Deciphering the molecular mechanism of Bu Yang Huan Wu Decoction in interference with diabetic pulmonary fibrosis via regulating oxidative stress and lipid metabolism disorder.

BACKGROUND: Diabetes mellitus type 2 and pulmonary fibrosis have been found to be closely related in clinical practice. Diabetic pulmonary fibrosis (DPF) is a complication of diabetes mellitus, but its treatment has yet to be thoroughly investigated. Bu Yang Huan Wu Decoction (BYHWD) is a well-known traditional Chinese prescription that has shown great efficacy in treating pulmonary fibrosis with hypoglycemic and hypolipidemic effects. METHODS: The active ingredients of BYHWD and the corresponding targets were retrieved from the Traditional Chinese Medicine Systematic Pharmacology Database (TCMSP) and SymMap2. Disease-related targets were obtained from the GeneCard, OMIM and CTD databases. GO enrichment and KEGG pathway enrichment were carried out using the DAVID database. AutoDock Vina software was employed to perform molecular docking. Molecular dynamics simulations of proteinligand complexes were conducted by Gromacs. Animal experiments were further performed to validate the effects of BYHWD on the selected core targets, markers of oxidative stress, serum lipids, blood glucose and pulmonary fibrosis. RESULTS: A total of 84 active ingredients and 830 target genes were screened in BYHWD, among which 56 target genes intersected with DPF-related targets. Network pharmacological analysis revealed that the active ingredients can regulate target genes such as IL-6, TNF-α, VEGFA and CASP3, mainly through AGE-RAGE signaling pathway, HIF-1 signaling pathway and TNF signaling pathway. Molecular docking and molecular dynamics simulations suggested that IL6-astragaloside IV, IL6-baicalein, TNFα-astragaloside IV, and TNFα-baicalein docking complexes could bind stably. Animal experiments showed that BYHWD could reduce the expression of core targets such as VEGFA, CASP3, IL-6 and TNF-α. In addition, BYHWD could reduce blood glucose, lipid, and MDA levels in DPF while increasing the activities of SOD, CAT and GSH-Px. BYHWD attenuated the expression of HYP and collagen I, mitigating pathological damage and collagen deposition within lung tissue. CONCLUSIONS: BYHWD modulates lipid metabolism disorders and oxidative stress by targeting the core targets of IL6, TNF-α, VEGFA and CASP3 through the AGE-RAGE signaling pathway, making it a potential therapy for DPF.

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

BACKGROUND: The 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. OBJECTIVE: This 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. METHODS: A 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. RESULTS: All 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. CONCLUSIONS: VSP-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.

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.

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.

Therapeutic Effect of Astragali Radix Extract Injection Combined with Bone Marrow Mesenchymal Stem Cells in Bleomycin-Induced Pulmonary Fibrotic Rats.

Pulmonary fibrosis is a serious disease for which effective drugs are unavailable. Here, we treated rat models of bleomycin (BLM)-induced pulmonary fibrosis with Astragali Radix extract injection (AI) combined with or without bone marrow mesenchymal stem cells (BMSCs). We injected rats intratracheally with BLM and transplanted BMSCs via tail vein injection 15 days later. We also intraperitoneally injected AI daily from days 15 to 28. Changes in lung pathology and function, as well as the levels of matrix metalloproteinases, collagen, C-X-C motif chemokine ligand 12 (CXCL12), and cluster of differentiation 90 (CD90) were assessed. The results revealed that compared with the BLM group, groups treated with ARE and BMSCs (alone or combined) reduced the expression levels of TGF-ß1 and collagens I and III, ameliorated pathological lung fibrotic damage, and improved lung function. The expression levels of MMP-1, MMP-3, and MMP-9 were reduced by either AI or BMSCs alone, whereas those of MMP-3, MMP-9, TIMP-1, CXCL12, and CD90 were elevated by combined AI and BMSCs compared with the BLM group. Overall, these findings demonstrated that AI and BMSCs both can reduce damage caused by PF in rats and that AI altered the expression of chemokines and surface markers in BMSCs.

The Network Pharmacology Study of Dahuang Fuzi Decoction for Treating Incomplete Intestinal Obstruction.

Objective: To explore the mechanism of Dahuang Fuzi decoction in the treatment of incomplete intestinal obstruction (IIO) based on network pharmacology and molecular docking. Methods: The chemical components of Rhubarb, Aconite, and Asarum were searched by the Traditional Chinese Medicine Systems Pharmacology database, where the possible active components were screened by oral bioavailability and drug likeness as filtering indicators. The relevant targets in the Swiss Target Prediction database were obtained according to the structure of the chemical components confirmed by the PubChem database. Disease targets of IIO were collected using GeneCards and OMIM databases. We obtained the cross-target using VENNY to capture the common targets. PPI analysis was performed on the intersection genes combined with Cytoscape 3.7.2. Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out by David database. The core targets and active ingredients were molecularly docked through AutoDock Vina software to predict the detailed molecular mechanism of Dahuang Fuzi decoction for treating IIO. Results: There are 45 active components in Dahuang Fuzi decoction, with 709 corresponding targets, 538 IIO targets, and 97 common targets, among which kaempferol, deltoin, and eupatin are the main active ingredients. 10 core targets were obtained by protein-protein interaction network analysis. Through GO enrichment analysis, it was found that Dahuang Fuzi decoction may be involved in biological processes such as signal transduction, anti-apoptosis, promotion of gene expression, regulation of cell proliferation, and differentiation. Besides, KEGG pathway analysis revealed that it mainly relates to PI3K-AKT signal pathway and HIF-1 signal pathway, etc. Molecular docking results showed that the active ingredients of Dahuang Fuzi decoction possess a good binding activity with the core targets. Conclusion: Dahuang Fuzi decoction may act on target genes such as TNF, IL6, AKT1, VEGFA, SRC, EGFR, and STAT3 through active ingredients such as kaempferol, deltoin, and eupatin to regulate signaling pathways such as PI3K-AKT and HIF-1 and reduce the expression of various inflammatory factors such as TNF-α, IL-6, iNOS, and COX-2 to play a role in the treatment of IIO.

Network Pharmacology and Molecular Docking Analysis on Pharmacological Mechanisms of Astragalus membranaceus in the Treatment of Gastric Ulcer.

BACKGROUND: Astragalus membranaceus (AM, family: Leguminosae) exerts significant therapeutic effect on gastric ulcer (GU); however, there are scarce studies on its molecular mechanism against GU. This study aims to explore the key ingredients, key targets, and potential mechanisms of AM in the treatment of GU by utilizing network pharmacology and molecular docking. METHODS: Several public databases were used to predict the targets of AM and GU, respectively, and the drug and disease targets were intersected to obtain the common targets. Next, the key ingredients and key targets were identified by constructing ingredient-target network and protein-protein-interaction (PPI) network. Gene Ontology biological processes (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out on the common targets in order to ascertain the biological processes and signaling pathways involved. Finally, molecular docking was conducted to verify the binding affinity between the key ingredients and key targets. RESULTS: A total of 552 predicted targets were obtained from 23 screened active ingredients, of which 203 targets were the common targets with GU. Quercetin, kaempferol, and isorhamnetin were identified as the key ingredients by constructing ingredient-target network, and TP53, AKT1, VEGFA, IL6, TNF, CASP3, and EGFR were selected as the key targets by constructing PPI network. GOBP and KEGG pathway enrichment analysis suggested that the therapeutic effect of AM on GU involved multiple biological processes and signaling pathways related to inflammation, oxidative stress, apoptosis, cell proliferation, and angiogenesis. Molecular docking validation demonstrated that all key ingredients had good binding affinity with the key targets. CONCLUSION: This study revealed the key ingredients, key targets, and potential mechanisms of AM against GU, and these data may provide some crucial references for subsequent research and development of drugs for treating GU.

Saikosaponin D: review on the antitumour effects, toxicity and pharmacokinetics.

CONTEXT: Bupleuri Radix, the dried root of Bupleurum chinense DC and Bupleurum scorzonerifolium Willd (Apiaceae), is an important medicinal herb widely used to treat cancers for hundreds of years in Asian countries. As the most antitumour component but also the main toxic component in Bupleuri Radix, saikosaponin D (SSD) has attracted extensive attention. However, no summary studies have been reported on the antitumour effects, toxicity and pharmacokinetics of this potential natural anticancer substance. OBJECTIVE: To analyse and summarise the existing findings regarding to the antitumour effects, toxicity and pharmacokinetics of SSD. MATERIALS AND METHODS: We collected relevant information published before April 2021 by conducting a search of literature available in various online databases including PubMed, Science Direct, CNKI, Wanfang database and the Chinese Biological Medicine Database. Bupleurum, Bupleuri Radix, saikosaponin, saikosaponin D, tumour, toxicity, and pharmacokinetics were used as the keywords. RESULTS: The antitumour effects of SSD were multi-targeted and can be realised through various mechanisms, including inhibition of proliferation, invasion, metastasis and angiogenesis, as well as induction of cell apoptosis, autophagy, and differentiation. The toxicological effects of SSD mainly included hepatotoxicity, neurotoxicity, haemolysis and cardiotoxicity. Pharmacokinetic studies demonstrated that SSD had the potential to alter the pharmacokinetics of some drugs for its influence on CYPs and P-gp, and the oral bioavailability and actual pharmacodynamic substances in vivo of SSD are still controversial. CONCLUSIONS: SSD is a potentially effective and relatively safe natural antitumour substance, but more research is needed, especially in vivo antitumour effects and pharmacokinetics of the compound.

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 ß-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.

Danggui Sini decoction for treating diabetic peripheral neuropathy: A protocol of systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetic patients, which seriously affects the quality of life of patients. At present, mainstream drugs have problems such as poor efficacy and side effects. Traditional Chinese medicine (TCM) has extensive clinical experience in the prevention and treatment of diabetes and chronic complications, and it also shows clear advantages in the treatment of DPN. Clinical studies have confirmed that Danggui Sini decoction (DSD), a TCM decoction, can improve the clinical symptoms and signs of DPN patients. Therefore, we will conduct a systematic review to clarify the effectiveness and safety of DSD for DPN. METHODS: We will search every database from the built-in to October 2020. Chinese literature comes from CNKI, Wanfang, VIP, and CBM databases. English literature mainly searches Cochrane Library, PubMed, Web of Science, and EMBASE. At the same time, we will also search for clinical registration tests and gray literatures. This study only screened clinical randomized controlled trials (RCT) for DSD for DPN. The two researchers independently conducted literature selection, data extraction and quality assessment. Dichotomous data is represented by relative risk (RR), continuous data is represented by mean difference (MD) or standard mean deviation (SMD), and the final data is fixed effect model (FEM) or random effect model (REM), depending on whether it exists Heterogeneity. The main result is clinical efficacy and nerve conduction velocity. Fasting blood glucose, 2 hours postprandial blood glucose, blood lipid, hemorheology, and adverse events are secondary results. Finally, a meta-analysis was conducted through Review Manager software version 5.3. RESULTS: This study will conduct a comprehensive analysis based on the currently released DSD data for the treatment of DPN and provide high-quality evidence of clinical efficacy and safety. CONCLUSION: This systematic review aims to provide new options for DSD treatment of DPN in terms of its efficacy and safety. ETHICS AND DISSEMINATION: The review is based solely on a secondary study of published literatures and does not require ethics committee approval. Its conclusion will be disseminated in conference papers, magazines, or peer-reviewed journals. INPLASY REGISTRATION NUMBER: INPLASY202040157.