Mechanism of Xuebijing Injection in treatment of sepsis-associated ARDS based on network pharmacology and in vitro experiment / 中国中药杂志

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.

Recent advances in clinical treatment and molecular mechanism of pulmonary fibrosis induced by paraquat poisoning / 医学研究生学报

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.

Relationship between neutrophil/lymphocyte ratio and lactate level and trauma severity and prognosis in trauma patients / 医学研究生学报

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.

Advances in prognostic related biomarkers of traumatic brain injury / 医学研究生学报

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.

Evaluation of red blood cell distribution width and platelet distribution width in combination with Glasgow Coma Score for the prognosis of patients with severe traumatic brain injury / 医学研究生学报

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.

Effects of Rg_1 on LPS-induced apoptosis and autophagy of lung epithelial cells / 中国中药杂志

This paper aimed to study the protective effect of ginsenoside Rg_1 on endotoxin(LPS)-induced apoptosis of lung epithelial cells and its mechanism of action. Mouse lung epithelial cells(MLE-12) were first treated with LPS. The autophagy changes and apoptosis and the relationship with concentration and time of LPS were observed. Then,the level of autophagy in MLE-12 was regulated at a specific concentration and action time of LPS,and the changes of apoptosis were observed. Secondly,ginsenoside Rg_1 and autophagy inhibitor 3-MA were added respectively at the same concentration and action time of LPS. The lung epithelial cells were grouped to observe the effect of ginsenoside Rg_1 on LPS-induced apoptosis of lung epithelial cells and its mechanism. In the animal experiment,the mice were grouped and tested by apoptosis protein,lung injury score and HE staining section to verify whether ginsenoside Rg_1 has a protective effect on LPS-induced lung injury. The results showed that apoptosis and autophagy increased as the rise of concentration after treatment with LPS for 12 h. The apoptosis increased gradually,and the autophagy increased first and then decreased over time at the LPS concentration of 25 g·L-1. The apoptosis of LPS group was higher than that of control group,and LPS+3-MA group increased further,while apoptosis decreased significantly in LPS+RAM(rapamycin,autophagy promoter) group. The autophagy increased in LPS group,decreased in LPS+3-MA group and increased in LPS+RAM group. The apoptosis of LPS group was higher than that of control group,and the apoptosis of LPS+Rg_1 group decreased. The apoptosis of LPS+Rg_1+3-MA group increased again. The autophagy of LPS group further increased after administration of ginsenoside Rg_1,but decreased after administration of 3-MA. In the in vivo experiments in mice,the apoptosis of LPS group increased significantly compared with the control group,while LPS + ginsenoside Rg_1 group decreased. Lung injury score and HE staining also conformed to the above trend. LPS can induce the apoptosis of lung epithelial cells in a time-dependent and concentration-dependent manner. The autophagy of lung epithelial cells increases with the rise of LPS concentration. At the specific concentration of LPS,autophagy increases first and then decreases after 12-16 hours. Proper increase of autophagy in lung epithelial cells within a certain period of time can reduce the apoptosis induced by LPS,while inhibition of autophagy can increase apoptosis. Ginsenoside Rg_1 has a protective effect on lung cancer epithelial cell apoptosis induced by autophagy.

Progress of bedside ultrasound in cardiac arrest / 医学研究生学报

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.

The predictive value of lactic acid and lactic acid clearance in survival rate and neurological outcome in patients with traumatic brain injury / 医学研究生学报

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.

A clinical research of prone position ventilation in the treatment of moderate and severe ARDS caused by acute paraquat poisoning / 医学研究生学报

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(P0.05).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.

Research progress on predicting the prognosis ofparaquat poisoning by serological indicators / 医学研究生学报

The clinical mortality rate of paraquat poisoning is high. At present, plasma paraquat concentration, urinary paraquat concentration, various scoring systems, and serological indicators are used to predict the prognosis of patients so that clinicians can estimate the condition of patient correctly and take appropriate treatment. Compared with other prediction Methods , serological indicators have the advantages of convenience, availability, low price, instant accuracy and repeatability, and have good predictive value for the prognosis of paraquat poisoning patients. In this paper, the research progress on the prognostic value of serological indicators in patients with paraquat poisoning in recent years is reviewed.

S100B protein in serum is elevated after global cerebral ischemic injury / 世界急诊医学杂志（英文）

@#BACKGROUND:S100B protein in patients with cardiac arrest, hemorrhagic shock and other causes of global cerebral ischemic injury will be dramatically increased. Ischemic brain injury may elevate the level of serum S100B protein and the severity of brain damage.METHODS:This article is a critical and descriptive review on S100B protein in serum after ischemic brain injury. We searched Pubmed database with key words or terms such as "S100B protein", "cardiac arrest", "hemorrhagic shock" and "ischemia reperfusion injury" appeared in the last five years.RESULTS:S100B protein in patients with cardiac arrest, hemorrhagic shock and other causes of ischemic brain injury will be dramatically increased. Ischemic brain injury elevated the level of serum S100B protein, and the severity of brain damage.CONCLUSION:The level of S100B protein in serum is elevated after ischemic brain injury, but its mechanism is unclear.

Effect of penehyclidine hydrochloride on patients with acute lung injury and its mechanisms / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To assess the effects of penehyclidine hydrochloride on patients with acute lung injury (ALI), to observe the expression of Toll-like receptor 4 (TLR4) on the peripheral monocytes of ALI patients and changes of inflammatory and anti-inflammatory cytokines and to investigate the mechanism of TLR4 in ALI.</p><p><b>METHODS</b>Forty-five patients with ALI were randomly divided into penehyclidine hydrochloride treatment group (P group, n equal to 21) and conventional treatment group (control group, C group, n equal to 24). Patients in both groups received conventional treatment, including active treatment of the primary disease, respiratory support, nutritional support and fluid management therapy, while those in P group were given penehyclidine hydrochloride (1 mg, im, q. 12 h) in addition. The TLR4 expression of 20 healthy volunteers were detected. The clinical effect, average length of stay in ICU and hospital, values of PaO2 and PaO2/FiO2, expression of TLR4 on the surface of peripheral blood mononuclear cells and some serum cytokines were evaluated for 48 h.</p><p><b>RESULTS</b>The general conditions of the two groups were improved gradually and PaO2 increased progressively. Compared with 0 h, PaO2 and PaO2/FiO2 at 6, 12, 24 and 48 h after treatment were significantly increased (P less than 0.05). The improvement in P group was obviously greater than that in C group (P less than 0.05). The average length of hospitalization showed no difference between the two groups, but penehyclidine hydrochloride significantly decreased the average length of stay in ICU (t equal to 3.485, P less than 0.01). The expression of TLR4 in two groups were both obviously higher than that of healthy volunteers (P less than 0.01). It decreased significantly at 24 h (t equal to 2.032, P less than 0.05) and 48 h (t equal to 3.620, P less than 0.01) and was lower in P group than in C group. The patients who showed a higher level of TLR4 expression in early stage had a worse prognosis and most of them developed acute respiratory distress syndrome (ARDS). The incidence of ARDS was 23.8% in P group and 29.17% in C group at 24 h. Untill 48 h, there were other two patients developing ARDS in control group. Serum IL-1, IL-8 and TNF-alpha expressions reduced after 24 h in both groups. The reduction in P group was more obvious than that in C group (P less than 0.05). IL-13 increased gradually from 0 h to 24 h, and decreased slightly at 48 h, which showed no difference between two groups (t equal to 1.028, P larger than 0.05).</p><p><b>CONCLUSIONS</b>Penehyclidine hydrochloride improves the arterial oxygen pressure, down-regulates the expression of TLR4 and restrains the inflammatory cytokines in the downstream of TLR4 signaling pathway. It prevents the development of ALI and can be considered as an important drug in ALI treatment.</p>

Serial analysis of gene expression in mice with lipopolysaccharide-induced acute lung injury / 中华创伤杂志(英文版)

<p><b>OBJECTIVE</b>To monitor the systemic gene expression profile in a murine model of lipopolysaccharide-induced acute lung injury.</p><p><b>METHODS</b>Acute lung injury was induced by intratracheal injection of lipopolysaccharide in 3 mice. Another 3 normal mice receiving same volume of normal saline were taken as the controls. The comprehensive gene expression profile was monitored by the recently modified long serial analysis of gene expression.</p><p><b>RESULTS</b>A total of 24,670 tags representing 12,168 transcripts in the control mice and 26,378 tags representing 13,397 transcripts in the mice with lung injury were identified respectively. There were 11 transcripts increasing and 7 transcripts decreasing more than 10 folds in the lipopolysaccharide-treated mice. The most overexpressed genes in the mice with lung injury included serum amyloid A3, metallothionein 2, lipocalin 2, cyclin-dependent kinase inhibitor 1A, lactate dehydrogenase 1, melatonin receptor, S100 calcium-binding protein A9, natriuretic peptide precursor, etc. Mitogen activated protein kinase 3, serum albumin, complement component 1 inhibitor, and ATP synthase were underexpressed in the lung injury mice.</p><p><b>CONCLUSIONS</b>Serial analysis of gene expression provides a molecular characteristic of acute lung injury.</p>