There has been extensive interest in metabolic dysfunction-associated steatotic liver disease and its more advanced stage, metabolic dysfunction-associated steatohepatitis (MASH). Although several studies have highlighted the importance of hepatocyte Notch signaling in MASH-related liver fibrosis, the role of macrophage Notch signaling in MASH-related fibrosis has been less explored. This study found that Notch1 signaling in hepatic macrophages was significantly activated in a high-fat diet (HFD)-induced mouse model of MASH. Depletion of myeloid Notch1 led to a significant reduction in disease progression in this HFD-induced MASH model, as evidenced by reduced hepatic inflammation, steatosis, and fibrosis in HFD-fed, myeloid-specific Notch1 knockout mice. Intriguingly, disruption of Notch1 suppressed the expression of Gli family zinc finger 1 (Gli1), a key transcription factor in the Hedgehog signaling pathway, and promoted M2-like macrophage polarization in the injured liver. Furthermore, the Notch1 deletion-mediated effects-namely, M2 macrophage polarization and the reduction in hepatic steatosis and fibrosis-were reversed by treatment with the Smoothened agonist (SAG) in HFD-fed mice. In vitro experiments further demonstrated that Notch1 deletion promoted a shift in macrophage polarization toward the M2 phenotype by inhibiting Gli1 expression. Collectively, these findings identify the Notch1-Gli1 axis as a novel regulator of macrophage polarization, hepatic inflammation, steatosis, and fibrosis in MASH.
Objective The purpose of the study was to construct the potential diagnostic model of immune-related genes during the development of heart failure caused by idiopathic dilated cardiomyopathy. Method GSE5406 and GSE57338 were downloaded from the GEO website ( https://www.ncbi.nlm.nih.gov/geo/ ). CIBERSORT was used for the evaluation of immune infiltration in idiopathic dilated cardiomyopathy (DCM) of GSE5406. Differently expressed genes were calculated by the limma R package and visualized by the volcano plot. The immune-related genes were downloaded from Immport, TISIDB, and InnateDB. Then the immune-related differential genes (IRDGs) were acquired from the intersection. Protein–protein interaction network (PPI) and Cytoscape were used to visualize the hub genes. Three machine learning methods such as random forest, logical regression, and elastic network regression model were adopted to construct the prediction model. The diagnostic value was also validated in GSE57338. Results Our study demonstrated the obvious different ratio of T cell CD4 memory activated, T cell regulatory Tregs, and neutrophils between DCM and control donors. As many as 2139 differential genes and 274 immune-related different genes were identified. These genes were mainly enriched in lipid and atherosclerosis, human cytomegalovirus infection, and cytokine-cytokine receptor interaction. At the same time, as many as fifteen hub genes were identified as the IRDGs (IFITM3, IFITM2, IFITM1, IFIT3, IFIT1, HLA-A, HLA-B, HLA-C, ADAR, STAT1, SAMHD1, RSAD2, MX1, ISG20, IRF2). Moreover, we also discovered that the elastic network and logistic regression models had a higher diagnostic value than that of random forest models based on these hub genes. Conclusion Our study demonstrated the pivotal role of immune function during the development of heart failure caused by DCM. This study may offer new opportunities for the detection and intervention of immune-related DCM.
Abstract Background As a result of the COVID-19 pandemic, venous and arterial thromboembolic events have increased dramatically in many patients. This study aimed to identify the potential biomarkers for COVID-19-associated venous thromboembolism (VTE). Methods The datasets about COVID-19 and VTE were downloaded from the Gene Expression Omnibus (GEO) dataset. Weighted gene co-expression network analysis (WGCNA) was conducted to identify the most critical module associated with the clinic results. The intersection of common modules was processed for further enrichment analysis. The hub genes were identified by combining the differentially expressed genes (DEGs) of VTEs and common module genes. Then, the final diagnostic value for VTE was verified through bioinformatics algorithms. Results As many as 78 common critical genes were summarized by the intersection of the most positive and negative modules of COVID-19 and VTE. These genes were mainly enriched in coronavirus disease, fluid shear stress and atherosclerosis, ribosome, NF-kappa B, and TNF signalling pathways. Four critical genes including GZMA, BCL2A1, CD52, and RANSE2 were selected by performing the intersection analysis with the DEGs in VTE. All these genes were found to be increased in VTE samples in GSE19151 and achieved a good diagnostic value with a relative proper area under the curve (AUC). Conclusions Our study found that similar changes occurred in COVID-19 and VTE. GZMA, BCL2A1, CD52, and RANSE2 can be utilized as potential diagnostic markers for COVID-19-related VTE. This study may offer new opportunities for the detection and prevention of COVID-19-induced hypercoagulable state and VTE.
COVID-19 has spread all over the world which poses a serious threat to social economic development and public health. Despite enormous progress has been made in the prevention and treatment of COVID-19, the specific mechanism and biomarker related to disease severity or prognosis have not been clarified yet. Our study intended to further explore the diagnostic markers of COVID-19 and their relationship with serum immunology by bioinformatics analysis. The datasets about COVID-19 were downloaded from the Gene Expression Omnibus (GEO) dataset. The differentially expressed genes (DEGs) were selected via the limma package. Then, weighted gene co-expression network analysis (WGCNA) was conducted to identify the critical module associated with the clinic status. The intersection DEGs were processed for further enrichment analysis. The final diagnostic genes for COVID-19 were selected and verified through special bioinformatics algorithms. There were significant DEGs between the normal and COVID-19 patients. These genes were mainly enriched in cell cycle, complement and coagulation cascade, extracellular matrix (ECM) receptor interaction, and the P53 signaling pathway. As much as 357 common intersected DEGs were selected in the end. These DEGs were enriched in organelle fission, mitotic cell cycle phase transition, DNA helicase activity, cell cycle, cellular senescence, and P53 signaling pathway. Our study also identified CDC25A, PDCD6, and YWAHE were potential diagnostic markers of COVID-19 with the AUC (area under curve), 0.958 (95% CI 0.920-0.988), 0.941(95% CI 0.892-0.980), and 0.929 (95% CI 0.880-0.971). Moreover, CDC25A, PDCD6, and YWAHE were correlated with plasma cells, macrophages M0, T cells CD4 memory resting, T cells CD8, dendritic cells, and NK cells. Our study discovered that CDC25A, PDCD6, and YWAHE can be used as diagnostic markers for COVID-19. Moreover, these biomarkers were also closely associated with immune cell infiltration, which plays a pivotal role in the diagnosis and progression of COVID-19.
Recent studies showed that RNA N6-methyladenosine (m6A) plays an important role in neurological diseases. We used methylated RNA immunoprecipitation sequencing (MeRIP-Seq) technology to generate the m6A modification map after traumatic spinal cord injury (TSCI). A total of 2,609 differential m6A peaks were identified after TSCI. Our RNA sequencing results after TSCI showed 4,206 genes with significantly altered expression. Cross-link analysis of m6A sequencing results and RNA sequencing results showed that 141 hyper-methylated genes were upregulated, 53 hyper-methylated genes were downregulated, 57 hypo-methylated genes were upregulated, and 197 hypo-methylated genes were downregulated. Among these, the important inflammatory response factor Tlr4 and the important member of the neurotrophin family Ngf were both upregulated and hyper-methylated after TSCI. This study provides that in the future, the epigenetic modifications of the genes could be used as an indicator of TSCI.
Oxidative stress is a crucial mechanism in the pathophysiology of lung injury/fibrosis and diaphragmatic dysfunction. Yes-associated protein 1 (YAP1) is a key oxidative stress response regulator. However, how lung injury/fibrosis and the subsequent YAP1 silencing treatment affect diaphragmatic function remains largely uncharacterized. In this study, mice models of acute lipopolysaccharide (LPS) and paraquat exposure were used to establish acute lung injury and chronic pulmonary fibrosis. AT2 and C2C12 cells were co-cultured under LPS and paraquat challenge. YAP1 was interfered with shRNA given in vivo and verteporfin administration in vitro. Pulmonary histology, contractile properties, and cross-sectional areas (CSAs) of the diaphragm and gastrocnemius were evaluated. Histological and biochemical analyses were performed for targeted biomarker determination. We found that LPS and paraquat caused significant lung injury/fibrosis and significantly reduced the diaphragmatic-specific force and CSAs compared with the control. YAP1 silencing alleviated inflammatory cell infiltration or collagen deposition in the lungs yet worsened the already impaired diaphragmatic function by increasing inflammatory cytokines (IL-6 and TNF-α), mitochondrial reactive oxidative species (ROS) emission, protein degradation (Murf-1, atrogin-1, and calpain), and decreasing antioxidant capabilities (superoxide dismutase 2 and glutathione peroxidase). No significant improvements were observed in diaphragmatic function by transient YAP1 knockdown in the gastrocnemius. In vitro, LPS- or paraquat-caused cytotoxicity in AT2 cells was mostly alleviated by verteporfin in a concentration that was 20-fold higher than that in C2C12 cells (20 and 1 μg/mL, respectively). Finally, 0.5 μg/mL of verteporfin significantly ameliorated hydrogen peroxide-induced proteolytic activity and antioxidant enzyme suppression in C2C12 cells, whereas 2 μg/mL of verteporfin deteriorated the same. Collectively, lung injury/fibrosis adversely affects the diaphragm. YAP1 inhibition alleviates lung injury/fibrosis but worsens diaphragmatic function potentially by enhancing inflammatory cytokines and ROS-mediated protein degradation. This disparity might be attributed to differences in susceptibility to YAP1 inhibition between muscles and the lungs.
目的 探讨新型冠状病毒肺炎(COVID-19)患者血浆D-二聚体水平与患者危重程度及预后的相关性.方法 回顾性分析2020年1月5日至2月15日该院隔离病房经核酸检测确诊的105例COVID-19患者资料.根据患者的急性生理和慢性健康评分(APACHE-Ⅱ)分值分为非重型组(n=22)、重型组(n=37)和危重型组(n=46),比较3组患者的血浆D-二聚体水平及病死率.根据预后将患者分为存活组(n=88)和死亡组(n=17),比较两组患者的APACHE-Ⅱ分值、血浆D-二聚体水平.分析血浆D-二聚体水平与APACHE-Ⅱ分值的相关性,并利用受试者工作曲线(ROC)分析血浆D-二聚体水平与预后之间的关系.结果 危重型组患者血浆D-二聚体水平明显高于重型组[(1785±420)ng/mL vs.(628±127)ng/mL,P<0.01],且重型组高于非重型组[(628±127)ng/mL vs.(277±87)ng/mL,P<0.01].危重型组、重型组和非重型组各有14、3、0例患者死亡.死亡组患者的血浆D-二聚体水平明显高于存活组[(1257±364)ng/mL vs.(461±384)ng/mL,P<0.01],APACHE-Ⅱ分值也明显高于存活组(17.7±4.6 vs.8.3±3.5,P<0.05).Pearson相关分析提示死亡患者的血浆D-二聚体水平与APACHE-Ⅱ分值呈正相关(r=0.647,P<0.01).ROC分析结果 表明血浆D-二聚体水平在1498 ng/mL阈值时,预测患者死亡的ROC曲线下面积为0.91,灵敏度为75%,特异度为93%.结论 COVID-19患者血浆D-二聚体水平与患者APACHE-Ⅱ分值呈正相关,对预测患者危重症程度及预后有一定评估价值.
Objective:To analyze the causes of SARS-CoV-2 nosocomial infection among healthcare workers (HCWs) and explore the effective precaution strategies in Emergency Center.Methods:The data of SARS-CoV-2 infected HCWs from January 5 to March 2, 2020 were retrospectively analyzed and compared under different conditions in Emergency Center of Zhongnan Hospital of Wuhan University.Results:Totally 13 SARS-CoV-2 infected HCWs (12 confirmed cases and 1 suspected case) were included in this study. The overall infection rate was 17.8% (13/73). The infection rates in outpatient/rescue room, isolation observation room and isolationin patient ward were 11.8% (4/34), 20.0% (3/15), 25% (6/24), respectively. The infection rate of physician was 13.0% (3/23), and the infection rate of nurse was 20.0% (10/50). All the infected HCWs had the definite exposure with confirmed or suspected COVID-19 patients. One asymptomatic cases were identified by laboratory findings of SARS-CoV-2 infection screening. There was no new confirmed SARS-CoV-2 infected HCWs after February 5, 2020. All the infected HCWs were cured.Conclusions:Under the epidemic of COVID-19, HCWs of Emergency Center have a high risk of occupational exposure and infection, especially for staffs working in COVID-19 isolation units. Scientific prevention and control management can effectively reduce the risk of SARS-CoV-2 infections and ensure the occupational safety for HCWs in Emergency Center.
[Purpose/significance]With the rapid development of web news images, images attached to the news are getting more and more attention, news image sentiment orientation analysis could be used for tracing news and assisting decision making for government.[Method/process]This paper used the VGKG and GKG news event image database provided by the GDELT project as raw data source, and selected 34401 images from 6 news websites include BBC and CNN. Through a quantitative analysis of the sentiment orientations of these images, we aimed at exploring the difference of sentiment orientations between different news websites and the relationship between image sentiment orientation and shooting angle.[Results/conclusion]In the six news websites, the characters face recognition is very clear, the shooting angle is dominated by the positive shooting, and the emotion of the image tends to be more plain and calm. Description of the image in the news is more objectively reported the news facts, as well as positive guidance of public opinion, this paper provides a theoretical and technical foundation for the research and application of web news image sentiment.
[目的/意义]通过社交媒体用户分享的图像、博文及用户标签进行数据挖掘,来判断和预测用户的真实兴趣,从而更好地为用户做个性化推荐和精准化服务.[方法/过程]在获取微博用户分享的图像、博文及用户标签的基础上,通过使用机器学习的方法利用图像、博文及用户标签数据来表达用户兴趣特征,基于三类特征使用SVM训练得到分类器进行用户兴趣类别预测,主要比较单模数据和多模数据的分类指标,探讨多模数据在有监督学习下的发多分类问题.[结果/结论]实验结果表明,利用图像、博文和用户标签合成的多模数据对用户兴趣进行分类识别,F值达到77%,比最好的单模数据提升10%.实验结论证实,多模(图像、博文和标签)数据与单模数据相比,提升了分类效果,同时为多模数据应用研究提供了一定的理论和技术基础.
目的 调查武汉某小学学生对意外伤害自救互救知识的了解程度、培训情况,探索适合该年龄阶段常见意外伤害自救互救的培训内容和方法.方法 自行设计调查问卷,以方便抽样法选取武汉某小学在校小学生128名为研究对象,进行问卷调查.结果 有79.69%的学生没有意外伤害自救互救的知识及学习经历;79.69%的学生认为有开设意外伤害自救互救课程的必要;43.75%的学生表示愿意参加医护人员开设的真实场景模拟演练培训课程.结论 小学生对意外伤害自救互救知识了解不够,救护技能掌握不熟练,需加强意外伤害自救互救知识的宣传与技能的培训.
Recent evidence indicates that the epithelial to mesenchymal transition (EMT) in primary alveolar cells (AECs) plays an important role in idiopathic pulmonary fibrosis (IPF). In vivo models have suggested that thalidomide (THL) has anti-fibrotic effects against pulmonary fibrosis, but the underlying mechanism of this effect is not clear. This study investigated whether THL regulates alveolar EMT and the possible mechanisms underlying this process. CCL-149 cells were treated with TGF-β1 in the presence of THL at the indicated concentrations. EMT was assessed by changes in cell morphology and in phenotypic markers. Signaling pathways involved in EMT were characterized by western blot analysis. THL inhibited the TGF-β1 induction of α-SMA, vimentin, MMP-2/-9 and collagen type IV expression and restored the morphological changes in primary alveolar epithelial cells caused by TGF-β1. TGF-β1 induction of α-SMA expression was partially dependent on the activation of p38, JNK, ERK, Akt, Smad 2 and Smad3. Moreover, THL inhibited TGF-β1-induced phosphorylation of p38, JNK, ERK, Akt, GSK3β, Smad 2 and Smad3 without altering the total expression levels of those proteins. These findings indicate that TGF-β1-induced EMT in alveolar epithelial cells is inhibited by THL via both Smad-dependent and non-Smad-dependent signaling pathways and suggests therapeutic approaches for targeting this process in pulmonary fibrosis.
本文通过对图书情报领域的科研论文进行内容分析,从科研论文研究方法的角度揭示图书情报学科的发展情况.在通过参考已有的科研论文研究方法分类体系的基础上,分析近十年科研论文中的研究方法得出了图书情报领域科研论文研究方法的分类体系.为揭示该学科科研论文中研究方法的演化规律,笔者对近十年发表在《情报学报》和《中国图书馆学报》两本权威期刊上共2556篇论文的研究方法进行分类标注并进行演化分析.结果表明:①图书情报学科的研究方法越来越重视定量的研究方法;②《情报学报》的研究方法从一开始的以定性研究为主逐渐发展为以数据为驱动的定量研究为主定性研究为辅;③《中国图书馆学报》的研究方法主要以定性研究为主,近年来定量研究占比有所增长,但是仍然以定性研究为主.
Objective To explore the effect of carrying out self and mutual medical aid training program after accidental injury for primary school students on the students ′relevant knowledge .Methods 98 primary school students in a certain primary school in Wuhan were selected by convenience sampling as objects . Training content and mode of self and mutual medical aid after common accidental injuries were designed basing on the students′age and interest .Their knowledge before and after the training was compared , and the training effect was thus determined .Results The students′post-training knowledge of self and mutual medical aid after common accidental injuries was higher than before the training , in the aspects of calling 120 correctly, 6-step hand washing method , treatment of small-area burn, bandaging of forearm skin damage , wound cleaning of animal bite (91.84%vs.57.14%, 83.67%vs.20.41%, 100.00% vs.67.35%, 77.55% vs.34.69%, 89.80%vs.25.51%) (P<0.01).Conclusions Reasonably-designed self and mutual medical aid training program after common accidental injuries can effectively strengthen primary school students ′relevant abilities , which makes it worth promoting in future training .
Text summarization of academic literature refers to automatical y generate abstract for a given paper. With the aid of automatic summarization, authors can improve the efficiency of writing and reading academic literature. Existing works evaluate and rank the sentences based on term frequency, they can' t reveal the main idea of an article from a deeper semantic dimension. Based on previous research, this article introduces citation context as an enhanced feature. Combining it with other existing features, we conduct an automatic re-scoring of each sentence by utilizing support vector regression (SVR) model. A significant improvement over traditional term frequency-based and graph-based method based on WE-ROUGE shows the effectiveness of citation context in automatical y text summarization.
Paper recommendation can recommend suitable documents for an author. With the aid of paper recommendation, authors can improve the efficiency of retrieving academic literatures. Due to the lack of empirical study on paper recommendation evolution, this paper aims at exploring the interaction on user satisfaction and continuing use wil ingness for three aspects such as recommended content quality, service quality and technical capacity. This paper col ects 299 valid questionnaires with questionnaires scale for users, and analyzes the samples by means of structural equation modeling (SEM). We find that recommended content quality, service quality and technical capacity have positive effects on user satisfaction, and further have positive effects on users' continuing use wil ingness.
Objective To explore the effect of thalidomide on the p38 MAPK and JNK expression during EMT and the possible mechanism of idiopathic pulmonary fibrosis ( IPF) , in order to find a new treatment target of IPF. Methods A549 cells were randomly divided into three groups:the control group, the group B ( TGF-β1+DM-SO), and the group C (TGF-β1+thalidomide) (10μg/ml). Cells and media were collected for phospho-JNK and phospho-p38 MAPK. Protein expression was detected by Western-blot, and p38 MAPK and JNK mRNA were detec-ted by quantitative real-time RT-PCR. Results Thalidomide could significantly mitigate the inhibition of the expres-sion of AEC markers. In addition, thalidomide also induced the expression of mesenchymal markers. Furthermore, the phosphorylation and mRNA of p38 MAPK and JNK were significantly lower in the group C ( TGF-β1 + thalido-mide) than that in the group B (TGF-β1+DMSO ) (P<0. 05). Conclusion Thalidomide could inhibit the EMT of A549 cells via interfering the activation of MAPKs.
[目的/意义]学术文献引文推荐是指对于给定的学术文献,自动化地为其推荐合适的引文和参考文献.借助于引文推荐,用户可以在一定程度上提高撰写学术文献的效率,降低对重要相关文献的漏引.[方法/过程]分析国内外引文推荐研究的最新进展,阐述引文推荐问题的演化过程,从局部引文推荐和全局引文推荐等方面对引文推荐进行梳理,重点归纳文档相似性、主题模型、翻译模型、协同过滤和混合推荐等5种引文推荐常用方法,并总结引文推荐常用数据集和测评方法.[结果/结论]已有引文推荐研究的主要问题在于未考虑用户偏好的动态变化性及研究领域的综合性,在用户研究和实际应用方面仍有所欠缺;未来引文推荐的研究可运用语义化表达方法和自然语言生成技术,从基于上下文的引文推荐和跨语言引文推荐等方面进行展开.
Objective To investigate the roles of p38 MAPK and JNK in transforming growth factor-β1 (TGF-β1)-induced human alveolar epithelial to mesenchymal transition (EMT),and to demonstrate the possible molecular mechanism of idiopathic pulmonary fibrosis.Methods A549 cells were treated with TGF-β1 (3 μg/L) for 48 hours to induce EMT.The expressions of mesenchymal phenotypic markers including desmin,α-smooth muscle actin (α-SMA) and vimentin,and expressions of epithelial phenotypic markers including E cadherin,zonula occludens-1 (ZO-1) and aquaporin-5 (AQP-5) were detected by Western blot.The role of p38 MAPK and JNK in TGF-β1-mediated EMT was investigated using gene silencing and inhibitor SB203580 and SP600125.Results The data showed that TGF-β1 induced A549 cells with alveolar epithelial type Ⅱ cell phenotype to undergo EMT.The process of EMT was accompanied by increased expression of the mesenchymal cell markers α-SMA,desmin and vimentin,and downregulation of the epithelial cell markers E-cadherin,ZO-1 and AQP-5.TGF-β1-induced EMT occurred through phosphorylation of p38 MAPK and JNK and was inhibited by inhibitor SB203580 and SP600125 and gene silencing.Conclusions Our data shows that TGF-β1 induces A549 alveolar epithelial cells to undergo EMT partially via p38 MAPK and JNK activation.
目的:了解湖北省急诊医师执行快速诱导气管插管(Rapid sequence induced intubation RSII)之现状.方法:通过分析首届湖北省急救技能大赛简易呼吸器麻醉诱导气管插管站点38名参赛选手麻醉诱导一栏的扣分情况,及各个分项执行情况所占百分比,并分析这种状况产生的原因及如何改善和提高.结果:没有麻醉诱导意识和选择错误药物或剂量的参赛选手各占42%和32%,能正确诱导的选手仅占26%.结论:急诊快速诱导气管插管技术在急诊需要进一步的推广,合适的药物的选择与剂量的规范需要专业系统的培训.