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Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection, of which the pathogenesis is complex and the mortality rate is high. However, current basic research is facing the dilemma of high heterogeneity and difficult translation to clinical practice. In-depth basic research is one of the most important ways to break through the "bottleneck" of clinical diagnosis and treatment of sepsis. The purpose of this review is to analyze the current progress and challenges in the field of basic research on sepsis, and look forward to the potential research directions in the future. Cell function, energy metabolism, microbiota, epigenetics and recovery period of sepsis may be the research priorities.
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Perioperative cardiac arrest is a significant cause of perioperative mortality in patients.The first clinical practice recommendation dedicated to the management of perioperative cardiac arrest was published in 2021 and contains 22 specific recommendations.This clinical practice recommendation includes indicators to monitor during treatment, the sequence of defibrillation and chest compressions, the use of epinephrine and antiarrhythmic drugs, treatment strategies for specific types of perioperative cardiac arrest, the use of adjunctive therapies such as ultrasound to assist in treatment, setting appropriate hemodynamic and respiratory parameters, and temperature management.This clinical practice recommendation is essential for effective management of perioperative cardiac arrest and will also provide guidance for further exploration of the management of perioperative cardiac arrest in the future.
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Objective:To evaluate the effect of methane on acetaminophen-induced acute liver injury (ALI) in mice and the role of autophagy.Methods:Forty clean-grade SPF healthy adult male C57BL/6 mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=10 each) using a random number table method: control group (group C), group ALI, methane-rich saline group (group MS) and methane-rich saline plus 3-methyladenine (3-MA) group (group MS+ 3-MA). Acetaminophen 300 mg/kg was injected intraperitoneally to establish ALI model.Group MS was injected intraperitoneally with methane-rich saline 10 ml/kg immediately after establishing the model and at 12 h after establishing the model.Group MS+ 3-MA was injected intraperitoneally with methane-rich saline 10 ml/kg and autophagy inhibitor 3-MA 30 mg/kg immediately after establishing the model and was injected intraperitoneally with methane-rich saline 10 ml/kg at 12 h after establishing the model.The equal volume of sterile saline was given intraperitoneally at the same time points in C and ALI groups.At 24 h after establishment of the model, blood samples from the eyeball were taken for measuring concentrations of alanine transaminase (ALT) and aspartate transaminase (AST) in serum (using biochemistry analyzer) and the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in serum (using enzyme-linked immunosorbent assay). The animals were then sacrificed and liver tissues were removed for determination of microtubule-associated protein 1 light chain 3 (LC3) and p62 (by Western blot) and for the examination of the number of autophagosomes (under a transmission electron microscope). Results:Compared with group C, the concentrations of ALT, AST, TNF-α and IL-6 in serum were significantly increased, LC3Ⅱ/LC3Ⅰ ratio was increased, expression of p62 was up-regulated, and the number of autophagosomes was increased in liver tissues in ALI, MS and MS+ 3-MA groups ( P<0.05). Compared with group ALI, the concentrations of ALT, AST, TNF-α and IL-6 in serum were significantly decreased, LC3Ⅱ/LC3Ⅰ ratio was increased, expression of p62 was down-regulated, and the number of autophagosomes in liver tissues was increased in group MS, and AST concentration in serum was decreased and LC3Ⅱ/LC3Ⅰ ratio was increased in group MS+ 3-MA ( P<0.05). Compared with group MS, the concentrations of ALT, AST, TNF-α and IL-6 were significantly increased, the LC3 II/LC3 I ratio and the number of autophagosomes were decreased in lung tissues in group MS+ 3-MA ( P<0.05). Conclusion:The mechanism by which methane can reduce acetaminophen-induced ALI is related to enhancement of the level of autophagy in liver cells in mice.
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In order to effectively prevent infection or severe acute respiratory syndrome coronavirus 2 transmission among medical staff during tracheal intubation in patients with suspected or confirmed coronavirus disease 2019(COVID-19), and to ensure the safety of personnel who will perform the endotracheal intubation, we made a literature review to analyze the airway management for SARS patients from China and abroad in 2003. Relevant documents, consensus of diagnosis and therapy for patients with COVID-19 from the National Health Commission, and guidelines of relevant academic societies were also reviewed.Thus, we provide suggestions on infection control for performing endotracheal intubation in patients with COVID-19 mainly as follows.Medical staff should fully understand the infection risk of COVID-19 and strengthen the training before the procedure.It is suggested that the indication of endotracheal intubation should be properly defined, and the need for intubation as emergent or elective should be evaluated early with preparation made in advance.During the implementation of endotracheal intubation, the procedure should be completed by the most experienced personnel in airway management using the tools they master best, and a rapid sequential induction of endotracheal intubation is recommended.
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Intestinal?barrier?act?as?the?crucial?defender?against?pathogen?invasion,?and?is?indispensable?in?maintaining?tissue?homeostasis?both?locally?and?systemically.?Severe?disease?can?lead?to?impaired?intestinal?barrier.?In?addition?to?cause?a?variety?of?gastrointestinal?diseases,?intestinal?barrier?damage?can?also?worsen?the?disease?progression?in?critically?ill?patients.?Innate?lymphoid?cells?(ILCs)?is?a?group?of?newly?defined?innate?immune?cells?which?have?some?characteristics?as?adaptive?immune?cells.?Group?3?innate?lymphoid?cells?(ILC3),?which?mainly?reside?at?gut?associate?mucosal?tissue,?have?been?reported?to?play?a?critical?role?in?maintaining?intestinal?barrier?function.?After?a?brief?introduction?about?its?origination?and?classification,?we?will?focus?on?function?of?ILC3?physiologically?and?pathologically,?and?provide?a?new?theoretical?basis?for?maintaining?intestinal?barrier?function?under?pathological?conditions?in??this?review.
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Immune metabolism is an emerging highlight in recent years.Revealing the metabolic characteristics of different immune cells in different responses may provide new perspective and direction for the pathogenesis and therapy of many immune-related diseases.Sepsis is a complex systemic inflammation caused by trauma,infection and other pathogenic factors.The immune cells have different metabolic features at different stages of the disease.These metabolic features are also involved in the regulation of immune cell proliferation,differentiation and function.By summarizing and analyzing the relevant literatures of immune cell metabolism and inflammation regulation in recent years,the metabolic regulatory factors of different immune cell subgroups and the related characteristics of immune cell metabolism in patients with sepsis were summarized.The in-depth understanding of the metabolic state in different immune cells,and the pathophysiological mechanism of septic immune disorders,especially the immune paralysis stage,would provide a theoretical basis for the clinical application of immune metabolic therapy.
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Objective To investigate the role and mechanism of ulinastatin on the hyper-permeability of vascular endothelial cell induced by matrix metalloproteinase-9 (MMP-9). Methods Human umbilical vein endothelial cells (HUVEC) were cultured in vitro to establish a complete monolayer vascular endothelial cell model. The monolayer vascular endothelial cells were randomly divided into three groups: blank control group [phosphate buffered saline (PBS) added], MMP-9 model group (1 mg/L MMP-9 added) and ulinastatin group (1 mg/L MMP-9 and 1 000 kU/L ulinastatin added). The permeability of monolayer vascular endothelial cells was measured by fluorescein isothiocyanate (FITC)-labeled dextran (FD40) leaking method; the soluble vascular endothelial cells calcium dependent adherin (VE-cadherin) concentration in culture solution was determined by enzyme linked immunosorbent assay (ELISA);the protein expression levels of zonular occlusion protein-1 or tight junction (ZO-1), VE-cadherin, claudin-5 were detected by Western Blot and immunofluorescence methods. Results Compared with the blank control group, the permeability of vascular endothelial cells in MMP-9 model group was significantly increased [(cm2/h, ×10-2):3.35±0.56 vs. 0.94±0.06, P < 0.05]; the concentrations of soluble VE-cadherin in the Transwell upper and lower chambers were increased significantly [upper chamber (μg/L): 5.02±0.40 vs. 3.83±0.42, lower chamber (μg/L):4.92±1.05 vs. 3.24±1.24, both P < 0.05]; the protein expression levels of ZO-1, VE-cadherin and claudin-5 were significantly decreased [ZO-1/β-actin: 0.152±0.067 vs. 0.262±0.090, VE-cadherin/β-actin: 0.137±0.048 vs. 0.246±0.094, claudin-5/β-actin: 0.148±0.062 vs. 0.336±0.119, all P < 0.05], and obvious rupture sites appeared in their fluorescent patterns, and fluorescent particles were significantly reduced; compared with MMP-9 model group, the permeability of vascular endothelial cells in ulinastatin group was significantly decreased [(cm2/h, ×10-2): 1.80±0.34 vs. 3.35±0.56, P < 0.05]; the soluble VE-cadherin concentrations were significantly reduced in upper and lower chambers than those in the MMP-9 model group [upper chamber (μg/L): 4.41±0.37 vs. 5.02±0.40, lower chamber (μg/L):3.85±1.04 vs. 4.92±1.05, both P < 0.05], the expressions of endothelial junction protein were significantly increased in ulinastatin group (ZO-1/β-actin: 0.229±0.097 vs. 0.152±0.067, VE-cadherin/β-actin: 0.236±0.089 vs. 0.137±0.048, claudin-5/β-actin: 0.262±0.101 vs. 0.148±0.062, all P < 0.05], and the continuity of their fluorescent patterns and fluorescent particles were both increased. Conclusion The in vitro experiment showed that the hyper-permeability of vascular endothelial cells induced by MMP-9 can be attenuated by ulinastatin through decreasing the destruction of VE-cadherin and maintaining the protein expression levels of ZO-1, VE-cadherin and claudin-5 in vascular endothelial cells.
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Sepsis is a leading cause of death in critically ill patients.The definitions of sepsis and septic shock were introduced in 1991 and last revised in 2001.Since considerable advances had occurred to its pathophysiology and management,an update definitions for sepsis and septic shock were released in February 2016 by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine.This article is to review the development and limitations of previous versions of sepsis definition,and summarize the sepsis 3.0 definition and its clinical diagnosis criteria.These updated definitions and clinical criteria will play vital roles in providing important reference frame for clinical trials,and facilitating early recognition and timely management of patients with sepsis.
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ObjectiveTo investigate the role of platelet in mouse pulmonary microvascular endothelial cell (PMVEC) injury caused by lipopolysaccharide( LPS)-activated neutrophil.MethodsPMVECs were obtained from pathogen-free C3H/HeN mice of both sexes aged 6-8 weeks weighing 18-25 g according to the method described by Lim YC et al.Platelets and neutrophils were isolated from mouse blood by twice centrifugation and denaity gradient centrifugation respectively.PMVECs were seeded into twelve- or six-well plates ( 1 or 2 ml/well) after 2-5 passages and were randomly divided into 4 groups (n =31 each): group LPS; group platelets (group P);group neutrophils (group N) and group platelets + neutrophils (group PN).Each well contained about 5 × 107/ml platelets and/or 5 × 105/ml neutrophils respectively.PMVECs were incubated with LPS1 μg/ml at 37 ℃ in a 5％ CO2 humidified atmosphere for 1,6,12,18 and 24 h respectively in all 4 groups.The cells were examined with phase contrast microscope for morphological changes and survival condition.Viability rate,apoptotic rate and activation rate of PMVECs were detected by flow cytometry at each time points.ResultsThere was no significant difference in morphology and number of endothelial cells (ECs) among the 4 groups,while the number of activated ECs was significantly increased but the number of living cells decreased in group PN compared with group LPS.The activation rate of ECs was significantly higher after being incubated with LPS for 6-12 h in groups P and N than in group LPS.The viability rate was significantly lower,while the apoptotic rate and activation rate were significantly higher after ECs were incubated with LPS in group PN than in groups LPS,P and N.ConclusionPlatelets play a decisive role in mouse PMVEC injury induced by LPS activated neutrophils.
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Objective To study the effects of sevoflurane on voltage-gated Na~+, K~+ and Ca~(2+) channels in rat dorsal root ganglion(DRG) cells.Methods Dorsal root ganglions were dissected from thoracic and upper lumbar segments of the spinal cord. DRG cells were prepared by digestion with collagenase and trypsin at 32-34℃ The whole cell Na~+, K~+ and Ca~(2+) currents were recorded by standard patch clamp technique. The changes in the currents from holding potential of-70 mV to test potential of 0 mV were recorded in a 10 mV increments in the presence and absence of sevoflurane. Results 0.4, 0.9 and 1.8 mmol?L~(-1) sevoflurane had no effect on Na~+ or K~+ currents but Ca~(2+) currents could be significantly suppressed by 0.4 mmol?L~(-1) sevoflurane. Conclusion Na~+ and K~+ channels in DRG cells are not involved in the spinal mechanism of sevoflurane. The inhibition of Ca~(2+) current in DRG cells by sevoflurane could be associated with the antinociceptive effect of sevoflurane at the spinal cord level.