Inflammation always accompanies infection during sepsis. Mitochondrial dysfunction and the role of reactive oxygen species (ROS) produced by mitochondria have been proposed in the pathogenesis of sepsis. Maresins have protective and resolving effects in experimental models of infection. In the present study, we investigated the effects of maresin 1 (MaR1) on mitochondrial function in cecal ligation and puncture (CLP)-induced sepsis and sepsis patients to identify mechanisms underlying maresin 1-mediated stimulation of ROS in mitochondria. We found that treatment with MaR1 significantly inhibited production of cytokines, decreased bacterial load in the peritoneal lavage fluid, reduced the number of neutrophils, decreased lactic acid level and upregulated cyclic AMP (cAMP) concentration, with the outcome of decreased lung injury in CLP-induced sepsis in mice. The effects of MaR1 on downregulation nitric oxide (NOX) activity, improvement CAT and SOD activity to inhibit ROS production in mitochondria was dependent on lipoxin receptor (ALX) and cAMP. Survival rates were significantly increased after the treatment of mice with MaR1. In BMDM stimulated with LPS, MaR1 inhibited the ROS production, downregulated enzyme activity, reduced mtO2 production, increased mitochondrial membrane potential, improved adenosine triphosphate (ATP) content and mitochondrial DNA (mtDNA) copy number. Finally, the effects of MaR1 on ROS production in the blood of healthy volunteers stimulated with LPS or sepsis patients were associated with ALX and cAMP. Taken together, these data suggest that treatment with MaR1 could attenuate mitochondrial dysfunction during sepsis through regulating ROS production.

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Background: Laparoscopic cholecystectomy (LC) is a common surgical procedure for managing gallbladder disease. Prolonged length of stay (LOS) in the postanesthesia care unit (PACU) may lead to overcrowding and a decline in medical resource utilization. In this work, we aimed to develop and validate a predictive nomogram for identifying patients who require prolonged PACU LOS.Methods: Data from 913 patients undergoing LC at a single institution in China between 2018 and 2019 were collected, and grouped into a training set (456, cases during 2018) and a test set (457, cases during 2019). The definition of PACU LOS is the duration between admission to discharge from PACU, which we can derive from the electronic medical record system. Using the least absolute shrinkage and selection operator regression model, the optimal feature was selected, and multivariable logistic regression analysis was used to build the prolonged PACU LOS risk model. The C-index, calibration plot, and decision curve analysis (DCA) were used in assessing the model calibration, discrimination, and clinical application value, respectively. For external validation, the test set data was evaluated. Results:The predictive nomogram had 8 predictor variables for prolonged PACU LOS, including age, American Society of Anesthesiologists (ASA) grade, active smoker, gastrointestinal disease, liver disease, and cardiovascular disease. This model displayed efficient calibration and moderate discrimination with a C-index of 0.662 (95% confidence interval, 0.603 to 0.721) for the training set, and 0.609 (95% confidence interval, 0.549 to 0.669) for the test set. DCA demonstrated that the prolonged PACU LOS nomogram was reliable for clinical application when an intervention was decided at the possible threshold of 7%. Conclusions:We developed and validated a predictive nomogram with efficient calibration and moderate discrimination, and can be applied to identify patients most likely to be subjected to prolonged PACU LOS. This novel tool may shun overcrowding in PACU and optimize medical resource utilization.

Momordica cochinchinensis (Lour.) Spreng is an indigenous South Asian edible fruit, and seeds of Momordica cochinchinensis have been used therapeutically in traditional Chinese medicine. Previous studies have shown that M. cochinchinensis seed (Momordicae Semen) has various pharmaceutical properties such as antioxidant and anti‐ulcer effects as well as contains secondary metabolites with potential anticancer activities such as triterpenoids and saponins. Recent studies reported that water extract and ethanol extract of M. cochinchinensi seed were tested on mammals using an acute toxic classic method as OECD guidelines 420. No matter injected intravenously or intramuscularly, animals died within several days. In this study, zebrafish embryos were exposed to various doses of Cochinchina momordica seed extract (CMSE) from 2 dpf (days post fertilization, dpf) to 3 dpf. CMSE‐induced cardiotoxicity such as pericardial edema, cardiac apoptosis, increased ROS production, cardiac neutrophil infiltration, decreased blood flow velocity, and reduced expression of three marker genes of cardiac functions were found in zebrafish roughly in a dose‐dependent manner. These results suggest that CMSE may induce cardiotoxicity through pathways involved in inflammation, oxidative stress, and apoptosis.

Background: Sepsis is a life-threatening organ dysfunction due to disturbance of the host's response to infection, and is often accompanied by shock. Timely and standardized hemodynamic management can effectively control disease progression. Mean arterial pressure (MAP) refers to tissue and organ perfusion and is one of the key factors for patient recovery. In this study, we focused on the relationship between MAP levels and 30-day mortality in patients with sepsis.Methods: This cohort study included 14,607 sepsis patients out of 38,597 adults admitted to Beth Israel Deaconess Medical Center in Boston between 2001 and 2012, according to the Sepsis 3.0 diagnostic criteria. According to the MAP value of the sepsis patients on the first day of intensive care unit (ICU) admission, they were divided into 5 groups (Q1 ≤67.4 mmHg, Q2 67.4-72.5 mmHg, Q3 72.5-77.6 mmHg, Q4 77.6-84.6 mmHg, Q5 ≥84.6 mmHg). At the same time, the baseline data of vital signs, critical illness score, comorbidities and laboratory examination were collected on the first day of admission to ICU. The 30-day mortality of the 5 groups of patients and the overall sepsis patients were recorded. Multivariate Cox regression analysis and smooth curve fitting were used to assess the independent association between MAP and 30-day mortality.Results: A total of 14,607 sepsis patients were screened. The mean age of participants was 67.2±16.3 years, approximately 46.9% were women, and the overall 30-day mortality rate was 21.0%. Multivariate Cox regression models and smooth curve fitting revealed a non-linear association between MAP and 30-day mortality. The inflection point occurred at 68.6 mmHg. The left side effect size of each 10-unit change in the exposure factor was [hazard ratio (HR): 0.479, 95% confidence interval (CI): 0.403-0.569, P<0.001]. To the right of the inflection point, the effect size was (HR: 0.996, 95% CI: 0.931-1.065, P<0.9018).Conclusions: Our study demonstrated a non-linear relationship between MAP and 30-day mortality in patients with sepsis. When MAP was less than 68.6 mmHg, it was a strong predictor of the potential risk of sepsis death, which is declined by 52.1% for every 10 mmHg growth in MAP.

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Background: Laparoscopic Cholecystectomy (LC) is a common surgical procedure for managing gallbladder disease. Prolonged length of stay (LOS) in the postanesthesia care unit (PACU) may lead to overcrowding and a decline in medical resource utilization. In this work, we aimed to develop and validate a predictive nomogram for identifying patients who require prolonged PACU LOS.Methods: Data from 913 patients undergoing LC at a single institution in China between 2018 and 2019 were collected, and grouped into a training set (cases during 2018) and a test set (cases during 2019). Using the least absolute shrinkage and selection operator regression model, the optimal feature was selected, and multivariable logistic regression analysis was used to build the prolonged PACU LOS risk model. The C-index, calibration plot, and decision curve analysis were used in assessing the model calibration, discrimination, and clinical application value, respectively. For external validation, the test set data was evaluated.Results: The predictive nomogram had 8 predictor variables for prolonged PACU LOS, including age, ASA grade, active smoker, gastrointestinal disease, liver disease, and cardiovascular disease. This model displayed efficient calibration and moderate discrimination with a C-index of 0.662 (95% confidence interval, 0.603 to 0.721) for the training set, and 0.609 (95% confidence interval, 0.549 to 0.669) for the test set. Decision curve analysis demonstrated that the prolonged PACU LOS nomogram was reliable for clinical application when an intervention was decided at the possible threshold of 7%.Conclusions: We developed and validated a predictive nomogram with efficient calibration and moderate discrimination, and can be applied to identify patients most likely to be subjected to prolonged PACU LOS. This novel tool may shun overcrowding in PACU and optimize medical resource utilization.