduced, whereas NAMPT overexpression increased the phosphorylation of p38 and Akt and the protein levels of VEGF and MMP2. More importantly, NAMPT overexpression partially reversed the effects of CUL5 overexpression on H2O2-stimulated HCAECs and the MAPK/phosphatidylinositol 3-kinase-Akt/VEGF/MMP signaling. In conclusion, CUL5 interacts with NAMPT in H2O2-stimulated HCAECs, suppressing cell viability, promoting cell apoptosis, and inhibiting cell mobility and tube formation. NAMPT overexpression protects against H2O2-induced HCAEC dysfunction by promoting cell viability, inhibiting cell apoptosis, and enhancing cell mobility and tube formation.

Depressive and Anxiety Symptoms of Healthcare Workers in Intensive Care Unit Under the COVID-19 Epidemic: An Online Cross-Sectional Study in China.

Background: Since the coronavirus disease-2019 (COVID-19) outbreak, intensive care unit (ICU) healthcare workers were responsible for the critical infected patients. However, few studies focused on the mental health of ICU healthcare workers. This study aimed to investigate the psychological impact of COVID-19 on ICU healthcare workers in China. Methods: We distributed the nine-item Patient Health Questionnaire (PHQ-9) and seven-item General Anxiety Disorder questionnaire (GAD-7) online to ICU healthcare workers in China. Respondents were divided into frontline and second-line according to whether they have contact with COVID-19 patients. Depressive and anxiety symptoms of all respondents were evaluated based on their questionnaire scores. Results: There were 731 ICU healthcare workers finally enrolled in our study, including 303 (41.5%) male, 383 (52.4%) doctors, and 617 (84.4%) aged 26-45 years. All in all, 482 (65.9%) ICU healthcare workers reported symptoms of depression, while 429 (58.7%) reported anxiety. There was no significant difference between frontline (n = 325) and second-line (n = 406) respondents in depression (P = 0.15) and anxiety severity (P = 0.56). Logistic regression analysis showed that being female, ICU work time >5 years, and night duty number ≥10 were risk factors of developing depressive and anxiety symptoms. Income reduction was separately identified as risk of anxiety. Additionally, ICU work time >5 years was also identified as risk of developing moderate-severe depressive and anxiety symptoms. Conclusions: Frontline ICU work was not associated with higher risk of depressive and anxiety symptoms during COVID-19 pandemic remission period in China. Actions like controlling night duty number, ensuring vacation, and increasing income should be taken to relieve mental health problem. Furthermore, we should pay close attention to those who had worked long years in ICU.

Evaluation of the exposure risk of SARS-CoV-2 in different hospital environment.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a significant impact on social and economic activities. As a high infectious pathogen, the existence of SARS-CoV-2 in public space is very important for its transmission. During the COVID-19 pandemic, hospitals are the main places to deal with the diseases. In this work, we evaluated the exposure risk of SARS-CoV-2 in hospital environment in order to protect healthcare workers (HCWs). Briefly, air and surface samples from 6 different sites of 3 hospitals with different protection levels were collected and tested for the SARS-CoV-2 nucleic acid by reverse transcription real-time fluorescence PCR method during the COVID-19 epidemic. We found that the positive rate of SARS-CoV-2 nucleic acid was 7.7 % in a COVID-19 respiratory investigation wards and 82.6 % in a ICUs with confirmed COVID-19 patients. These results indicated that in some wards of the hospital, such as ICUs occupied by COVID-19 patients, the nucleic acid of SARS-CoV-2 existed in the air and surface, which indicates the potential occupational exposure risk of HCWs. This study has clarified retention of SARS-CoV-2 in different sites of hospital, suggesting that it is necessary to monitor and disinfect the SARS-CoV-2 in hospital environment during COVID-19 pandemic, and will help to prevent the iatrogenic infection and nosocomial transmission of SARS-CoV-2 and to better protect the HCWs.

Pentamidine protects mice from cecal ligation and puncture-induced brain damage via inhibiting S100B/RAGE/NF-κB.

The brain is one of the earliest organs to be influenced during sepsis. Sepsis-associated encephalopathy (SAE) is frequent, but seldomly recognized and has no testified pharmacological therapy. In this study, we demonstrated that pentamidine, an antiprotozoal drug, is a good candidate since it blocks S100B/RAGE/NF-κB signaling pathway. Pentamidine ameliorated cecal ligation and puncture (CLP)-induced brain damage assessed by crystal violet staining and hematoxylin and eosin (H&E) staining. Moreover, pentamidine reduced neuroinflammation in mouse hippocampi. Immunofluorescence and Western blot analysis also showed that pentamidine inhibited CLP-induced gliosis and S100B/RAGE/NF-κB pathway activation. Interestingly, it could also attenuate oxidative stress indicated by decreased protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and attenuation of malondialdehyde (MDA) accumulation and superoxide dismutase (SOD) consumption. Thus the S100B/RAGE/NF-κB pathway may be crucial in the pathogenesis of SAE and may be a promising pharmacological target to prevent SAE.

lncRNA GAS5/miR-223/NAMPT axis modulates the cell proliferation and senescence of endothelial progenitor cells through PI3K/AKT signaling.

Endothelial progenitor cells (EPCs) have been reported to replace the damaged endothelial cells to repair the injured or dead endothelium. However, EPC senescence might lead to the failure in EPC function. Thus, developing an in-depth understanding of the mechanism of EPC senescence might provide novel strategies for related vascular disorders' treatments. Herein, nicotinamide phosphoribosyltransferase (NAMPT) overexpression could increase cell proliferation and suppress cell senescence in EPCs. miR-223 directly bound to the 3'-untranslated region of NAMPT to inhibit its expression, therefore modulating EPC proliferation and senescence through NAMPT and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling. Long noncoding RNA (lncRNA) GAS5 sponges miR-223, consequently downregulating miR-223 expression. GAS5 knockdown inhibited EPC proliferation and promoted senescence. GAS5 might serve as a competing endogenous RNA for miR-223 to counteract miR-223-mediated suppression on NAMPT, thus regulating EPC proliferation and senescence via the PI3K/AKT signaling pathway. In summary, our findings provide a solid experimental basis for understanding the role and mechanism of lncRNA GAS5/miR-223/NAMPT axis in EPC proliferation and senescence.

Angiotensin-(1-7)/Mas Signaling Inhibits Lipopolysaccharide-Induced ADAM17 Shedding Activity and Apoptosis in Alveolar Epithelial Cells.

A disintegrin and metalloproteinase (ADAM) 17, constitutively expressed in alveolar epithelium, is the pivotal shedding enzyme mediating acute lung inflammation. On the other hand, angiotensin (Ang)-(1-7)/Mas signaling has been shown to improve acute respiratory distress syndrome and protect alveolar epithelial cells from apoptosis. In this study, we explored the effect of Ang-(1-7)/Mas signaling on the expression and activity of ADAM17 and assessed its impact on apoptosis in lipopolysaccharide (LPS)-treated human alveolar epithelial cells. LPS markedly induced the shedding activity of ADAM17 in alveolar epithelial cells, which was blocked by selective c-Jun N-terminal kinase (JNK) inhibitor SP600125. Ang-(1-7) concentration-dependently inhibited LPS-induced ADAM17 shedding activity, which was abolished by selective Mas blocker A779 and Mas shRNA. LPS and Ang-(1-7) showed no significant effect on the expression of ADAM17. Overexpression of ADAM17 synergized with LPS on increasing the shedding activity of ADAM17 and apoptosis in alveolar epithelial cells, counteracting the inhibitory effects of Ang-(1-7). In addition, LPS significantly increased the JNK activity in alveolar epithelial cells; Ang-(1-7) concentration-dependently inhibited LPS-induced JNK activity, which was abolished by A779 and Mas shRNA. In conclusion, this study suggests that Ang-(1-7)/Mas signaling inhibits LPS-induced alveolar epithelial cell apoptosis by inhibiting LPS-induced shedding activity of ADAM17, likely by a JNK-dependent mechanism.

PBEF promotes the apoptosis of pulmonary microvascular endothelial cells and regulates the expression of inflammatory factors and AQP1 through the MAPK pathways.

Pre-B cell colony-enhancing factor (PBEF) has been shown to have a variety of biological functions. Studies have proven that PBEF plays a functional role in acute lung injury (ALI). Therefore, in this study, we aimed to confirm the importance of PBEF in ALI. The effects of PBEF overexpression on the apoptosis of human pulmonary microvascular endothelial cells (HPMECs) were analyzed by flow cytometry, and the results indicated that PBEF promoted the apoptosis of HPMECs, which aggravated the development of ALI. Comparative experiments involving increasing and decreasing PBEF expression demonstrated that PBEF promoted the expression of inflammatory factors, such as interleukin (IL)­1ß, IL­6 and IL­8 in the HPMECs , thus intensifying the inflammatory response. PBEF also inhibited the expression of aquaporin 1 (AQP1), which caused a dysfunction and imbalance in water transport. Moreover, we also found that tumor necrosis factor (TNF)­α promoted the expression of PBEF in the HPMECs. After blocking the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways, we found that PBEF regulated the expression of inflammatory factors and AQP1, mainly through the MAPK pathways. Taken together, these results demonstrate that the increase in intracellular PBEF expression promoted the apoptosis of HPMECs and the expression of inflammatory factors and thus enhanced the inflammatory response and inhibited the expression of AQP1, which resulted in abnormal water transport, diminishing the regulatory effects of AQP1 on water transport.

Neutrophil gelatinase-associated lipocalin attenuates injury in the rat cecal ligation and puncture model of sepsis via apoptosis inhibition.

AIM: The aim of this study was to investigate the effect of neutrophil gelatinase-associated lipocalin (NGAL) on the rat cecal ligation and puncture (CLP)-induced sepsis and the possible mechanism. METHODS: Thirty male Sprague-Dawley rats underwent CLP as sepsis models and were randomized into three groups including the sham-operated group (sham, n = 10), which only underwent a laparotomy; the sepsis group (sepsis, n = 10), which underwent CLP and subcutaneous injection of normal saline; and the sepsis + NGAL group (sepsis + NGAL, n = 10), which underwent CLP and subcutaneous injection of NGAL. Urine, blood and kidney tissue samples were collected for the determination of urine NGAL (uNGAL), plasma NGAL (pNGAL), serum creatinine (Scr), blood urea nitrogen (BUN), histomorphological and immunohistochemical examination, lipid peroxidation product malondialdehyde (MDA) and superoxide dismutase (SOD), and expression of heme oxygenase-1 (HO)-1. RESULTS: The levels of uNGAL, pNGAL, Scr, BUN, kidney injury score, positive TUNEL staining, activated Caspase-3 and Bax, and kidney tissue MDA levels in the sepsis group were significantly increased compared with those in the sham-operated group and the sepsis + NGAL group (P < 0.05). SOD level and HO-1 expression in sepsis + NGAL group were significantly higher than those in the sham-operated group and the sepsis group (P < 0.05). CONCLUSION: NGAL can attenuate kidney injury and apoptosis in the rat CLP model of sepsis. And the protective effect of NGAL was probably due to the inhibition of apoptosis and lipid peroxidation, and increased expression of HO-1.

JAZF1 regulates visfatin expression in adipocytes via PPARα and PPARß/δ signaling.

OBJECTIVE: Current whole genome-wide association study has identified the association of JAZF1 with type 2 diabetes; its close relation with glucose and lipid metabolism has also been revealed. However, to date, JAZF1 remains a relatively new gene with unknown function. MATERIALS/METHODS: We constructed JAZF1 overexpression vector and synthesized JAZF1 siRNA, then transfected them into 3T3-L1 adipocytes, investigated the relationship between the regulations of JAZF1, visfatin, and other adipokines, researched the specific function of JAZF1 in glucose and lipid metabolism. RESULTS: This study found that the expression of JAZF1 was gradually but significantly upregulated during the induced differentiation of 3T3-L1 preadipocytes, and that the trend of its expression was consistent with that of visfatin. Further studies indicated that JAZF1 promoted the expressions of visfatin, PPARα, and PPARß/δ in adipocytes but simultaneously inhibited the expressions of TAK1 and PPARγ. Luciferase reporter assay revealed that JAZF1 activated the transcription of visfatin, but ChIP assay results indicated that JAZF1 did not directly bind to visfatin PPRE. Our results also showed that the JAZF1 overexpression-increased visfatin expression was abolished by the addition of PPARα antagonist GW 6471 and PPARß/δ antagonist GSK 3787 respectively. And these results were further confirmed by the experiment with PPARα and PPARß/δ siRNAs. Meanwhile, we also found that JAZF1 inhibited the lipid accumulation during the differentiation of 3T3-L1 into mature adipocyte. CONCLUSIONS: Our results indicate that JAZF1 might firstly upregulated the expression of PPARα and PPARß/δ, which in turn activated the transcription of visfatin. JAZF1 plays an important role in lipid metabolism and may thus provide a potential tool for the treatment of obesity and lipid metabolism disorders among other diseases.

[Effects of simvastatin on lipopolysaccharide induced α-subunit epithelial sodium channel mRNA in rat lung alveolar type II epithelial cells].

OBJECTIVE: To study the impact of simvastatin on α-subunit epithelial sodium channel (α-ENaC) mRNA expression in primary culture alveolar typeII (ATII) epithelial cell of rats induced by lipopolysaccharide (LPS) in vitro. METHODS: ATII of primary generation were isolated from adult Sprague-Dawley (SD) rats. The cells were randomly divided into five groups: blank control group, LPS injured group (final concentration of LPS 1 mg/L), simvastatin low and high concentration groups (final concentration of simvastatin 20 µmol/L, 30 µmol/L, respectively), solution control group. Then, after being intervened for 1, 12 and 24 hours, the level of human tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were monitored by enzyme-linked immunosorbent assay (ELISA), and α-ENaC mRNA expression was tested by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: After being intervened for 1, 12 and 24 hours, expressions of TNF-α and IL-1ß in LPS injured group were obviously higher than those in blank control group. Expressions of TNF-α and IL-1ß at 1, 12 and 24 hours in simvastatin low concentration group were significantly decreased compared with those in LPS injured group (TNF-α 1 hour: 1178.80±127.43 ng/L vs. 2336.00±170.04 ng/L, 12 hours: 1003.60±59.61 ng/L vs. 2479.80±210.41 ng/L, 24 hours: 695.80±25.24 ng/L vs. 1167.60±132.72 ng/L; IL-ß 1 hour: 285.00±42.60 ng/L vs. 429.60±27.39 ng/L, 12 hours: 238.60±24.12 ng/L vs. 822.20±12.74 ng/L, 24 hours: 213.40±17.87 ng/L vs. 637.60±22.96 ng/L, all P<0.05). Expressions of TNF-α and IL-1ß in high concentration group were decreased more obviously than those in low concentration group (TNF-α 1 hour: 965.60±24.45 ng/L vs. 1178.80±127.43 ng/L, 12 hours: 522.80±16.89 ng/L vs. 1003.60±59.61 ng/L, 24 hours: 252.40±17.64 ng/L vs. 695.80±25.24 ng/L; IL-1ß 1 hour: 225.60±34.44 ng/L vs. 285.00±42.60 ng/L, 12 hours: 190.60±17.64 ng/L vs. 238.60±24.12 ng/L, 24 hours: 152.80±14.70 ng/L vs. 213.40±17.87 ng/L, all P<0.05), but increased compared with those in blank control group. After being intervened for 1 hour, no evident changes were observed in expression of α-ENaC mRNA in all groups. After being intervened for 12 hours and 24 hours, evident decrease in expression of α-ENaC mRNA (A value) was observed in LPS injured group compared with blank control group (12 hours: 0.211±0.021 vs. 0.496±0.027, 24 hours: 0.253±0.030 vs. 0.482±0.030, both P<0.05). Expressions of α-ENaC mRNA in simvastatin low concentration group evidently increased compared with those in LPS injured group (12 hours: 0.363±0.030 vs. 0.211±0.021, 24 hours: 0.309±0.024 vs. 0.253±0.030, both P<0.05). Expressions of α-ENaC mRNA in simvastatin high concentration group increased more obviously compared with those in low concentration group (12 hours: 0.413±0.034 vs. 0.363±0.030, 24 hours: 0.346±0.024 vs. 0.309±0.024, both P<0.05), but decreased compared with blank control group. No evident difference in expressions of all indexes in solution control group was observed compared with those in blank control group. CONCLUSIONS: High dose simvastatin could improve α-ENaC mRNA expression in primary culture ATII epithelial cells of rats. This may act by modulation the level of TNF-α and IL-1ß.

[Significance of central venous-to-arterial carbon dioxide difference for early goal-directed therapy in septic patients].

OBJECTIVE: To determine whether central venous-to-arterial carbon dioxide tension difference (Pcv-aCO(2)) could still be used as a goal of fluid resuscitation in septic patients who already had ScvO2 greater than 70% after early resuscitation. METHODS: A prospective observational study was performed on 56 septic patients admitted to the Intensive Care Unit (ICU) in a single University Hospital, who already had ScvO2 greater than 70% after early resuscitation. They were divided into two groups, based on whether the patients' initial Pcv-aCO2 was less than 6 mmHg (low gap group) or greater than or equal to 6 mmHg (high gap group). The following data were collected at 0, 12, and 24 hours (T(0), T(12), T(24)) after study inclusion: hemodynamic indices [mean blood pressure (MAP), heart rate (HR), cardiac output (CO), central venous pressure (CVP)], perfusion-related indexes [ScvO(2), Pcv-aCO2, serum lactate (Lac), Lac clearance rate], organ function- related indices [oxygenation index (PaO2/FiO(2)), serum creatinine (SCr), creatine kinase (CK-MB)], APACHE II score, SOFA score, and 24 hours amounts of fluid infusion. RESULTS: Twenty patients (42.9%) with initial Pcv-aCO(2) ≥ 6 mmHg were included in the high gap group and another thirty-two patients were included in the low gap group. At T12 and T24, ScvO(2) and CO were significantly higher, and Lac and SCr were significantly lower in low gap patients than high gap patients (P<0.05). At T(12) and T(24), Lac clearance rate was significantly higher (P<0.05), and 24-hours amounts of fluid infusion was significantly less [(3449.47 ± 695.41) mL vs (4070.66 ± 757.43) mL, P= 0.002] for the low gap group than for the high gap group, as well as the descrease of SOFA score at T(24) (P<0.05). There was no significant difference of APACHE II score between the 2 groups (P<0.05). CO and Pcv-aCO(2) values were inversely correlated (P< 0.05). CONCLUSION: Septic patients targeting only ScvO(2) may still have inappropriate tissue perfusion, especially when Pcv-aCO2 ≥6 mmHg, which indicates insufficient resuscitation. When ScvO(2) > 70% has achieved after early resuscitation, Pcv-aCO2 can still be used as a goal of fluid resuscitation in septic patients .

Prognostic indicators of patients with acute kidney injury in intensive care unit.

BACKGROUND: Acute kidney injury (AKI) is associated with a high mortality. This study was undertaken to detect the factors associated with the prognosis of AKI. METHODS: We retrospectively reviewed 98 patients with AKI treated from March 2008 to August 2009 at this hospital. In these patients, 60 were male and 38 female. Their age ranged from 19 to 89 years (mean 52.4±16.1 years). The excluded patients were those who died within 24 hours after admission to ICU or those who had a history of chronic kidney disease or incomplete data. After 60 days of treatment, the patients were divided into a survival group and a death group. Clinical data including gender, age, history of chronic diseases, the worst laboratory values within 24 hours after diagnosis (values of routine blood tests, blood gas analysis, liver and renal function, levels of serum cystatin C, and blood electrolytes) were analyzed. Acute physiology, chronic health evaluation (APACHE) II scores and 60-day mortality were calculated. Univariate analysis was performed to find variables relevant to prognosis, odds ratio (OR) and 95% confidence interval (CI). Multiple-factor analysis with logistic regression analysis was made to analyze the correlation between risk factors and mortality. RESULTS: The 60-day mortality was 34.7% (34/98). The APACHE II score of the death group was higher than that of the survival group (17.4±4.3 vs. 14.2±4.8, P<0.05). The mortality of the patients with a high level of cystatin C>1.3 mg/L was higher than that of the patients with a low level of cystatin C (<1.3 mg/L) (50% vs. 20%, P<0.05). The univariate analysis indicated that organ failures≥2, oliguria, APACHE II>15 scores, cystatin C>1.3 mg/L, cystatin C>1.3 mg/L+APACHE II>15 scores were the risk factors of AKI. Logistic regression analysis, however, showed that organ failures≥2, oliguria, cystatin C>1.3 mg/L +APACHE II>15 scores were the independent risk factors of AKI. CONCLUSION: Cystatin C>1.3 mg/L+APACHE II>15 scores is useful in predicting adverse clinical outcomes in patients with AKI.

Fas inhibition attenuates lipopolysaccharide-induced apoptosis and cytokine release of rat type II alveolar epithelial cells.

The aim of this study is to investigate whether silencing of Fas could have an influence on type II alveolar epithelial cell (AEC) apoptosis and inflammatory cytokine production, which prevents alveolar healing after acute lung injury (ALI). Rat primary type II AECs were isolated by elastase cell dispersion and IgG panning. The cells were transfected with Fas-specific small interfering RNA (siRNA) followed by treatment with lipopolysaccharide (LPS), Fas ligand (FasL) or both. The effects of siRNA-mediated silencing of Fas on LPS-induced apoptosis and cytokine release were then assessed. Notably, LPS, either alone or together with FasL, significantly stimulated type II AEC apoptosis and the release of tumor necrosis factor-alpha (TNF-α) and monocyte chemoattractant protein 1 (MCP-1) (P < 0.05 versus the control without treatment). Moreover, the effects exerted by both LPS and FasL were considerably counteracted by pretreatment with Fas-siRNA (P < 0.05 versus treatment with LPS and FasL). In conclusion, inhibition of Fas can diminish LPS-induced apoptosis and inflammatory cytokine production in type II AECs, and Fas specific siRNAs may have therapeutic potentials for intervention of ALI/ARDS.