OBJECTIVE: To explore the potential effects and mechanisms of Liang-Ge-San (LGS) for the treatment of acute respiratory distress syndrome (ARDS) through network pharmacology analysis and to verify LGS activity through biological experiments. METHODS: The key ingredients of LGS and related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform. ARDS-related targets were selected from GeneCards and DisGeNET databases. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed using the Metascape Database. Molecular docking analysis was used to confirm the binding affinity of the core compounds with key therapeutic targets. Finally, the effects of LGS on key signaling pathways and biological processes were determined by in vitro and in vivo experiments. RESULTS: A total of LGS-related targets and 496 ARDS-related targets were obtained from the databases. Network pharmacological analysis suggested that LGS could treat ARDS based on the following information: LGS ingredients luteolin, wogonin, and baicalein may be potential candidate agents. Mitogen-activated protein kinase 14 (MAPK14), recombinant V-Rel reticuloendotheliosis viral oncogene homolog A (RELA), and tumor necrosis factor alpha (TNF-α) may be potential therapeutic targets. Reactive oxygen species metabolic process and the apoptotic signaling pathway were the main biological processes. The p38MAPK/NF-κ B signaling pathway might be the key signaling pathway activated by LGS against ARDS. Moreover, molecular docking demonstrated that luteolin, wogonin, and baicalein had a good binding affinity with MAPK14, RELA, and TNF α. In vitro experiments, LGS inhibited the expression and entry of p38 and p65 into the nucleation in human bronchial epithelial cells (HBE) cells induced by LPS, inhibited the inflammatory response and oxidative stress response, and inhibited HBE cell apoptosis (P<0.05 or P<0.01). In vivo experiments, LGS improved lung injury caused by ligation and puncture, reduced inflammatory responses, and inhibited the activation of p38MAPK and p65 (P<0.05 or P<0.01). CONCLUSION LGS could reduce reactive oxygen species and inflammatory cytokine production by inhibiting p38MAPK/NF-κ B signaling pathway, thus reducing apoptosis and attenuating ARDS.
Drugs, Chinese Herbal/pharmacology* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; NF-kappa B/metabolism* ; Animals ; Signal Transduction/drug effects* ; Molecular Docking Simulation ; Humans ; Male ; Network Pharmacology ; Apoptosis/drug effects* ; Mice

OBJECTIVE: To identify the underlying mechanism by which quercetin (Que) alleviates sepsis-related acute respiratory distress syndrome (ARDS). METHODS: In vivo, C57BL/6 mice were assigned to sham, cecal ligation and puncture (CLP), and CLP+Que (50 mg/kg) groups (n=15 per group) by using a random number table. The sepsisrelated ARDS mouse model was established using the CLP method. In vitro, the murine alveolar macrophages (MH-S) cells were classified into control, lipopolysaccharide (LPS), LPS+Que (10 μmol/L), and LPS+Que+acetylcysteine (NAC, 5 mmol/L) groups. The effect of Que on oxidative stress, inflammation, and apoptosis in mice lungs and MH-S cells was determined, and the mechanism with reactive oxygen species (ROS)/p38 mitogen-activated protein kinase (MAPK) pathway was also explored both in vivo and in vitro. RESULTS: Que alleviated lung injury in mice, as reflected by a reversal of pulmonary histopathologic changes as well as a reduction in lung wet/dry weight ratio and neutrophil infiltration (P<0.05 or P<0.01). Additionally, Que improved the survival rate and relieved gas exchange impairment in mice (P<0.01). Que treatment also remarkedly reduced malondialdehyde formation, superoxide dismutase and catalase depletion, and cell apoptosis both in vivo and in vitro (P<0.05 or P<0.01). Moreover, Que treatment diminished the release of inflammatory factors interleukin (IL)-1β, tumor necrosis factor-α, and IL-6 both in vivo and in vitro (P<0.05 or P<0.01). Mechanistic investigation clarifified that Que administration led to a decline in the phosphorylation of p38 MAPK in addition to the suppression of ROS expression (P<0.01). Furthermore, in LPS-induced MH-S cells, ROS inhibitor NAC further inhibited ROS/p38 MAPK pathway, as well as oxidative stress, inflammation, and cell apoptosis on the basis of Que treatment (P<0.05 or P<0.01). CONCLUSION Que was found to exert anti-oxidative, anti-inflammatory, and anti-apoptotic effects by suppressing the ROS/p38 MAPK pathway, thereby conferring protection for mice against sepsis-related ARDS.
Animals ; Sepsis/drug therapy* ; Quercetin/therapeutic use* ; Respiratory Distress Syndrome/enzymology* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; Mice, Inbred C57BL ; Reactive Oxygen Species/metabolism* ; Apoptosis/drug effects* ; Male ; Oxidative Stress/drug effects* ; MAP Kinase Signaling System/drug effects* ; Lung/drug effects* ; Mice ; Lipopolysaccharides ; Macrophages, Alveolar/pathology* ; Inflammation/pathology* ; Protective Agents/therapeutic use*

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.
Humans ; Network Pharmacology ; Vascular Endothelial Growth Factor A ; NF-kappa B ; Interleukin-6 ; Lipopolysaccharides ; Molecular Docking Simulation ; Respiratory Distress Syndrome ; Tumor Necrosis Factor-alpha ; Sepsis/genetics* ; NLR Proteins

The main causes of death for paraquat poisoning are irreversible pulmonary fibrosis, respiratory failure and even multiple organ failure. Currently, the main clinical treatment methods are gastric lavage, catharsis, blood purification and symptomatic supportive treatment, but the effectiveness is not satisfactory. It has made some progress in clinical treatment of paraquat poisoning and the study of molecular mechanisms at home and abroad. The article simply reviews in the clinical treatment of pulmonary fibrosis induced by paraquat poisoning such as blood purification, antioxidants, glucocorticoid, Chinese medicine treatment, and the molecular mechanism research such as epithelial-mesenchymal transition, Wnt/β- catenin pathway, the NF-κB pathway and Akt-Nrf-2 pathways.

ObjectiveAt present, there are few studies on prognostic indicators for patients with severe traumatic brain injury (STBI). This paper aims to explore its significance by analyzing the demographic characteristics of patients with STBI, as well as parameters such as clinical laboratory test indicators.MethodsA retrospective analysis was performed on 139 STBI patients admitted to the Department of Emergency Medicine, General Hospital of Eastern Theater Command from January 2017 to December 2018. According to the 28-day death event, the participants were divided into the survival group (n=108) and the death group (n=31). Indicators such as Glasgow Coma Score (GCS), red blood cell distribution width (RDW), platelet distribution width (PDW) and clot-related indicators were collected. Univariate and multivariate logistic regression were used to analyze the risk factors related to death, and receiver operating characteristic (ROC) curve was adopted to determine their prognostic values.ResultsThere were significant differences in GCS, RDW and PDW between the two groups. RDW (OR=4.577, 95% CI: 1.704-12.291), PDW (OR=1.346, 95% CI: 1.093-1.657) and GCS (OR=0.469, 95% CI: 0.301-0.730) were risk factors for death of STBI patients. The area under the curve (AUC) of RDW, PDW and GCS scores were 0.735 (0.640-0.840), 0.675 (0.553-0.796) and 0.737 (0.638-0.837), respectively, and the AUC of the combination of the three was 0.840 (0.748-0.932), which was significantly better than that of single diagnosis.ConclusionRDW, PDW combined with GCS can effectively evaluate the prognosis of patients with STBI, which has important guiding value for clinicians′ diagnosis and treatment.

Traumatic brain injury（TBI）is a kind of clinical emergency with high incidence, disability and mortality, with serious impact on patients, families and society. To some extent, prognostic related biomarkers of TBI can not only reflect the pathogenetic mechanism and pathophysiological process of injury, but also have important values in evaluating the severity, predicting adverse outcomes, making treatment decisions and so on. This article aims to review the studies about the prognosis biomarkers of TBI, such as coagulation related biomarkers, inflammation related biomarkers, biomarkers related to nervous system injury and so on.

ObjectiveThe pathophysiological changes caused by trauma are complex, and there is still a lack of effective markers for injury monitoring and prognosis judgment. This paper aims to investigate the relationship between neutrophil/lymphocyte ratio (NLR) and lactate level and trauma severity and prognosis in trauma patients.MethodsThe data of 169 trauma patients who met the inclusion criteria in the Department of Emergency Medicine, General Hospital of the Eastern Theater Command from January to December 2017 were retrospectively analyzed. Their gender, age, cause of injury, injury severity score (ISS), acute physiology and chronic health evaluation II (APACHE II), Glasgow coma index (GCS), NLR and lactate levels within 24 hours after the injury and other laboratory results were recorded. According to the ISS score, the patients were divided into mild injury group (ISS<16, n=78), severe injury group (16≤ISS<25, n=53), and critical injury group (ISS≥25, n=38); According to the 28-day outcomes, they were divided into death group (n=22) and survival group (n=147). The correlation between NLR and lactate levels and ISS score was analyzed, and the prognostic value was analyzed by receiver operating characteristic (ROC) curve.ResultsNLR was positively correlated with ISS (r=0.34, P<0.001), and there were significant differences among three trauma groups (P<0.001). Lactate was positively correlated with ISS (r=0.28, P=0.002) too, and significant differences were shown among three trauma groups (P=0.003). The area under the ROC curve of NLR and lactate for predicting 28-day death in trauma patients was 0.785 and 0.686, respectively.ConclusionNLR and lactate are positively correlated with trauma severity and they might play an important part in the early prognosis evaluation of trauma patients.

Objective Prone position ventilation is one of the most important Methods for the treatment of acute lung injury/acute respiratory distress syndrome (ARDS). Currently, there are fewer researches on prone position ventilation for ARDS caused by acute paraquat poisoning. This article aims to evaluate the value of prone position ventilation in the treatment of moderate and severe ARDS caused by acute paraquat poisoning.Methods Retrospective analysis the clinical data of 43 patients with acute paraquat poisoning complicated with moderate-to-severe ARDS from January 2016 to December 2017 in the Department of Emergency Medicine, Eastern Theater of the Eastern Theater. The patients were divided into two groups according to whether they were in prone position ventilation: experimental group (prone position ventilation, n=13)and control group(no prone position ventilation, n=30). The gender, age, APACHEII score and plasma paraquat concentration of the two groups were statistically analyzed. The oxygenation index, respiratory rate, carbon dioxide partial pressure and mean arterial pressure were compared between the two groups during the first five days after hospitalization. At the same time, the hospital mortality, hospitalization time, mechanical ventilation time were also compared.Results Compared with control group, the oxygenation index (176±13) and carbon dioxide partial pressure \[(33.6±4.3) mmHg\] in the experimental group were significantly increased from the 2nd day to 5th day after hospitalization(P<0.05), but the respiratory rate was significantly decreased(P<0.05). There were no significant differences in hospital mortality, hospitalization time, mechanical ventilation time, and airway accident rate between the two groups (P>0.05).Conclusion Prone position ventilation is safe for patients with moderate to severe ARDS caused by acute paraquat poisoning, which improves oxygenation in these patients but fails to improve prognosis. It provides a theoretical basis for prone position ventilation in the treatment of acute paraquat poisoning complicated with ARDS.

Objective The level of lactic acid in blood can reflect the degree of ischemia and hypoxia of brain tissue and cerebral perfusion pressure. The aim of this paper is to explore the value of blood lactate and lactate clearance in evaluating the survival rate and neurological outcome of patients with craniocerebral trauma. Methods The clinical data of 497 craniocerebral trauma patients admitted to our hospital from September 2017 to July 2018 were collected and retrospectively analyzed. Patients were divided into groups with different 6 h lactate clearance rates and admission lactate levels, and the differences in mortality and outcome of neurological function in each group were compared. Results The serum admission lactate levels、serum lactate levels at 6 hours, 28-day mortality and 28-day poor nerve function prognosis rate of patients with different 6h lactate clearance rates were statistically significant differences(P < 0. 05). The efficacy of 6h lactic acid to predict the mortality rate of patients was better than that of admission lactic acid and 6h lactate clearance rate (Z=3.71、Z=3.95,P<0.05). However, in predicting the neurological function of patients, the lactate clearance rate is not better than blood lactate level at any time(Z=1.30，Z=0.81，P>0.05). Conclusion 6h lactic acid has the best ability to judge the mortality of patients while lactic acid clearance rate is not better than the blood lactate level at any time in predicting the neurological function of patients.

Cardiac arrest is the most critical condition for patients. Early identification of the cause of cardiac arrest and timely intervention on different causes are the key to treatment. Bedside ultrasound can simply, quickly, and effectively assess the cause of cardiac arrest, select the appropriate tracheal tube for the patient, confirm the position of the endotracheal tube, confirm the position of the endotracheal tube, and effectively evaluate the effect of mechanical ventilation and organ resuscitation after interventions. This article reviews bedside ultrasound in identifying the reversible causes of cardiac arrest, airway management, and evaluating organ function after resuscitation.