Mechanism exploration and prognosis study of Astragali Radix-Spreading hedyotis herb for the treatment of lung adenocarcinoma based on bioinformatics approaches and molecular dynamics simulation

Background: Herb pair of Astragali Radix (AR) and Spreading Hedyotis Herb (SH) has been frequently prescribed in clinical for the treatment of lung cancer owing to its favorable efficacy. Yet, the mechanism under the therapeutic effects remained unveiled, which has limited its clinical applications, and new drug development for lung cancer.Methods: The bioactive ingredients of AR and SH were retrieved from the Traditional Chinese Medicine System Pharmacology Database, with the targets of obtained components predicted by Swiss Target Prediction. Genes related to lung adenocarcinoma (LUAD) were acquired from GeneCards, OMIM and CTD databases, with the hub genes of LUAD screened by CTD database. The intersected targets of LUAD and AR-SH were obtained by Venn, with David Database employed to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Survival analysis of the hub genes of LUAD was carried out using TCGA-LUAD dataset. Molecular docking of core proteins and active ingredients was performed by Auto-Dock Vina software, followed by molecular dynamics simulations of protein-ligand complexes with well-docked conformations.Results: 29 active ingredients were screened out with 422 corresponding targets predicted. It is revealed that AR-SH can act on various targets such as EGFR, MAPK1, and KARS by ursolic acid (UA), Astragaloside IV(ASIV), and Isomucronulatol 7,2′-di-O-glucoside (IDOG) to alleviate the symptoms of LUAD. Biological processes involved are protein phosphorylation, negative regulation of apoptotic process, and pathways involved are endocrine resistance, EGFR tyrosine kinase inhibitor resistance, PI3K-Akt, and HIF-1 pathway. Molecular docking analysis indicated that the binding energy of most of the screened active ingredients to proteins encoded by core genes was less than −5.6 kcal/mol, with some active ingredients showing even lower binding energy to EGFR than Gefitinib. Three ligand-receptor complexes including EGFR-UA, MAPK1-ASIV, and KRAS-IDOG were found to bind relatively stable by molecular dynamics simulation, which was consistent with the results of molecule docking.Conclusion: We suggested that the herb pair of AR-SH can act on targets like EGFR, MAPK1 and KRAS by UA, ASIV and IDOG, to play a vital role in the treatment and the enhancement of prognosis of LUAD

Using Network Pharmacology and Molecular Docking to Explore the Mechanism of Shan Ci Gu (Cremastra appendiculata) Against Non-Small Cell Lung Cancer

Background: In recent years, the incidence and mortality rates of non-small cell lung cancer (NSCLC) have increased significantly. Shan Ci Gu is commonly used as an anticancer drug in traditional Chinese medicine; however, its specific mechanism against NSCLC has not yet been elucidated. Here, the mechanism was clarified through network pharmacology and molecular docking.Methods: The Traditional Chinese Medicine Systems Pharmacology database was searched for the active ingredients of Shan Ci Gu, and the relevant targets in the Swiss Target Prediction database were obtained according to the structure of the active ingredients. GeneCards were searched for NSCLC-related disease targets. We obtained the cross-target using VENNY to obtain the core targets. The core targets were imported into the Search Tool for the Retrieval of Interacting Genes/Proteins database, and Cytoscape software was used to operate a mesh chart. R software was used to analyze the Gene Ontology biological processes (BPs) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The core targets and active compounds were molecularly docked through Auto-Dock Vina software to predict the detailed molecular mechanism of Shan Ci Gu for NSCLC treatment. We did a simple survival analysis with hub gene to assess the prognosis of NSCLC patients.Results: Three compounds were screened to obtain 143 target genes and 1,226 targets related to NSCLC, of which 56 genes were related to NSCLC treatment. Shan Ci Gu treatment for NSCLC involved many BPs and acted on main targets including epidermal growth factor receptor (EGFR), ESR1, and SRC through signaling pathways including the endocrine resistance, EGFR tyrosine kinase inhibitor resistance, and ErbB signaling pathways. Shan Ci Gu might be beneficial for treating NSCLC by inhibiting cell proliferation and migration. Molecular docking revealed that the active compounds β-sitosterol, stigmasterol, and 2-methoxy-9,10-dihydrophenanthrene-4,5-diol had good affinity with the core target genes (EGFR, SRC, and ESR1). Core targets included EGFR, SRC, ESR1, ERBB2, MTOR, MCL1, matrix metalloproteinase 2 (MMP2), MMP9, KDR, and JAK2. Key KEGG pathways included endocrine resistance, EGFR tyrosine kinase inhibitor resistance, ErbB signaling, PI3K-Akt signaling, and Rap1 signaling pathways. These core targets and pathways have an inhibitory effect on the proliferation of NSCLC cells.Conclusion: Shan Ci Gu can treat NSCLC through a multi-target, multi-pathway molecular mechanism and effectively improve NSCLC prognosis. This study could serve as a reference for further mechanistic research on wider application of Shan Ci Gu for NSCLC treatment

Elucidating shared biomarkers in gastroesophageal reflux disease and idiopathic pulmonary fibrosis: insights into novel therapeutic targets and the role of angelicae sinensis radix

Background: The etiological underpinnings of gastroesophageal reflux disease (GERD) and idiopathic pulmonary fibrosis (IPF) remain elusive, coupled with a scarcity of effective therapeutic interventions for IPF. Angelicae sinensis radix (ASR, also named Danggui) is a Chinese herb with potential anti-fibrotic properties, that holds promise as a therapeutic agent for IPF.Objective: This study seeks to elucidate the causal interplay and potential mechanisms underlying the coexistence of GERD and IPF. Furthermore, it aims to investigate the regulatory effect of ASR on this complex relationship.Methods: A two-sample Mendelian randomization (TSMR) approach was employed to delineate the causal connection between gastroesophageal reflux disease and IPF, with Phennoscanner V2 employed to mitigate confounding factors. Utilizing single nucleotide polymorphism (SNPs) and publicly available microarray data, we analyzed potential targets and mechanisms related to IPF in GERD. Network pharmacology and molecular docking were employed to explore the targets and efficacy of ASR in treating GERD-related IPF. External datasets were subsequently utilized to identify potential diagnostic biomarkers for GERD-related IPF.Results: The IVW analysis demonstrated a positive causal relationship between GERD and IPF (IVW: OR = 1.002, 95%CI: 1.001, 1.003; p < 0.001). Twenty-five shared differentially expressed genes (DEGs) were identified. GO functional analysis revealed enrichment in neural, cellular, and brain development processes, concentrated in chromosomes and plasma membranes, with protein binding and activation involvement. KEGG analysis unveiled enrichment in proteoglycan, ERBB, and neuroactive ligand-receptor interaction pathways in cancer. Protein-protein interaction (PPI) analysis identified seven hub genes. Network pharmacology analysis demonstrated that 104 components of ASR targeted five hub genes (PDE4B, DRD2, ERBB4, ESR1, GRM8), with molecular docking confirming their excellent binding efficiency. GRM8 and ESR1 emerged as potential diagnostic biomarkers for GERD-related IPF (ESR1: AUCGERD = 0.762, AUCIPF = 0.725; GRM8: AUCGERD = 0.717, AUCIPF = 0.908). GRM8 and ESR1 emerged as potential diagnostic biomarkers for GERD-related IPF, validated in external datasets.Conclusion: This study establishes a causal link between GERD and IPF, identifying five key targets and two potential diagnostic biomarkers for GERD-related IPF. ASR exhibits intervention efficacy and favorable binding characteristics, positioning it as a promising candidate for treating GERD-related IPF. The potential regulatory mechanisms may involve cell responses to fibroblast growth factor stimulation and steroidal hormone-mediated signaling pathways

Video Lecture Design in Online Learning: A Systematic Review

The flexibility and cost-effectiveness of online learning provide the public with the opportunities to learn anywhere and at any time. Its popularity has surged since the emergence of MOOCs in 2011 and after the global outbreak of the Covid-19 pandemic in 2019. As the central element in current online learning platforms, video lecture plays important role in affecting learners’ engagement, performance, and satisfaction. To shed light on the key components of video lecture design and their effects on learner-level outcomes in online learning, this research identifies the literature on video lecture design and conducts a systematic review with bibliometric analysis. Specifically, the bibliometric analysis illustrates the literature on video lecture design in terms of publication year, journal source, citations, and keyword co-occurrence. The thematic analysis identifies three themes that are widely investigated in video lecture design literature such as instructor presence, instructor characteristics, and content presentation. This research contributes to online learning literature by illustrating the current landscape of research on video lecture design in online learning for the first time

Exploring the role and mechanism of Astragalus membranaceus and radix paeoniae rubra in idiopathic pulmonary fibrosis through network pharmacology and experimental validation

Abstract Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrotic disease with an unclear etiology and no effective treatment. This study aims to elucidate the pathogenic mechanism networks involving multiple targets and pathways in IPF. Extracts and metabolites of Astragalus membranaceus (AM) and Radix paeoniae rubra (RPR), two well-known traditional Chinese medicines, have demonstrated therapeutic effects on IPF. However, the underlying mechanisms of AM and RPR remain unclear. Utilizing network pharmacology analysis, differentially expressed genes (DEGs) associated with IPF were obtained from the GEO database. Targets of AM and RPR were identified using the TCM Systems Pharmacology Database and Analysis Platform and SwissTargetPrediction. A protein–protein interaction (PPI) network was subsequently constructed and analyzed using the STRING database and Cytoscape software. Gene ontology enrichment analysis and kyoto encyclopedia of genes and genomes analysis were conducted using Metascape. Additionally, a component-target-pathway network and a Sankey diagram were employed to identify the main active components, and molecular docking was performed between these components and proteins encoded by key targets. Finally, in vivo studies were conducted based on network pharmacology. A total of 117 common targets between DEGs of IPF and drug targets were identified and included in the PPI network, in which AKT1, MAPK3, HSP90AA1, VEGFA, CASP3, JUN, HIF1A, CCND1, PTGS2, and MDM2 were predicted as key targets. These 117 targets were enriched in the PI3K-AKT pathway, HIF-1 signaling pathway, apoptosis, and microRNAs in cancer. Astragaloside III, (R)-Isomucronulatol, Astragaloside I, Paeoniflorin, and β-sitosterol were selected as the main active components. Docking scores ranged from − 4.7 to − 10.7 kcal/mol, indicating a strong binding affinity between the main active compounds and key targets. In vivo studies have indeed shown that AM and RPR can alleviate the pathological lung fibrotic damage caused by bleomycin treatment. The treatment with AM and RPR resulted in a reduction of mRNA levels for key targets AKT1, HSP90AA1, CASP3, MAPK3, and VEGFA. Additionally, the protein expression levels of AKT1, HSP90AA1, and VEGFA were also reduced. These results support the therapeutic potential of AM and RPR in ameliorating pulmonary fibrosis and provide insight into the molecular mechanisms involved in their therapeutic effects

Virtual Standardized Patients Versus Traditional Academic Training for Improving Clinical Competence Among Traditional Chinese Medicine Students: Prospective Randomized Controlled Trial

BackgroundThe practical training course of internal medicine of traditional Chinese medicine (PTC-IMTCM) is primarily based on traditional case teaching, which can be stressful for teachers. The use of virtual standardized patient (VSP) applications could be an alternative; however, there is limited evidence regarding their feasibility and effectiveness. ObjectiveThis study aimed to build a VSP-TCM application according to the characteristics of PTC-IMTCM and the needs of students and to compare its efficacy with that of traditional teaching in improving TCM clinical competence among students. MethodsA prequestionnaire investigation was conducted before the course, and a VSP-TCM system was developed based on the results of the questionnaire. A randomized controlled trial was then conducted between February 26, 2020, and August 20, 2021. A total of 84 medical students were included and were divided into 2 groups: an observation group, trained with VSP-TCM (n=42, 50%), and a control group, trained with traditional academic training (n=42, 50%). Formative and summative assessments were conducted to evaluate teaching effectiveness. After completing the course, the students were administered a questionnaire to self-assess their satisfaction with the course. A questionnaire was also administered to 15 teachers to uncover their perspectives on VSP-TCM. ResultsAll participants completed the study. In the formative assessment, the VSP-TCM group performed better in medical interviewing ability (mean 7.19, SD 0.63, vs mean 6.83, SD 0.81; P=.04), clinical judgment (mean 6.48, SD 0.98, vs mean 5.86, SD 1.04; P=.006), and comprehensive ability (mean 6.71, SD 0.59, vs mean 6.40, SD 0.58; P=.02) than the control group. Similarly, in the summative evaluation, the VSP-TCM group performed better in the online systematic knowledge test (OSKT; mean 86.62, SD 2.71, vs mean 85.38, SD 2.62; P=.046), application of TCM technology (mean 87.86, SD 3.04, vs mean 86.19, SD 3.08; P=.02), TCM syndrome differentiation and therapeutic regimen (mean 90.93, SD 2.42, vs mean 89.60, SD 2.86; P=.03), and communication skills (mean 90.67, SD 4.52, vs mean 88.24, SD 4.56; P=.02) than the control group. There was no significant difference in medical writing between both groups (mean 75.07, SD 3.61, vs mean 75.71, SD 2.86; P=.37). The postcourse feedback questionnaire indicated that VSP-TCM can better enhance students’ TCM thinking ability (n=39, 93%, vs n=37, 88%; P=.002), medical history collection (n=38, 90%, vs n=30, 72; P=.001), syndrome differentiation and treatment and critical thinking (n=38, 90%, vs n=37, 88%; P=.046), comprehensive clinical application ability (n=40, 95%, vs n=36, 86%; P=.009), interpersonal communication skills (n=36, 86%, vs n=28, 67%; P=.01), and autonomous learning ability (n=37, 88%, vs n=28, 67%; P=.01) than traditional academic training. Similarly, the teachers held a positive perspective on VSP-TCM. ConclusionsVSP-TCM enhances students’ TCM clinical competence and dialectical thinking and improves their ability to work autonomously. Moreover, the VSP-TCM system is feasible, practical, and cost-effective and thus merits further promotion in TCM education

Student standardized patients versus occupational standardized patients for improving clinical competency among TCM medical students: a 3-year prospective randomized study

Abstract Background Standardized patient (SP) simulations are well-recognized patterns for practicing clinical skills and interactions. Our previous study showed that a simulation program using occupational SP for Traditional Chinese Medicine (OSP-TCMs) was efficient, however, a high cost and time-intensive nature have limited its use. TCM postgraduates trained as student SPs (SSP-TCMs) present a potentially cost-effective alternative. The purpose of this study was to examine and determine whether SSP simulation offered more benefits over didactic training alone for improving clinical competency among TCM medical students, and conduct a multifaceted analysis comparing SSP-TCMs and OSP-TCMs. Methods This was a prospective, single-blinded, randomized controlled trial. Fourth-year TCM undergraduates were recruited as trainees from the Clinical Medical School, Chengdu University of TCM. Data were collected from September 2018 to December 2020. Trainees were randomly divided into the three following groups: traditional method training group, OSP-TCM training group, and SSP-TCM training group (1:1:1). At the end of a 10-week curriculum, trainees received a two-station examination comprising a systematic online knowledge test and an offline clinical performance examination. Post-training and post-exam questionnaires were administered to collect feedback from these trainees. Results Students assigned to the SSP-TCM training and OSP-TCM training groups received favorable marks for the “systematic knowledge test” and “TCM clinical skills” (2018, Pa=0.018, Pb=0.042; 2019, Pa=0.01, Pb=0.033; 2020, Pa=0.035, Pb=0.039) compared to the TM trainees. Additionally, trainees in the intervention groups demonstrated a positive post-training edge in scores of “medical records” (2018, Pa=0.042, Pb=0.034; 2019, Pa=0.032, Pb=0.042; 2020, Pa=0.026, Pb=0.03) and “TCM syndrome differentiation and therapeutic regimen” (2018, Pb=0.032; 2019, Pa=0.037, Pb=0.024; 2020, Pa=0.036, Pb=0.043). For the simulation encounter assessment given by SP-TCMs, OSP-TCM trainees and SSP-TCM trainees scored higher than TM trainees (2018, Pa=0.038, Pb=0.037; 2019, Pa=0.024, Pb=0.022; 2020, Pa=0.019, Pb=0.021). For the feedback questionnaires, the students in TM group provided less positive feedback for training efficacy and test performance compared to those in the SSP-TCM and OSP-TCM groups. The trainees responded that the training effect of clinical simulations was similar between the SSP-TCM and OSP-TCM groups. SSP-TCMs were more responsive to unexpected emergencies (Pa=0.022, Pb>0.05) and more likely to encourage questioning (Pa=0.029, Pb>0.05) but tended to provide implied hints (Pc=0.015) and utilize medical jargon (Pc=0.007) as compared to OSP-TCMs. Conclusion Simulation training for SSP-TCMs and OSP-TCMs showed great benefits for enhancing clinical competency. SSP-TCM simulation was feasible, practical, and cost-effective, and may serve as an alternative method to OSP-TCM simulation