Using the sympathetic system, beta blockers and alpha-2 agonists, to address acute respiratory distress syndrome.

Acute Respiratory Distress Syndrome (ARDS) manifests as an acute inflammatory lung injury characterized by persistent hypoxemia, featuring a swift onset, high mortality, and predominantly supportive care as the current therapeutic approach, while effective treatments remain an area of active investigation. Adrenergic receptors (AR) play a pivotal role as stress hormone receptors, extensively participating in various inflammatory processes by initiating downstream signaling pathways. Advancements in molecular biology and pharmacology continually unveil the physiological significance of distinct AR subtypes. Interventions targeting these subtypes have the potential to induce specific alterations in cellular and organismal functions, presenting a promising avenue as a therapeutic target for managing ARDS. This article elucidates the pathogenesis of ARDS and the basic structure and function of AR. It also explores the relationship between AR and ARDS from the perspective of different AR subtypes, aiming to provide new insights for the improvement of ARDS.

The Anesthesiologists' Perception of Malignant Hyperthermia and Availability of Dantrolene in China: A Cross-Sectional Survey.

Background: Malignant hyperthermia (MH) is a hypermetabolic syndrome with high mortality rates. Early detection and prompt intravenous administration of dantrolene are crucial for effective management of MH. However, there is currently a lack of comprehensive nationwide surveys on the availability of dantrolene and anesthesiologists' understanding of MH in China. Methods: A nationwide survey was conducted between January 2022 and June 2022. Online questionnaires on the cognition of MH among anesthesiologists in China were sent through social platforms to anesthesiologists in mainland China. Data regarding participants' perception of MH-related knowledge, availability of domestic dantrolene, and reported MH cases were collected in this study. Results: Responses were collected from a total of 11,354 anesthesiologists representing 31 provinces across the Chinese mainland. Among the 11 scoring questions, the highest accuracy rates were observed for the question regarding therapeutic drugs for MH (99.3%) and the characteristics of MH (98.0%). Conversely, the question pertaining to the earliest clinical signs of MH had the lowest accuracy rate (23.5%). Significant variations were observed in the scores among different professional titles (P=0.003), academic degree (P<0.001), hospital classification (P<0.001), and urban hierarchy (P<0.001). Of the respondents, 919 (8.1%) anesthesiologists reported dantrolene availability in their hospitals, and 631 (5.6%) indicated unclear. A total of 136 hospitals in this survey reported at least one previous case of MH. Conclusion: Mainland China faces challenges such as insufficient experience in diagnosing and treating MH, as well as difficulty in obtaining dantrolene. To improve the public awareness of MH, it is imperative to establish and promote a refined MH training system. Additionally, a streamlined and rapid dantrolene linkage emergency system should be implemented to ensure prompt access to the drug.

Advances of presepsin in sepsis-associated ARDS.

This article reviews the correlation between presepsin and sepsis and the resulting acute respiratory distress syndrome (ARDS). ARDS is a severe complication of sepsis. Despite the successful application of protective mechanical ventilation, restrictive fluid therapy, and neuromuscular blockade, which have effectively reduced the morbidity and mortality associated with ARDS, the mortality rate among patients with sepsis-associated ARDS remains notably high. The challenge lies in the prediction of ARDS onset and the timely implementation of intervention strategies. Recent studies have demonstrated significant variations in presepsin (PSEP) levels between patients with sepsis and those without, particularly in the context of ARDS. Moreover, these studies have revealed substantially elevated PSEP levels in patients with sepsis-associated ARDS compared to those with nonsepsis-associated ARDS. Consequently, PSEP emerges as a valuable biomarker for identifying patients with an increased risk of sepsis-associated ARDS and to predict in-hospital mortality.

Epidemiological and clinical features of malignant hyperthermia: A scoping review.

Malignant hyperthermia (MH) is a potentially fatal inherited pharmacogenetic disorder related to pathogenic variants in the RYR1, CACNA1S, or STAC3 genes. Early recognition of the occurrence of MH and prompt medical treatment are indispensable to ensure a positive outcome. The purpose of this study was to provide valuable information for the early identification of MH by summarizing epidemiological and clinical features of MH. This scoping review followed the methodological framework recommended by Arksey and O'Malley. PubMed, Embase, and Web of science databases were searched for studies that evaluated the epidemical and clinical characteristics of MH. A total of 37 studies were included in this review, of which 26 were related to epidemiology and 24 were associated with clinical characteristics. The morbidity of MH varied from 0.18 per 100 000 to 3.9 per 100 000. The mortality was within the range of 0%-18.2%. Identified risk factors included sex, age, disorders associated with MH, and others. The most frequent initial clinical signs included hyperthermia, sinus tachycardia, and hypercarbia. The occurrence of certain signs, such as hypercapnia, delayed first temperature measurement, and peak temperature were associated with poor outcomes. The epidemiological and clinical features of MH varied considerably and some risk factors and typical clinical signs were identified. The main limitation of this review is that the treatment and management strategies were not assessed sufficiently due to limited information.

Curdione ameliorates sepsis-induced lung injury by inhibiting platelet-mediated neutrophil extracellular trap formation.

Sepsis-associated acute lung injury remains to be a major cause of morbidity and mortality worldwide, and there is a lack of effective therapeutic drugs. Curdione, an activeingredient of Curcuma zedoary, a traditional Chinese medicine (TCM), possesses a variety of pharmacological actions, such as anti-inflammatory, antioxidant and inhibition of platelet aggregation. However, whether curdione protects against sepsis-induced lung injury is still undetermined. In this study, we investigated the effects of curdione on sepsis-induced lung injury. Cecal ligation and puncture (CLP) surgery was performed in mice to establish a model of sepsis. Twenty-four hours after CLP, bronchoalveolar lavage fluid (BALF) and lung tissue samples were harvested for investigation. The protective effects of curdione on acute lung injury and potential mechanisms were explored by detecting pathological sections, exudative proteins, oxidative responses, inflammatory factors, platelet activation, neutrophil infiltration, and neutrophil extracellular trap (NET) formation in the lung and were further verified in vitro. We showed that treatment with curdione clearly relieved histopathological changes, reduced inflammatory cytokine elevation and total protein concentrations in BALF, and decreased oxidative stress responses in lung tissues. In addition, curdione inhibited platelet activation, further blocking the interaction between platelets and neutrophils. Finally, neutrophil infiltration and NET formation was also reduced in mice treated with curdione. In conclusion, curdione alleviates sepsis-induced lung injury by inhibiting platelet-mediated neutrophil recruitment, infiltration, and NET formation as well as its anti-inflammatory and antioxidant properties. Curdione has great therapeutic potential in sepsis.

[Establishment and verification of LIPS score combined with APACHE II score and oxygenation index to predict the occurrence model of ARDS].

OBJECTIVE: To construct and verify the occurrence model of acute respiratory distress syndrome (ARDS) using lung injury prediction score (LIPS) combined with acute physiology and chronic health evaluation II (APACHE II) score and oxygenation index (PaO2/FiO2). METHODS: Using a prospective cohort study method, 244 patients with complete medical records who were admitted to the intensive care unit (ICU) of Peking University Third Hospital from December 2020 to July 2022 were selected as research objects according to the inclusion and exclusion criteria. They were divided into training set (173 cases) and validation set (71 cases). Patients' gender, age, body mass index (BMI), various causes (shock, sepsis, craniocerebral injury, pulmonary contusion, multiple trauma, aspiration, pneumonia, acute abdomen, hypoproteinemia, acidosis, major surgery, etc.), underlying diseases (diabetes, malignant tumor, cerebrovascular disease, liver disease, kidney disease) and laboratory test indicators were collected. According to the above data, the LIPS score, APACHE II score, sequential organ failure assessment (SOFA) and PaO2/FiO2, etc within 24 hours after admission to the ICU were calculated. Univariate analysis was used to screen the influencing factors for the occurrence of ARDS, and the factors with P < 0.2 were included in the multivariate Logistic regression analysis to screen out the independent predictive factors for the occurrence of ARDS. According to the results of multivariate Logistic regression analysis, the risk score of patients with ARDS was obtained to construct the risk prediction model of ARDS, the receiver operator characteristic curve (ROC curve) was drawn, and the area under the ROC curve (AUC) was calculated. The established ARDS prediction model was externally validated, and ROC curves were drawn to evaluate the predictive accuracy of the prediction model for the occurrence of ARDS in critically ill patients, and the AUC of the validation set was calculated to analyze the predictive performance of each risk factor on the occurrence of ARDS. RESULTS: A total of 173 patients were enrolled in the training set, including 121 patients without ARDS and 52 patients with ARDS; 77 cases of acute abdomen, 64 cases of sepsis, 60 cases of shock, 51 cases of acidosis, 40 cases of hypoproteinemia, 37 cases of diabetes, 34 cases of craniocerebral injury, 34 cases of abnormal liver function, 28 cases of multiple trauma, 23 cases of malignant tumor, 23 cases of spinal orthopedic surgery, 17 cases of obesity, 12 cases of pneumonia, 11 cases of pulmonary contusion, and 7 cases of chronic kidney disease, chemotherapy in 6 cases, and aspiration in 2 cases. The rates of shock, sepsis, acute abdomen, acidosis, abnormal liver function, lung contusion, pneumonia and aspiration, gender, age, LIPS score, APACHE II score, and SOFA score in the ARDS group were significantly higher than those in the non-ARDS group (all P < 0.05), moreover, PaO2/FiO2 ratio was significantly lower than that of non-ARDS group (P < 0.01). Multivariate Logistic regression analysis showed that LIPS score, APACHE II score, and PaO2/FiO2 ratio were independent risk factors for ARDS in ICU patients with high risk factors for ARDS, and the odds ratio (OR) was 1.768 [95% confidence interval (95%CI) was 1.380-2.266], 1.242 (95%CI was 1.089-1.417), 0.985 (95%CI was 0.978-0.991), all P < 0.05. ROC curve analysis showed that the AUC of the ARDS prediction model training set was 0.920, the sensitivity was 86.5%, and the specificity was 86.8%; the AUC of the verification set was 0.896, the sensitivity was 96.8%, and the specificity was 76.6%. CONCLUSIONS: LIPS score, APACHE II score and PaO2/FiO2 are independent risk factors for the occurrence of ARDS in ICU patients with high risk factors for ARDS. The ARDS risk prediction model established based on these three indicators has a good predictive ability for the occurrence of ARDS in critically ill patients, wihich needs to be verified by multicenter cohort studies.

Inhibition of visfatin alleviates sepsis-induced intestinal damage by inhibiting Hippo signaling pathway.

BACKGROUND: The aim of this study is to investigate role of Visfatin, one of the pro-inflammatory adipokines, in sepsis-induced intestinal injury and to clarify the potential mechanism. METHODS: C57BL/6 mice underwent cecal ligation and puncture (CLP) surgery to establish sepsis model in vivo. Intestinal epithelial cells were stimulated with LPS to mimic sepsis-induced intestinal injury in vitro. FK866 (the inhibitor of Visfatin) with or without XMU-MP-1 (the inhibitor of Hippo signaling) was applied for treatment. The expression levels of Visfatin, NF-κB and Hippo signaling pathways-related proteins were detected by western blot or immunohistochemistry. The intestinal cell apoptosis and intestinal injury were investigated by TUNEL staining and H&E staining, respectively. ELISA was used to determine the production of inflammatory cytokines. RESULTS: The expression of Visfatin increased in CLP mice. FK866 reduced intestinal pathological injury, inflammatory cytokines production, and intestinal cell apoptosis in sepsis mice. Meanwhile, FK866 affected NF-κB and Hippo signaling pathways. Additionally, the effects of FK866 on inflammatory response, apoptosis, Hippo signaling and NF-κB signaling were partly abolished by XMU-MP-1, the inhibitor of Hippo signaling. In vitro experiments also revealed that FK866 exhibited a protective role against LPS-induced inflammatory response and apoptosis in intestinal cells, as well as regulating NF-κB and Hippo signaling, whereas addition of XMU-MP-1 weakened the protective effects of FK866. CONCLUSION: In short, this study demonstrated that inhibition of Visfatin might alleviate sepsis-induced intestinal injury through Hippo signaling pathway, supporting a further research on Visfatin as a therapeutic target.

[Gender difference in acute respiratory distress syndrome].

Acute respiratory distress syndrome (ARDS) is a common critical disease in clinic, which refers to acute hypoxic respiratory failure caused by various insults, with bilateral fluffy infiltrates on chest radiography. It is reported that gender may play a critical role in the occurrence, severity, and outcomes of ARDS. Nevertheless, gender difference in ARDS is still controversial because of the complexity of the disease. This paper summarized the sex difference in epidemiology of ARDS according to different etiologies such as sepsis, trauma and respiratory viruses, and discussed gender-bias in the occurrence, severity and outcomes of ARDS. Moreover, we clarified briefly the mechanism that may contribute to the gender-bias to provide novel ideas for clinical treatment of ARDS.

α1-adrenoceptor stimulation ameliorates lipopolysaccharide-induced lung injury by inhibiting alveolar macrophage inflammatory responses through NF-κB and ERK1/2 pathway in ARDS.

Introduction: Catecholamines such as norepinephrine or epinephrine have been reported to participate in the development of acute respiratory distress syndrome (ARDS) by activating adrenergic receptors (ARs). But the role of α1-AR in this process has yet to be elucidated. Methods: In this study, ARDS mouse model was induced by intratracheal instillation of lipopolysaccharide. After treatment with α1-AR agonist phenylephrine or antagonist prazosin, lung pathological injury, alveolar barrier disruption and inflammation, and haemodynamic changes were evaluated. Cytokine levels and cell viability of alveolar macrophages were measured in vitro. Nuclear factor κB (NF-κB), mitogen-activated protein kinase, and Akt signalling pathways were analysed by western blot. Results: It showed that α1-AR activation alleviated lung injuries, including reduced histopathological damage, cytokine expression, and inflammatory cell infiltration, and improved alveolar capillary barrier integrity of ARDS mice without influencing cardiovascular haemodynamics. In vitro experiments suggested that α1-AR stimulation inhibited secretion of TNF-α, IL-6, CXCL2/MIP-2, and promoted IL-10 secretion, but did not affect cell viability. Moreover, α1-AR stimulation inhibited NF-κB and enhanced ERK1/2 activation without significantly influencing p38, JNK, or Akt activation. Discussion: Our studies reveal that α1-AR stimulation could ameliorate lipopolysaccharide-induced lung injury by inhibiting NF-κB and promoting ERK1/2 to suppress excessive inflammatory responses of alveolar macrophages.

Development and Trends in Artificial Intelligence in Critical Care Medicine: A Bibliometric Analysis of Related Research over the Period of 2010-2021.

BACKGROUND: The intensive care unit is a center for massive data collection, making it the best field to embrace big data and artificial intelligence. OBJECTIVE: This study aimed to provide a literature overview on the development of artificial intelligence in critical care medicine (CCM) and tried to give valuable information about further precision medicine. METHODS: Relevant studies published between January 2010 and June 2021 were manually retrieved from the Science Citation Index Expanded database in Web of Science (Clarivate), using keywords. RESULTS: Research related to artificial intelligence in CCM has been increasing over the years. The USA published the most articles and had the top 10 active affiliations. The top ten active journals are bioinformatics journals and are in JCR Q1. Prediction, diagnosis, and treatment strategy exploration of sepsis, pneumonia, and acute kidney injury were the most focused topics. Electronic health records (EHRs) were the most widely used data and the "-omics" data should be integrated further. CONCLUSIONS: Artificial intelligence in CCM has developed over the past decade. With the introduction of constantly growing data volume and novel data types, more investigation on artificial intelligence ethics and model correctness and extrapolation should be performed for generalization.

α2A-adrenoceptor deficiency attenuates lipopolysaccharide-induced lung injury by increasing norepinephrine levels and inhibiting alveolar macrophage activation in acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is a severe condition with high morbidity and mortality and few interventions. The role of sympathetic stress in the pathogenesis of ARDS has attracted recent research attention. Blockade of α-2 or α2A-adrenoceptor (α2A-AR) has been shown to attenuate lung injury induced by lipopolysaccharide (LPS) in rats. However, the mechanism is unclear. We confirmed the role of α2A-AR in ARDS using knockout mice and alveolar macrophages following LPS stimulation to assess the underlying mechanisms. We found that α2A-AR deficiency decreased the permeability of the alveolar capillary barrier in ARDS mice and suppressed lung inflammation by reducing inflammatory cell infiltration and the production of TNF-α, interleukin (IL)-6, and CXCL2/MIP-2. LPS stimulation decreased NF-κB activation in lung tissues of α2A-AR deficient mice and increased norepinephrine concentrations. In vitro, we found that norepinephrine inhibited the production of TNF-α, IL-6, and CXCL2/MIP-2 and promoted the secretion of IL-10 from LPS-stimulated murine alveolar macrophages. Blockade of α2A-AR by a specific antagonist further inhibited the production of TNF-α, IL-6, and IL-10. Furthermore, norepinephrine down-regulated NF-κB activation in stimulated alveolar macrophages. Altogether, these results suggest that α2A-AR deficiency ameliorates lung injury by increasing norepinephrine concentrations in lung tissues and inhibiting the activation of alveolar macrophages.

Inhibition of LPS-induced Nox2 activation by VAS2870 protects alveolar epithelial cells through eliminating ROS and restoring tight junctions.

Inhibiting the production of reactive oxygen species (ROS) in alveolar epithelial cells (AECs) under oxidative distress becomes a new therapeutic strategy for acute respiratory distress syndrome (ARDS). Herein in the present study, we investigated effects of Nox2, the catalytic subunit of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase type 2, on LPS-induced epithelium injury in ARDS mice and in human alveolar epithelial A549 cells. Severe lung injury, disruption of alveolar-capillary barrier with the loss of zonula occluden (ZO)-1 and up-regulated expression of Nox2 in AECs were exhibited in ARDS mice. In vitro, LPS induced decreased cell viability coupled with activated Nox2, high level of ROS, and destroyed ZO-1 distribution. Moreover, VAS2870 proved to inhibit Nox2 expression, reduce ROS generation, restore epithelium barrier integrity, and preserve cell viability in LPS-induced A549 cells. These data demonstrate that Nox2/ROS/ZO-1 axis is of great importance in AECs damage induced by LPS, and the utilization of VAS2870 to inhibit this pathway might lighten LPS-induced ARDS.

α2A -AR antagonism by BRL-44408 maleate attenuates acute lung injury in rats with downregulation of ERK1/2, p38MAPK, and p65 pathway.

Acute respiratory distress syndrome (ARDS), characterized by acute hypoxic respiratory dysfunction or failure, is a manifestation of multiple organ failure in the lung, and the most common risk factor is sepsis. We previously showed that blocking α2 -adrenoceptor (α2 -AR) could attenuate lung injury induced by endotoxin in rats. α2A -adrenoceptor (α2A -AR), a subtype of α2 -AR plays a key role in inflammatory diseases, but the mechanism remains unknown. Here, we explored the effect of BRL-44408 maleate (BRL), a specific α2A -AR antagonist, on cecal ligation puncture (CLP)-induced ARDS in rats and the underlying mechanism. Preadministration of BRL-44408 maleate significantly alleviated CLP-induced histological injury, macrophage infiltration, inflammatory response, and wet/dry ratio in lung tissue. However, there was no statistical difference in survival rate between the CLP and CLP+BRL groups. Extracellular regulated protein kinase (ERK1/2), p38MAPK, and p65 were activated in the CLP group, and BRL-44408 maleate inhibited the activation of these signal molecules, c-Jun N-terminal kinase (JNK) and protein kinase A (PKA) showed no changes in activation between these two groups. BRL-44408 maleate decreased lipopolysaccharide (LPS)-induced expression of cytokines in NR8383 rat alveolar macrophages and reduced phosphorylation of ERK1/2, p38MAPK, and p65. JNK and PKA were not influenced by LPS. Together, these findings suggest that antagonism of α2A -AR improves CLP-induced acute lung injury and involves the downregulation of ERK1/2, p38MAPK, and p65 pathway independent of the activation of JNK and PKA.

[The role of nicotinamide-adenine dinucleotide phosphate oxidase NOX family in acute lung injury].

OBJECTIVE: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are common critical syndromes. The causes of the syndrome are complex and diverse. The main pathological features are the diffuse inflammatory and protein-rich pulmonary edema caused by destruction of the blood-air barrier. Reactive oxygen species (ROS) mediate oxidative damage by oxidizing bio-macromolecules, including lipids, proteins and nucleic acid. Among many systems producing ROS, nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase-mediated ROS is the main source, and its functional subunit is the transmembrane subunit NOX family. The distribution of NOX family proteins in lung tissue is cell type dependent. NOX-derived ROS is involved in the defense function of lung tissue and related to the occurrence and development of ALI/ARDS. This review mainly describes the cell distribution, activation factors, and its relationship with the occurrence and development of ALI of the NOX family.

[BRL-44408 maleate, the antagonist of α2A-adrenoceptor, attenuates endogenous lipopolysacchride-induced acute lung injury through inhibiting the mitogen-activated protein kinase kinase/extracellular regulated protein kinases signaling pathway in mice].

OBJECTIVE: To explore the effects and mechanism of α2A-adrenergic receptor (α2A-AR) antagonist BRL-44408 maleate on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. METHODS: Sixty male C57BL/6 mice were randomly divided into three groups (n = 20): sham group, LPS group and BRL-44408 maleate pre-treated group (BRL+LPS group). The model of ALI was replicated by intratracheally administrated of LPS (5 mg/kg), and the mice in the sham group were received an equal volume of saline. Mice in the BRL+LPS group were treated with additionally BRL-44408 maleate (5 mg/kg, i.p) at 4 hours before LPS administration. The mice were sacrificed at 6 hours and 24 hours after LPS administration in each group. Among them, 5 mice were used to collect the bronchoalveolar lavage fluid (BALF) and the other 5 mice were sacrificed for lung tissues. The levels of norepinephrine (NE), tumor necrosis factor-α (TNF-α), interleukins (IL-6, IL-10) in BALF were measured by enzyme linked immunosorbent assay (ELISA). The level of protein in BALF was measured by bicinchoninic acid (BCA) method. The histopathological changes and wet/dry (W/D) ratio of lung tissue were observed. The expression of lung phosphorylated mitogen-activated protein kinase kinase (p-MEK) and phosphorylated extracellular regulated protein kinases (p-ERK) were detected by Western Blot. RESULTS: Compared with the sham group, the lung histopathological injury was significantly aggravated, and the histopathological injury score was significantly increased, the lung W/D ratio, and total protein content, NE, TNF-α, IL-6, IL-10 in BALF, and p-MEK and p-ERK expressions were significantly increased in LPS group at 6 hours after model setup [the lung histopathological injury score: 0.70±0.04 vs. 0.14±0.13, W/D ratio: 4.79±0.15 vs. 4.35±0.17, protein content (g/L): 1.51±0.36 vs. 0.46±0.13, NE (ng/L): 85.02±11.28 vs. 47.18±10.30, TNF-α (ng/L): 186.61±21.93 vs. 9.18±2.86, IL-6 (ng/L): 193.45±26.54 vs. 13.58±2.54, IL-10 (ng/L): 113.46±31.23 vs. 25.66±9.41, p-MEK/ß-actin: 0.246±0.019 vs. 0.178±0.030, p-ERK/ß-actin: 0.257±0.013 vs. 0.175±0.014, all P < 0.05], and increase with time after model setup. Compared with the LPS group, BRL-44408 maleate pretreatment for 6 hours could significantly improve the degree of lung injury and reduce the lung histopathological injury score (0.61±0.05 vs. 0.70±0.04), reduce lung W/D weight ratio (4.51±0.22 vs. 4.79±0.15); the expression of NE, TNF-α, IL-6 in BALF were inhibited [NE (ng/L): 55.77±15.86 vs. 85.02±11.28, TNF-α(ng/L): 54.79±12.68 vs. 186.61±21.93, IL-6 (ng/L): 67.66±20.08 vs. 193.45±26.54], in addition, the up-regulation of p-MEK, p-ERK were significantly inhibited (p-MEK/ß-actin: 0.204±0.008 vs. 0.246±0.019, p-ERK/ß-actin: 0.186±0.024 vs. 0.257±0.013), with statistically significant differences (all P < 0.05). The protein content and the expression of IL-10 in BALF showed no significant difference. CONCLUSIONS: α2A-AR blocker BRL-44408 maleate could alleviate endogenous ALI induced by LPS in mice by inhibiting the MEK/ERK pathway.

[Effect mechanism of α-adrenoceptor on sepsis-induced acute respiratory distress syndrome].

OBJECTIVE: Acute respiratory distress syndrome (ARDS), characterized by acute hypoxic respiratory dysfunction or failure, is a manifestation of multiple organ failure (MOF) in the lung, which often caused by various non-cardiac reasons, included severe trauma, infection, shock; and the most common risk factor is sepsis which would cause uncontrolled host response to infecting factors. As a strong stressor during sepsis, the severe infectious state of the body triggers serious stress reaction. The hypothalamus-pituitary-adrenal cortical (HPA) axis and sympathetic-adrenal medulla axis were activated and participated the initiation and progression of the stress response through the production of adrenocorticotropic hormone (ACTH), glucocorticoid (GC), epinephrine and norepinephrine (NE). As the main hormones during sepsis, catecholamines (CA), including epinephrine and NE, could bind to adrenergic receptor (AR). After the binding, CA could play its role through the complicated signal way. Therefore, to explore the signal transduction pathway of α-AR, during sepsis, is important for revealing the mechanism of sepsis-induced ARDS.

Nesfatin-1 acts on the dopaminergic reward pathway to inhibit food intake.

Nesfatin-1 is a novel 82-amino acid anorectic peptide. Previous studies of nesfatin-1 have focused on hypothalamic and brainstem circuits implicated in feeding regulation. Recently, nesfatin-1 expression was also reported in the nucleus accumbens (NAc), amygdaloid nucleus and insular cortex of mice, areas that are related to the control of reward behavior. Therefore, it is possible that nesfatin-1 might also inhibit food intake via central reward circuits. Using electrophysiology and electrochemical and behavioral tests, we investigated the effect of nesfatin-1 on the dopaminergic reward pathway between the ventral tegmental area (VTA) and the NAc. Our results showed that injection of nesfatin-1 into the VTA significantly inhibited dark-phase cumulative food intake in mice. The excitability of VTA dopaminergic neurons was inhibited by nesfatin-1. In addition, nesfatin-1 decreased dopamine release in the NAc. Therefore, we concluded that nesfatin-1 acts on dopaminergic neurons, and these effects might contribute to the decrease of food intake that results from the injection of nesfatin-1 into the VTA.