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Sepsis-associated organ dysfunction plays a critical role in its high mortality, mainly in connection with mitochondrial dysfunction. Whether the inhibition of mitochondrial fission is beneficial to sepsis-related organ dysfunction and underlying mechanisms are unknown. Cecal ligation and puncture induced sepsis in rats and dynamic related protein 1 knockout mice, lipopolysaccharide-treated vascular smooth muscle cells and cardiomyocytes, were used to explore the effects of inhibition of mitochondrial fission and specific mechanisms. Our study showed that mitochondrial fission inhibitor Mdivi-1 could antagonize sepsisinduced organ dysfunction including heart, vascular smooth muscle, liver, kidney, and intestinal functions, and prolonged animal survival. The further study showed that mitochondrial functions such as mitochondrial membrane potential, adenosinetriphosphate contents, reactive oxygen species, superoxide dismutase and malonaldehyde were recovered after Mdivi-1 administration via improving mitochondrial morphology. And sepsis-induced inflammation and apoptosis in heart and vascular smooth muscle were alleviated through inhibition of mitochondrial fission and mitochondrial function improvement. The parameter trends in lipopolysaccharidestimulated cardiomyocytes and vascular smooth muscle cells were similar in vivo. Dynamic related protein 1 knockout preserved sepsis-induced organ dysfunction, and the animal survival was prolonged. Taken together, this finding provides a novel effective candidate therapy for severe sepsis/septic shock and other critical clinical diseases. [ABSTRACT FROM AUTHOR]

Abstract Focus on the implications of common perioperative drugs for mitochondrial quality control and their subsequent impact on the overall physiological condition has been increasing. This review discusses the effects of perioperative drugs, such as intravenous and inhaled anesthetics, analgesics, local anesthetics on mitochondrial quality and their underlying mechanisms. These drugs influence mitochondrial properties, including morphology, dynamics, energy metabolism, and protein expression, thereby affecting the clinical outcomes of patients undergoing surgery. Such effects can be either protective or detrimental and are contingent upon multiple variables such as the specific drug used, dosage, application timing, and the patient's overall health status. Recognizing the effects of these perioperative drugs on mitochondrial quality control is crucial to selecting safer anesthetic protocols, reducing postoperative complications, enhancing postoperative recovery, and gaining insights into the development of innovative treatment methodologies and optimization of perioperative care.

Xiaowei Zhou, Liyong Zou, Haoyue Deng, Yuanqun Zhou, Yue Wu, Xingnan Ouyang, Liangming Liu, Li Wang,* Tao Li* Department of Shock and Transfusion, Army Medical Center of Army Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Wang; Tao Li, Department of Shock and Transfusion, Army Medical Center of Army Medical University, Chongqing, People’s Republic of China, Email wangli8134@163.com; lt200132@tmmu.edu.cnPurpose: Cold seawater immersion aggravates hemorrhagic shock-induced homeostasis imbalance and organ dysfunction, leading to increased mortality. Previous studies have shown that treatments targeting oxidative stress and mitochondrial dysfunction have limited efficacy for cold seawater immersion combined with hemorrhagic shock (SIHS). Thus, the mechanisms responsible for SIHS need further investigation.Methods and Results: Data from the hemorrhagic shock transcriptome and cold seawater immersion targets used for bioinformatics analysis revealed the involvement of endoplasmic reticulum stress (ERS) in SIHS occurrence and progression. Based on these findings, the effects and possible mechanism of inhibiting ERS in SIHS rats were investigated. SIHS causes a lethal triad and impairment of vital organ function, leading to death. Compared to lactated Ringer’s solution, the ERS inhibitor 4-phenylbutyric acid (PBA)significantly ameliorated acidosis and coagulopathy and protected vital organ function while prolonging survival and the golden treatment time. Through target screening and validation, 7 targets were identified for the ERS inhibitor PBA for the treatment of SIHS, among which S1PR1, MMP8 and CFTR may play more important roles.Conclusion: ERS plays a crucial role in the progression of SIHS. Inhibition of ERS caused by SIHS alleviates the lethal triad, protects organ function, and prolongs survival and the golden treatment time. The ERS inhibitor PBA may be an effective therapeutic measure for treating SIHS.Keywords: cold seawater immersion, hemorrhagic shock, lethal triad, organ function, ER stress, 4-phenylbutyric acid

Focus on the implications of common perioperative drugs for mitochondrial quality control and their subsequent impact on the overall physiological condition has been increasing. This review discusses the effects of perioperative drugs, such as intravenous and inhaled anesthetics, analgesics, local anesthetics on mitochondrial quality and their underlying mechanisms. These drugs influence mitochondrial properties, including morphology, dynamics, energy metabolism, and protein expression, thereby affecting the clinical outcomes of patients undergoing surgery. Such effects can be either protective or detrimental and are contingent upon multiple variables such as the specific drug used, dosage, application timing, and the patient's overall health status. Recognizing the effects of these perioperative drugs on mitochondrial quality control is crucial to selecting safer anesthetic protocols, reducing postoperative complications, enhancing postoperative recovery, and gaining insights into the development of innovative treatment methodologies and optimization of perioperative care. [ABSTRACT FROM AUTHOR]

The document is a corrigendum for an article on the protective effects of inhibiting mitochondrial fission on organ function after sepsis. It acknowledges errors in Figures 2 and 3 of the original publication, where images were misused and confirms that these errors do not impact the scientific conclusions of the study. The corrected figures show the effects of Mdivi-1 on vital organ function and mitochondrial morphology in septic rats. The study was conducted by researchers from the State Key Laboratory of Trauma, Burns, and Combined Injury in Chongqing, China. [Extracted from the article]

Background: After hypovolemic shock caused by severe burns, lipid peroxidation is an important factor in tissue edema and multiorgan dysfunction syndrome (MODS). Many studies have shown that valproic acid (VPA) inhibits lipid peroxidation and reduces tissue and organ injury. Objectives: This study investigated whether the VPA treatment of scalded rats reduced tissue edema by inhibiting lipid peroxidation, thereby improving organ function and survival rate. Materials and Methods: A total of 60 male Sprague-Dawley rats (weighing: 280–300 g) with a 50% total body surface area (TBSA) full-thickness dermal burn were randomly assigned to the following 3 groups (with 20 rats per group): (I) the no infusion resuscitation (NR) group; (II) the sodium lactate Ringer's solution (LR) group; and (III) the sodium valproate Ringer's solution (VR) group. After scalding, the following hemodynamic parameters were measured: Copper2+-Zinc2+-superoxide dismutase (Cu2+-Zn2+-SOD) activity, thiobarbituric acid reactive substances (TBARSs), oxidized glutathione (GSSG), reduced glutathione (GSH), and antioxidant enzyme activities. Organ function parameters and water content were also measured. Another 60 male Sprague-Dawley rats were used to observe the 24-h survival rate of the rats using the same scald model and fluid resuscitation. Results: VPA significantly increased the mean arterial pressure (MAP) and cardiac output (CO), and significantly decreased the pulmonary vascular permeability index (PVPI) and extravascular lung water index (ELWI). VPA also increased plasma Cu2+-Zn2+-SOD activity and decreased the plasma TBARS level. VPA reduced the TBARS level and GSSG in various tissues and increased the concentration of GSH. VPA decreased glutathione peroxidase (GPx) and catalase (CAT) activity, but significantly increased glutathione reductase (GR) activity in various tissues. VPA significantly improved organ functions and decreased water content. VPA significantly improved the survival rate, and the 24-h survival rate of the VR group was double that of the LR group. Conclusion: Resuscitation with VPA reduced tissue edema, protected visceral functions, and improved the survival rate of rats with severe burn shock (BS) by alleviating lipid peroxidation. [ABSTRACT FROM AUTHOR]

Objective: Acetaminophen (APAP), an antipyretic and analgesic commonly used during pregnancy, has been recognized as a novel environmental contaminant. Preliminary evidence suggests that prenatal acetaminophen exposure (PAcE) could adversely affect offspring’s gonadal and neurologic development, but there is no systematic investigation on the characteristics of APAP’s fetal developmental toxicity. Methods: Pregnant mice were treated with 100 or 400 mg/kg∙d APAP in the second-trimester, or 400 mg/kg∙d APAP in the second- or third-trimester, or different courses (single or multiple) of APAP, based on clinical regimen. The effects of PAcE on pregnancy outcomes, maternal/fetal blood phenotypes, and multi-organ morphological and functional development of fetal mice were analyzed. Results: PAcE increased the incidence of adverse pregnancy outcomes and altered blood phenotypes including aminotransferases, lipids, and sex hormones in dams and fetuses. The expression of key functional genes in fetal organs indicated that PAcE inhibited hippocampal synaptic development, sex hormone synthesis, and osteogenic and chondrogenic development, but enhanced hepatic lipid synthesis and uptake, renal inflammatory hyperplasia, and adrenal steroid hormone synthesis. PAcE also induced marked pathological alterations in the fetal hippocampus, bone, kidney, and cartilage. The sensitivity rankings of fetal organs to PAcE might be hippocampus/bone > kidney > cartilage > liver > gonad > adrenal gland. Notably, PAcE-induced multi-organ developmental toxicity was more considerable under high-dose, second-trimester, and multi-course exposure and in male fetuses. Conclusion: This study confirmed PAcE-induced alterations in multi-organ development and function in fetal mice and elucidated its characteristics, which deepens the comprehensive understanding of APAP's developmental toxicity.

Abstract Background Sepsis, the life-threatening host response to infection, is a major cause of mortality. Obesity increases vulnerability to sepsis; however, some degree of obesity may be protective, called the “obesity paradox”. This scoping review systematically maps the literature on outcomes associated with diet-induced obesity and sepsis-induced organ injury, focusing on non-transgenic murine models. Methods A literature search of primary articles was conducted from database inception to June 2023. Eligible articles compared diet-induced obesity to non-obese mice in sepsis models involving live pathogens. Two reviewers screened articles and extracted data on obesogenic and sepsis models utilized, and organ injury outcomes, including physiological dysfunction, histological alterations, and biochemical changes. Results Seventeen studies met eligibility criteria; 82% used male C57BL/6 mice, and 88% used cecal ligation and puncture to induce sepsis. Most studies used 60% high-fat diets compared to 10–16% fat in controls. Seven (64%) studies reported increased mortality in obese septic mice, one (9%) observed a decrease, and three (37%) found no significant difference. The liver, lungs, and kidneys were the most studied organs. Alanine transaminase results were inconclusive. Myeloperoxidase levels were increased in the livers of two studies and inconclusive in the lungs of obese septic mice. Creatinine and neutrophil gelatinase-associated lipocalin were elevated in obese septic mice. Conclusions There is variability in the methodology and measured outcomes in murine models of diet-induced obesity and sepsis and a lack of studies in female mice. The absence of standardized models has produced conflicting findings on the impact of obesity on sepsis outcomes.

• Fetuses might be more susceptible to prenatal amoxicillin exposure (PAmE) than mothers. • PAmE induced abnormal fetal development with organ-, stage- and course-differences. • Most obvious changes in fetuses were in high-dose, late-pregnancy and multi-course. • There were sex differences in fetal developmental and functional changes caused by PAmE. • Male fetuses were more affected by PAmE during mid-/late-pregnancy than females. Amoxicillin, a widely used antibiotic in human and veterinary pharmaceuticals, is now considered as an "emerging contaminant" because it exists widespreadly in the environment and brings a series of adverse outcomes. Currently, systematic studies about the developmental toxicity of amoxicillin are still lacking. We explored the potential effects of amoxicillin exposure on pregnancy outcomes, maternal/fetal serum phenotypes, and fetal multiple organ development in mice, at different doses (75, 150, 300 mg/(kg·day)) during late-pregnancy, or at a dose of 300 mg/(kg·day) during different stages (mid-/late-pregnancy) and courses (single-/multi-course). Results showed that prenatal amoxicillin exposure (PAmE) had no significant influence on the body weights of dams, but it could inhibit the physical development and reduce the survival rate of fetuses, especially during the mid-pregnancy. Meanwhile, PAmE altered multiple maternal/fetal serum phenotypes, especially in fetuses. Fetal multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis, long bone/cartilage and hippocampal development, and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis, and the order of severity might be gonad (testis, ovary) > liver > others. Further analysis found that PAmE-induced multi-organ developmental and functional alterations had differences in stages, courses and fetal gender, and the most obvious changes might be in high-dose, late-pregnancy and multi-course, but there was no typical rule of a dose-response relationship. In conclusion, this study confirmed that PAmE could cause abnormal development and multi-organ function alterations, which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Sepsis, the life-threatening host response to infection, is a major cause of mortality. Obesity increases vulnerability to sepsis; however, some degree of obesity may be protective, called the "obesity paradox". This scoping review systematically maps the literature on outcomes associated with diet-induced obesity and sepsis-induced organ injury, focusing on non-transgenic murine models. Methods: A literature search of primary articles was conducted from database inception to June 2023. Eligible articles compared diet-induced obesity to non-obese mice in sepsis models involving live pathogens. Two reviewers screened articles and extracted data on obesogenic and sepsis models utilized, and organ injury outcomes, including physiological dysfunction, histological alterations, and biochemical changes. Results: Seventeen studies met eligibility criteria; 82% used male C57BL/6 mice, and 88% used cecal ligation and puncture to induce sepsis. Most studies used 60% high-fat diets compared to 10–16% fat in controls. Seven (64%) studies reported increased mortality in obese septic mice, one (9%) observed a decrease, and three (37%) found no significant difference. The liver, lungs, and kidneys were the most studied organs. Alanine transaminase results were inconclusive. Myeloperoxidase levels were increased in the livers of two studies and inconclusive in the lungs of obese septic mice. Creatinine and neutrophil gelatinase-associated lipocalin were elevated in obese septic mice. Conclusions: There is variability in the methodology and measured outcomes in murine models of diet-induced obesity and sepsis and a lack of studies in female mice. The absence of standardized models has produced conflicting findings on the impact of obesity on sepsis outcomes. [ABSTRACT FROM AUTHOR]

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Introduction: The recent discovery of TAK981(Subasumstat), the first-in-class selective inhibitor of SUMOylation, enables new immune treatments. TAK981 is already in clinical trials to potentiate immunotherapy in metastatic tumors and hematologic malignancies. Cancer patients have more than ten times higher risk of infections, but the effects of TAK981 in sepsis are unknown and previous studies on SUMO in infections are conflicting. Methods: We used TAK981 in two sepsis models; polymicrobial peritonitis (CLP) and LPS endotoxemia. Splenectomy was done in both models to study the role of spleen. Western blotting of SUMO-conjugated proteins in spleen lysates was done. Global SUMO1 and SUMO3 knockout mice were used to study the specific SUMO regulation of inflammation in LPS endotoxemia. Splenocytes adoptive transfer was done from SUMO knockouts to wild type mice to study the role of spleen SUMOylation in experimental sepsis. Results and discussion: Here, we report that inhibition of SUMOylation with TAK981 improved survival in mild polymicrobial peritonitis by enhancing innate immune responses and peritoneal bacterial clearance. Thus, we focused on the effects of TAK981 on the immune responses to bacterial endotoxin, showing that TAK981 enhanced early TNFα production but did not affect the resolution of inflammation. Splenectomy decreased serum TNFα levels by nearly 60% and TAK981-induced TNFα responses. In the spleen, endotoxemia induced a distinct temporal and substrate specificity for SUMO1 and SUMO2/3, and both were inhibited by TAK981. Global genetic depletion of SUMO1, but not SUMO3, enhanced TNFα production and metabolic acidosis. The transfer of SUMO1-null, but not wild-type, splenocytes into splenectomized wild-type mice exacerbated TNFα production and metabolic acidosis in endotoxemia. Conclusion: These results suggest that specific regulation of splenic SUMO1 can modulate immune and metabolic responses to bacterial infection. [ABSTRACT FROM AUTHOR]

Traumatic shock is a main cause for early death of war wound and trauma. As for the early treatment of war wound and traumatic shock, many new concepts and techniques have been raised in recent years, such as limited fluid resuscitation, permissive fluid resuscitation and expanding golden hour care window. Based on the needs of our medical support and combat casualty care, the features and new treatment measures of war wound and traumatic shock at high altitude and marine, we discuss the new mechanisms and treatments of intestinal and vascular barrier function after sepsis and the new anti-shock fluids-malic acid fluid, and bring forward to the future research trends based on the new types of resuscitative fluid and new targets for war wound and traumatic shock.

Objective To determine the effects of seawater immersion at 21 ℃ on survival, organ functions, tissue metabolism and homeostasis in rats with hemorrhagic shock. Methods A total of 128 healthy male SD rats were randomly divided into 4 groups: normal control group (NC), 40% hemorrhagic shock group (HS), normal rats with 21 ℃ seawater immersion (2 h) group (SI), and 40% hemorrhagic shock rats combined with 21 ℃ seawater immersion (2 h) group (HS+SI). The survival rate in each group was observed for 72 h in 2 h after modeling, the changes of cardiac function [cardiac troponin T (cTnT)], liver function [alanine transaminase (ALT) and aspartate aminotransferase (AST) levels], renal function [blood urea nitrogen (BUN) and serum creatinine (SCr) levels], tissue metabolism and internal environment were detected in each group. Results As compared with the NC group, the plasma osmolality (OSM), concentrations of Na+, K+, Cl- and water contents in the lung and brain were increased, while the Na+/K+-ATPase activity in the lung and brain was decreased in the HS and SI groups. With the elevation of the damage indexes in heart, liver and kidney functions, the mortality was increased as well in the HS and SI groups. Combination of 21 ℃ seawater immersion resulted in more severe damages induced by simple 40% hemorrhagic shock, shown as further increases in plasma OSM, Na+, K+ and Cl- concentrations, and water contents of the lung and brain, as well as further declined Na+/K+-ATPase activity in the lung (3.81±0.30 U/mg) and brain (7.17±0.51 U/mg) (P < 0.05). Serious deterioration was observed in the functions of the heart, liver and kidney, with levels of cTnT, ALT, AST, BUN and SCr elevated to 7.25±0.66 μg/L, 118.60±13.29 U/L, 455.95±46.76 U/L, 19.74±2.12 mmol/L and 56.73±4.08 μmol/L, respectively (P < 0.05). The survival rate was reduced to 18.75%, and the median survival time was shortened to 10.50 h in the rats of the HS+SI group. Conclusion Seawater immersion at 21℃ exacerbates disorders of the internal environment and tissue metabolism in 40% hemorrhagic shock rats, leading to aggravated multiple organ injury and thus increased mortality.

IntroductionThe recent discovery of TAK981(Subasumstat), the first-in-class selective inhibitor of SUMOylation, enables new immune treatments. TAK981 is already in clinical trials to potentiate immunotherapy in metastatic tumors and hematologic malignancies. Cancer patients have more than ten times higher risk of infections, but the effects of TAK981 in sepsis are unknown and previous studies on SUMO in infections are conflicting.MethodsWe used TAK981 in two sepsis models; polymicrobial peritonitis (CLP) and LPS endotoxemia. Splenectomy was done in both models to study the role of spleen. Western blotting of SUMO-conjugated proteins in spleen lysates was done. Global SUMO1 and SUMO3 knockout mice were used to study the specific SUMO regulation of inflammation in LPS endotoxemia. Splenocytes adoptive transfer was done from SUMO knockouts to wild type mice to study the role of spleen SUMOylation in experimental sepsis.Results and discussionHere, we report that inhibition of SUMOylation with TAK981 improved survival in mild polymicrobial peritonitis by enhancing innate immune responses and peritoneal bacterial clearance. Thus, we focused on the effects of TAK981 on the immune responses to bacterial endotoxin, showing that TAK981 enhanced early TNFα production but did not affect the resolution of inflammation. Splenectomy decreased serum TNFα levels by nearly 60% and TAK981-induced TNFα responses. In the spleen, endotoxemia induced a distinct temporal and substrate specificity for SUMO1 and SUMO2/3, and both were inhibited by TAK981. Global genetic depletion of SUMO1, but not SUMO3, enhanced TNFα production and metabolic acidosis. The transfer of SUMO1-null, but not wild-type, splenocytes into splenectomized wild-type mice exacerbated TNFα production and metabolic acidosis in endotoxemia.ConclusionThese results suggest that specific regulation of splenic SUMO1 can modulate immune and metabolic responses to bacterial infection.

Semen Semenovich Zimnitsky is an outstanding Russian internist of the early XX century. He created a functional direction and made a significant contribution to internal medicine, infectiology, immunology and microbiology, but his studies of gastroenterology are fundamental. The Zimnitsky’s works on hepatology, pancreatic diseases, and balneology are interesting. S. S. Zimnitsky discovered 5 types of gastric secretion, which turned out to be reversible, and proposed a repeated breakfast. The pinnacle of his work is Zimnitsky’s test, which makes it possible to determine the renal function without resorting to any invasive procedures and in no way burdening the patient. The onset of test creation was laid by S. S. Zimnitsky in his doctoral dissertation devoted to gastroenterology.

The pinnacle of S. S. Zimnitsky scientific heritage is the Zimnitsky, which makes it possible to assess the renal function without invasive procedures and burdening the patient. Proposed a hundred years ago, the Zimnitsky test shows its effectiveness at the present time. S. S. Zimnitsky proposed an original classification of hydronephrosis, described a special form of nephritis and rejected the filtration theory of urine formation, promoting the secretory one. In his purely scientific nephrological articles, S. S. Zimnitsky acts as a sincere and ardent patriot of his great homeland.

Marine casualties are increasing, and mortality from trauma associated with immersion in seawater is high. However, the associated pathophysiological characteristics remain unclear, limiting research into the early emergency treatment strategy. Healthy and 50% hemorrhagic shock rats were soaked in 15°C and 21°C seawater for 2 h, 4 h and 6 h, respectively, and the effects on vital signs, internal environment, tissue metabolism, lethal triad, vital organ functions and survival were observed. Immersion in seawater can cause death in healthy rats. Rats with hemorrhagic shock in 15°C seawater showed a lower survival rate than the corresponding groups in 21°C seawater. Moreover, compared with 21°C seawater, 15°C seawater played a more remarkable role in decreasing mean arterial pressure, heart rate, and respiration rate, increasing water content and decreasing Na+/K+-ATPase activity in the brain and lung; increase in plasma osmolality, Na+, K+, Cl−, and the occurrence of the lethal triad manifested by a decrease in core body temperature, pH, lactate, and an increase in coagulation parameters, as well as damage to cardiac, intestinal, hepatic, and renal functions in rats with hemorrhagic shock. Immersion in seawater at low temperatures could be lethal to healthy rats, causing the occurrence of a lethal triad and damage to vital organs. Furthermore, 15°C-seawater had a more significant effect than 21°C-seawater on aggravating the imbalance of internal environment and tissue metabolism, resulting in a higher incidence of the lethal triad and thus aggravating the dysfunctions of vital organs, which eventually resulted in higher mortality in rats with hemorrhagic shock. [ABSTRACT FROM AUTHOR]

Chinese baijiu, an ancient fermented alcoholic beverage, contains ethanol and a variety of compounds. One of the most popular types of Chinese baijiu is Jiang-flavor baijiu. To investigate the effects of Jiang-flavor baijiu on organ function and gut microbiota, we developed a moderate drinking mouse model and studied its effects on the liver, kidney biomarkers, memory function, and gut microbiota. The results showed that ethanol caused more hepatic steatosis, liver and kidney damage, and memory impairment than Jiang-flavour baijiu consumption. Furthermore, Jiang-flavor baijiu altered the gut microbiota by increasing the abundance of beneficial taxa such as Lactobacillus and Akkermansia , whereas ethanol increased the abundance of harmful bacteria such as Prevotella and Mucispirillum. Our findings provide preliminary evidence that moderate dose Jiang-flavor baijiu regulates gut microbiota and organ function and provide a theoretical foundation for future research on the positive health effects of particular varieties of Chinese baijiu. [Display omitted] [ABSTRACT FROM AUTHOR]

Sepsis syndrome develops through enhanced secretion of pro-inflammatory cytokines and the generation of reactive oxygen species (ROS). Sepsis syndrome is characterized by vascular hyperpermeability, hypotension, multiple organ dysfunction syndrome (MODS), and increased mortality, among others. Endotoxemia-derived sepsis is an important cause of sepsis syndrome. During endotoxemia, circulating endotoxin interacts with endothelial cells (ECs), inducing detrimental effects on endothelium function. The endotoxin induces the conversion of ECs into fibroblasts, which are characterized by a massive change in the endothelial gene-expression pattern. This downregulates the endothelial markers and upregulates fibrotic proteins, mesenchymal transcription factors, and extracellular matrix proteins, producing endothelial fibrosis. Sepsis progression is modulated by the consumption of specific nutrients, including ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoids. However, the underlying mechanism is poorly described. The notion that gene expression is modulated during inflammatory conditions by nutrient consumption has been reported. However, it is not known whether nutrient consumption modulates the fibrotic endothelial gene-expression pattern during sepsis as a mechanism to decrease vascular hyperpermeability, hypotension, MODS, and mortality. Therefore, the aim of this study was to investigate the impact of the consumption of dietary ω-3 fatty acids, ascorbic acid, and polyphenolic antioxidant flavonoid supplements on the modulation of fibrotic endothelial gene-expression patterns during sepsis and to determine the effects on sepsis outcomes. Our results indicate that the consumption of supplements based on ω-3 fatty acids and polyphenolic antioxidant flavonoids was effective for improving endotoxemia outcomes through prophylactic ingestion and therapeutic usage. Thus, our findings indicated that specific nutrient consumption improves sepsis outcomes and should be considered in treatment. [ABSTRACT FROM AUTHOR]

Over the last two decades, hydrogen sulfide (H2S) has emerged as an endogenous regulator of a broad range of physiological functions. H2S belongs to the class of molecules known as gasotransmitters, which typically include nitric oxide (NO) and carbon monoxide (CO). Three enzymes are recognized as endogenous sources of H2S in various cells and tissues: cystathionine c-lyase (CSE), cystathionine b-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3-MST). The present article reviews the regulation of these enzymes as well as the pathways of their enzymatic and nonenzymatic degradation and elimination. The multiple interactions of H2S with other labile endogenous molecules (e.g., NO) and reactive oxygen species are also outlined. Next, the various biological targets and signaling pathways are outlined, with special reference to H2S or oxidative posttranscriptional modification (persulfidation or sulfhydration) of proteins and the effect of H2S on various channels and intracellular second messenger pathways, the regulation of gene transcription and translation, and the regulation of cellular bioenergetics and metabolism. The pharmacological and molecular tools currently available to study H2S physiology are also reviewed, including their utility and limitations. In subsequent sections, the role of H2S in the regulation of various physiological and cellular functions is reviewed, including the regulation of membrane potential, endo- and exocytosis, regulation of various cell organelles (endoplasmic reticulum, Golgi, mitochondria), regulation of cell movement, cell cycle, cell differentiation, and physiological aspects of regulated cell death. Next, the physiological roles of H2S in various cell types and organ systems are overviewed, including the role of H2S in red blood cells, immune cells, the central and peripheral nervous systems (with focus on neuronal transmission, learning, and memory formation), and regulation of vascular function (including angiogenesis as well as its specialized roles in the cerebrovascular, renal, and pulmonary vascular beds) and the role of H2S in the regulation of special senses, vision, hearing, taste and smell, and pain-sensing. Finally, the roles of H2S in the regulation of various organ functions (lung, heart, liver, kidney, urogenital organs, reproductive system, bone and cartilage, skeletal muscle, and endocrine organs) are presented, with a focus on physiology (including physiological aging) but also extending to some common pathophysiological conditions. From these data, a wide array of significant roles of H2S in the physiological regulation of all organ functions emerges and the characteristic bell-shaped biphasic effects of H2S are highlighted. In addition, key pathophysiological aspects, debated areas, and future research and translational areas are identified. [ABSTRACT FROM AUTHOR]

Developmental programming is the concept that 'stressors' during development (i.e. pregnancy, the perinatal period and infancy) can cause long-term changes in gene expression, leading to altered organ structure and function. Such long-term changes are associated with an increased risk of a host of chronic pathologies, or non-communicable diseases including abnormal growth and body composition, behavioural or cognitive dysfunction, metabolic abnormalities, and cardiovascular, gastro-intestinal, immune, musculoskeletal and reproductive dysfunction. Maternal nutrition during the periconceptual period, pregnancy and postnatally can have profound influences on the developmental program. Animal models, including domestic livestock species, have been important for defining the mechanisms and consequences of developmental programming. One of the important observations is that maternal nutritional status and other maternal stressors (e.g. environmental temperature, high altitude, maternal age and breed, multiple fetuses, etc.) early in pregnancy and even periconceptually can affect not only embryonic/fetal development but also placental development. Indeed, altered placental function may underlie the effects of many maternal stressors on fetal growth and development. We suggest that future directions should focus on the consequences of developmental programming during the offspring's life course and for subsequent generations. Other important future directions include evaluating interventions, such as strategic dietary supplementation, and also determining how we can take advantage of the positive, adaptive aspects of developmental programming. Developmental programming, sometimes called fetal programming, is the concept that insults to the embryo/fetus during development can have long-term consequences throughout the lifetime of the offspring, including a host of chronic health problems. One of the most obvious and well-studied insults is poor maternal nutrition. This review discusses our current understanding of how developmental programming occurs, strategies to minimise its negative consequences (and, perhaps, take advantage of its positive consequences), as well as future directions for research. [ABSTRACT FROM AUTHOR]

Hypotension resuscitation is an important principle for the treatment after trauma. Current hypotensive resuscitation strategies cannot obtain an ideal outcome for remote regions. With the uncontrolled hemorrhagic shock (UHS) model in rats, the effects of norepinephrine (NE) on the tolerance time of hypotensive resuscitation, blood loss, vital organ functions, and animal survival were observed. Before bleeding was controlled, only the LR infusion could effectively maintain the MAP to 50–60 mmHg for 1 h, while the MAP gradually decreased with prolonging time, even with increasing infusion volume. Low-dose NE during hypotensive resuscitation prolonged the hypotensive tolerance time to 2–3 h, and the effect of 0.3 μg/kg/min NE was the best. Further studies showed that 0.3 μg/kg/min NE during hypotensive resuscitation significantly lightened the damage of organ function induced by UHS via protecting mitochondrial function, while the LR infusion did not. At the same time, NE administration improved Hb content, DO2, and VO2, and restored liver and kidney blood flow. The survival results showed that low-dose NE administration increased the survival rate and prolonged the survival time. Together, low-dose NE during hypotensive resuscitation was suitable for the early treatment of UHS, which can strive for the golden window of emergency treatment for serious trauma patients by reducing blood loss and protecting vital organ functions. [ABSTRACT FROM AUTHOR]

Hura crepitans seed oil (HCSO) remains under-utilized, largely due to the scarcity in data regarding its biochemical properties. To investigate the functional and pro-inflammatory responses to HCSO, twenty-four male rats were grouped into four and received compounded diets containing 5%-HCSO; 10%-HCSO; 15%-HCSO; and 15%-AHO (as control) for eight weeks. The functional responses and the expression of pro-inflammatory cytokines and their receptors were appraised. The organ function biomarkers in rats fed with HCSO-supplemented diets were statistically similar to those of control rats, except for uric acid and creatine levels, which were significantly lower in the HCSO-fed groups, and the urea level, which was elevated in all HCSO-fed groups. Also, HCSO significantly downregulated the expression of pro-inflammatory cytokines (TNF-a, IL-1a, IL-1ß, and IL-6) and their receptors (IL-1R and IL-6R), when compared to the control group. Our results highlight the reno- and cardio-protective potentials of HCSO, as well as its anti-inflammatory potentials. [ABSTRACT FROM AUTHOR]

Abstract Background Individualized positive end-expiratory pressure (PEEP) by electrical impedance tomography (EIT) has potential interest in the optimization of ventilation distribution in acute respiratory distress syndrome (ARDS). The aim of the study was to determine whether early individualized titration of PEEP with EIT improved outcomes in patients with ARDS. Methods A total of 117 ARDS patients receiving mechanical ventilation were randomly assigned to EIT group (n = 61, PEEP adjusted based on ventilation distribution) or control group (n = 56, low PEEP/FiO2 table). The primary outcome was 28-day mortality. Secondary and exploratory outcomes were ventilator-free days, length of ICU stay, incidence of pneumothorax and barotrauma, and difference in Sequential Organ Failure Assessment (SOFA) score at day 1 (ΔD1-SOFA) and day 2 (ΔD2-SOFA) compared with baseline. Measurements and main results There was no statistical difference in the value of PEEP between the EIT group and control group, but the combination of PEEP and FiO2 was different between groups. In the control group, a significantly positive correlation was found between the PEEP value and the corresponding FiO2 (r = 0.47, p

BackgroundThe mortality of trauma combined with seawater immersion is higher than that of land injury, however, research on how to treat this critical case and which treatments to adopt is lacking.MethodsThe effect of the thiol compound, N-acetyl-L-Cysteine (NAC), on survival, acidosis, coagulopathy, vital signs, oxidative stress, and mitochondrial and multi-organ function was assessed in a rat model of hemorrhagic shock combined with seawater immersion (Sea-Shock).ResultsHemorrhagic shock combined with seawater immersion caused a severe lethal triad: multi-organ impairment, oxidative stress, and mitochondrial dysfunction. NAC (30 mg/kg) with lactated Ringer’s (LR) solution (2 × blood volume lost) significantly improved outcomes compared to LR or hetastarch (HES 130/0.4) alone. NAC significantly prolonged survival time to 52.48 ± 30.09 h and increased 72 h survival rate to 11/16 (68%). NAC relieved metabolic acidosis and recovered the pH back to 7.33. NAC also restored coagulation, with APTT, PT, and PT-INR decreased by 109.31, 78.09, and 73.74%, respectively, while fibrinogen level increased 246.23% compared with untreated Sea-Shock. Administration of NAC markedly improved cardiac and liver function, with some improvement of kidney function.ConclusionThe addition of NAC to crystalloid resuscitation fluid alleviated oxidative stress, restored redox homeostasis, and provided multi-organ protection in the rats after Sea-Shock. NAC may be an effective therapeutic measure for hemorrhagic shock combined with seawater immersion.

Previous studies found that seawater immersion combined with hemorrhagic shock (SIHS) induced serious organ function disorder, and lethal triad was a critical sign. There were no effective treatments of SIHS. Fluid resuscitation was the initial measurement for early aid following hemorrhagic shock, while the proper fluid for SIHS is not clear. Effects of different osmotic pressures [lactated Ringer’s (LR) solution, 0.3% saline, 0.6% saline, and 0.9% normal saline] on the lethal triad, mitochondrial function, vital organ functions, and survival were observed following SIHS in rats. The results showed that SIHS led to an obvious lethal triad, which presented the decrease of the body temperature, acidosis, and coagulation functions disorder in rats. Fluid resuscitation with different osmotic pressures recovered the body temperature and corrected acidosis with different levels; effects of 0.6% normal saline were the best; especially for the coagulation function, 0.6% normal saline alleviated the lethal triad significantly. Further studies showed that SIHS resulted in the damage of the mitochondrial function of vital organs, the increase of the vascular permeability, and, at the same time, the organ function including cardiac, liver, and kidney was disordered. Conventional fluid such as LR or 0.9% normal saline could not improve the mitochondrial function and vascular leakage and alleviate the damage of the organ function. While moderate hypotonic fluid, the 0.6% normal saline, could lighten organ function damage via protecting mitochondrial function. The 0.6% normal saline increased the left ventricular fractional shortening and the left ventricular ejection fraction, and decreased the levels of aspartate transaminase, alanine transferase, blood urea nitrogen, and creatinine in the blood. The effects of fluids with different osmotic pressures on the mean arterial pressure (MAP) had a similar trend as above parameters. The survival results showed that the 0.6% normal saline group improved the survival rate and prolonged the survival time, the 72 h survival rate was 7/16, as compared with the LR group (3/16). The results indicate that appropriate hypotonic fluid is suitable after SIHS, which alleviates the lethal triad, protects the mitochondrial function and organ functions, and prolongs the survival time.

Background: The mortality of trauma combined with seawater immersion is higher than that of land injury, however, research on how to treat this critical case and which treatments to adopt is lacking. Methods: The effect of the thiol compound, N-acetyl-L-Cysteine (NAC), on survival, acidosis, coagulopathy, vital signs, oxidative stress, and mitochondrial and multi-organ function was assessed in a rat model of hemorrhagic shock combined with seawater immersion (Sea-Shock). Results: Hemorrhagic shock combined with seawater immersion caused a severe lethal triad: multi-organ impairment, oxidative stress, and mitochondrial dysfunction. NAC (30 mg/kg) with lactated Ringer's (LR) solution (2 × blood volume lost) significantly improved outcomes compared to LR or hetastarch (HES 130/0.4) alone. NAC significantly prolonged survival time to 52.48 ± 30.09 h and increased 72 h survival rate to 11/16 (68%). NAC relieved metabolic acidosis and recovered the pH back to 7.33. NAC also restored coagulation, with APTT, PT, and PT-INR decreased by 109.31, 78.09, and 73.74%, respectively, while fibrinogen level increased 246.23% compared with untreated Sea-Shock. Administration of NAC markedly improved cardiac and liver function, with some improvement of kidney function. Conclusion: The addition of NAC to crystalloid resuscitation fluid alleviated oxidative stress, restored redox homeostasis, and provided multi-organ protection in the rats after Sea-Shock. NAC may be an effective therapeutic measure for hemorrhagic shock combined with seawater immersion. [ABSTRACT FROM AUTHOR]

Previous studies found that seawater immersion combined with hemorrhagic shock (SIHS) induced serious organ function disorder, and lethal triad was a critical sign. There were no effective treatments of SIHS. Fluid resuscitation was the initial measurement for early aid following hemorrhagic shock, while the proper fluid for SIHS is not clear. Effects of different osmotic pressures [lactated Ringer's (LR) solution, 0.3% saline, 0.6% saline, and 0.9% normal saline] on the lethal triad, mitochondrial function, vital organ functions, and survival were observed following SIHS in rats. The results showed that SIHS led to an obvious lethal triad, which presented the decrease of the body temperature, acidosis, and coagulation functions disorder in rats. Fluid resuscitation with different osmotic pressures recovered the body temperature and corrected acidosis with different levels; effects of 0.6% normal saline were the best; especially for the coagulation function, 0.6% normal saline alleviated the lethal triad significantly. Further studies showed that SIHS resulted in the damage of the mitochondrial function of vital organs, the increase of the vascular permeability, and, at the same time, the organ function including cardiac, liver, and kidney was disordered. Conventional fluid such as LR or 0.9% normal saline could not improve the mitochondrial function and vascular leakage and alleviate the damage of the organ function. While moderate hypotonic fluid, the 0.6% normal saline, could lighten organ function damage via protecting mitochondrial function. The 0.6% normal saline increased the left ventricular fractional shortening and the left ventricular ejection fraction, and decreased the levels of aspartate transaminase, alanine transferase, blood urea nitrogen, and creatinine in the blood. The effects of fluids with different osmotic pressures on the mean arterial pressure (MAP) had a similar trend as above parameters. The survival results showed that the 0.6% normal saline group improved the survival rate and prolonged the survival time, the 72 h survival rate was 7/16, as compared with the LR group (3/16). The results indicate that appropriate hypotonic fluid is suitable after SIHS, which alleviates the lethal triad, protects the mitochondrial function and organ functions, and prolongs the survival time. [ABSTRACT FROM AUTHOR]

Purpose: The benefit of surgery for older patients with extrahepatic cholangiocarcinoma (EHCC) has not been established and the differences in the general condition of younger vs. older patients remain unclear. Methods: Patients who underwent curative surgery for EHCC were divided into two groups according to age: those younger than 75 years old (younger group) and those aged 75 years or older (older group). We analyzed the clinical data of the two groups retrospectively. Results: Among the 116 patients analyzed, 45 (38.8%) were in the older group. Regarding comorbidity, only cardiac disease was significantly more common in the older patients; however, the cardiac function of the two groups was identical. There were no significant differences in the prevalence of kidney and lung disease, but renal function was significantly deteriorated and the incidence of the mixed ventilatory defect was significantly greater in the older group. The overall 5-year survival rates for the younger and older groups were 52.4% vs. 50.4% of all cholangiocarcinoma patients (p = 0.458), 42.4% vs. 51.3% of those with hilar cholangiocarcinoma (p = 0.718), and 69.0% vs. 49.1% of those with distal cholangiocarcinoma (p = 0.534), respectively. Conclusions: Improved survival after surgery can be expected in well-selected older cholangiocarcinoma patients. Comorbidities were not necessarily reflected in organ function, with precise organ function assessment being more important when selecting surgical candidates. [ABSTRACT FROM AUTHOR]

Acetaminophen (APAP), an antipyretic and analgesic commonly used during pregnancy, has been recognized as a novel environmental contaminant. Preliminary evidence suggests that prenatal acetaminophen exposure (PAcE) could adversely affect offspring's gonadal and neurologic development, but there is no systematic investigation on the characteristics of APAP's fetal developmental toxicity. Pregnant mice were treated with 100 or 400 mg/kg∙d APAP in the second-trimester, or 400 mg/kg∙d APAP in the second- or third-trimester, or different courses (single or multiple) of APAP, based on clinical regimen. The effects of PAcE on pregnancy outcomes, maternal/fetal blood phenotypes, and multi-organ morphological and functional development of fetal mice were analyzed. PAcE increased the incidence of adverse pregnancy outcomes and altered blood phenotypes including aminotransferases, lipids, and sex hormones in dams and fetuses. The expression of key functional genes in fetal organs indicated that PAcE inhibited hippocampal synaptic development, sex hormone synthesis, and osteogenic and chondrogenic development, but enhanced hepatic lipid synthesis and uptake, renal inflammatory hyperplasia, and adrenal steroid hormone synthesis. PAcE also induced marked pathological alterations in the fetal hippocampus, bone, kidney, and cartilage. The sensitivity rankings of fetal organs to PAcE might be hippocampus/bone > kidney > cartilage > liver > gonad > adrenal gland. Notably, PAcE-induced multi-organ developmental toxicity was more considerable under high-dose, second-trimester, and multi-course exposure and in male fetuses. This study confirmed PAcE-induced alterations in multi-organ development and function in fetal mice and elucidated its characteristics, which deepens the comprehensive understanding of APAP's developmental toxicity. [Display omitted] • Prenatal acetaminophen exposure (PAcE) altered male and female fetus blood phenotypes. • Functional genes in multiple organs are affected by PAcE. • Significant alterations manifest after high-dose, second-trimester, and multi-course PAcE • Male fetuses are more affected by PAcE than females. [ABSTRACT FROM AUTHOR]

Sepsis is currently a major problem and challenge facing the medical community. With rapid development and progress of modern medicine, researchers have put more and more attention on sepsis; meanwhile, the morbidity and mortality of sepsis remains high despite great efforts from experts in various fields. According to updated guidelines, sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Infection is the initial step of sepsis progression, and development from infection to sepsis is a complex pathophysiological process, including pathogen invasion, cytokine release, capillary leakage, microcirculation dysfunction, etc. which finally leads to organ metabolic disorders and functional failure. According to the latest recommended international guidelines of Sepsis 3.0, the presence of infection and SOFA score ≥ 2 are considered as the diagnostic criteria for sepsis, and the “rescue” measures mainly focus on reversal of organ dysfunction. However, despite nearly two decades of efforts, the “Save Sepsis Campaign” has not achieved satisfactory results. Emergency medicine is the frontier subject of acute and severe illness which treats patients with acute infections at the earliest. If at this stage, physicians can predict the possibility of sepsis progression from demographic characteristics, localize the pathogen and infection, detect the inflammatory storms by tests of cytokines and evaluate the severity of the infection with more effective clinical scoring system, and then take effective measures to prevent infection from developing into sepsis in high-risk patients, the morbidity and mortality of sepsis in patients with acute infection will be greatly reduced. Based on this situation, Chinese emergency medicine experts proposed the concept of “preventing and blocking” sepsis, and launched the nationwide “Preventing Sepsis Campaign in China (PSCC)” nationwide. The main concept is summarized as “three early and two reduces” which includes early detection, early diagnosis and early intervention during the “pre-symptomatic” and “peri-septic” stage in order to reduce the incidence of sepsis and it proposed a new approach for diagnosis and treatment of acute severe infection. This consensus is jointly advocated, discussed and written by four academic associations in the field of emergency medicine and five scholarly publishing organizations. More than 40 experts from fields of emergency medicine, critical care medicine, infectious diseases, pharmacy and laboratory medicine have participated in several rounds of deliberation and finally reached consensus on the criteria of identifying patients with acute infection, taking anti-infective treatments, screening of high-risk patients with sepsis, detection and treatment of inflammatory storm, protection of vascular endothelial cells and the regulation of coagulation function, as well as strategies of liquid support and organ function protection etc. The consensus summarizes the commonly used clinical diagnosis criteria and treatment measures of sepsis both in Western medicine and traditional Chinese medicine for clinicians in order to provide evidence for the diagnosis and treatment of the disease.

Sepsis-associated organ dysfunction plays a critical role in its high mortality, mainly in connection with mitochondrial dysfunction. Whether the inhibition of mitochondrial fission is beneficial to sepsis-related organ dysfunction and underlying mechanisms are unknown. Cecal ligation and puncture induced sepsis in rats and dynamic related protein 1 knockout mice, lipopolysaccharide-treated vascular smooth muscle cells and cardiomyocytes, were used to explore the effects of inhibition of mitochondrial fission and specific mechanisms. Our study showed that mitochondrial fission inhibitor Mdivi-1 could antagonize sepsis-induced organ dysfunction including heart, vascular smooth muscle, liver, kidney, and intestinal functions, and prolonged animal survival. The further study showed that mitochondrial functions such as mitochondrial membrane potential, adenosine-triphosphate contents, reactive oxygen species, superoxide dismutase and malonaldehyde were recovered after Mdivi-1 administration via improving mitochondrial morphology. And sepsis-induced inflammation and apoptosis in heart and vascular smooth muscle were alleviated through inhibition of mitochondrial fission and mitochondrial function improvement. The parameter trends in lipopolysaccharide-stimulated cardiomyocytes and vascular smooth muscle cells were similar in vivo. Dynamic related protein 1 knockout preserved sepsis-induced organ dysfunction, and the animal survival was prolonged. Taken together, this finding provides a novel effective candidate therapy for severe sepsis/septic shock and other critical clinical diseases.

Sepsis-associated organ dysfunction plays a critical role in its high mortality, mainly in connection with mitochondrial dysfunction. Whether the inhibition of mitochondrial fission is beneficial to sepsis-related organ dysfunction and underlying mechanisms are unknown. Cecal ligation and puncture induced sepsis in rats and dynamic related protein 1 knockout mice, lipopolysaccharide-treated vascular smooth muscle cells and cardiomyocytes, were used to explore the effects of inhibition of mitochondrial fission and specific mechanisms. Our study showed that mitochondrial fission inhibitor Mdivi-1 could antagonize sepsis-induced organ dysfunction including heart, vascular smooth muscle, liver, kidney, and intestinal functions, and prolonged animal survival. The further study showed that mitochondrial functions such as mitochondrial membrane potential, adenosine-triphosphate contents, reactive oxygen species, superoxide dismutase and malonaldehyde were recovered after Mdivi-1 administration via improving mitochondrial morphology. And sepsis-induced inflammation and apoptosis in heart and vascular smooth muscle were alleviated through inhibition of mitochondrial fission and mitochondrial function improvement. The parameter trends in lipopolysaccharide-stimulated cardiomyocytes and vascular smooth muscle cells were similar in vivo. Dynamic related protein 1 knockout preserved sepsis-induced organ dysfunction, and the animal survival was prolonged. Taken together, this finding provides a novel effective candidate therapy for severe sepsis/septic shock and other critical clinical diseases. [ABSTRACT FROM AUTHOR]

Background: Individualized positive end-expiratory pressure (PEEP) by electrical impedance tomography (EIT) has potential interest in the optimization of ventilation distribution in acute respiratory distress syndrome (ARDS). The aim of the study was to determine whether early individualized titration of PEEP with EIT improved outcomes in patients with ARDS.Methods: A total of 117 ARDS patients receiving mechanical ventilation were randomly assigned to EIT group (n = 61, PEEP adjusted based on ventilation distribution) or control group (n = 56, low PEEP/FiO2 table). The primary outcome was 28-day mortality. Secondary and exploratory outcomes were ventilator-free days, length of ICU stay, incidence of pneumothorax and barotrauma, and difference in Sequential Organ Failure Assessment (SOFA) score at day 1 (ΔD1-SOFA) and day 2 (ΔD2-SOFA) compared with baseline.Measurements and Main Results: There was no statistical difference in the value of PEEP between the EIT group and control group, but the combination of PEEP and FiO2 was different between groups. In the control group, a significantly positive correlation was found between the PEEP value and the corresponding FiO2 (r = 0.47, p < 0.00001) since a given matched table was used for PEEP settings. Diverse combinations of PEEP and FiO2 were found in the EIT group (r = 0.05, p = 0.68). There was no significant difference in mortality rate (21% vs. 27%, EIT vs. control, p = 0.63), ICU length of stay (13.0 (7.0, 25.0) vs 10.0 (7.0, 14.8), median (25th-75th percentile); p = 0.17), and ventilator-free days at day 28 (14.0 (2.0, 23.0) vs 19.0 (0.0, 24.0), p = 0.55) between the two groups. The incidence of new barotrauma was zero. Compared with control group, significantly lower ΔD1-SOFA and ΔD2-SOFA were found in the EIT group (p < 0.001) in a post hoc comparison. Moreover, the EIT group exhibited a significant decrease of SOFA at day 2 compared with baseline (paired t-test, difference by - 1 (- 3.5, 0), p = 0.001). However, the control group did show a similar decrease (difference by 1 (- 2, 2), p = 0.131).Conclusion: Our study showed a 6% absolute decrease in mortality in the EIT group: a statistically non-significant, but clinically non-negligible result. This result along with the showed improvement in organ function might justify further reserach to validate the beneficial effect of individualized EIT-guided PEEP setting on clinical outcomes of patients with ARDS.Trial Registration: ClinicalTrials, NCT02361398. Registered 11 February 2015-prospectively registered, https://clinicaltrials.gov/show/NCT02361398 . [ABSTRACT FROM AUTHOR]

&lt;b&gt;Background and Objective:&lt;/b&gt; Probiotics have been known as a potential alternative to replace antibiotic growth promotors and have many benefits for poultry health. This research investigated that how administering a combination of probiotics affects the health and physiological parameters of laying chickens. This includes understanding if and how probiotics can enhance organ function and influence blood biochemistry profiles in these birds, therefore they are used to increase the production of laying hens. &lt;b&gt;Materials and Methods:&lt;/b&gt; A Completely Randomized Design (CRD) with 56 hens was used. The treatments with two consortium yogurt B1 (&lt;i&gt;Bifidobacterium&lt;/i&gt; spp. and &lt;i&gt;L. acidophilus&lt;/i&gt;) and B2 (&lt;i&gt;L. bulgaricus&lt;/i&gt;, &lt;i&gt;S. thermophilus&lt;/i&gt;, &lt;i&gt;L. acidophilus&lt;/i&gt; and &lt;i&gt;B. bifidum&lt;/i&gt;) consisted of a control group that was not given the same treatment as the control group (T0), Group-1 was treated with WSPE probiotic B1 2% (T1), Group-2 was treated with WSPE probiotic B2 2% (T2), Group-3 was treated with 2% probiotic B1 powder (T3), Group-4 was treated with 3% probiotic B1 powder (T4), Group-5 were treated with 2% B2 probiotic powder (T5) and Group-6 were treated with 3% B2 probiotic powder (T6), data were analyzed using Analysis of Variance (ANOVA) and followed by Duncan's multiple range test. &lt;b&gt;Results:&lt;/b&gt; The giving consortium probiotics to laying hens has a significant effect on uric acid levels as well as decreased SGOT, SGPT and creatinine levels also increasing total protein, albumin and globulin levels. &lt;b&gt;Conclusion:&lt;/b&gt; The use of probiotics 2% increased organ function, namely an increase in total protein, albumin and globulin levels.

Extensive research on the nutritional and medical application of selenium nanoparticles (SeNPs) was performed in past decades. Besides nutritional values, new characteristics such as antibacterial and anticancer properties depict a bright future for high Selenium (Se) consumption in the coming years. Se is essential for the proper functioning of most of the major body organ systems meanwhile it could be highly toxic and even cancerous. The current knowledge of Se interaction with major organ systems functionality such as the central nervous system isn’t well studied and many physiological aspects aren’t clear to the science community. Meanwhile, various results were published on increasing organ system functionality through administrated SeNPs. So with the rapid entrance of SeNPs in the medical and nutritional industry, it may cause unintended complications. The intent of this review is to investigate current knowledge of SeNPs interaction with major body organ systems functionality. Investigated pharmacokinetic parameters of SeNPs was also reviewed.

The biological effect of atrial natriuretic peptide (ANP) in traumatic hemorrhagic shock (THS) is unknown. This study was to evaluate whether ANP therapy can show organ protection in THS. Thirty male Sprague-Dawley rats were divided into three groups: ANP group, sham group, and control group. Pressure-controlled THS was induced in rats in ANP group and control group. ANP at a rate of 0.025 μg/kg/min was infused in ANP group during near-80 min of shock. After that, animals were resuscitated for 60 min and observed until 24 h. Hemodynamic parameters during shock and resuscitation were measured. Serum levels of ANP and lactate dehydrogenase, tissue oxidative stress and inflammatory factors, as well as liver and kidney function were determined. Tissue apoptosis was also assessed. There was no statistically significant difference between ANP group and control group in arterial pressure throughout the 150 min monitoring period. Blood urea nitrogen at 90 min and 24 h in ANP group was significantly lower than control group. Alanine transaminase and aspartate aminotransferase activity at 90 min in control group were significantly higher than that in sham group. However, hepatic enzyme activity at 90 min in ANP group was not significantly different compared with sham or control group. After 24 h, myocardial expression of caspase 3 protein in ANP group was significantly reduced compared with control group. Jejunal and hepatic Malondialdehyde was increased following ANP treatment. ANP therapy during early THS has no significant adverse effect on hemodynamics but can exert oxidative stress and certain protective effect on multiple organs. Our study may shed light on the novel therapy of THS with regard to organ protection. The mechanisms underlying the organ protection require further study. [ABSTRACT FROM AUTHOR]

Introduction: Intraabdominal pressure (IAP) is related to clinical outcome of patients. It is measured as intravesical pressure through a Foley catheter in the supine position. During pregnancy, there are data showing elevated IAP and also a suggestion that it may be a false increase due to pressure on the urinary bladder by the gravid uterus in the supine position. Additionally, it is not known whether the elevated IAP during pregnancy is merely a physiological change or is associated with impairment of organ functions. We thus aimed to establish a normal value of IAP in supine (IAPsupine) as well as 10° left lateral (IAPlateral‐tilt) positions, and their association with organ functions as well as certain maternal risk characteristics. Material and methods: This prospective cross‐sectional cohort study included 100 consenting parturients with term gestation posted for elective cesarean section under single‐shot subarachnoid block. IAP was measured via an indwelling Foley catheter with a transducer connected to it, as per the recommended technique. Organ dysfunction was defined as Sequential Organ Failure Assessment (SOFA) subscore ≥1 for the particular system. Trial registration: ctri.gov.in (CTRI/2017/11/010527). Results: The IAPsupine was significantly higher than IAPlateral‐tilt (13.8 ± 2.4 vs 12 ± 2.3 mm Hg) (P <.001). The incidence of intraabdominal hypertension as per conventional definition, that is, IAP ≥12 mm Hg, was also higher in the supine position (77% vs 55%) (P <.001). None of the patients had dysfunction of the cardiovascular, renal or central nervous system. The incidence of respiratory, hepatic and hematologic dysfunction was 2%, 15% and 32%, respectively. Receiver operating characteristic analysis showed insignificant association of IAPsupine and IAPlateral‐tilt with various organ dysfunctions (P >.05). There was a significant correlation of intraabdominal hypertension when considering IAPsupine or IAPlateral‐tilt, with obesity (P =.004 and.000, respectively), as well as preeclampsia (P =.006 and.000, respectively). Conclusions: In nonlaboring patients undergoing elective cesarean section, IAP is significantly higher in the supine vs 10° left lateral position. In neither position is IAP significantly associated with organ dysfunction. Thus, the usual recommendation of a supine position for measuring IAP to diagnose intraabdominal hypertension, formulated consequent to its pathological effects on organ functions, may not be applicable to pregnant patients and needs urgent validation studies. [ABSTRACT FROM AUTHOR]

Glucocorticoids (GCs) are stress hormones that regulate developmental and physiological processes and are among the most potent anti-inflammatory drugs to suppress chronic and acute inflammation. GCs act through the glucocorticoid receptor (GR), a ubiquitously expressed ligand-activated transcription factor, which translocates into the nucleus and can act via two different modes, as a GR monomer or as a GR dimer. These two modes of action are not clearly differentiated in practice and may lead to completely different therapeutic outcomes. Detailed aspects of GR mechanisms are often not taken into account when GCs are used in different clinical scenarios. Patients, with critical illness-related corticosteroid insufficiency, treated with natural or synthetic GCs are still missing a clearly defined therapeutic strategy. This review discusses the different modes of GR function and its importance on organ function in vivo. [ABSTRACT FROM AUTHOR]

Lung cancer is a prevalent and highly lethal disease often complicated by lower respiratory tract infections. Microbial patterns in these infections vary based on treatment modalities. The present study explored the impact of lung cancer treatments on pathogens and clinical characteristics in the presence of lower respiratory tract infections to inform antimicrobial drug selection. A retrospective analysis was performed that included data from 93 patients diagnosed with advanced lung cancer and lower respiratory tract infections between January 2019 and December 2021. Patients were divided into the targeted therapy and chemoradiotherapy groups. Clinical, nutritional, biochemical, infection and pathogenetic indicators were compared. Of the 93 cases, 24 were in the targeted therapy group and 69 were in the chemoradiotherapy group. Pathological type and hospitalization duration differed significantly (P<0.05), but age, sex, smoking history, alcohol consumption and underlying diseases did not (P>0.05). Lymphocyte counts differed (P<0.05), while body mass index, albumin, hemoglobin, alanine aminotransferase and creatinine levels, erythrocyte sedimentation rate, hypersensitive C-reactive protein and procalcitonin levels, and the percentage of neutrophils did not (P>0.05). Pathogenetic testing was negative in 15 patients and positive in 78 patients, with Gram-negative bacteria (61.77%), fungi (17.65%) and viruses (11.76%) predominant in the targeted therapy group. In the chemoradiotherapy group, Gram-negative bacteria (47.46%), fungi (28.81%) and viruses (16.95%) were also more prevalent. Candida albicans was the most frequent fungal infection in both groups, and mixed infections were common (50% in targeted therapy and 73.92% in chemoradiotherapy). The chemoradiotherapy group had significantly more mixed infections (P<0.05). Overall, common pathogens in both groups included Gram-negative bacteria, fungi and viruses. Chemoradiotherapy patients experienced longer hospital stays and a higher incidence of mixed infections, predominantly involving Gram-negative bacteria and fungi. The results provide valuable insights into the rational selection of empirical antibiotics and antifungals for critically ill patients with lung cancer and lower respiratory tract infections in targeted therapy or chemoradiotherapy. [ABSTRACT FROM AUTHOR]