S100A9 exacerbates sepsis-induced acute lung injury via the IL17-NFκB-caspase-3 signaling pathway.

BACKGROUND: Sepsis-induced acute lung injury (ALI) is associated with considerable morbidity and mortality in critically ill patients. S100A9, a key endothelial injury factor, is markedly upregulated in sepsis-induced ALI; however, its specific mechanism of action has not been fully elucidated. METHODS: The Gene Expression Omnibus database transcriptome data for sepsis-induced ALI were used to screen for key differentially expressed genes (DEGs). Using bioinformatics analysis methods such as Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses, the pathogenesis of sepsis-induced ALI was revealed. Intratracheal infusion of lipopolysaccharide (LPS, 10 mg/kg) induced ALI in wild-type (WT) and S100A9 knockout mice. Multiomics analyses (transcriptomics and proteomics) were performed to investigate the potential mechanisms by which S100A9 exacerbates acute lung damage. Hematoxylin-eosin, Giemsa, and TUNEL staining were used to evaluate lung injury and cell apoptosis. LPS (10 µg/mL)-induced murine lung epithelial MLE-12 cells were utilized to mimic ALI and were modulated by S100A9 lentiviral transfection. The impact of S100A9 on cell apoptosis and inflammatory responses were identified using flow cytometry and PCR. The expression of interleukin (IL)-17-nuclear factor kappa B (NFκB)-caspase-3 signaling components was identified using western blotting. RESULTS: Six common DEGs (S100A9, S100A8, IFITM6, SAA3, CD177, and MMP9) were identified in the six datasets related to ALI in sepsis. Compared to WT sepsis mice, S100A9 knockout significantly alleviated LPS-induced ALI in mice, with reduced lung structural damage and inflammatory exudation, decreased exfoliated cell and protein content in the lung lavage fluid, and reduced apoptosis and necrosis of pulmonary epithelial cells. Transcriptomic analysis revealed that knocking out S100A9 significantly affected 123 DEGs, which were enriched in immune responses, defense responses against bacteria or lipopolysaccharides, cytokine-cytokine receptor interactions, and the IL-17 signaling pathway. Proteomic analysis revealed that S100A9 knockout alleviated muscle contraction dysfunction and structural remodeling in sepsis-induced ALI. Multiomics analysis revealed that S100A9 may be closely related to interferon-induced proteins with tetratricopeptide repeats and oligoadenylate synthase-like proteins. LPS decreased MLE12 cell activity, accompanied by high expression of S100A9. The expression of IL-17RA, pNFκB, and cleaved-caspase-3 were increased by S100A9 overexpression and reduced by S100A9 knockdown in LPS-stimulated MLE12 cells. S100A9 knockdown decreases transcription of apoptosis-related markers Bax, Bcl and caspase-3, alleviating LPS-induced apoptosis. CONCLUSIONS: S100A9 as a key biomarker of sepsis-induced acute lung injury, and exacerbates lung damage and epithelial cell apoptosis induced by LPS via the IL-17-NFκB-caspase-3 signaling pathway.

PINK1 protects against dendritic cell dysfunction during sepsis through the regulation of mitochondrial quality control.

BACKGROUND: Dendritic cell (DC) dysfunction plays a central role in sepsis-induced immunosuppression. Recent research has indicated that collective mitochondrial fragmentation contributes to the dysfunction of immune cells observed during sepsis. PTEN-induced putative kinase 1 (PINK1) has been characterized as a guide for impaired mitochondria that can keep mitochondrial homeostasis. However, its role in the function of DCs during sepsis and the related mechanisms remain obscure. In our study, we elucidated the effect of PINK1 on DC function during sepsis and its underlying mechanism of action. METHODS: Cecal ligation and puncture (CLP) surgery and lipopolysaccharide (LPS) treatment were used as in vivo and in vitro sepsis models, respectively. RESULTS: We found that changes in mitochondrial PINK1 expression of DCs paralleled changes in DC function during sepsis. The ratio of DCs expressing MHC-II, CD86, and CD80, the mRNAs level of dendritic cells expressing TNF-α and IL-12, and the level of DC-mediated T-cell proliferation were all decreased, both in vivo and in vitro during sepsis, when PINK1 was knocked out. This suggested that PINK1 knockout prevented the function of DCs during sepsis. Furthermore, PINK1 knockout inhibited Parkin RBR E3 ubiquitin protein (Parkin)-dependent mitophagy and enhanced dynamin-related protein 1 (Drp1)-related mitochondrial fission, and the negative effects of PINK1 knockout on DC function following LPS treatment were reversed by Parkin activation and Drp1 inhibitor. Knockout of PINK1 also increased apoptosis of DCs and the mortality of CLP mice. CONCLUSION: Our results indicated that PINK1 protected against DC dysfunction during sepsis through the regulation of mitochondrial quality control.

Abnormalities of serum lipid metabolism in patients with acute paraquat poisoning caused by ferroptosis.

As the mechanism of paraquat (PQ) poisoning is still not fully elucidated, and no specific treatment has been developed in medical practice, the management of PQ poisoning continues to present a medical challenge. In this study, the objective was to investigate the early metabolic changes in serum metabolism and identify the key metabolic pathways involved in patients with PQ poisoning. Quantitative analysis was conducted to determine the relevant metabolites. Additionally, experiments were carried out in both plasma and cell to elucidate the mechanisms underlying metabolic disorder and cell death in PQ poisoning. The study found that polyunsaturated fatty acids (PUFAs) and their metabolites, such as arachidonic acid (AA) and hydroxy eicosatetraenoic acids (HETEs), were significantly increased by non-enzymatic oxidative reaction. Reactive oxygen species (ROS) production increased rapidly at 2 h after PQ poisoning, followed by an increase in PUFAs at 12 h, and intracellular glutathione, cysteine (Cys), and Fe2+ at 24 h. However, at 36 h later, intracellular glutathione and Cys decreased, HETEs increased, and the expression of SLC7A11 and glutathione peroxidase 4 (GPX4) decreased. Ultrastructural examination revealed the absence of mitochondrial cristae. Deferoxamine was found to alleviate lipid oxidation, and increase the viability of PQ toxic cells in the low dose. In conclusion, unsaturated fatty acids metabolism was the key metabolic pathways in PQ poisoning. PQ caused cell death through the induction of ferroptosis. Inhibition of ferroptosis could be a novel strategy for the treatment of PQ poisoning.

A new criteria for acute on preexisting kidney dysfunction in critically ill patients.

Critically ill patients with preexisting kidney dysfunction (PKD) are at high risk for acute kidney injury (AKI). Nevertheless, there is no criteria for screening and classifying AKI in patients with PKD. In this study, after assessing relationship between the change in SCr from baseline and in-hospital mortality, a new criteria, named APKD, for identifying AKI in PKD was proposed. APKD defined AKI in critically ill patients with PKD as an absolute increase of ≥ 0.2 mg/dL in SCr within 48 h or an increase in SCr ≥ 1.1 times over baseline within 7 d. APKD detected more AKI among PKD patients compared with the other criteria. Additionally, the AKI patients identified by APKD but missed by the other criteria had higher mortality than those without AKI. APKD shows higher sensitivities than KDIGO criteria in predicating in-hospital mortality. APKD, but not the KDIGO, is effective for staging the severity of AKI in patients with PKD. In conclusion, APKD is more effective in screening and classifying AKI in critically ill patients with PKD compared with the earlier criteria, and it may helpful in guiding clinical treatment and predicting prognosis.

Prevalence and predictors in self-neglect: A cross-sectional study of domestic migrant older adults in China.

Insufficient information is available on the prevalence and predictors of self-neglect among Chinese domestic migrant older adults resulting from rapid aging and mass population migration. This cross-sectional study was conducted on 597 older adults in four districts of Wenzhou from May to November 2020. A self-neglect scale was used to assess the prevalence of self-neglect among such adults. Sixteen potential predictors were considered in the domains of sociodemographic, health condition, socioeconomic, social isolation, intergenerational relationship, and filial piety. The prevalence of self-neglect within this population was 72.7%. Social isolation (OR = 0.823; 95%CI 0.684-0.990), physical health (OR = 0.966; 95%CI 0.941-0.992), intergenerational ambivalence (OR = 1.240; 95%CI 1.013-1.519), and affective-cognitive solidarity (OR = 0.796; 95%CI 0.719-0.880) were found to be independent predictors of self-neglect in this population. We suggest that community health service organizations should prioritize migrant older adults with a poor health status and those with intergenerational ambivalence to reduce self-neglect in migrant older adults. Such older adults should also be encouraged to participate in community activities for more social integration.

A latent profile analysis of emotional expression among patients with unintentional injuries.

BACKGROUND: Emotional expression has been suggested to affect the well-being of individuals with unintentional injuries. However, few studies have investigated it as a heterogeneous phenomenon. The purpose of this study was to characterize the patterns of emotional expression among patients with unintentional injuries using latent profile analysis, and to examine the relationship among these latent profiles and cognitive processing, posttraumatic growth, and posttraumatic stress disorder. METHODS: A cross-sectional study was carried out at two general hospitals in Wenzhou, China. In total, 352 patients with unintentional injuries completed the socio-demographic questionnaire, Berkeley Expressivity Questionnaire, Ambivalence Over Emotional Expression Questionnaire, Event-Related Rumination Inventory, the Posttraumatic Growth Inventory, and PTSD Checklist-Civilian Version.  RESULTS: Three unique profiles were identified: high emotional expressivity (n = 238, 67.6%), moderate emotional expressivity (n = 45, 12.8%), and low emotional expressivity (n = 69, 19.6%). The ANOVA and chi-square tests demonstrated significant differences among the three groups concerning deliberate rumination and posttraumatic growth. Multinomial logistic regression analysis indicated that monthly income and time since injury significantly predicted profile membership. CONCLUSIONS: Most patients showed high emotional expressivity after an unintentional injury. Emotional expression profiles were associated with deliberate rumination and posttraumatic growth. Emotional expression interventions tailored for different profiles are warranted after an unintentional injury.

Diagnostic potential of a gradient boosting-based model for detecting pediatric sepsis.

Pediatric sepsis is a major cause of mortality of children worldwide. However, there is still a lack of easy-to-use predictive tools that can accurately diagnose sepsis in children. This study aimed to develop an optimal gene model for the diagnosis of pediatric sepsis using statistics and machine learning approaches. Combining gene expression profiles from a training cohort of 364 pediatric samples with a Least Absolute Shrinkage and Selection Operator analysis produced eighteen genes as diagnostic markers. With the implementation of a Gradient Boosting algorithm, a model designated PEDSEPS-GBM, that aggregated these markers was developed with optimal performance for the diagnosis of pediatric samples in the validation and two independent cohorts. Moreover, a web calculator with a user-friendly interface was established for PEDSEPS-GBM. This study presents a diagnostic model that holds great potential for the detection of pediatric sepsis, and demonstrates the biologic and clinical relevance of this model.

Intensive care unit dignified care: Development and validation of a questionnaire.

BACKGROUND: Patient dignity is sometimes neglected in intensive care unit (ICU) settings, which may potentially cause psychological harm to critically ill patients. However, no instrument has been specifically developed to evaluate the behaviors of dignified care among critical care nurses. AIM: This study aimed to develop and evaluate ICU Dignified Care Questionnaire (IDCQ) for measurement of self-assessed dignity-conserving behaviors of critical care nurses during care. METHODS: The instrument was developed in 3 phases. Phase 1: item generation; phase 2: a two-round Delphi survey and a readability pilot study; phase 3: cross-sectional survey with model estimation. The questionnaire was evaluated by item analysis, exploratory and confirmatory factor analysis, assessment of internal consistency reliability, and test-retest reliability. The investigation was conducted using a convenience sample of 392 critical care nurses from 6 cities in Zhejiang Province, China, of which 30 participated in the test-retest reliability survey 2 weeks later. ETHICAL CONSIDERATIONS: The study was approved by ethics committee. All participants provided written informed consent before the survey. The questionnaire survey was anonymous. RESULTS: The results showed acceptable reliability and validity of the IDCQ. The 17-item final version questionnaire was divided into 2 dimensions: absolute dignity and relative dignity. These two factors accounted for 62.804% of the total variance, and model fitting results were acceptable. The Cronbach's alpha coefficient of the questionnaire was 0.94, and the test-retest intraclass correlation coefficient (ICC) was 0.88 after 2 weeks. CONCLUSIONS: This study developed a brief and reliable instrument (IDCQ) to assess dignified care in ICU nursing. It can help critical care nurses identify their behaviors in maintaining patient dignity and discover their deficiencies. It may also serve as a clinical nursing management tool to help reduce patient disrespect experience in ICU.

Individual factors in dignified care: A cross-sectional study of critical care nurses.

AIM: To determine the level of dignified care provided by critical care nurses, and explore the associated individual factors. BACKGROUND: Dignity is a fundamental right of human beings. Critically ill patients are dependent on nurses. Their need for respect and dignity is liable to be neglected in intensive care unit settings. Both critically ill survivors and dying patients suffer mental anguish due to loss of dignity. METHOD: This was a cross-sectional study of 526 critical care nurses working at intensive care units for adults in Zhejiang Province, China. Data were collected from February 2021 to May 2021 using the Intensive Care Unit Dignified Care Questionnaire, Wong and Law Emotional Intelligence Scale, Jefferson Scale of Empathy-Health Professional and Nurses Professional Values Scale-Revised. RESULTS: The total score of dignified care was 67.37 (8.83), with the standard score as 74.07 (12.99). Participants who performed poorly in absolute and relative dignity accounted for 8.4% and 31.2% of the total sample, respectively. Emotional intelligence (ß = .379, p < .001), empathy (ß = .319, p < .001), professional values (ß = .147, p < .001), age (ß = .075, p = .003) and training in dignified care (ß = .074, p = .010) were associated with dignified care, explaining 67.6% of the variance. CONCLUSION: The average level of participants' behaviours of maintaining patient dignity was medium. Critical care nurses need to improve their ability to maintain relative dignity of patients. Emotional intelligence, empathy, professional values, age level and training in dignified care were predictors of dignified care. IMPLICATIONS FOR NURSING MANAGEMENT: Improving emotional intelligence, empathy and professional values of critical care nurses and training them (especially less experienced nurses) will enhance their ability in dignified care. This study provides a novel perspective to help nursing managers develop interventions to promote humanized care in the intensive care unit.

Inhibition of the long non-coding RNA ZFAS1 attenuates ferroptosis by sponging miR-150-5p and activates CCND2 against diabetic cardiomyopathy.

Diabetic cardiomyopathy (DbCM) is responsible for increased morbidity and mortality in patients with diabetes and heart failure. However, the pathogenesis of DbCM has not yet been identified. Here, we investigated the important role of lncRNA-ZFAS1 in the pathological process of DbCM, which is associated with ferroptosis. Microarray data analysis of DbCM in patients or mouse models from GEO revealed the significance of ZFAS1 and the significant downregulation of miR-150-5p and CCND2. Briefly, DbCM was established in high glucose (HG)-treated cardiomyocytes and db/db mice to form in vitro and in vivo models. Ad-ZFAS1, Ad-sh-ZFAS1, mimic miR-150-5p, Ad-CCND2 and Ad-sh-CCND2 were intracoronarily administered to the mouse model or transfected into HG-treated cardiomyocytes to determine whether ZFAS1 regulates miR-150-5p and CCND2 in ferroptosis. The effect of ZFAS1 on the left ventricular myocardial tissues of db/db mice and HG-treated cardiomyocytes, ferroptosis and apoptosis was determined by Masson staining, immunohistochemical staining, Western blotting, monobromobimane staining, immunofluorescence staining and JC-1 staining. The relationships among ZFAS1, miR-150-5p and CCND2 were evaluated using dual-luciferase reporter assays and RNA pull-down assays. Inhibition of ZFAS1 led to reduced collagen deposition, decreased cardiomyocyte apoptosis and ferroptosis, and attenuated DbCM progression. ZFAS1 sponges miR-150-5p to downregulate CCND2 expression. Ad-sh-ZFAS1, miR-150-5p mimic, and Ad-CCND2 transfection attenuated ferroptosis and DbCM development both in vitro and in vivo. However, transfection with Ad-ZFAS1 could reverse the positive effects of miR-150-5p mimic and Ad-CCND2 in vitro and in vivo. lncRNA-ZFAS1 acted as a ceRNA to sponge miR-150-5p and downregulate CCND2 to promote cardiomyocyte ferroptosis and DbCM development. Thus, ZFAS1 inhibition could be a promising therapeutic target for the treatment and prevention of DbCM.

Plasma Concentration After the First Hemoperfusion has a High Predictive Value in Medium Level Acute Paraquat-Poisoned Patients.

BACKGROUND: Paraquat ( PQ) is very poisonous to humans and animals and there is no effective clinical antidote . The efficacy of hemoperfusion (HP) treatment for PQ poisoning remains controversial. To explore new ways to predict the prognosis of patients with acute PQ poisoning and assist in the development of better hemopurification treatment strategies. METHODS: The clinical data of patients who were intoxicated with PQ through contact were diagnosed with PQ poisoning by high-performance liquid chromatography. Samples were collected by the Emergency Intensive Care Unit of the First Affiliated Hospital of Wenzhou Medical University from January 2012 to November 2016. Based on the prognosis, the patients were grouped into survival and death groups. Comparisons of the differences in the clinical indexes were performed, including the initial concentration of PQ at admission, PQ concentration after first HP, the number of HP cartridges used for the first hemoperfusion, whether HP was combined with continuous renal replacement therapy, and the number of concurrent organ injuries between the 2 groups. In addition, data were analyzed using multivariate logistic regression models and receiver operating characteristic curves. Moreover, prognostic factors in patients with acute PQ poisoning were analyzed. RESULTS: Overall, 128 patients with acute PQ poisoning were enrolled in this study. The median plasma PQ concentrations of the patients at admission were 21 and 834 ng/mL (range: 50-1,099,118 ng/mL). The multiple logistic regression model revealed that the initial concentration of PQ and the PQ concentration after the first perfusion were independent risk factors for death in patients with acute PQ poisoning. The PQ concentration in the survival group after the first HP was <516 ng/mL and was mainly distributed at approximately 100 ng/mL. The percentage of patients whose concentration after the first HP was <516 ng/mL in the death group was only 19%. CONCLUSIONS: The initial plasma PQ concentration after admission and PQ concentration after the first HP are risk factors for death in patients with acute PQ poisoning. Moreover, PQ concentration after the first HP had a high predictive value for death. When the initial plasma PQ concentration after admission ranges from 50 ng/mL to 5000 ng/mL, the rapid reduction in plasma PQ concentration after HP treatment could improve the prognosis of patients with acute PQ poisoning.

Thyroid hormone levels as a predictor marker predict the prognosis of patients with sepsis.

BACKGROUND: Sepsis is a systemic inflammatory response syndrome with high mortality. There is an upward trend in sepsis prevalence and mortality worldwide. Early and accurate prediction of outcome in sepsis is important. There remains a great need to improve a reliable prognostic model for sepsis patients with widely available variables. The aim of this study was to explore the correlation between serum thyroid hormone levels and prognosis in sepsis patients. METHODS: Septic patients were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Factors that were found to contribute to the outcome in the uni-variate analysis at P value <0.1 were included in the multivariate. Multivariate analysis was performed by binary logistic regression analysis, which allows adjust for confounding factors. We combined an assessment of thyroid hormone and some variables together, which improve the accurate prediction of outcome. The accuracy of the test was assessed measuring the area under the ROC curve (AUROC). RESULTS: A total of 929 eligible septic patients were included in the data analysis. Seventy hundred and three patients had a good functional outcome, whereas 226 patients had a bad functional outcome. Thyroxin (T4) level was significantly decreased in patients with an unfavorable functional outcome as compared to patients with a favorable functional outcome (P < 0.01). Binary logistic regression analyses revealed that lower thyroxin concentrations on admission were associated with a risk for poor outcomes (OR 0.556, 95% CI 0.41-0.75; P < 0.01). In addition, in ROC curve analysis, the combined model AUROC was 0.82 for ICU survival, which was significantly higher than the AUROCs of original fT4 (0.65 and 0.65), T4 (0.71 and 0.71) and SAPSII (0.70 and 0.72) (all P < 0.05). CONCLUSIONS: Low serum thyroxin levels can be a predictive marker of short-term outcome after sepsis. A combined model (fT4, T4 and SAPSII score) can add significant additional predictive information to the clinical score of the SAPSII.

Emodin alleviates LPS-induced myocardial injury through inhibition of NLRP3 inflammasome activation.

Myocardial injury and cardiovascular dysfunction are serious consequences of sepsis and contribute to high mortality. Currently, the pathogenesis of myocardial injury in sepsis is still unclear, and therapeutic approaches are limited. In this study, we investigated the protective effect of emodin on septic myocardial injury and the underlying mechanism. Lipopolysaccharide (LPS)-induced C57BL/6 mice and cardiomyocytes were used as models of sepsis in vivo and in vitro, respectively. The results showed that emodin alleviated cardiac dysfunction, myocardial injury and improved survival rate in LPS-induced septic mice. Emodin attenuated the levels of inflammatory cytokines and cardiac inflammation induced by LPS. Emodin reduced NOD-like receptor protein 3 (NLRP3) and Gasdermin D (GSDMD) expression in the heart tissue of LPS-induced septic mice. In vitro, emodin alleviated LPS-induced cell injury and inflammation in cardiomyocytes by inhibiting NLRP3 inflammasome activation. In addition, an NLRP3 inhibitor was used to further confirm the function of the NLRP3 inflammasome in LPS-induced myocardial injury. Taken together, our findings suggest that emodin improves LPS-induced myocardial injury and cardiac dysfunction by alleviating the inflammatory response and cardiomyocyte pyroptosis by inhibiting NLRP3 inflammasome activation, which provides a feasible strategy for preventing and treating myocardial injury in sepsis.

Diastasis recti abdominis in adult women based on abdominal computed tomography imaging: Prevalence, risk factors and its impact on life.

AIMS AND OBJECTIVES: This study aimed to obtain the incidence of diastasis recti abdominis (DRA) and analyse possible risk factors in adult females. Moreover, the relationships between DRA and lower back pain, pelvic floor function and quality of life were also analysed. BACKGROUND: Diastasis recti abdominis is a separation of the abdominal muscles at the linea alba. Currently, studies on the prevalence rates, risk factors and consequences of DRA are varied. In particular, reports on DRA among adult women are lacking. DESIGN: A one-sample questionnaire study design is used following the STROBE checklist. METHODS: The inter-rectus distance was measured by computed tomography in 644 women. Custom questionnaires, the Oswestry Disability Index, The International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form and the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) were used to investigate personal information, the subjects' back pain, pelvic floor function and quality of life, respectively. RESULTS: The incidence of DRA was 28.4%. Age, the number of pregnancies, BMI and diabetes were influencing factors for DRA. After age stratification, pregnancy and diabetes were found to be risk factors for DRA in young women, and obesity and diabetes were risk factors for DRA in older women. This study showed that the association between DRA and low back pain was highly significant. CONCLUSIONS: Diastasis recti abdominis is common in adult women. Avoiding multiple pregnancies, preventing diabetes and controlling weight may prevent DRA, which may be beneficial for decreasing low back pain in women. RELEVANCE TO CLINICAL PRACTICE: The findings have important implications for the health of adult women which can provide the basis for appropriate nursing implementation for DRA patients. The application of specific prevention and intervention measures for the risk factors may reduce the severity of low back pain.

Association between furosemide administration and outcomes in critically ill patients with acute kidney injury.

BACKGROUND: Although current guidelines for AKI suggested against the use of furosemide in AKI management, the effect of furosemide on outcomes in real-world clinical settings remains uncertain. The aim of the present study was to investigate the association between furosemide administration and outcomes in critically ill patients with AKI using real-world data. METHODS: Critically ill patients with AKI were identified from the Medical Information Mart for Intensive Care (MIMIC)-III database. Propensity score (PS) matched analysis was used to match patients receiving furosemide to those without diuretics treatment. Linear regression, logistic regression model, and Cox proportional hazards model were used to assess the associations between furosemide and length of stay, recovery of renal function, and in-hospital and 90-day mortality, respectively. RESULTS: A total of 14,154 AKI patients were included in the data analysis. After PS matching, 4427 pairs of patients were matched between the patients who received furosemide and those without diuretics treatment. Furosemide was associated with reduced in-hospital mortality [hazard ratio (HR) 0.67; 95% CI 0.61-0.74; P < 0.001] and 90-day mortality [HR 0.69; 95% CI 0.64-0.75; P < 0.001], and it was also associated with the recovery of renal function [HR 1.44; 95% CI 1.31-1.57; P < 0.001] in over-all AKI patients. Nevertheless, results illustrated that furosemide was not associated with reduced in-hospital mortality in patients with AKI stage 0-1 defined by UO criteria, AKI stage 2-3 according to SCr criteria, and in those with acute-on-chronic (A-on-C) renal injury. CONCLUSIONS: Furosemide administration was associated with improved short-term survival and recovery of renal function in critically ill patients with AKI. Furosemide was especially effective in patients with AKI UO stage 2-3 degree. However, it was not effective in those with AKI SCr stage 2-3 and chronic kidney disease. The results need to be verified in randomized controlled trials.

Mdivi-1 Protects CD4+ T Cells against Apoptosis via Balancing Mitochondrial Fusion-Fission and Preventing the Induction of Endoplasmic Reticulum Stress in Sepsis.

Apoptosis of CD4+ T cells plays a central role in the progression of sepsis because it is associated with subsequent immunosuppression and the lack of specific treatment. Thus, developing therapeutic strategies to attenuate the apoptosis of CD4+ T cells in sepsis is critical. Several studies have demonstrated that Mdivi-1, which is a selective inhibitor of the dynamin-related protein 1 (Drp1), attenuates apoptosis of myocardial cells and neurons during various pathologic states. The present study revealed the impact of Mdivi-1 on the apoptosis of CD4+ T cells in sepsis and the potential underlying mechanisms. We used lipopolysaccharide (LPS) stimulation and cecal ligation and puncture (CLP) surgery as sepsis models in vitro and in vivo, respectively. Our results showed that Mdivi-1 attenuated the apoptosis of CD4+ T cells both in vitro and in vivo. The potential mechanism underlying the protective effect of Mdivi-1 involved Mdivi-1 reestablishing mitochondrial fusion-fission balance in sepsis, as reflected by the expression of the mitofusin 2 (MFN2) and optic atrophy 1 (OPA1) , Drp1 translocation, and mitochondrial morphology, as observed by electron microscopy. Moreover, Mdivi-1 treatment reduced reactive oxygen species (ROS) production and prevented the induction of endoplasmic reticulum stress (ERS) and associated apoptosis. After using tunicamycin to activate ER stress, the protective effect of Mdivi-1 on CD4+ T cells was reversed. Our results suggested that Mdivi-1 ameliorated apoptosis in CD4+ T cells by reestablishing mitochondrial fusion-fission balance and preventing the induction of endoplasmic reticulum stress in experimental sepsis.

Diagnostic value of complete blood count in paraquat and organophosphorus poisoning patients.

Complete blood count (CBC) is one of the most extensively used tests in clinical practice. In order to determine the diagnostic value of the CBC in paraquat (PQ) and organophosphorus (OPPs) poisoning, the CBC indices of PQ- and OPPs-poisoned patients were investigated in this study. A total of 96 PQ poisoning patients, 90 OPPs poisoning patients, and 188 healthy subjects were included in this study. The PQ- and OPPs-poisoned patients were divided into different groups according to their clinical symptoms. All CBC indices were analyzed by Fisher discriminant, partial least-squares discriminant analysis (PLS-DA), variance analysis, and receiver operating characteristic (ROC). The discriminant results showed that 87.7% of original grouped cases correctly classified between PQ-poisoned patients, OPPs-poisoned patients, and healthy subjects. The PLS-DA results showed that the important variable order was different in PQ- and OPPs-poisoned patients. Both white blood cell (WBC) and neutrophil (NE) counts were the most important indexes in PQ- and OPPs-poisoned patients. In OPPs poisoning patients, WBC and NE showed statistical differences between the severe poisoning group and the moderate poisoning group. Their areas under the ROC curve (AUC) were 0.673 (WBC) and 0.669 (NE), which were higher than cholinesterase (CHE; AUC 0.326). In conclusion, the CBC indices had a diagnostic value in PQ and OPPs poisoning; WBC and NE were the first responses and had clinical significance in PQ and OPPs poisoning; moreover, they are better than CHE in diagnosing OPPs poisoning.

Early Metabolome Profiling and Prognostic Value in Paraquat-Poisoned Patients: Based on Ultraperformance Liquid Chromatography Coupled To Quadrupole Time-of-Flight Mass Spectrometry.

Paraquat (PQ) has caused countless deaths throughout the world. There remains no effective treatment for PQ poisoning. Here we study the blood metabolome of PQ-poisoned patients using ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS). Patients were divided into groups according to blood PQ concentration. Healthy subjects served as controls. Metabolic features were statistically analyzed using multivariate pattern-recognition techniques to identify the most important metabolites. Selected metabolites were further compared with a series of clinical indexes to assess the prognostic value. PQ-poisoned patients showed substantial differences compared with healthy subjects. Based on variable of importance in the project (VIP) values and statistical analysis, 17 metabolites were selected and identified. These metabolites well-classified low PQ-poisoned patients, high PQ-poisoned patients, and healthy subjects, which was better than that of a complete blood count (CBC). Among the 17 metabolites, 20:3/18:1-PC (PC), LPA (0:0/16:0) (LPA), 19-oxo-deoxycorticosterone (19-oxo-DOC), and eicosapentaenoic acid (EPA) had prognostic value. In particular, EPA was the most sensitive one. Besides, the levels of EPA was correlated with LPA and 19-oxo-DOC. If EPA was excessively consumed, then prognosis was poor. In conclusion, the serum metabolome is substantially perturbed by PQ poisoning. EPA is the most important biomarker in early PQ poisoning.

Growth Arrest-Specific 6 Enhances the Suppressive Function of CD4+CD25+ Regulatory T Cells Mainly through Axl Receptor.

Background. Growth arrest-specific (Gas) 6 is one of the endogenous ligands of TAM receptors (Tyro3, Axl, and Mertk), and its role as an immune modulator has been recently emphasized. Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are essential for the active suppression of autoimmunity. The present study was designed to investigate whether Tregs express TAM receptors and the potential role of Gas6-TAM signal in regulating the suppressive function of Tregs. Methods. The protein and mRNA levels of TAM receptors were determined by using Western blot, immunofluorescence, flow cytometry, and RT-PCR. Then, TAM receptors were silenced using targeted siRNA or blocked with specific antibody. The suppressive function of Tregs was assessed by using a CFSE-based T cell proliferation assay. Flow cytometry was used to determine the expression of Foxp3 and CTLA4 whereas cytokines secretion levels were measured by ELISA assay. Results. Tregs express both Axl and Mertk receptors. Gas6 increases the suppressive function of Tregs in vitro and in mice. Both Foxp3 and CTLA-4 expression on Tregs are enhanced after Gas6 stimulation. Gas6 enhances the suppressive activity of Tregs mainly through Axl receptor. Conclusion. Gas6 has a direct effect on the functions of CD4+CD25+Tregs mainly through its interaction with Axl receptor.

Mitofusin 2 Promotes Apoptosis of CD4+ T Cells by Inhibiting Autophagy in Sepsis.

Apoptosis of CD4+ T cells is a primary pathophysiological mechanism of immune dysfunction in the pathogenesis of sepsis. Mitofusin 2 (Mfn2), an integral mitochondrial outer membrane protein, has been confirmed to be associated with cellular metabolism, proliferation, and apoptosis. The function of Mfn2 in CD4+ T cell apoptosis in sepsis is poorly understood. Here, we discovered increased in vivo Mfn2 expression, autophagy deficiency, and elevated cell apoptosis in murine splenic CD4+ T cells after cecal ligation and puncture (CLP). We also observed almost identical results in splenic CD4+ T cells upon lipopolysaccharide (LPS) stimulation in vitro. Furthermore, overexpression of Mfn2 resulted in impaired autophagy and increased apoptosis in Jurkat cells. Pharmacological inhibition of autophagy with 3-methyladenine enhanced Mfn2 overexpression-induced cell apoptosis. In addition, overexpression of Mfn2 downregulated phorbol myristate acetate (PMA)/ionomycin-, rapamycin- and starvation-induced autophagy in Jurkat T cells. Taken together, these data indicate a critical role of Mfn2 in CD4+ T cell apoptosis in sepsis and the underlying mechanism of autophagy deficiency.