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BACKGROUND: Guipi decoction (GPD) not only improves gastrointestinal (GI) function, but also depressive mood. The bioinformatics study aimed to reveal potential crosstalk genes and related pathways between depression and GI disorders. A network pharmacology approach was used to explore the molecular mechanisms and potential targets of GPD for the simultaneous treatment of depression comorbid GI disorders. METHODS: Differentially expressed genes (DEGs) of major depressive disorder (MDD) were identified based on GSE98793 and GSE19738, and GI disorders-related genes were screened from the GeneCards database. Overlapping genes between MDD and GI disorders were obtained to identify potential crosstalk genes. Protein-protein interaction (PPI) network was constructed to screen for hub genes, signature genes were identified by LASSO regression analysis, and single sample gene set enrichment analysis (ssGSEA) was performed to analyze immune cell infiltration. In addition, based on the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, we screened the active ingredients and targets of GPD and identified the intersection targets of GPD with MDD and GI disorder-related genes, respectively. A "component-target" network was constructed using Cytoscape, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. RESULTS: The MDD-corrected dataset contained 2619 DEGs, and a total of 109 crosstalk genes were obtained. 14 hub genes were screened, namely SOX2, CRP, ACE, LEP, SHH, CDH2, CD34, TNF, EGF, BDNF, FN1, IL10, PPARG, and KIT. These genes were identified by LASSO regression analysis for 3 signature genes, including TNF, EGF, and IL10. Gamma.delta.T.cell was significantly positively correlated with all three signature genes, while Central.memory.CD4.T.cell and Central.memory.CD8.T.cell were significantly negatively correlated with EGF and TNF. GPD contained 134 active ingredients and 248 targets, with 41 and 87 relevant targets for the treatment of depression and GI disorders, respectively. EGF, PPARG, IL10 and CRP overlap with the hub genes of the disease. CONCLUSION: We found that GPD may regulate inflammatory and oxidative stress responses through EGF, PPARG, IL10 and CRP targets, and then be involved in the treatment of both depression and GI disorders.
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Transtorno Depressivo Maior , Medicamentos de Ervas Chinesas , Gastroenteropatias , Humanos , Farmacologia em Rede , Depressão/tratamento farmacológico , Depressão/genética , Fator de Crescimento Epidérmico , Interleucina-10 , PPAR gama , Comorbidade , Biologia ComputacionalRESUMO
Ischemic stroke (IS) remains one of the leading causes of death and disability in humans. Unfortunately, none of the treatments effectively provide functional benefits to patients with IS, although many do so by targeting different aspects of the ischemic cascade response. The advantages of traditional Chinese medicine (TCM) in preventing and treating IS are obvious in terms of early treatment and global coordination. The efficacy of TCM and its bioactive constituents has been scientifically proven over the past decades. Based on clinical trials, this article provides a review of commonly used TCM patent medicines and herbal decoctions indicated for IS. In addition, this paper also reviews the mechanisms of bioactive constituents in TCM for the treatment of IS in recent years, both domestically and internationally. A comprehensive review of preclinical and clinical studies will hopefully provide new ideas to address the threat of IS.
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Medicamentos de Ervas Chinesas , AVC Isquêmico , Humanos , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , AVC Isquêmico/tratamento farmacológicoRESUMO
To systematically evaluate the efficacy and safety of Tianma Gouteng Granules combined with conventional anti-hypertensive drugs in the treatment of essential hypertension. The clinical randomized controlled trials(RCTs) on the treatment of essential hypertension with Tianma Gouteng Granules combined with conventional anti-hypertensive drugs were searched in PubMed, EMbase, Cochrane Library, VIP, CNKI, Wanfang, SinoMed since the establishment of the databases to April 2020 based on inclusion and exclusion criteria, and Meta-analysis was conducted by using RevMan 5.3 software. A total of 15 RCTs were included, involving a total of 1 508 patients. Meta-analysis results showed that Tianma Gouteng Granules combined with conventional Western medicine were supe-rior to the control group in reducing systolic blood pressure(MD=-10.24, 95%CI[-13.54,-6.95], P<0.000 01), diastolic blood pressure(MD=-5.33, 95%CI[-7.21,-3.45], P<0.000 01), improving the clinical efficacy of patients(RR=1.22, 95%CI[1.15, 1.28], P<0.000 01) and curative effect of traditional Chinese medicine syndrome(RR=1.26, 95%CI[1.02, 1.57], P=0.04), increasing nitric oxide content(MD=9.59, 95%CI[7.23, 11.96], P<0.000 01), reducing endothelin-1(MD=-10.74, 95%CI[-15.74,-5.75], P<0.000 1), tumor necrosis factor(MD=-0.28, 95%CI[-0.36,-0.19], P<0.000 01), and interleukin-6(MD=-39.71, 95%CI[-43.40,-36.03], P<0.000 01). There was no statistically significant difference between the test group and the control group in the incidence of adverse reactions. No liver and kidney dysfunction occurred. The results of the subgroup analysis showed that the effect of Tianma Gouteng Granules combined with ARB drugs was more obvious in reducing the systolic and diastolic pressure. Trial sequential analysis showed that the studies accumulatively included for clinical efficacy crossed the traditional threshold and the TSA threshold, further affirming its clinical efficacy. The clinical application of Tianma Gouteng Granules combined with conventional Western medicine in the treatment of primary hypertension and accompanying symptoms has clear efficacy and certain safety, so it is recommended for clinical application.
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Anti-Hipertensivos , Medicamentos de Ervas Chinesas , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Anti-Hipertensivos/uso terapêutico , Hipertensão Essencial/tratamento farmacológico , HumanosRESUMO
To systematically evaluate the efficacy and safety of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and its accompanying symptoms. PubMed, EMbase, Cochrane Library, VIP, CNKI, Wanfang, and China biomedical database(CBD) were searched to screen out from the establishment of the database to April 2020 about the clinical randomized controlled trials of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and accompanying symptoms. The articles were selected according to the inclusion and exclusion criteria. RevMan 5.3 software was used for Meta-analysis. TSA 0.9.5.10 Beta software was used for sequential analysis, and GRADE 3.6 was used for evidence quality evaluation. A total of 4 532 patients were included in 34 randomized controlled trials. Meta-analysis results showed that: Yangxue Qingnao Granules combined with conventional anti-hypertensive agents reduced systolic blood pressure(MD=-10.56, 95%CI[-13.63,-7.50], P<0.000 01) and diastolic blood pressure(MD=-8.21, 95%CI[-10.84,-5.59], P<0.000 01), improved total effective rate(RR=1.21, 95%CI[1.14, 1.29], P<0.000 01), improved patients dizziness(RR=1.29, 95%CI[1.21, 1.37], P<0.000 01), insomnia(RR=1.66, 95%CI[1.44, 1.91], P<0.000 01), headache(RR=1.32, 95%CI[1.21, 1.43], P<0.000 01), chest distress(RR=1.26, 95%CI[1.12, 1.42], P=0.000 1), memory loss(RR=1.24, 95%CI[1.10, 1.40], P=0.000 4), palpitation(RR=1.28, 95%CI[1.17, 1.41], P<0.000 01), and improved traditional Chinese medicine symptom scores(MD=-4.24, 95%CI[-5.25,-3.23], P<0.000 01) and headache symptom improvement scores(MD=-2.02, 95%CI[-2.51,-1.53], P<0.000 01) as compared with Western medicine group alone. Subgroup analysis results showed that Yang-xue Qingnao Granules combined with ACEI drug had more obvious effects in lowering systolic blood pressure and diastolic blood pressure. There was no statistically significant difference in the incidence of adverse reactions, and no abnormal liver and kidney function was observed in each study. Trial sequential analysis showed that the total effective rate was cumulative across the traditional and TSA thresholds, further confirming its clinical efficacy. The evidence level was mostly low or extremely low in GRADE evaluation. The clinical application of Yangxue Qingnao Granules combined with conventional Western medicine in the treatment of essential hypertension and its accompanying symptoms is clear and safe, so it is recommended for clinical application.
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Medicamentos de Ervas Chinesas , Anti-Hipertensivos/efeitos adversos , China , Medicamentos de Ervas Chinesas/efeitos adversos , Hipertensão Essencial , Humanos , Medicina Tradicional Chinesa , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
To evaluate the efficacy and safety of Songling Xuemaikang Capsules combined with conventional Western medicine in the treatment of essential hypertension. PubMed, VIP, CNKI, Wanfang and other databases were retrieved from the establishment of the database to February 2020 for clinical randomized controlled trial(RCT) about Songling Xuemaikang Capsules combined with conventional Western medicine in the treatment of essential hypertension. The literatures were screened out according to the inclusion criteria, and RevMan 5.3 software was used for Meta-analysis. A total of 3 100 patients in 27 RCTs were enrolled. According to Meta-analysis, Songling Xuemaikang Capsules combined with conventional Western medicine could effectively reduce systolic blood pressure(MD=-7.88,95%CI[-9.68,-6.08],P<0.000 01) and diastolic blood pressure(MD=-7.85, 95%CI[-9.07,-6.62], P<0.000 01), triglyceride(MD=-0.46, 95%CI[-0.66,-0.26], P<0.000 01) and total cholesterol(MD=-0.92, 95%CI[-1.49,-0.35], P=0.001), but increase HDL cholesterol(MD=0.51, 95%CI[0.28, 0.73], P<0.000 01), with a better effect than the Western medicine group alone. The results of LDL-C analysis showed that there was no significant difference between the two groups(MD=-0.91, 95%CI[-1.82, 0.01], P=0.05). The subgroup analysis suggested that reduced systolic blood pressure may be related to the use of ARB. There was a close correlation between CCB drugs and the decrease of diastolic blood pressure. In addition, there was no significant difference in the compliance and the incidence of adverse reactions. Clinical application of Songling Xuemaikang Capsules combined with Western medicine in the treatment of patients with essential hypertension has clear efficacy and certain safety. More clinical randomized controlled trials are needed for verification in the future.
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Antagonistas de Receptores de Angiotensina , Medicamentos de Ervas Chinesas , Inibidores da Enzima Conversora de Angiotensina , Cápsulas , Hipertensão Essencial/tratamento farmacológico , HumanosRESUMO
Objectives: The purpose of the study was to comprehensively evaluate efficacy and safety of CDDP in patients with AMI undergoing PCI. Methods: A computerised search was conducted on the CNKI, WF, VIP, CBM, PubMed, Embase, Web of Science, and Cochrane Library databases for RCTs of CDDP adjuvant therapy for AMI up to May 2023. STATA 17.0 was used to perform meta-analyses, sensitivity analyses, subgroup analyses, meta-regression, and publication bias assessments. TSA 0.9.5.10 Beta was used for trial sequential analysis (TSA). Evidence confidence of meta results was evaluated by GRADE (Grading of Recommendations Assessment, Development and Evaluation) according to the instructions. Results: The results of the meta-analysis showed that CDDP combined with conventional western treatment (CWT) was superior to CWT in increasing LVEF and TCER and decreasing LVEDD, hs-CRP, IL-6 and TNF-α. The quality of evidence for TCER was moderate, LVEF, LVEDD, IL-6, and TNF-α were low. The TSA results showed that the total number of samples collected in this study met the requirements for meta-analysis and excluded the possibility of false positives, further confirming the efficacy of CDDP for the treatment of AMI undergoing PCI. Conclusion: Adjuvant treatment of AMI with CDDP has shown exciting and safe benefits in improving cardiac function and reducing inflammatory response in patients with AMI undergoing PCI, but the quality of some of the included studies was poor, and the results should be interpreted with caution until further confirmation by well-designed RCTs. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42023453293].
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Glutamate plays an important role in excitotoxicity and ferroptosis. Excitotoxicity occurs through over-stimulation of glutamate receptors, specifically NMDAR, while in the non-receptor-mediated pathway, high glutamate concentrations reduce cystine uptake by inhibiting the System Xc-, leading to intracellular glutathione depletion and resulting in ROS accumulation, which contributes to increased lipid peroxidation, mitochondrial damage, and ultimately ferroptosis. Oxidative stress appears to crosstalk between excitotoxicity and ferroptosis, and it is essential to maintain glutamate homeostasis and inhibit oxidative stress responses in vivo. As researchers work to develop natural compounds to further investigate the complex mechanisms and regulatory functions of ferroptosis and excitotoxicity, new avenues will be available for the effective treatment of ischaemic stroke. Therefore, this paper provides a review of the molecular mechanisms and treatment of glutamate-mediated excitotoxicity and ferroptosis.
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The aim of this study was to systematically review the efficacy and safety of Shuxuening injection combined with conventional Western medicine in the treatment of unstable angina. Randomized controlled trials of Shuxuening injection combined with conventional Western medicine in the treatment of unstable angina were searched by the computer system from PubMed, EMBASE, Cochrane Library, VIP, CNKI, Wanfang Database, and Chinese Biomedical Database since the establishment of the database until June 2020, according to the inclusion and exclusion criteria for the selection of literature, using Rev Man5.3 Meta-analysis Software. The 28 randomized controlled trials were included, with a total of 3,127 patients. Meta-analysis results showed that Shuxuening injection combined with conventional western medicine was effective in improving the clinical efficacy of angina pectoris (RR = 1.23, 95% CI [1.19, 1.27], P<0.00001), improvement of ECG (RR = 1.31, 95% CI [1.23, 1.40], P < 0.00001), reduction of angina pectoris attack frequency (MD = -1.28, 95% CI [-1.88, -0.67], P < 0.0001), duration of angina (MD = -3.36, 95% CI [-3.69, -3.03], P < 0.00001), nitroglycerin dosage (MD = -0.39, 95% CI [-0.65, -0.13], P = 0.003), C-reactive protein (MD = -2.72, 95% CI [-3.41, -2.03], P < 0.00001), BNP (MD = -23.33, 95% CI [-27.87, -18.79], P < 0.00001), lower triglycerides (MD = -0.72, 95% CI [-1.05, -0.38], P < 0.0001), total cholesterol (MD = -1.39, 95% CI [-1.84, -0.94], P < 0.00001), and LDL cholesterol (MD = -1.20, 95% CI [-2.12, -0.29], P = 0.01) which is better than that of control group. The effect on raising HDL cholesterol was comparable between the two groups (MD = 0.49, 95% CI [-0.06, 1.04], P = 0.08) and the incidence of adverse reactions to differences had no statistical significance (RR = 0.99, 95% CI [0.54, 1.81], P = 0.97). The Shuxuening injection combined with conventional Western medicine in the treatment of unstable angina has clear efficacy and a certain degree of safety, so it is recommended for clinical application.
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Background: Myocardial ischemia-reperfusion injury (MIRI) has become a thorny and unsolved clinical problem. The pathological mechanisms of MIRI are intricate and unclear, so it is of great significance to explore potential hub genes and search for some natural products that exhibit potential therapeutic efficacy on MIRI via targeting the hub genes. Methods: First, the differential expression genes (DEGs) from GSE58486, GSE108940, and GSE115568 were screened and integrated via a robust rank aggregation algorithm. Then, the hub genes were identified and verified by the functional experiment of the MIRI mice. Finally, natural products with protective effects against MIRI were retrieved, and molecular docking simulations between hub genes and natural products were performed. Results: 230 integrated DEGs and 9 hub genes were identified. After verification, Emr1, Tyrobp, Itgb2, Fcgr2b, Cybb, and Fcer1g might be the most significant genes during MIRI. A total of 75 natural products were discovered. Most of them (especially araloside C, glycyrrhizic acid, ophiopogonin D, polyphyllin I, and punicalagin) showed good ability to bind the hub genes. Conclusions: Emr1, Tyrobp, Itgb2, Fcgr2b, Cybb, and Fcer1g might be critical in the pathological process of MIRI, and the natural products (araloside C, glycyrrhizic acid, ophiopogonin D, polyphyllin I, and punicalagin) targeting these hub genes exhibited potential therapeutic efficacy on MIRI. Our findings provided new insights to explore the mechanism and treatments for MIRI and revealed new therapeutic targets for natural products with protective properties against MIRI.
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OBJECTIVE: To predict the main active ingredients, potential targets, and key pathways of Jiawei Chaiqin Wendan decoction treatment in vestibular migraine and explore possible mechanisms by network pharmacology and molecular docking technology. METHODS: The active ingredients and related targets of Jiawei Chaiqin Wendan decoction were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). The corresponding genes of the target were queried by UniProt database, and the "drug-compound-target-disease" network was constructed by Cytoscape 3.7.2 software. GO functional enrichment analysis and KEGG pathway enrichment analysis were carried out by R software and Bioconductor, and column chart and bubble chart were drawn by Prism software and OmicShare database for visualization. Finally, the mechanism and potential targets of Jiawei Chaiqin Wendan decoction in the treatment of vestibular migraine were predicted. RESULTS: The "drug-compound-target-disease" network contains 154 active ingredients and 85 intersection targets. The key targets include AKT1, IL6, MAPK3, VEGFA, EGFR, CASP3, EGF, MAPK1, PTGS2, and ESR1. A total of 1939 items were obtained by GO functional enrichment analysis (P < 0.05). KEGG pathway enrichment analysis screened 156 signal pathways (P < 0.05), involving PI3K-Akt signal pathway, AGE-RAGE signal pathway in diabetes complications, MAPK signal pathway, HIF-1 signal pathway, IL-17 signal pathway, etc. Molecular docking results showed that quercetin, luteolin, kaempferol, tanshinone IIa, wogonin, naringenin, nobiletin, dihydrotanshinlactone, beta-sitosterol, and salviolone have good affinity with core target proteins IL6, PTGS2, MAPK1, MAPK3, and CGRP1. CONCLUSION: The active ingredients in Jiawei Chaiqin Wendan decoction may regulate the levels of inflammatory factors and neurotransmitters by acting on multiple targets such as IL6, MAPK3, MAPK1, and PTGS2, so as to play a therapeutic role in vestibular migraine.
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To systematically evaluate the efficacy and safety of sofren injection combined with conventional Western medicine in the treatment of angina pectoris. Randomized controlled trials (RCTs) on the treatment of angina pectoris with sofren injection combined with Western medicine were collected by searching PubMed, the Cochrane Library, Embase, Web of Science, CNKI, Wanfang Database, Weipu Database, and China Biomedical Literature Service System (CBM) by computer with the retrieval time from establishment of database to August 2020. After literature screening according to the predetermined inclusion and exclusion criteria, data of eligible studies were extracted, and then, a meta-analysis was conducted with the RevMan 5.3 software. The results of meta-analysis showed that the combination of sofren injection and Western medicine improved the platelet aggregation rate of patients (MD = -5.53, 95% CI (-6.42, -4.64), P < 0.00001), PAI-1 (SMD = -2.29, 95% CI (-2.57, -2.01), P < 0.00001), TXB2 (MD = -11.91, 95% CI (-14.50, -9.32), P < 0.00001), duration of angina attack (MD = -2.01, 95% CI (-3.14, -0.87), P=0.0005), ECG symptoms (RR = 1.29, 95% CI (1.20, 1.37), P < 0.00001), whole blood viscosity (MD = -1.07, 95% CI (-1.66, -0.48), P=0.0004), plasma viscosity (MD = -0.27, 95% CI (-0.35, -0.20), P < 0.00001), fibrinogen (MD = -0.67, 95% CI (-0.84, -0.50), P < 0.00001), whole blood high shear viscosity (MD = -1.04, 95% CI (-1.30, -0.79), P < 0.00001), whole blood low shear viscosity (MD = -2.03, 95% CI (-2.53, -1.53), P < 0.00001), CRP (MD = -1.96, 95% CI (-3.01, -0.91), P=0.0003), IL-6 (MD = -2.79, 95% CI (-4.02, -1.55), P < 0.00001), and TNF-α (MD = -17.34, 95% CI (-25.86, -8.81), P < 0.00001) and better than the Western medicine group, and there was no statistical significance in the incidence of adverse reactions between the two groups (P=0.48). The clinical application of sofren injection combined with conventional Western medicine in the treatment of angina pectoris is clear and safe, so it is recommended for clinical application.