EFFECTS OF HYPERBARIC OXYGEN THERAPY ON INTESTINAL ISCHEMIA-REPERFUSION AND ITS MECHANISM

Intestinal ischemia-reperfusion injury is a critical medical condition that poses an important therapeutic challenge. The article by Song et al. (pp. 650–659) provides an overview of the pathophysiologic mechanisms of ischemia-reperfusion injury and highlights the potential beneficial effects of hyperbaric oxygen therapy on modulating inflammation, oxidative stress, angiogenesis while promoting tissue repair.

MORTALITY AND ASSOCIATED FACTORS AMONG INTENSIVE CARE UNIT ADMITTED ADULT PATIENTS WITH MECHANICAL VENTILATION IN ETHIOPA: SYSTEMATIC REVIEW AND META-ANALYSIS

Patients requiring mechanical ventilation are at risk for ventilator-associated complications which require extensive critical care resources. Alamaw et al. (pp. 660–665) provide a systematic review and meta-analysis on mortality of adult patients requiring mechanical ventilation in Ethiopa. They found a high pooled mortality rate among patients requiring mechanical ventilation and identified factors contributing to mortality.

IMMUNOSUPPRESSION CORRELATES WITH THE DETERIORATION OF SEPSIS-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION

The host response plays a role in the pathophysiology of sepsis-induced disseminated intravascular coagulation (DIC). The study by Sun et al. (pp. 666–674) studied the prediction value of immune indicators for the development of DIC. The study found a combination of the anti-inflammatory cytokine IL-10 and mHLA-DR at day one upon enrollment had superior predictive value for predicting DIC deterioration in sepsis.

CIRC-MARC2 SILENCING PROTECTS HUMAN CARDIOMYOCYTES FROM HYPOXIA/REOXYGENATION–INDUCED INJURY BY MODULATING MIR-335-5P/TRPM7 AXIS

Circular RNAs (circRNAs) have been shown to regulate pathophysiologic responses in cardiovascular diseases. Using an in vitro model of hypoxia and reoxygenation in human ventricular cardiomyocytes, Deng et al. (pp. 675–684) showed that circ-mitochondrial amidoxime reducing component 2 (circ-MARC2) was overexpressed and was associated with apoptosis and inhibition of cell proliferation after hypoxia and reoxygenation. At molecular analysis, the authors described a pathway involving the microRNA-335-5p and its target, the transient receptor potential channel 7.

THE THERAPEUTIC EFFICACY OF PLASMAPHERESIS FOR SEPSIS WITH MULTIPLE ORGAN FAILURE: A PROPENSITY SCORE-MATCHED ANALYSIS BASED ON THE MIMIC-IV DATABASE

Therapies to improve sepsis mortality are limited. In the study by Yan et al. (pp. 685–694) the authors utilized a large, critical care database (Medical Information Mart for Intensive Care IV [MIMIC-IV]) and retrospectively analyzed patients with sepsis who underwent plasmapheresis compared to those who did not with and without propensity score matching. Plasmapheresis was associated with a reduced risk of 28-day mortality, 1-year mortality and in-hospital mortality. The improvement with PE was associated with an improvement in organ function and markers of inflammation and coagulopathy.

EQUOL, A SOYBEAN METABOLITE WITH ESTROGEN-LIKE FUNCTIONS, DECREASES LIPOPOLYSACCHARIDE-INDUCED HUMAN NEUTROPHIL EXTRACELLULAR TRAPS IN VITRO

Although important for their antimicrobial activity, neutrophil extracellular traps (NETs) can exacerbate inflammation when released in excess during sepsis. Using neutrophils isolated from healthy volunteers, Murakami et al. (pp. 695–704) investigated the potential modulatory effects of equol, a natural estrogenic metabolite of soybean isoflavones, on NET formation upon stimulation with lipopolysaccharide. The authors showed that equol decreased formation of NETs via inhibition of the peptidyl arginine deiminase 4 pathway. Interestingly, the effect of equol treatment on NET formation was observed on neutrophils of male volunteers with low levels of circulating endogenous equol, thus suggesting that the potential therapeutic effects of exogenous equol may be influenced by the biological variables of sex and physiological concentration of the phytoestrogen.

CIRC_0003907 MODULATES SEPSIS-INDUCED MYOCARDIAL INJURY VIA ENHANCING MYD88/NLRP3/NF-ΚB AXIS BY SPONGING MIR-944

Lv et al. (pp. 705–711) provides insights into the molecular mechanisms of sepsis-induced cardiomyopathy. The authors demonstrated that the circular RNA circ_0003907 was overexpressed and was associated with apoptosis, release of inflammatory cytokines, oxidative stress, and inhibition of cell proliferation in human ventricular cardiomyocytes upon stimulation with lipopolysaccharide. At molecular analysis, the authors showed that circ_0003907 exerted his cytotoxic effects through inhibition of microRNA-944, thus enhancing the pro-inflammatory TLR/MYD88/NF-κB signaling pathway. Circ_0003907 expression was also found to be increased in serum from patients with sepsis-induced cardiomyopathy, further supporting a potential pathological role of this circular RNA.

DEVELOPMENT AND VALIDATION OF A NOMOGRAM FOR PREDICTING 28-DAY IN-HOSPITAL MORTALITY IN SEPSIS PATIENTS BASED ON AN OPTIMIZED ACUTE PHYSIOLOGY AND CHRONIC HEALTH EVALUATION II: SCORE

Early prediction models for patients with sepsis are informative. The study by Yuan et al. (pp. 718–727) aimed to establish a nomogram that correlates APACHE II score with sepsis indicators to build a model for sepsis prediction. They utilized a training group from a large critical care database of patients with sepsis (MIMIC-IV database) and externally validated with patients from a separate ICU. They established an Optimized score to predict the prognosis of adult patients with sepsis and integrated the Optimized score with sepsis-related markers to construct a nomogram model which was compared to SOFA and APACHE II scores. The nomogram demonstrated good predictive value for sepsis outcomes.

ANALYSIS AND IDENTIFICATION OF FERROPTOSIS-RELATED GENE SIGNATURE FOR ACUTE LUNG INJURY

Wang et al. (pp. 728–739) provided a large and complex analysis into the gene signatures related to the programmed cell death by ferroptosis during acute lung injury. Using the public large database from the Gene Expression Omnibus, the authors determined four key genes related to ferroptosis (PROK2, IL6, TNF, SLC7A11) by applying bioinformatics, immune infiltration, and functional enrichment analyses. The authors also validated the expression of these genes and their association with tissue injury in three animal models of sepsis, endotoxemia and hemorrhagic shock, further supporting the role of ferroptosis as pathogenetic event of lung injury.

IN VITRO EVALUATION OF A NOVEL AUTOMATIC INTRAOPERATIVE BLOOD LOSS MONITOR

Intraoperative blood loss measurements are usually based on visual estimates and experience during surgery. The study by Bai et al. (pp. 740–747) evaluated a novel automatic intraoperative blood loss monitor which can measure free blood volume and blood content in surgical sponges in real time. The monitor uses an integrated photelectric probe to gauge hemoglobin levels in surgical sponges. The study compared actual values to automatic monitor measurements using human and pig blood. Bai et al. found the new automatic monitor was accurate and reliable to detect blood loss.

SALVIANOLIC ACID A ATTENUATES ANGIOTENSIN II-INDUCED CARDIAC FIBROSIS THROUGH REGULATING TXNIP SIGNALING PATHWAY

Salvia miltiorrhiza (Danshen) is one of the commonly used drugs in traditional Chinese medicine and has a long history of clinical application in cardiovascular diseases. The article by Ye et al. (pp. 748–757) focused on the potential protective effects of Salvianolic acid A, a bioactive compound of Danshen, against cardiac fibrosis. Using a murine animal model of Angiotensin II-induced cardiac fibrosis in vivo and mouse cardiofibroblasts in vitro, the authors showed that Salvianolic acid A reduced cardiac remodeling and cell proliferation, and alleviated inflammatory and oxidative stress responses. RNA sequencing analysis and molecular docking studies revealed that thioredoxin interacting protein (TXNIP) is a likely target of salvianolic acid A, further supporting the potential of the danshen compound as a therapeutic agent for cardiac fibrosis.

MAN VERSUS MACHINE: PROVIDER DIRECTED VERSUS PRECISION AUTOMATED CRITICAL CARE MANAGEMENT IN A PORCINE MODEL OF DISTRIBUTIVE SHOCK

Current resuscitation efforts are based on clinical decision making. The study by Sanin et al. (pp. 758–765) investigates the use of an automated closed-loop system. The study compares the efficacy of Precision Automated Critical Care Management (PACC-MAN) which modulates vasopressor titration and crystalloid administration in response to real-time physiologic data and hemodynamic triggers in comparison to provider-directed management. The authors found that automatic resuscitation has equivalent outcomes to provider-directed management in swine hemorrhagic shock.

HYDROGEN PREVENTS LIPOPOLYSACCHARIDE-INDUCED PULMONARY MICROVASCULAR ENDOTHELIAL CELL INJURY BY INHIBITING STORE-OPERATED CA2+ ENTRY REGULATED BY STIM1/ORAI1

Molecular hydrogen has been demonstrated to exert antioxidant, anti-inflammatory, and antiapoptotic effects, leading to cell protective benefits. Using a murine animal model of lipopolysaccharide-induced acute lung injury in vivo and mouse pulmonary microvascular endothelial cells in vitro, Yuan Li et al. (pp. 766–775) showed that hydrogen gas treatment reduced acute lung injury by alleviating endothelial barrier dysfunction. The mechanistic analysis revealed that hydrogen gas treatment regulated calcium homeostasis through interactions with the stromal interaction molecule 1 (STIM1) and the Ca2+ release–activated Ca2+ channel protein1 (Orai1), further supporting the role of the gas as a cytoprotective agent in oxidative stress.

EFFECT OF MIR-21-3P ON INTESTINAL INJURY IN RATS WITH TRAUMATIC HEMORRHAGIC SHOCK RESUSCITATED WITH THE SODIUM BICARBONATE RINGER’S SOLUTION

Recent studies have provided evidence on the critical role of the microRNA miR-21 in the dysregulation of apoptotic and inflammatory processes. Using a rat model of traumatic hemorrhagic shock, Lei Li et al. (pp. 776–782) showed that overexpression of miR-21-3p by lentiviral vector injection aggravated intestinal tissue injury and intestinal glycocalyx damage through the PI3K/Akt/NF-κB signaling pathway. The authors also determined the different impacts of the resuscitation strategies with sodium lactate or sodium bicarbonate Ringer’s solutions on intestinal glycocalyx and miR-21-3p expression. The authors suggested that sodium bicarbonate may be less harmful than sodium lactate Ringer’s solution on intestinal injury.

REMIMAZOLAM IMPROVES THE MARKERS OF POSTRESUSCITATION CEREBRAL INJURY IN A SWINE MODEL OF CARDIAC ARREST

Sedation has been used as an essential part of targeted temperature management at post-resuscitation. Preclinical studies suggest that sedatives exert neuroprotective effects in animals subjected to brain ischemia and reperfusion. Shen et al. (pp. 783–790) investigated the effect of a novel GABAa receptor agonist, remimazolam, on cerebral outcome after cardiac arrest and resuscitation in swine. The authors showed that remimazolam treatment after resuscitation did not affect hemodynamics parameters, the success rate of resuscitation or survival. Remimazol treatment significantly reduced tissue inflammation, oxidative stress, apoptosis, and necroptosis in the brain and ameliorated neurological functions, thus suggesting a specific effect of the sedative agent in improving cerebral injury.

PRMT6-FOXO3A ATTENUATES APOPTOSIS BY UPREGULATING PARKIN EXPRESSION IN INTESTINAL ISCHEMIA-REPERFUSION INJURY

Apoptosis is a crucial pathophysiological event of intestinal ischemia-reperfusion injury. Wu et al. (pp. 791–800) provided novel insights into the potential mechanisms by which the protein arginine methyltransferase 6 (PRMT6), Forkhead box O3a (FoxO3a), and Parkin may regulate intestinal epithelial cell death. The authors adopted a large multidisciplinary approach by using an in vitro model of hypoxia and reoxygenation in glucose deprived human colon carcinoma cells and an in vivo model of mesenteric ischemia and reperfusion injury in genetically modified mice. They showed that PRMT6 is an essential requisite to counteract apoptosis by regulating methylation of the transcription factor FoxO3a, potentially leading to regulation of Parkin expression. Because of this interplay, the authors suggested that Parkin might represent a promising therapeutic target in intestinal ischemia-reperfusion injury.