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Traditional Chinese medicine compounds for the treatment of functional dyspepsia: an updated meta-analysis of randomized, double-blind, placebo-controlled trials 中药复方治疗功能性消化不良:一项随机、双盲、安慰剂对照试验的最新meta分析
Q3 Medicine Pub Date : 2021-12-01 DOI: 10.1016/j.dcmed.2021.12.003
Luo Xiaoying , Yang Yang , Mao Xinyong , Song Gengqing , Liu Qian , Jiang Tianyuan , Wei Wei

Objective

To evaluate the efficacy and safety of traditional Chinese medicine (TCM) compounds for the treatment of functional dyspepsia (FD).

Methods

The PubMed, Embase, Cochrane Library, Web of Science, Chinese Biomedical Database (CBM), Wanfang Data, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (VIP) were searched to collect randomized, double-blind, and placebo-controlled trials of FD treated with TCM compounds. The search duration was from the establishment of the database to March 2, 2021. After two researchers independently screened the literature, extracted the data, and evaluated the bias risk included in the study, they used RevMan 5.4 software for meta-analysis.

Results

A total of 23 clinical trials were included, including 2 898 patients. Meta-analysis showed that the overall remission rate of FD treated with TCM compounds was significantly higher than that of placebo (73.8% vs. 46.2%) [RR = 1.50, 95% CI (1.29, 1.76), P < 0.000 01]. Among the single symptoms, TCM compounds were superior to the placebo in improving epigastric pain [MD =-0.99, 95% CI (-1.37,-0.61), P < 0.000 01], epigastric burning sensation [MD =-0.32, 95% CI (-0.59,-0.05), P = 0.02], postprandial fullness discomfort [MD = -1.59, 95% CI (-1.96, -1.21), P < 0.000 01], and early satiety symptoms [MD = -0.93, 95% CI (-1.32, -0.54), P < 0.000 01]. Compared with the placebo, TCM compounds treatment can obviously improve TCM syndrome in patients with FD [MD = -5.58, 95% CI (-7.55,-3.61), P < 0.000 01], gastric emptying rate [MD = 12. 22, 95% CI (8.90, 15.55), P < 0.00001], and helped to improve patients' quality of life [MD = 11.27, 95% CI (0.10, 22.43), P = 0.05]. No severe adverse events were reported between the two groups [RR = 1.34, 95% CI (0.91, 1.96), P = 0.14].

Conclusion

Our results showed that TCM compounds treatment could significantly alleviate FD symptoms, improve gastric emptying in FD patients, and help to improve their quality of life. No severe adverse reactions have been reported in clinical applications. Due to the limitation of the quantity and quality of the included studies, the above conclusions need to be verified by more high-quality studies.

目的评价中药复方治疗功能性消化不良(FD)的疗效和安全性。方法检索PubMed、Embase、Cochrane图书馆、Web of Science、中国生物医学数据库(CBM)、万方数据、中国知网(CNKI)和中国科技期刊数据库(VIP),收集中药复方治疗FD的随机、双盲和安慰剂对照试验。检索时间为数据库建立至2021年3月2日。两位研究者独立筛选文献、提取资料、评估纳入研究的偏倚风险后,使用RevMan 5.4软件进行meta分析。结果共纳入23项临床试验,纳入患者2 898例。meta分析显示,中药复方治疗FD的总缓解率显著高于安慰剂组(73.8% vs 46.2%) [RR = 1.50, 95% CI (1.29, 1.76), P <0.000 01]。在单一症状中,中药复方在改善胃脘痛方面优于安慰剂[MD =-0.99, 95% CI (-1.37,-0.61), P <0.000 01]、上胃烧灼感[MD =-0.32, 95% CI (-0.59,-0.05), P = 0.02]、餐后饱腹不适[MD = -1.59, 95% CI (-1.96, -1.21), P <0.000 01]和早期饱腹症状[MD = -0.93, 95% CI (-1.32, -0.54), P <0.000 01]。与安慰剂相比,中药复方治疗可明显改善FD患者中医证候[MD = -5.58, 95% CI (-7.55,-3.61), P <0.000 01],胃排空率[MD = 12]。22, 95% CI (8.90, 15.55), P <0.00001],有助于改善患者的生活质量[MD = 11.27, 95% CI (0.10, 22.43), P = 0.05]。两组间无严重不良事件发生[RR = 1.34, 95% CI (0.91, 1.96), P = 0.14]。结论中药复方治疗可明显缓解FD患者的症状,改善FD患者的胃排空,提高患者的生活质量。临床应用中未见严重不良反应的报道。由于纳入研究的数量和质量的限制,上述结论需要更多高质量的研究来验证。
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引用次数: 4
In silico prediction of phytoconstituents from Ehretia laevis targeting TNF-α in arthritis 青黄体植物成分靶向关节炎TNF-α的计算机预测
Q3 Medicine Pub Date : 2021-10-01 DOI: 10.1016/j.dcmed.2021.09.003
Subhash R. Yende , Sapan K. Shah , Sumit K. Arora , Keshav S. Moharir , Govind K. Lohiya

Objective

Rheumatoid arthritis (RA) is an autoimmune disease involving the synovial lining of the major joints. Current therapies have noteworthy side effects. Our study involved in silico evaluation of Ehretia laevis (E. laevis) phytoconstituents targeting tumor necrosis factor-α (TNF-α).

Methods

Molecular docking studies performed to investigate the binding pattern of the plant E. laevis phytoconstituents along with the crystal structure of TNF-α (PDB ID: 2AZ5) using AutoDock Vina followed by a study of interacting amino acid residues and their influence on the inhibitory potentials of the active constituents. Further the pharmacokinetic profile and toxicity screening carried out using SwissADME and pkCSM.

Results

The docked results suggest that lupeol (− 9.4 kcal/mol) and α-amyrin (− 9.4 kcal/mol) has best affinity towards TNF-α compared to standard drug thalidomide (− 7.4 kcal/mol). The active chemical constituents represents better interaction with the conserved catalytic residues, leading to the inhibition/blockade of the TNF-α-associated signaling pathway in RA. Furthermore, pharmacokinetics and toxicity parameters of these phytochemicals were within acceptable limits according to ADMET studies.

Conclusion

The binding potential of phytoconstituents targeting TNF-α showed promising results. Nonetheless, it encourages the traditional use of E. laevis and provides vital information on drug development and clinical treatment.

目的类风湿关节炎(RA)是一种累及主要关节滑膜的自身免疫性疾病。目前的治疗方法有明显的副作用。我们的研究涉及针对肿瘤坏死因子-α (TNF-α)的laevis (E. laevis)植物成分的硅片评价。方法采用AutoDock Vina软件进行分子对接研究,研究紫叶藤植物成分与肿瘤坏死因子α (PDB ID: 2AZ5)晶体结构的结合模式,并研究相互作用氨基酸残基及其对活性成分抑制电位的影响。进一步使用SwissADME和pkCSM进行药代动力学分析和毒性筛选。结果与标准药物沙利度胺(- 7.4 kcal/mol)相比,lupeol (- 9.4 kcal/mol)和α-amyrin (- 9.4 kcal/mol)对TNF-α的亲和力最好。活性化学成分与保守的催化残基表现出更好的相互作用,导致RA中TNF-α-相关信号通路的抑制/阻断。此外,根据ADMET的研究,这些植物化学物质的药代动力学和毒性参数在可接受的范围内。结论植物成分与TNF-α的结合潜力较好。尽管如此,它还是鼓励传统地使用紫肠杆菌,并提供有关药物开发和临床治疗的重要信息。
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引用次数: 8
Investigation of the active components and mechanism of Sanao Decoction in treating chronic cough by network pharmacology and molecular docking 网络药理学与分子对接研究三脑汤治疗慢性咳嗽的有效成分及作用机制
Q3 Medicine Pub Date : 2021-10-01 DOI: 10.1016/j.dcmed.2021.09.004
SHENG Mengke , LIU Xing , LIAO Yuyao , LI Zhixun , LYU Lijing , YANG Jiaqi , SHI Xinyuan

Objective

To investigate the active components and mechanism of Sanao Decoction (三拗汤, SAD) in treating chronic cough based on network pharmacology and molecular docking.

Methods

Active components and their targets were obtained from the Traditional Chinese Medicine Systems and Pharmacology Database and Analysis Platform (TCMSP), Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) database, and the literature. The component-target regulatory network and protein-protein interaction (PPI) network were constructed by Cytoscape 3.7.2, and a bioinformatics analysis was performed to identify the significant pathways and their relevant targets. Molecular docking of the core active components and relevant targets was performed.

Results

A total of 98 active components of SAD and the corresponding 113 drug targets were identified. The component-target regulatory network and PPI network were successfully established. Results of the bioinformatics analysis indicated that 2 281 Gene Ontology (GO) terms were enriched in chronic cough, including 2 062 terms were in biological processes, 77 in cellular components, and 142 in molecular functions, and top 20 significant pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Molecular docking study demonstrated that quercetin, luteolin, kaempferol, and naringenin were in good agreement with the corresponding targets.

Conclusion

The active compounds of SAD, such as quercetin, luteolin, kaempferol, and naringenin, may act on AKT1, MAPK1, RELA, EGFR, and Bcl-2 and regulate the PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, and fluid shear stress and atherosclerosis pathway to exert the effects of anti-inflammatory, anti-airway remodeling, anti-oxidant stress effects, and repair airway damage, thus treating chronic cough.

目的基于网络药理学和分子对接研究三脑汤治疗慢性咳嗽的有效成分及作用机制。方法从中药系统药理学数据库与分析平台(TCMSP)、中药分子机制生物信息学分析工具(BATMAN-TCM)数据库和文献中获得活性成分及其靶点。利用Cytoscape 3.7.2构建组分-靶点调控网络和蛋白-蛋白相互作用(protein-protein interaction, PPI)网络,并进行生物信息学分析,确定重要通路及其相关靶点。将核心活性成分与相关靶点进行分子对接。结果共鉴定出SAD的98个有效成分和113个药物靶点。成功建立了组分-目标调控网络和PPI网络。生物信息学分析结果显示,慢性咳嗽基因本体(GO)词条富集2 281个,其中生物过程词条富集2 062个,细胞成分词条富集77个,分子功能词条富集142个,京都基因与基因组百科全书(KEGG)分析富集前20个显著通路。分子对接研究表明槲皮素、木犀草素、山奈酚和柚皮素与相应的靶点吻合良好。结论SAD活性物质槲皮素、木草素、山奈普酚、柚皮素等可能通过作用于AKT1、MAPK1、RELA、EGFR、Bcl-2,调控PI3K-Akt信号通路、AGE-RAGE信号通路、液体剪切应力和动脉粥样硬化通路,发挥抗炎、抗气道重塑、抗氧化应激、修复气道损伤的作用,从而治疗慢性咳嗽。
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引用次数: 0
Mechanism of Pingyang Jiangya Formula in treating hypertension based on network pharmacology and in vivo study 平阳降压方治疗高血压的机制:基于网络药理学和体内研究
Q3 Medicine Pub Date : 2021-10-01 DOI: 10.1016/j.dcmed.2021.09.006
Liu Deguo , Li Zirong , Chen Qihua , Wang Yuhong , Xiao Changjiang

Objective

This study aimed to analyze the mechanism of action of the Pingyang Jiangya Formula (平阳降压方, PYJYF) in treating hypertension, based on network pharmacology, and to verify the subsequent predictions through animal experiments.

Methods

The active components and related target genes of PYJYF were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM), Encyclopedia of Traditional Chinese Medicine (ETCM), and DrugBank databases and available literature. The hypertension target genes were screened based on Therapeutic Target Database (TTD), GeneCards, Online Mendelian Inheritance in Man (OMIM), UniProt, and relevant literature. The component-disease-target network intersection target genes were inputted into the STRING database, and the key target genes were selected according to the degree algorithm. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the multitarget mechanism of action and molecular regulatory network of PYJYF in the treatment of hypertension. To verify this prediction, we used PYJYF to intervene in spontaneously hypertensive rats (SHRs) and Wistar–Kyoto rats (WKY) as normal control, and the noninvasive tail artery manometry method was used to measure systolic blood pressure (SBP) in the rat tail before PYJYF intervention. After drug intervention, the SBP of each group rats were measured and compared every week. Enzyme-linked immunosorbent assay (ELISA) was used to test plasma renin, angiotensin II (Ang II), and aldosterone (Ald) levels, and hematoxylin-eosin (HE) staining was used to observe pathological damage to the renal vessels in each group of rats. Western blot and reverse transcription real-time quantitative PCR (RT-PCR) were used to detect the protein and mRNA expression levels of PI3K, AKT1, BAX, and Bcl-2, respectively.

Results

A total of 4 123 hypertension targets were obtained from related databases. From the TCMSP and chemical databases, 78 active components of PYJYF and the corresponding 401 drug targets were retrieved. Data analysis revealed that 208 drug targets directly interacted with the hypertension targets in PYJYF. The 10 targets most closely related to hypertension target proteins in PYJYF were directly retrieved from relevant databases. GO analysis revealed that 10 direct target proteins were involved in all aspects of the antihypertensive effects of PYJYF, as well as molecular biological processes, such as the regulation of blood pressure, renin-angiotensin-aldosterone system (RAAS), angiotensin-mediated ligand reactions, and biological stimulation of cardiomyocyte apoptosis. KEGG pathway enrichment analysis revealed that PYJYF directly affected 20 signaling pathways associated with hypertension. In animal

目的基于网络药理学分析平阳降压方治疗高血压的作用机制,并通过动物实验验证后续预测。方法利用中药系统药理学数据库与分析平台(TCMSP)、中药分子机制生物信息学分析工具(BATMAN-TCM)、中国中医百科全书(ETCM)和DrugBank数据库及现有文献筛选PYJYF的有效成分及相关靶基因。基于治疗靶基因数据库(Therapeutic target Database, TTD)、GeneCards、在线孟德尔遗传(Online Mendelian Inheritance in Man, OMIM)、UniProt及相关文献筛选高血压靶基因。将组件-疾病-靶点网络相交的靶基因输入STRING数据库,并根据度算法选择关键靶基因。通过基因本体(GO)分析和京都基因基因组百科全书(KEGG)途径富集分析,探索PYJYF治疗高血压的多靶点作用机制和分子调控网络。为了验证这一预测,我们采用PYJYF干预自发性高血压大鼠(SHRs)和Wistar-Kyoto大鼠(WKY)作为正常对照,并采用无创尾动脉测压法测量PYJYF干预前大鼠尾部收缩压(SBP)。药物干预后,每周测量各组大鼠收缩压并进行比较。采用酶联免疫吸附法(ELISA)检测各组大鼠血浆肾素、血管紧张素II (Ang II)、醛固酮(Ald)水平,苏木精-伊红(HE)染色观察各组大鼠肾血管病理损伤情况。采用Western blot和RT-PCR分别检测PI3K、AKT1、BAX和Bcl-2蛋白和mRNA的表达水平。结果从相关数据库中共获得4 123个高血压指标。从TCMSP和化学数据库中检索到PYJYF的78个有效成分和401个相应的药物靶点。数据分析显示,PYJYF中有208个药物靶点与高血压靶点直接相互作用。直接从相关数据库中检索PYJYF中与高血压靶蛋白关系最密切的10个靶点。氧化石墨烯分析发现,10个直接靶蛋白参与PYJYF降压作用的各个方面,以及调节血压、肾素-血管紧张素-醛固酮系统(RAAS)、血管紧张素介导的配体反应、生物刺激心肌细胞凋亡等分子生物学过程。KEGG通路富集分析显示,PYJYF直接影响高血压相关的20条信号通路。在动物实验中,PYJYF可降低PI3K、Akt、Bax蛋白和mRNA水平,上调Bcl-2蛋白和mRNA水平,降低血浆肾素、Ang II和Ald水平,改善RAAS亢进,显著降低SHRs收缩压。结论pyjyf是一种多化合物、多靶点作用的治疗高血压的有效药物。其可能的分子机制包括通过调节PI3K/Akt信号通路抑制RAAS,增加Bcl-2/Bax蛋白比例,抑制细胞凋亡,从而介导高血压引起的肾脏及肾血管损伤的修复。这些发现值得进一步研究用于临床设置。
{"title":"Mechanism of Pingyang Jiangya Formula in treating hypertension based on network pharmacology and in vivo study","authors":"Liu Deguo ,&nbsp;Li Zirong ,&nbsp;Chen Qihua ,&nbsp;Wang Yuhong ,&nbsp;Xiao Changjiang","doi":"10.1016/j.dcmed.2021.09.006","DOIUrl":"10.1016/j.dcmed.2021.09.006","url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to analyze the mechanism of action of the Pingyang Jiangya Formula (平阳降压方, PYJYF) in treating hypertension, based on network pharmacology, and to verify the subsequent predictions through animal experiments.</p></div><div><h3>Methods</h3><p>The active components and related target genes of PYJYF were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM), Encyclopedia of Traditional Chinese Medicine (ETCM), and DrugBank databases and available literature. The hypertension target genes were screened based on Therapeutic Target Database (TTD), GeneCards, Online Mendelian Inheritance in Man (OMIM), UniProt, and relevant literature. The component-disease-target network intersection target genes were inputted into the STRING database, and the key target genes were selected according to the degree algorithm. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to explore the multitarget mechanism of action and molecular regulatory network of PYJYF in the treatment of hypertension. To verify this prediction, we used PYJYF to intervene in spontaneously hypertensive rats (SHRs) and Wistar–Kyoto rats (WKY) as normal control, and the noninvasive tail artery manometry method was used to measure systolic blood pressure (SBP) in the rat tail before PYJYF intervention. After drug intervention, the SBP of each group rats were measured and compared every week. Enzyme-linked immunosorbent assay (ELISA) was used to test plasma renin, angiotensin II (Ang II), and aldosterone (Ald) levels, and hematoxylin-eosin (HE) staining was used to observe pathological damage to the renal vessels in each group of rats. Western blot and reverse transcription real-time quantitative PCR (RT-PCR) were used to detect the protein and mRNA expression levels of PI3K, AKT1, BAX, and Bcl-2, respectively.</p></div><div><h3>Results</h3><p>A total of 4 123 hypertension targets were obtained from related databases. From the TCMSP and chemical databases, 78 active components of PYJYF and the corresponding 401 drug targets were retrieved. Data analysis revealed that 208 drug targets directly interacted with the hypertension targets in PYJYF. The 10 targets most closely related to hypertension target proteins in PYJYF were directly retrieved from relevant databases. GO analysis revealed that 10 direct target proteins were involved in all aspects of the antihypertensive effects of PYJYF, as well as molecular biological processes, such as the regulation of blood pressure, renin-angiotensin-aldosterone system (RAAS), angiotensin-mediated ligand reactions, and biological stimulation of cardiomyocyte apoptosis. KEGG pathway enrichment analysis revealed that PYJYF directly affected 20 signaling pathways associated with hypertension. In animal","PeriodicalId":33578,"journal":{"name":"Digital Chinese Medicine","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2589377721000343/pdfft?md5=bea7367fac2a14d4d42c86ee1d00a60d&pid=1-s2.0-S2589377721000343-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72791319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Medicinal properties and anti-inflammatory components of Phytolacca (Shanglu) 上陆陆的药用特性及抗炎成分
Q3 Medicine Pub Date : 2021-10-01 DOI: 10.1016/j.dcmed.2021.09.001
Christian Bailly

Phytolacca

(Shanglu) is a well-known traditional herbal medicine that has been used for thousands of years in China. Phytolacca is also used worldwide in different traditional phyto-medicines and homeopathic preparations. The present work reviewed advances in the traditional uses, plant origin, chemical constituents, pharmacology, and medicinal properties of Phytolacca. Phytolacca is usually made from the roots of Phytolacca acinosa and P. esculenta, but the invasive plant P. americana (American pokeweed) is also widely used. Different types of medicinal products made with Phytolacca are available, as well as various types of Phytolacca extracts, showing a range of pharmacological activities including antioxidant, anti-inflammatory, anti-parasitic, antifungal, anticancer, and insecticidal effects. The marked anti-inflammatory activity of Phytolacca extracts supports its use in treating diseases such as arthritis, nephritis, and rheumatism, as well as in combatting cancer. Several bioactive natural products have been identified from Phytolacca, including glycosylated saponins such as esculentosides and phytolaccosides, as well as a few flavones (cochliophilin A) and phytosterols (α-spinasterol), which contribute to Phytolacca’s anti-inflammatory and/or anticancer effects. A quality evaluation of Phytolacca-based extracts and products is highly recommended; nevertheless, the use of Phytolacca can be encouraged to help regulate cytokine production and combat inflammatory diseases.

上陆是一种著名的传统草药,在中国已经使用了数千年。在世界范围内,植甲也被用于不同的传统植物药物和顺势疗法制剂中。本文综述了植物的传统用途、植物来源、化学成分、药理作用和药用特性等方面的研究进展。植陆通常由植陆(Phytolacca acinosa)和植陆(P. esculenta)的根制成,但入侵植物美洲商陆(P. americana)也被广泛使用。用植六甲制成的不同类型的医药产品,以及各种类型的植六甲提取物,显示出一系列的药理活性,包括抗氧化、抗炎、抗寄生虫、抗真菌、抗癌和杀虫作用。植物提取物显著的抗炎活性支持其用于治疗疾病,如关节炎、肾炎和风湿病,以及对抗癌症。从植六甲中已鉴定出几种具有生物活性的天然产物,包括糖基化皂苷,如蛇皮苷和植物甾醇苷,以及一些黄酮类(胆碱素a)和植物甾醇(α-spinasterol),它们有助于植六甲的抗炎和/或抗癌作用。强烈建议对植藻脂提取物和产品进行质量评价;然而,可以鼓励使用植甲来帮助调节细胞因子的产生和对抗炎症性疾病。
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引用次数: 10
Clinical efficacy and safety of TCM prescriptions combined with nucleoside (acid) analogues in treating chronic hepatitis B: a meta-analysis 中药方剂联合核苷(酸)类似物治疗慢性乙型肝炎的临床疗效及安全性荟萃分析
Q3 Medicine Pub Date : 2021-10-01 DOI: 10.1016/j.dcmed.2021.09.002
XIA Yu , LI Xin , MAN Rongyong , WANG Aibing , CAO Jianzhong

Objective

There are many clinical reports on traditional Chinese medicine (TCM) combined with nucleoside (acid) analogues (NAs) for the treatment of chronic hepatitis B (CHB), but its efficacy and safety are not completely clear. This meta-analysis aims to evaluate the clinical efficacy and safety thus providing evidence for clinical applications.

Methods

We searched Chinese databases the China National Knowledge Infrastructure (CNKI), Wanfang Data, and China Science and Technology Journal Database (VIP), as well as English databases PubMed and Cochrane Library, from time of establishment to April 14, 2021. Literature quality was evaluated according to the bias risk assessment criteria of Cochrane Collaboration network. RevMan 5.3 and Stata 12.0 software were used to perform this research.

Results

A total of 23 articles, 3 282 patients, and 25 TCM prescriptions were included in this study. NAs plus TCM remarkably improved the clinical total effective rate [Odds ratio (OR) = 3.92, P < 0.000 01], TCM syndrome score (Mean difference = − 3.73, P < 0.000 01), hepatitis B virus (HBV) DNA negative conversion rate (OR = 1.49, P = 0.000 1), hepatitis Be antigen (HBeAg) negative conversion rate (OR = 2.03, P < 0.000 01), alanine aminotransferase levels [Std mean difference (SMD) = − 0.95, P < 0.000 01], and aspartate aminotransferase levels (SMD = − 0.70, P = 0.000 4). Adverse reaction rates did not increase in the combined treatment group (OR = 0.97, P = 0.84). A comprehensive analysis of the 25 TCM prescriptions suggested that the combination of spleen-strengthening prescriptions with NAs showed better effects than other prescriptions.

Conclusion

TCM in combination with NAs, demonstrated better clinical efficacy against CHB than NAs alone. In addition, the combination of spleen-strengthening prescriptions and NAs was identified as the best therapeutic strategy. However, more randomized controlled trials of high quality are needed to provide more reliable clinical basis for the application of TCM.

目的中药联合核苷(酸)类似物治疗慢性乙型肝炎(CHB)的临床报道较多,但其疗效和安全性尚不完全清楚。本荟萃分析旨在评价其临床疗效和安全性,为临床应用提供依据。方法检索中国知网(CNKI)、万方数据、中国科技期刊库(VIP)等中文数据库,以及PubMed、Cochrane Library等英文数据库,检索时间为研究成立至2021年4月14日。根据Cochrane协作网的偏倚风险评估标准评价文献质量。本研究采用RevMan 5.3和Stata 12.0软件进行。结果共纳入文献23篇,患者3 282例,中药处方25个。NAs联合中药显著提高临床总有效率[优势比(OR) = 3.92, P <0.000 01],中医证候评分(平均差异= - 3.73,P <乙型肝炎病毒(HBV) DNA阴性转换率(OR = 1.49, P = 0.000 1)、乙型肝炎抗原(HBeAg)阴性转换率(OR = 2.03, P <0.000 01),丙氨酸转氨酶水平[Std平均差(SMD) = - 0.95, P <[0.000 01]、天冬氨酸转氨酶水平(SMD = - 0.70, P = 0.000 4)。联合治疗组不良反应发生率未增加(OR = 0.97, P = 0.84)。综合分析25个中药方剂,健脾方与NAs合用疗效优于其他方剂。结论中药联合NAs治疗慢性乙型肝炎的临床疗效优于单用NAs。此外,健脾方联合NAs是最佳治疗策略。然而,需要更多高质量的随机对照试验,为中医药的应用提供更可靠的临床依据。
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引用次数: 1
MF2ResU-Net: A Multi-Feature Fusion Deep Learning Architecture for Retinal Blood Vessel Segmentation MF2ResU-Net:一种用于视网膜血管分割的多特征融合深度学习架构
Q3 Medicine Pub Date : 2021-06-28 DOI: 10.21203/rs.3.rs-627790/v1
Zhenchao Cui, Shujie Song, Liping Chen, Xiangyang Chen, Jing Qi
Segmentation of blood vessels becomes an essential step in computer aided diagnosis system for the diseases in several departments of ophthalmology, neurosurgery, oncology, cardiology, and laryngology. Aiming at the problem of insufficient segmentation of small blood vessels by existing methods, a novel method based on multi-module fusion residual neural network model (MF2ResU-Net) was proposed. In the proposed networks, to obtain refined features of vessels, three cascade connected U-Net networks were employed as main networks. To deal with the problem of over-fitting, residual paths were used in main networks. In the blocks of U-Net in MF2ResU-Net, in order to remove the semantic difference in low-level and high-level, shortcut connections were used to combine the encoder layers and decoder layers in the blocks. Furthermore, atrous spatial pyramid pooling was embedded between the encoder and decoder to achieve multi-scale feature of blood vessels. During the training of the networks, to deal with the imbalance between background and foreground, a novel joint loss function was proposed based on the dice and cost- sensitive, which could greatly reduce the impact of unbalance in classes of samples. In experiment section, two retinal datasets, DRIVE and CHASE DB1, were used to test our method, and experiments showed that MF2ResU-Net was superior to existing methods on the criteria of sensitivity (Sen), specificity (Spe), accuracy (Acc), and area under curve (AUC), the values of which are 0.8013 and 0.8102, 0.9842 and 0.9809, 0.9700 and 0.9776, and 0.9797 and 0.9837 respectively for DRIVE and CHASE DB1. The results of experiments demonstrated the effectiveness and robustness of the model in the segmentation of complex curvature and small blood vessels.
血管分割已成为眼科、神经外科、肿瘤科、心脏科、喉科等科室疾病计算机辅助诊断系统的重要环节。针对现有方法对小血管分割不足的问题,提出了一种基于多模块融合残差神经网络模型(MF2ResU-Net)的新方法。在该网络中,为了获得更精细的船舶特征,采用3个级联U-Net网络作为主网络。为了解决过拟合问题,在主网络中采用残差路径。在MF2ResU-Net的U-Net块中,为了消除低级和高级的语义差异,使用快捷连接将块中的编码器层和解码器层组合在一起。在编码器和解码器之间嵌入空间金字塔池,实现血管的多尺度特征。在网络的训练过程中,为了处理背景和前景之间的不平衡,提出了一种基于骰子和代价敏感的联合损失函数,可以大大减少样本类别不平衡的影响。实验部分采用DRIVE和CHASE DB1两个视网膜数据集对方法进行验证,实验结果表明,MF2ResU-Net在灵敏度(Sen)、特异度(Spe)、准确度(Acc)和曲线下面积(AUC)等指标上均优于现有方法,DRIVE和CHASE DB1分别为0.8013和0.8102、0.9842和0.9809、0.9700和0.9776、0.9797和0.9837。实验结果证明了该模型在复杂曲率和小血管分割中的有效性和鲁棒性。
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引用次数: 0
Comparison of mechanisms and efficacies of five formulas for improving blood circulation and removing blood stasis 五种活血化瘀方的作用机理及疗效比较
Q3 Medicine Pub Date : 2021-06-01 DOI: 10.1016/j.dcmed.2021.06.007
L.I. Jinxia , Z.H.O.U. Xiaoqing , Z.H.E.N.G. Caixing , L.A.I. Lina , L.I. Ling

Objective

This study aimed to compare the mechanisms and efficacies of five formulas that improve blood circulation and remove blood stasis.

Methods

(1) A network pharmacology method was used to determine the targets of five formulas that promote circulation and remove blood stasis. Compounds of the five formulas, namely Danshen Yin (丹参饮, DSY), Huoluo Xiaoling Dan (活络效灵丹, HLXLD), Shixiao San (失笑散, SXS), Taohong Siwu Tang (桃红四物汤, THSWT), and Xuefu Zhuyu Tang (血府逐瘀汤, XFZYT), were retrieved from the Traditonal Chinese Medicine System Pharmacology Database (TCMSP), the Shanghai Institute of Organic Chemistry of CAS, and the TCM Integrated Database. Drug target network was constructed by searching the Swiss Target Prediction database and the STITCH database. The target network of stasis was extracted from the PharmGKB database, the Online Mendelian Inheritance in Man (OMIM) database, the Genetic Association Database (GAD), and the Therapeutic Target Database (TTD). Candidate targets were determined using protein–protein interaction (PPI) network extension and topology selection. Thereafter, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was used to determine the differentiation of the mechanism of the five formulas. (2) Animal experiments were conducted to explore the efficacies of the five formulas in treating blood stasis. Seventy New Zealand rabbits were exposed to high-fat feeding + epinephrine injection to construct a blood stasis syndrome model. The rabbits were evenly divided into control, model, DSY, HLXLD, SXS, THSWT, and XFZYT groups. The latter five groups were orally administered the corresponding formulas [DSY: 3.92 g/(kg·d), XFZYT: 7.10 g/(kg·d), SXS: 1.12 g/(kg·d), HLXLD: 5.60 g/(kg·d), THSWT: 4.48 g/(kg·d)]. Serum lipid and blood rheology were analyzed, and pathology slices were observed.

Results

(1) A total of 269, 358, 288, 370, and 376 candidate targets of DSY, HLXLD, SXS, THSWT, and XFZYT were obtained among which were 232 shared candidate targets. Fluid shear stress and atherosclerosis were the biological processes common to the five formulas. HLXLD, SXS, DSY, and THSWT regulated lipolysis in adipocytes, and XFZYT, HLXLD, SXS, and THSWT regulated the AGE-RAGE signaling pathway and complement and coagulation cascades. HLXLD, SXS, and XFZYT regulated the HIF-1 signaling pathway, DSY regulated the cGMP-PKG signaling pathway, HLXLD reduced platelet activation, SXS regulated the calcium signaling pathway, and XFZYT regulated the PPAR signaling pathway. (2) In the animal experiments, the values of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), TC/HDL, and TG/HDL in each group decreased, among which the ones seen in XFZYT, HLXLD, and SXS groups were statistically significant (P < 0.05). XFZYT presented the best effect, followed by HLXLD and SXS. XFZYT and HLXL

目的比较5种活血化瘀方的作用机理及疗效。方法(1)采用网络药理学方法确定5种活血化瘀方的作用靶点。化合物5的公式,即丹参阴(丹参饮,DSY), Huoluo小玲丹(活络效灵丹,HLXLD), Shixiao圣(失笑散,SXS的),Taohong四物汤(桃红四物汤,THSWT),和Xuefu Zhuyu唐(血府逐瘀汤,XFZYT),从传统中药系统药理学数据库检索(TCMSP),中科院上海有机化学研究所和中医综合数据库。通过检索Swiss target Prediction数据库和STITCH数据库构建药物靶点网络。从PharmGKB数据库、Online Mendelian Inheritance in Man (OMIM)数据库、Genetic Association database (GAD)和Therapeutic target database (TTD)中提取瘀血靶点网络。利用蛋白相互作用(PPI)网络扩展和拓扑选择确定候选靶点。随后,利用京都基因与基因组百科全书(KEGG)富集分析确定五方的辨析机制。(2)通过动物实验,探讨五方方治疗血瘀的疗效。采用高脂喂养+肾上腺素注射法建立新西兰兔70只血瘀证模型。将家兔平均分为对照组、模型组、DSY组、HLXLD组、SXS组、THSWT组和XFZYT组。后5组小鼠分别口服相应配方[DSY: 3.92 g/(kg·d), XFZYT: 7.10 g/(kg·d), SXS: 1.12 g/(kg·d), HLXLD: 5.60 g/(kg·d), THSWT: 4.48 g/(kg·d)]。结果(1)分别获得DSY、HLXLD、SXS、THSWT、XFZYT的候选靶点269、358、288、370、376个,其中共有候选靶点232个。流体剪切应力和动脉粥样硬化是五方所共有的生物学过程。HLXLD、SXS、DSY和THSWT调节脂肪细胞的脂肪分解,XFZYT、HLXLD、SXS和THSWT调节AGE-RAGE信号通路以及补体和凝血级联反应。HLXLD、SXS、XFZYT调节HIF-1信号通路,DSY调节cGMP-PKG信号通路,HLXLD降低血小板活化,SXS调节钙信号通路,XFZYT调节PPAR信号通路。(2)动物实验中,各组总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL)、高密度脂蛋白胆固醇(HDL)、TC/HDL、TG/HDL值均降低,其中XFZYT组、HLXLD组、SXS组差异有统计学意义(P <0.05)。XFZYT效果最好,其次是HLXLD和SXS。XFZYT和HLXLD降低载脂蛋白B100 (apoB100),增加载脂蛋白A1/apoB100 (P <0.05)。XFZYT降低红细胞压积(HCT)、血浆粘度、全血粘度(WBV);HLXLD和SXS影响HCT;DSY和THSWT调节WBV (P <0.05)。5种配方均降低了光密度值和斑块面积值,其中XFZYT和HLXLD具有统计学意义(P <0.05)。结论调节体液剪应力、减轻内皮细胞损伤可能是五方活血化瘀的共同作用机制。不同的配方也有其独特的作用靶点,可为临床药物选择提供指导。通过调节不同指标,五方均能调节血瘀模型家兔血脂和血液流变学,改善血瘀状态,降低主动脉斑块程度。XFZYT和HLXLD的疗效高于DSY、THSWT和SXS。
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引用次数: 3
Analysis of the hotspots and trends in traditional Chinese medicine immunomodulation research based on bibliometrics 基于文献计量学的中药免疫调节研究热点与趋势分析
Q3 Medicine Pub Date : 2021-06-01 DOI: 10.1016/j.dcmed.2021.06.002
Xiao Li , Ma Ning , Lai Han , Yan Junfeng , Peng Qinghua

Objective

To analyze the intellectual structure, hotspots and trends of traditional Chinese medicine (TCM) in immune regulation research.

Methods

The data were extracted from the Web of Science Core Collection (WoSCC) and the China National Knowledge Infrastructure (CNKI) and verified by two experienced TCM researchers. The time of literature retrieval is up to 2020. CiteSpace 5.7.R1 and Microsoft Excel 2016 were used for the statistical analysis and bibliometric diagrams, including the co-occurrence network of authors, institutions, countries, keywords, references, dual-map overlays of journals and citation bursts, etc.

Results

A total of 12 270 publications related to TCM in immune regulation were included. The annual number of publications has increased in this field. There was close cooperation of countries and institutions, while the distribution of scholars was scattered. China was the core of the cooperation network. The dual-map overlays analysis of journals showed that core and marginal fields had increased. The keywords and references analysis showed that network pharmacology, metabolism and cancer were the most high-frequency keywords with high-intensity bursts.

Conclusion

TCM in immune regulation has attracted wider attention, with multi-country, multi-field, multi-disciplinary and multi-level research developing toward informatization. Network pharmacology, metabolism and cancer may be the focus of future research in this field.

目的分析中药在免疫调节领域的知识结构、研究热点和发展趋势。方法数据从中国科学网(Web of Science Core Collection, WoSCC)和中国知网(China National Knowledge Infrastructure, CNKI)中提取,并由两名经验丰富的中医研究人员进行验证。文献检索时间到2020年。CiteSpace 5.7。采用R1和Microsoft Excel 2016进行统计分析和文献计量图,包括作者、机构、国家、关键词、参考文献、期刊双图叠加、引文爆发等共现网络。结果共纳入中医药免疫调节相关文献12 270篇。这一领域每年的出版物数量有所增加。国家和机构之间的合作密切,而学者的分布却是分散的。中国是合作网络的核心。双图叠加分析表明,核心油田和边缘油田有所增加。关键词和文献分析显示,网络药理学、代谢和癌症是高强度爆发频率最高的关键词。结论中医药在免疫调节中的应用已受到越来越广泛的关注,多国家、多领域、多学科、多层次的研究正朝着信息化方向发展。网络药理学、代谢和癌症可能是该领域未来研究的重点。
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引用次数: 5
Network pharmacology research and experimental verification of Huangqi (Astragalus Radix) and Jinyingzi (Rosae Laevigatae Fructus) in treating benign prostatic hyperplasia 黄芪、金莹子治疗良性前列腺增生的网络药理学研究及实验验证
Q3 Medicine Pub Date : 2021-06-01 DOI: 10.1016/j.dcmed.2021.06.006
Huan Zhou , Meng Yang , Yipin Yu , Hui Liu , Zhixing Qing , Qihua Chen

Objective

This study aimed to analyze the mechanism of action of Huangqi (Astragalus Radix, HQ) - Jinyingzi (Rosae Laevigatae Fructus, JYZ) in the treatment of benign prostatic hyperplasia (BPH) based on network pharmacology and to verify the prediction through animal experimentation.

Methods

Based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) databases, and literature, the active components and related target genes of HQ and JYZ were screened. The BPH target genes were screened based on the DisGeNET and GeneGards databases, and Excel was used to merge and remove duplicates. The Perl language was used to obtain drug-BPH target genes by intersecting shared target genes. A drug-component-target gene network diagram was constructed using Cytoscape software. The drug-BPH intersection target genes were inputted into the STRING database, and the key target genes were selected according to the degree algorithm. The output formed the basis for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to determine the potential mechanism of HQ and JYZ in BPH treatment. High, medium, and low doses of HQ and JYZ extract were used to intervene in BPH rats, and then the prostate volume, wet weight, and prostate index of the BPH rats were determined. Changes in prostate histopathology and microvessel density (MVD) were evaluated using immunohistochemistry, and the optimal HQ and JYZ extract dose was confirmed. Finally, the optimal dose was used to intervene in a BPH rat model, and AKT1 and VEGF expressions were examined by immunohistochemistry.

Results

Based on network pharmacology, 33 active components and 772 target genes were identified from HQ and JYZ, along with 817 BPH target genes and 112 drug-BPH common target genes. Among them were 10 key target genes, including AKT1, JUN, MAPK1, IL-6, TNF, ESR1, and VEGFA. KEGG enrichment analysis revealed 135 signaling pathways, including PI3K/AKT, IL-17, TNF, p53, MAPK, VEGF, JAK-STAT, and NF-κB pathways. The animal experiment showed that HQ and JYZ significantly improved prostate volume, wet weight, prostate index, and prostate histopathology of BPH rats, reducing MVD. In addition, HQ and JYZ inhibited the expression of AKT1 and VEGF in the prostate tissue of rats, promoted epithelial cell apoptosis, and inhibited angiogenesis, consistent with the prediction.

Conclusion

The combination of HQ and JYZ is effective for BPH therapy through multi-compound and multi-target collaboration. Its possible mechanism in treating BPH includes regulation of AKT1, VEGF protein, PI3K/Akt, and VEGF signaling pathways related to apoptosis, angiogenesis, and inflammation, with potential for clinical use and research.

目的基于网络药理学分析黄芪-金莹子治疗良性前列腺增生(BPH)的作用机制,并通过动物实验验证其预测。方法基于中药系统药理学数据库与分析平台(TCMSP)、中药分子机制生物信息学分析工具(BATMAN-TCM)数据库及文献资料,筛选黄芪芪和JYZ的有效成分及相关靶基因。根据DisGeNET和GeneGards数据库筛选BPH靶基因,并使用Excel进行合并和去除重复基因。利用Perl语言通过交叉共享靶基因获得药物bph靶基因。利用Cytoscape软件构建药物组分-靶基因网络图。将药物- bph交叉靶基因输入STRING数据库,根据度算法选择关键靶基因。该结果为基因本体(GO)和京都基因与基因组百科全书(KEGG)途径富集分析奠定了基础,以确定HQ和JYZ治疗BPH的潜在机制。采用高、中、低剂量黄芪和JYZ提取物对BPH大鼠进行干预,测定BPH大鼠前列腺体积、湿重和前列腺指数。采用免疫组化方法观察大鼠前列腺组织病理学和微血管密度的变化,确定黄芪和JYZ提取物的最佳剂量。最后,采用最佳剂量干预BPH大鼠模型,免疫组化检测AKT1和VEGF的表达。结果基于网络药理学方法,从黄芪和江蓠中共鉴定出有效成分33个,靶基因772个,BPH靶基因817个,药物-BPH共同靶基因112个。其中有10个关键靶基因,包括AKT1、JUN、MAPK1、IL-6、TNF、ESR1和VEGFA。KEGG富集分析发现135条信号通路,包括PI3K/AKT、IL-17、TNF、p53、MAPK、VEGF、JAK-STAT和NF-κB通路。动物实验结果显示,黄芪芪和JYZ均能显著改善BPH大鼠前列腺体积、湿重、前列腺指数和前列腺组织病理学,降低MVD。此外,黄芪和JYZ抑制大鼠前列腺组织中AKT1和VEGF的表达,促进上皮细胞凋亡,抑制血管生成,与预测一致。结论黄芪与JYZ联合治疗BPH是一种多化合物、多靶点协同治疗的有效方法。其治疗BPH的可能机制包括调控AKT1、VEGF蛋白、PI3K/Akt以及与细胞凋亡、血管生成和炎症相关的VEGF信号通路,具有临床应用和研究潜力。
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Digital Chinese Medicine
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