MicroRNA-411-3p motivates methotrexate's cellular uptake and cytotoxicity via targeting Yin-yang 1 in leukemia cells.

This study aimed to figure out how microRNA (miR)-411-3p's impacts on methotrexate (MTX)'s cellular uptake and cytotoxicity in acute lymphoblastic leukaemia (ALL) CEM-C1 cells by targeting Yin-yang 1 (YY1). miR-411-3p and YY1 were detected by RT-qPCR or Western blot. Intracellular MTX concentration was measured by enzyme-linked immunosorbent assay. Cell viability and apoptosis were evaluated by CCK-8, clonal formation assay, and flow cytometry. Verification of miR-411-3p and YY1's targeting link was manifested. It came out that miR-411-3p mimic or si-YY1 elevated intracellular MTX, MTX-induced cytotoxicity and apoptosis rate in CEM-C1. However, the inverse results were noticed in cells introduced with miR-411-3p inhibitor or oe-YY1. Meanwhile, it was found that cell relative luciferase activity was reduced after co-transfection of miR-411-3p mimic with YY1-WT, indicating that miR-411-3p targeted YY1. Elevation of YY1 could turn around elevating miR-411-3p's impacts on MTX's cellular uptake and cytotoxicity in CEM-C1 cells. These findings convey that miR-411-3p motivated MTX's cellular uptake and cytotoxic impacts via targeting YY1 in leukemia cells. This study is helpful for learning about the mechanisms underlying MTX responses in ALL patients.

Expanding potential targets of herbal chemicals by node2vec based on herb-drug interactions.

BACKGROUND: The identification of chemical-target interaction is key to pharmaceutical research and development, but the unclear materials basis and complex mechanisms of traditional medicine (TM) make it difficult, especially for low-content chemicals which are hard to test in experiments. In this research, we aim to apply the node2vec algorithm in the context of drug-herb interactions for expanding potential targets and taking advantage of molecular docking and experiments for verification. METHODS: Regarding the widely reported risks between cardiovascular drugs and herbs, Salvia miltiorrhiza (Danshen, DS) and Ligusticum chuanxiong (Chuanxiong, CX), which are widely used in the treatment of cardiovascular disease (CVD), and approved drugs for CVD form the new dataset as an example. Three data groups DS-drug, CX-drug, and DS-CX-drug were applied to serve as the context of drug-herb interactions for link prediction. Three types of datasets were set under three groups, containing information from chemical-target connection (CTC), chemical-chemical connection (CCC) and protein-protein interaction (PPI) in increasing steps. Five algorithms, including node2vec, were applied as comparisons. Molecular docking and pharmacological experiments were used for verification. RESULTS: Node2vec represented the best performance with average AUROC and AP values of 0.91 on the datasets "CTC, CCC, PPI". Targets of 32 herbal chemicals were identified within 43 predicted edges of herbal chemicals and drug targets. Among them, 11 potential chemical-drug target interactions showed better binding affinity by molecular docking. Further pharmacological experiments indicated caffeic acid increased the thermal stability of the protein GGT1 and ligustilide and low-content chemical neocryptotanshinone induced mRNA change of FGF2 and MTNR1A, respectively. CONCLUSIONS: The analytical framework and methods established in the study provide an important reference for researchers in discovering herb-drug interactions, alerting clinical risks, and understanding complex mechanisms of TM.

Clinicopathological features and expression of regulatory mechanism of the Wnt signaling pathway in colorectal sessile serrated adenomas/polyps with different syndrome types.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide, with the fourth highest mortality among all cancers. Reportedly, in addition to adenomas, serrated polyps, which account for 15%-30% of CRCs, can also develop into CRCs through the serrated pathway. Sessile serrated adenomas/polyps (SSAs/Ps), a type of serrated polyps, are easily misdiagnosed during endoscopy. AIM: To observe the difference in the Wnt signaling pathway expression in SSAs/Ps patients with different syndrome types. METHODS: From January 2021 to December 2021, patients with SSAs/Ps were recruited from the Endoscopy Room of Shanghai Traditional Chinese Medicine-Integrated Hospital, affiliated with Shanghai University of Traditional Chinese Medicine. Thirty cases each of large intestine damp-heat (Da-Chang-Shi-Re, DCSR) syndrome and spleen-stomach weakness (Pi-Wei-Xu-Ruo) syndrome were reported. Baseline comparison of the general data, typical tongue coating, colonoscopy findings, and hematoxylin and eosin findings was performed in each group. The expression of the Wnt pathway-related proteins, namely ß-catenin, adenomatous polyposis coli, and mutated in colorectal cancer, were analyzed using immunohistochemistry. RESULTS: Significant differences were observed with respect to the SSAs/Ps size between the two groups of patients with different syndrome types (P = 0.001). The other aspects did not differ between the two groups. The Wnt signaling pathway was activated in patients with SSAs/Ps belonging to both groups, which was manifested as ß-catenin protein translocation into the nucleus. However, SSAs/Ps patients with DCSR syndrome had more nucleation, higher ß-catenin expression, and negative regulatory factor (adenomatous polyposis coli and mutated in colorectal cancer) expression (P < 0.0001) than SSA/P patients with Pi-Wei-Xu-Ruo syndrome. In addition, the SSA/P size was linearly correlated with the related protein expression. CONCLUSION: Patients with DCSR syndrome had a more obvious Wnt signaling pathway activation and a higher risk of carcinogenesis. A high-quality colonoscopic diagnosis was essential. The thorough assessment of clinical diseases can be improved by combining the diseases of Western medicine with the syndromes of traditional Chinese medicine.

Network pharmacology and molecular docking reveal zedoary turmeric-trisomes in Inflammatory bowel disease with intestinal fibrosis.

BACKGROUND: Inflammatory bowel disease (IBD) is a complex chronic IBD that is closely associated with risk factors such as environment, diet, medications and lifestyle that may influence the host microbiome or immune response to antigens. At present, with the increasing incidence of IBD worldwide, it is of great significance to further study the pathogenesis of IBD and seek new therapeutic targets. Traditional Chinese medicine (TCM) treatment of diseases is characterized by multiple approaches and multiple targets and has a long history of clinical application in China. The mechanism underlying the effect of zedoary turmeric-trisomes on inducing mucosal healing in IBD is not clear. AIM: To explore the effective components and potential mechanism of zedoary turmeric-trisomes in the treatment of IBD with intestinal fibrosis using network pharmacology and molecular docking techniques. METHODS: The chemical constituents and targets of Rhizoma zedoary and Rhizoma sanarum were screened using the TCMSP database. The GeneCards database was searched to identify targets associated with intestinal fibrosis in IBD. The intersection of chemical component targets and disease targets was obtained using the Venny 2.1 online analysis platform, and the common targets were imported into the STRING 11.0 database to construct a protein interaction regulatory network. A "zedoary turmeric-trisomes-chemical composition-target-disease" network diagram was subsequently constructed using Cytoscape 3.7.2 software, and the topological properties of the network were analyzed using the "Network Analysis" plug-in. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the common targets were performed using the DAVID 6.8 database to elucidate the mechanism of zedoary turmeric-trisomes in the treatment of IBD. Subsequently, molecular docking of the compounds and targets with the highest intermediate values in the "zedoary turmeric-trisomes-chemical composition-target-disease" network was performed using Sybyl-x 2.1.1 software. RESULTS: A total of 5 chemical components with 60 targets were identified, as well as 3153 targets related to IBD and 44 common targets. The protein-protein interaction network showed that the core therapeutic targets included JUN, MAPK14, CASP3, AR, and PTGS2. The GO enrichment analysis identified 759 items, and the KEGG enrichment analysis yielded 52 items, including the cancer pathway, neuroactive ligand-receptor interaction, hepatitis B, and the calcium signaling pathway, reflecting the complex biological processes of the multicomponent, multitarget and multipathway treatment of diseases with zedoary turmeric-trisomes. Molecular docking showed that the compound bonded with the target through hydrogen bond interactions and exhibited good docking activity. CONCLUSION: This study identified the potential mechanism of action of zedoary turmeric-trisomes in the treatment of inflammatory bowel fibrosis using network pharmacology and molecular docking technology, providing a scientific basis for further expansion of their clinical use.

A network pharmacology-based study on the quality control markers of antithrombotic herbs: Using Salvia miltiorrhiza - Ligusticum chuanxiong as an example.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza (Danshen, DS), the dried root and rhizome of Salvia miltiorrhiza Bunge and Ligusticum chuanxiong (Chuanxiong, CX), the dried rhizomes of Ligusticum striatum DC are effective in invigorating blood circulation and eliminating stasis which is highly related with cardiovascular disease (CVD). AIM OF STUDY: The identification of activity-based chemical markers is very important, but the complex mechanism of "multi-component, multi-target, and multi-effect" within traditional Chinese medicine (TCM) poses a great challenge to this work. In this study, we combined network pharmacological prediction with experimental validation of the DS and CX to explore an effective method for discovering quality control (QC) of antithrombotic herbs by clarifying the intermediate layer "module/cluster" between the whole complex system and a single component. MATERIALS AND METHODS: Based on structural similarity analysis of compound and the thrombosis network published before, we firstly modularized two layers called chemical cluster (CC) network and functional module (FM) network respectively and linked them into one bilayer modularized compound target (BMCT) network. "Two-step" calculation was applied on identifying the significant compounds as the potential QC markers from CC. The in vitro inhibitory activity of selected QC marker compounds on thrombin was evaluated to partially verify their pharmacological activities. HPLC was used to determine contents. RESULTS: According to the network-based analysis, nine compounds with great importance in the BMCT network were identified as QC markers of DS-CX, including tanshinone I, tanshinone IIA, cryptotanshinone, salvianolic acid B, ferulic acid, salvianolic acid A, rosmarinic acid, chlorogenic acid, and coniferyl ferulate. Enzyme inhibitory test partially verified the activity of tanshinone I and tanshinone IIA. Chemical profiling indicated that the nine marker compounds are the main components in the herbal pair. CONCLUSIONS: This study identified activity-based QC markers of DS-CX herbal pair and provided a new methodology that can be used in the QC of other herbs, herbal pairs, or formulas.

[CiteSpace knowledge map analysis of research progress on Tripterygium wilfordii toxicity].

This study systematically searched CNKI and Web of Science(WoS) for the research papers on the toxicity of Tripterygium wilfordii included from database inception to August 31, 2021, and visually displayed the authors, research institutions, keywords, and other contents using bibliometrics and CiteSpace 5.8.3. Furthermore, the current situation and research progress on T. wilfordii safety were also analyzed based on information extraction to find the research hotspot, evolution path, and development trend, and to provide references for future research. A total of 1 876 Chinese papers and 243 English papers were included in the study. The analysis of authors showed that WANG Qi and ZHANG Luyong had the most publications in Chinese and English papers, respectively. According to the analysis of research institutions, National Institutes for Food and Drug Control and China Pharmaceutical University possessed the largest number of Chinese and English papers, respectively, but there was less cooperation between them. The analysis of keywords in Chinese and English papers showed that the research contents of the safety of T. wilfordii mainly focused on clinical monitoring, mechanism, dosage form improvement, quality standard, component analysis, monomer research, efficiency and toxicity reduction, etc. Metabonomics, tripterine, and the underlying mechanism of toxicity were the research hotspots in the future. At present, the research on the toxicity of T. wilfordii is still under development. It is necessary to highlight the in-depth research and strengthen the inter-group and inter-region cooperation of authors or institutions to provide references for the research on the toxicity of T. wilfordii.

Jianpi Qingchang Decoction Ameliorates Chronic Colitis in Piroxicam-Induced IL-10 Knockout Mice by Inhibiting Endoplasmic Reticulum Stress.

BACKGROUND: Excessive endoplasmic reticulum (ER) stress in intestinal epithelial cells (IEC) may lead to impaired intestinal mucosal barrier function and then participate in the pathogenesis of ulcerative colitis (UC). Jianpi Qingchang decoction (JPQCD) has been shown to have protective effects on UC. However, further studies are needed to determine whether JPQCD regulates PERK/eIF2α/ATF4/CHOP pathways to play a role in treating UC. METHODS: IL-10 -/- mice were randomly assigned into five groups: control, model, low-dose JPQCD (JPQCD L), middle-dose JPQCD (JPQCD M), and high-dose JPQCD (JPQCD H). All groups except for the control group were given model feed containing 200 ppm piroxicam for 10 d to induce colitis. As a comparison, we used wild-type mice that were the progeny of IL-10 +/- matings, bred in the same facility. The control group and wild-type mice were fed with common feed. At the same time, mice in each group were given corresponding drugs by gavage for 14 d. The disease activity index of mice in each group was evaluated daily. Colon tissues of mice were collected, colon length was measured, and pathological changes and ultrastructure of colon epithelial cells were observed. The effects of JPQCD on the PERK/eIF2α/ATF4/CHOP pathways were evaluated by western blotting and reverse transcription-polymerase chain reaction (RT-PCR). The expression of CHOP in colon tissue was detected by tissue immunofluorescence assay. The expression of NF-κB, p-NF-κB p65 protein was analyzed by western blotting; the level of IL-17 in colon tissue was detected by enzyme-linked immunosorbent assay (ELISA) and verified by examining NF-κB and IL-17 mRNA levels by RT-PCR. RESULTS: Compared with the control group, the model group showed significant colitis symptoms and severe colonic tissue damage. The results showed that JPQCD significantly reduced body weight loss, ameliorated disease activity index, and restored colon length in IL-10 -/- mice with piroxicam-induced colitis. Western blotting and RT-PCR showed that the PERK/eIF2α/ATF4/CHOP pathway was activated in colon tissue of model mice, suggesting that the pathway is involved in the pathogenesis of ulcerative colitis (UC) and could become a potential therapeutic target. The JPQCD treatment inhibited the activation of the PERK/eIF2α/ATF4/CHOP pathway, alleviated the ER stress, and played a role in preventing and treating UC. In addition, JPQCD can also downregulate the protein of NF-κB, p-NF-κB p65, downregulate the mRNA expression of NF-κB, and reduce the content of IL-17 and its mRNA expression in colon tissues. CONCLUSION: JPQCD may play a protective role in UC by regulating the PERK/eIF2α/ATF4/CHOP signaling pathway and relieving endoplasmic reticulum stress.

[Traditional Chinese medicine network pharmacology: development in new era under guidance of network pharmacology evaluation method guidance].

Traditional Chinese medicine(TCM) has unique advantages in the prevention and treatment of diseases owing to its holistic view and more than 2 000 years of experience in the clinical use of natural medicine. The "holistic" characteristic of TCM gives birth to a new generation of research paradigm featuring "network" and "system", which has been developing rapidly in the era of biomedical big data and artificial intelligence. Network pharmacology, a representative research field, provides new ideas and methods for the research of the interdiscipline of artificial intelligence and medicine, the analysis of massive biomedical data, and the transformation from data to knowledge. TCM plays an important role in proposing the core theory of "network target" and promoting the establishment and development of network pharmacology, and has taken the lead in formulating the first international standard of network pharmacology--Network Pharmacology Evaluation Method Guidance. In terms of theory, network target can systematically link drugs and diseases and quantitatively interpret the overall regulatory mechanism of drugs. In the aspect of method, network pharmacology is developing towards a research model that combines computational, experimental, and clinical approaches. This review introduces the resent important progress of TCM network pharmacology in predicting drug targets, understanding the biological basis of drugs and diseases, and searching for disease and syndrome biomarkers. Under the guidance of Network Pharmacology Evaluation Method Guidance, the development of network pharmacology is expected to become more and more standardized and healthy. Network target will help produce more high-quality research outcomes in TCM and effectively boost the modernization and internationalization of TCM.

Moxibustion for diarrhea-predominant irritable bowel syndrome: A systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common functional gastrointestinal disorder that imposes heavy burden on individuals and society. Asan external therapy of traditional Chinese medicine (TCM), moxibustion is usually used to treat IBS-D. This study aimed to explore the efficacy of moxibustion in treating patients with IBS-D. METHODS: A systematic search for randomized controlled trials (RCTs) that reported the use of moxibustion in IBS-D treatment was performed in eight databases. RESULTS: Eleven RCTs including 725 participants meet the inclusion criteria. Compared with other positive treatments (Western medicine, TCM prescription, and acupuncture), moxibustion treatment had superior effects against IBS-D according to the meta-analysis. CONCLUSION: This systematic review provided preliminary research evidence that moxibustion is effective in treating IBS-D. Rigorously designed and large-scale RCTs are required to provide more robust evidence in this area.

Traditional Chinese medicine network pharmacology: development in new era under guidance of network pharmacology evaluation method guidance / 中国中药杂志

Traditional Chinese medicine(TCM) has unique advantages in the prevention and treatment of diseases owing to its holistic view and more than 2 000 years of experience in the clinical use of natural medicine. The "holistic" characteristic of TCM gives birth to a new generation of research paradigm featuring "network" and "system", which has been developing rapidly in the era of biomedical big data and artificial intelligence. Network pharmacology, a representative research field, provides new ideas and methods for the research of the interdiscipline of artificial intelligence and medicine, the analysis of massive biomedical data, and the transformation from data to knowledge. TCM plays an important role in proposing the core theory of "network target" and promoting the establishment and development of network pharmacology, and has taken the lead in formulating the first international standard of network pharmacology--Network Pharmacology Evaluation Method Guidance. In terms of theory, network target can systematically link drugs and diseases and quantitatively interpret the overall regulatory mechanism of drugs. In the aspect of method, network pharmacology is developing towards a research model that combines computational, experimental, and clinical approaches. This review introduces the resent important progress of TCM network pharmacology in predicting drug targets, understanding the biological basis of drugs and diseases, and searching for disease and syndrome biomarkers. Under the guidance of Network Pharmacology Evaluation Method Guidance, the development of network pharmacology is expected to become more and more standardized and healthy. Network target will help produce more high-quality research outcomes in TCM and effectively boost the modernization and internationalization of TCM.

Screening of Potential Thrombin and Factor Xa Inhibitors from the Danshen-Chuanxiong Herbal Pair through a Spectrum-Effect Relationship Analysis.

In this study; a spectrum-effect relationship analysis combined with a high-performance liquid chromatography-mass spectrometry (LC-MS) analysis was established to screen and identify active components that can inhibit thrombin and factor Xa (THR and FXa) in Salviae Miltiorrhizae Radix et Rhizoma-Chuanxiong Rhizoma (Danshen-Chuanxiong) herbal pair. Ten potential active compounds were predicted through a canonical correlation analysis (CCA), and eight of them were tentatively identified through an LC-MS analysis. Furthermore; the enzyme inhibitory activity of six available compounds; chlorogenic acid; Z-ligustilide; caffeic acid; ferulic acid; tanshinone I and tanshinone IIA; were tested to verify the feasibility of the method. Among them; chlorogenic acid was validated to possess a good THR inhibitory activity with IC50 of 185.08 µM. Tanshinone I and tanshinone IIA are potential FXa inhibitors with IC50 of 112.59 µM and 138.19 µM; respectively. Meanwhile; molecular docking results show that tanshinone I and tanshinone IIA; which both have binding energies of less than -7.0 kcal·mol-1; can interact with FXa by forming H-bonds with residues of SER214; GLY219 and GLN192. In short; the THR and FXa inhibitors in the Danshen-Chuanxiong herbal pair have been successfully characterized through a spectrum-effect relationship analysis and an LC-MS analysis.

Mechanism of Jianpi Qingchang Huashi Recipe in treating ulcerative colitis: A study based on network pharmacology and molecular docking.

BACKGROUND: Ulcerative colitis (UC) is a refractory intestinal disease with alternating onset and remission and a long disease course, which seriously affects the health and quality of life of patients. The goal of treatment is to control clinical symptoms, induce and maintain remission, promote mucosal healing, and reduce recurrence. Clinical trials have shown unsatisfactory clinical response rates. As a supplementary alternative medicine, traditional Chinese medicine has a rich history and has shown good results in the treatment of UC. Because of the quality of herbal medicine and other factors, the curative effect of traditional Chinese medicine is not stable enough. The mechanism underlying the effect of Jianpi Qingchang Huashi Recipe (JPQCHSR) on inducing UC mucosal healing is not clear. AIM: To investigate the potential mechanism of JPQCHSR for the treatment of UC based on network pharmacology and molecular docking. METHODS: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform was used to extract the active components and action targets of JPQCHSR, and the target names were standardized and corrected through UniProt database. The related targets of UC were obtained through GeneCards database, and the intersection targets of drugs and diseases were screened by jvenn online analysis tool. The visual regulatory network of "Traditional Chinese medicine-active components-target-disease" was constructed using Cytoscape software, the protein interaction network was constructed using STRING database, and enrichment analysis of gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways was conducted through R software. At last, the active components were docked with the core target through SYBYL-X 2.1.1 software. RESULTS: Through database analysis, a total of 181 active components, 302 targets and 205 therapeutic targets were obtained for JPQCHSR. The key compounds include quercetin, luteolin, kaempferol, etc. The core targets involved STAT3, AKT1, TP53, MAPK1, MAPK3, JUN, TNF, etc. A total of 2861 items were obtained by GO enrichment analysis, and 171 items were obtained by KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analysis. The results of molecular docking showed that the key active components in JPQCHSR had certain affinity with the core target. CONCLUSION: The treatment of UC with JPQCHSR is a complex process of multi-component, multi-target and multi-pathway regulation. The mechanism of this Recipe in the treatment of UC can be predicted through network pharmacology and molecular docking, so as to provide theoretical reference for it to better play its therapeutic role.

Exploring the molecular targets and mechanisms of [10]-Gingerol for treating triple-negative breast cancer using bioinformatics approaches, molecular docking, and in vivo experiments.

BACKGROUND: Triple-negative breast cancer (TNBC) is the most aggressive among breast cancer subtypes with the worst prognosis. Ginger is widely used in pharmaceuticals and as food. Its anticancer properties are known, but the mechanism is still unclear. [10]-Gingerol is one of the main phenolic compounds isolated from ginger. Studying the biological effects of [10]-Gingerol is of great significance to understand the efficacy of ginger. METHODS: In this study, the therapeutic effects of [10]-Gingerol on TNBC cells were studied using network pharmacology, molecular docking, and in vitro experiments, and the target and mechanism of action were explained. RESULTS: A total of 48 targets of ginger for the treatment of TNBC were found. These targets might interfere with the growth of TNBC by participating in many pathways, such as endocrine resistance, progesterone-mediated oocyte maturation, estrogen signaling pathway, and cellular senescence. Prognostic analyses indicated that the JUN, FASN, ADRB2, ADRA2A, and PGR were the hub genes, while molecular docking predicted the stable binding of ADRB2 protein with drug compounds. Additionally, [10]-Gingerol could induce apoptosis by regulating the caspase activation. CONCLUSIONS: [10]-Gingerol affects the growth of TNBC through multiple action targets and participating in multiple action pathways. ADRB2 and apoptosis pathways might be important target pathways for [10]-Gingerol in the treatment of TNBC.

A brief discussion on evidence-based clinical research of traditional Chinese medicine.

BACKGROUND: The evaluation of clinical efficacy of traditional Chinese medicine (TCM) is the focus of the development of Chinese medicine, but at present there is no internationally recognized clinical efficacy evaluation system, which prevents TCM going abroad. Evidence-based medicine (EBM) research methods have achieved good results in the evaluation of TCM, but there are still some problems. How to use EBM methods in accordance with China's national conditions and develop evidence-based TCM that meets its own characteristics is the key to the current discussion. METHODS: Search websites such as PubMed, China National Knowledge Infrastructure, Wanfang Data and VIP by computer, and search papers related to evidence-based clinical research of TCM. RESULTS: A total of 15 high quality representative research papers published in internationally renowned journals were selected for example, including 4 randomized controlled trials (RCTs) related to Chinese medicine, 9 RCTs related to acupuncture, and 2 observational studies on the safety of TCM. CONCLUSIONS: EBM method is suitable for clinical research of TCM. There are differences between "disease" and "syndromes" in the use of TCM. Based on the further standardization of syndromes and classification of TCM, modern clinical research methods can be reasonably applied. However, the quality of clinical research related to TCM is not high, and there is a lack of research related to the safety of it, which should be paid attention to and improved in future research.

Salvianolate ameliorates oxidative stress and podocyte injury through modulation of NOX4 activity in db/db mice.

Podocyte injury is associated with albuminuria and the progression of diabetic nephropathy (DN). NADPH oxidase 4 (NOX4) is the main source of reactive oxygen species (ROS) in the kidney and NOX4 is up-regulated in podocytes in response to high glucose. In the present study, the effects of Salvianolate on DN and its underlying mechanisms were investigated in diabetic db/db mice and human podocytes. We confirmed that the Salvianolate administration exhibited similar beneficial effects as the NOX1/NOX4 inhibitor GKT137831 treated diabetic mice, as reflected by attenuated albuminuria, reduced podocyte loss and mesangial matrix accumulation. We further observed that Salvianolate attenuated the increase of Nox4 protein, NOX4-based NADPH oxidase activity and restored podocyte loss in the diabetic kidney. In human podocytes, NOX4 was predominantly localized to mitochondria and Sal B treatment blocked HG-induced mitochondrial NOX4 derived superoxide generation and thereby ameliorating podocyte apoptosis, which can be abrogated by AMPK knockdown. Therefore, our results suggest that Sal B possesses the reno-protective capabilities in part through AMPK-mediated control of NOX4 expression. Taken together, our results identify that Salvianolate could prevent glucose-induced oxidative podocyte injury through modulation of NOX4 activity in DN and have a novel therapeutic potential for DN.

[Analysis of volatile organic compounds (VOCs) fingerprint of raw and honey-fried licorice based on headspace-gas-chromatography ion-mobility spectrometry (HS-GC-IMS)].

Licorice is one of the most commonly used traditional Chinese medicine. In clinic, raw licorice and honey-fried licorice are used in medicines, with the main effects in clearing away heat and detoxifying, moistening lungs and removing phlegm. Honey-fried licorice has effects in nourishing the spleen and stomach and replenishing Qi and pulse. Because traditional Chinese medicine exerts the effects through multiple components and multiple targets, the index components used in the quality evaluation of licorice are often difficult to reflect their real quality. In addition, most of studies for the quality standards have shown that honey-fried licorice are the same as licorice, with a lack of quality evaluation standards that can demonstrate their processing characteristics. The quality of medicine is directly related to its clinical efficacy, so it is necessary to establish a more effective quality control method. Licorice has a beany smell, which is one of the main quality identification characteristics. In this study, by taking advantage of the odor characteristics, a headspace-gas chromatography-ion migration mass spectrometry technology was used to establish a quality evaluation method. A total of 76 volatile components were identified. Through the dynamic principal component analysis, 7 kinds of volatile substances in raw licorice and 13 kinds of volatile substances in honey-fried licorice were statistically obtained, and could be taken as index components for the quality evaluation of raw and honey-fried licorice, respectively. This study could help realize the combination and unification of modern detection and traditional quality evaluation methods, and make a more realistic evaluation for the quality of licorice.

Efficacy and safety of Bujing Yishi tablet for glaucoma with controlled IOP: study protocol for a multi-centre randomized controlled trial.

BACKGROUND: As an irreversible, intractable disease with vision loss, glaucoma leads to permanent and progressive damage of visual function. Lowering high intraocular pressure (HIOP) is the first choice for treating glaucoma; however, the control of HIOP is not enough to prevent progressive vison loss. Currently, the therapies to treat glaucoma with controlled IOP (GPCI) are unsatisfactory. Chinese medicine is effective for improving visual function in patients with GPCI. Bujing Yishi tablets (BJYSP) have been the standard preparation for treating GPCI in our hospital for decades. However, no rigorous randomized controlled clinical studies have investigated its effects and safety. METHODS: This study will be a 6-month, multicenter, stratified trial following a prospective, randomized, open-label, blinded endpoint (PROBE) protocol. A total of 216 eligible GPCI patients aged 18-75 years will be stratified according to the early, moderate, and advanced stages of glaucoma. After stratifying, the participants will be randomly assigned to the BJYSP group or control group at a ratio of 1:1. Following randomization, participants in the BJYSP group and control group will receive BJYSP and mecobalamin tablets, respectively, for the same 6-month period. The primary outcomes will include the best-corrected visual acuity (BCVA), visual field assessment, visual evoked potential (VEP) test, and Heidelberg retina tomography II (HRT II); the secondary outcomes will include intraocular pressure (IOP) and Traditional Chinese medicine (TCM) clinical symptom scales. The primary and secondary outcomes will be measured at baseline and 8, 16, and 24 weeks thereafter. Safety assessments will also be evaluated at baseline and 12 and 24 weeks thereafter. DISCUSSION: This study will be a standardized, scientific, clinical trial designed to evaluate the therapeutic effects and safety of BJYSP as a novel therapeutic strategy for improving visual function in patients with GPCI. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1800016431. Registered on 1 June 2018.

[Efficacy of Shensong Yangxin Capsules in treating bradycardia combined with premature beat: a systematic review and Meta-analysis of randomized clinical trials].

To analyze the efficacy and safety of Shensong Yangxin Capsules in treatment of bradycardia combined with premature beat. Databases, such as CNKI, VIP, WanFang, SinoMed, PubMed, Cochrane Library, ClinicalTrials were retrieved by computers for relevant randomized controlled trials of Shensong Yangxin Capsules in treatment of bradycardia combined with premature beat. Two researchers independently screened out the literatures, extracted data according to the inclusion criteria, and applied the Risk of Bias assessment tool in assessing the methodological quality. The Cochrane systematic evaluation software RevMan 5.3 was used for data analysis. Totally 9 randomized controlled trials including 706 subjects were included. The intervention measure was the single administration with Shensong Yangxin Capsules, and the control measure was the blank control. The results showed that Shensong Yangxin Capsules had an obvious effect on average heart rate(MD=6.59, 95%CI[3.87, 9.31], I~2=90%), premature beat efficacy(RR=1.72, 95%CI[1.53, 1.93], I~2=0%), heart rate efficacy(RR=1.74, 95%CI[1.40, 2.17], I~2=47%), and objective efficacy(RR=1.50, 95%CI[1.31, 1.70], I~2=31%). Eight studies reported safety events, with no significant adverse reaction. In conclusion, the single administration with Shensong Yangxin Capsules may have a certain effect in improving heart rate, controlling premature beats and alleviating clinical symptoms in patients with bradycardia combined with premature beat, with no obvious adverse reaction. Shensong Yangxin Capsules can be used in clinic. This potential conclusion needs to be confirmed in future trials using rigorous methodology.

[Discussion on design of clinical trial scheme for doctor-patient co-construction of traditional Chinese medicine and Western medicine under concept of narrative medicine].

With the continuous improvement of modern medical technology, medical practice has become more and more procedural. The medical process is often dominated by doctors, while the value orientation of patients is often ignored, lacking effective communication between doctors and patients. In response to this phenomenon, Charon R proposed the concept of narrative medicine, which has been recognized by all walks of life. In recent years, the value of medical humanism has attracted more attention, and the research on narrative medicine at home and abroad is increasing gradually. But at present, most of the research on narrative medicine is in terms of theory, lacking clinical research. How to make narrative medicine applied in the real world is the focus of current research. Following the concept of narrative medicine, and taking the study on doctor-patient parallel medical record to evaluate the real clinical efficacy of traditional Chinese medicine(TCM) and Western medicine(WM) in the treatment of digestive diseases as an example, this study is to explore the design contents and key points of the clinical trial scheme of doctor-patient co-construction of TCM and WM under narrative medicine, and discuss the activity form and clinical efficacy evaluation method under narrative medicine. Clinical trial design includes four aspects: medicine, ethics, statistics and trial management. This study explored the design of the doctor-patient co-construction clinical trial scheme under narrative medicine from both theoretical and practical aspects, providing reference for the design and research of future doctor-patient co-construction scheme, and expecting to establish a better efficacy evaluation method of TCM and WM.

[Study on internal and external quality control methods of Platycladi Cacumen Carbonisata based on QAMS and color recognition].

In order to effectively solve the over-processing problem of Platycladi Cacumen Carbonisata, which was commonly used as a hemostatic drug in clinical application, we used the quantitative analysis method of multi-components by single marker(QAMS) in this study, with quercetin as internal reference to simultaneously determine the content of six flavonoids which can be used to control the internal quality of Platycladi Cacumen Carbonisata. Based on the comparison of QAMS and external standard method(ESM) results, the limit standards of contents were established as follows: isoquercitroside ≥0.002 0%, quercitroside ≥0.050%, quercetin ≥0.030%, kaempferol and amentoflavone both ≥0.010%, hinokiflavone ≥0.050%. Based on the color detection of Platycladi Cacumen and Platycladi Cacumen Carbonisata with different processing degrees, the law of influence of different processing degrees on the color of Platycladi Cacumen Carbonisata was found. A new external quality standard of Platycladi Cacumen Carbonisata was established by fitting curve of color recognition for the external quality control, based on which the standard ranges of ΔL~*, Δb~* and ΔE were-50.00--44.00, 6.00-11.00 and 45.00-50.00 respectively. Effective combination of established internal and external quality control standards by this study can be used to evaluate the processing degree and quality of Platycladi Cacumen Carbonisata more comprehensively and objectively, which can guarantee its clinical efficacy. At the same time, this study also provides reference and basis for further improving the quality control standard of Platycladi Cacumen Carbonisata.