​Comprehensive mendelian randomization analysis of plasma proteomics to identify new therapeutic targets for the treatment of coronary heart disease and myocardial infarction.

BACKGROUND: Ischemic heart disease is one of the leading causes of mortality worldwide, and thus calls for development of more effective therapeutic strategies. This study aimed to identify potential therapeutic targets for coronary heart disease (CHD) and myocardial infarction (MI) by investigating the causal relationship between plasma proteins and these conditions. METHODS: A two-sample Mendelian randomization (MR) study was performed to evaluate more than 1600 plasma proteins for their causal associations with CHD and MI. The MR findings were further confirmed through Bayesian colocalization, Summary-data-based Mendelian Randomization (SMR), and Transcriptome-Wide Association Studies (TWAS) analyses. Further analyses, including enrichment analysis, single-cell analysis, MR analysis of cardiovascular risk factors, phenome-wide Mendelian Randomization (Phe-MR), and protein-protein interaction (PPI) network construction were conducted to verify the roles of selected causal proteins. RESULTS: Thirteen proteins were causally associated with CHD, seven of which were also causal for MI. Among them, FES and PCSK9 were causal proteins for both diseases as determined by several analytical methods. PCSK9 was a risk factor of CHD (OR = 1.25, 95% CI: 1.13-1.38, P = 7.47E-06) and MI (OR = 1.36, 95% CI: 1.21-1.54, P = 2.30E-07), whereas FES was protective against CHD (OR = 0.68, 95% CI: 0.59-0.79, P = 6.40E-07) and MI (OR = 0.65, 95% CI: 0.54-0.77, P = 5.38E-07). Further validation through enrichment and single-cell analysis confirmed the causal effects of these proteins. Moreover, MR analysis of cardiovascular risk factors, Phe-MR, and PPI network provided insights into the potential drug development based on the proteins. CONCLUSIONS: This study investigated the causal pathways associated with CHD and MI, highlighting the protective and risk roles of FES and PCSK9, respectively. FES. Specifically, the results showed that these proteins are promising therapeutic targets for future drug development.

Efficacy and safety of Qiangli Dingxuan tablet combined with amlodipine besylate for essential hypertension: a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial.

Background: Hypertension, a major cardiovascular risk factor, severely impacts patients' quality of life. Qiangli Dingxuan tablet (QDT) is a formally approved Chinese patent medicine, which has been widely used as an adjunctive treatment for hypertension. This study aimed to investigate the antihypertensive efficacy and safety of QDT combined with amlodipine besylate in patients with essential hypertension. Methods: In this randomized, double-blind, placebo-controlled, parallel-group, multicenter trial conducted in China, patients diagnosed with grade 1 to 2 essential hypertension were randomly assigned in a 1:1 to the treatment of QDT or placebo for 12 weeks, alongside their ongoing treatment with amlodipine besylate. The primary outcome was the change in office blood pressure (BP) from baseline to 12 weeks. In addition, safety analysis included the assessment of vital signs and laboratory values. Results: At baseline, 269 patients were randomly assigned to the QDT group (n = 133) or the placebo group (n = 136), and there were no significant differences in baseline characteristics between the two groups. The primary outcome based on the full analysis set from baseline to 12 weeks showed that the mean difference in the change of office systolic BP reduction between the two groups was 6.86 mmHg (95%CI, 4.84 to 8.88, p < 0.0001), for office diastolic BP, the mean difference in the change of office diastolic BP reduction between the two groups was 4.64 mmHg (95%CI, 3.10 to 6.18, p < 0.0001). In addition, traditional Chinese medicine symptom scores were significantly decreased in the QDT group compared with the placebo group. No severe adverse events attributable to QDT were reported. Conclusion: The combination of QDT and amlodipine besylate demonstrates superior efficacy compared to amlodipine besylate monotherapy in the management of essential hypertension. QDT shows potential as an adjunctive treatment for essential hypertension. However, further rigorous clinical trials are warranted to validate these findings. Clinical Trial Registration: [https://clinicaltrials.gov/study/NCT05521282?cond=NCT05521282&rank=1]; Identifier: [NCT05521282].

Combining bioinformatics and machine learning to identify common mechanisms and biomarkers of chronic obstructive pulmonary disease and atrial fibrillation.

Background: Patients with chronic obstructive pulmonary disease (COPD) often present with atrial fibrillation (AF), but the common pathophysiological mechanisms between the two are unclear. This study aimed to investigate the common biological mechanisms of COPD and AF and to search for important biomarkers through bioinformatic analysis of public RNA sequencing databases. Methods: Four datasets of COPD and AF were downloaded from the Gene Expression Omnibus (GEO) database. The overlapping genes common to both diseases were screened by WGCNA analysis, followed by protein-protein interaction network construction and functional enrichment analysis to elucidate the common mechanisms of COPD and AF. Machine learning algorithms were also used to identify key biomarkers. Co-expression analysis, "transcription factor (TF)-mRNA-microRNA (miRNA)" regulatory networks and drug prediction were performed for key biomarkers. Finally, immune cell infiltration analysis was performed to evaluate further the immune cell changes in the COPD dataset and the correlation between key biomarkers and immune cells. Results: A total of 133 overlapping genes for COPD and AF were obtained, and the enrichment was mainly focused on pathways associated with the inflammatory immune response. A key biomarker, cyclin dependent kinase 8 (CDK8), was identified through screening by machine learning algorithms and validated in the validation dataset. Twenty potential drugs capable of targeting CDK8 were obtained. Immune cell infiltration analysis revealed the presence of multiple immune cell dysregulation in COPD. Correlation analysis showed that CDK8 expression was significantly associated with CD8+ T cells, resting dendritic cell, macrophage M2, and monocytes. Conclusions: This study highlights the role of the inflammatory immune response in COPD combined with AF. The prominent link between CDK8 and the inflammatory immune response and its characteristic of not affecting the basal expression level of nuclear factor kappa B (NF-kB) make it a possible promising therapeutic target for COPD combined with AF.

Gastrodia elata Blume: A review of its mechanisms and functions on cardiovascular systems.

Gastrodia elata Blume (GEB), commonly called Tianma in Chinese, is a valuable and extensively used herbal Traditional Chinese Medicine with a wide range of clinical applications. It has been used to treat headaches, dizziness, stroke, epilepsy, amnesia, spasm, and other disorders since ancient times. Hundreds of compounds, including phenols, glycosides, polysaccharides, steroids, organic acids, and others, have been isolated and identified from this plant. Modern pharmacological studies have shown that its active ingredients possess many pharmacological effects, such as neuroprotective, analgesic, sedation and hypnosis, anti-anxiety, anti-depressant, anti-convulsant, anti-dizziness, blood pressure lowering, blood lipids lowering, liver protection, anti-tumor, and immunity enhancement effects. The present review discusses the pharmacological actions and mechanisms of various components of GEB in cardiovascular diseases to provide a reference for further study of GEB.

Effect of Xuefu Zhuyu Capsule on Myocardial Infarction: Network Pharmacology and Experimental Verification.

Background: Myocardial infarction (MI) is the most severe manifestation of cardiovascular disease. Xuefu Zhuyu Capsule (XFC), a proprietary Chinese medicine, is widely used in various cardiovascular diseases. At present, the molecular mechanism of XFC remains unclear. Objective: To explore the mechanism of anti-MI effects of XFC by combining network pharmacology and experiments. Methods: TCMSP, GeneCards, and DisGeNET databases were used to find the target of XFC. PPI analysis was performed by the STRING database. KEGG and GO analyses were performed by Metascape Database. Molecular docking was performed by Autodock Vina. HE staining, echocardiography, immunofluorescence, and TUNEL were performed to verify the prediction results. Results: Network pharmacology showed that quercetin, kaempferol, ß-sitosterol, luteolin, and baicalein were the main active ingredients of XFC. TNF, IL6, TP53, VEGFA, JUN, CASP3, and SIRT1 were the main targets of XFC. KEGG results showed that key genes were mainly enriched in lipid and atherosclerosis, PI3K-Akt signaling pathway, MAPK signaling pathway, and NF-κB signaling pathway. HE staining showed that XFC could improve the morphology of myocardial tissue. Echocardiography showed that XFC could improve cardiac function. TUNEL showed that XFC could reduce cardiomyocyte apoptosis. Immunofluorescence showed that XFC could reduce the expression of α-smooth muscle actin (α-SMA) and increase the expression of CD31. In addition, we found that XFC may exert its therapeutic effects through SIRT1. Conclusion: This study demonstrated that SIRT1 may be the target of XFC in the treatment of MI. The active ingredients of XFC and SIRT1 can be stably bound. XFC could inhibit apoptosis, promote angiogenesis, and improve myocardial fibrosis through SIRT1.

[Review and prospect of traditional Chinese medicine in treatment of hypertension].

Hypertension, a primary cause of cardiovascular and cerebrovascular events, has become a major global public health problem and caused a heavy burden of health economics on the society. In "the 20 Most Important and Most Preventable Health Problems" released by the Chinese Academy of Engineering, hypertension was ranked the second. Due to the disease complexity, many hypertension patients need to take antihypertensive drugs for life. Although significant progress has been achieved in blood pressure lowering by western medicines, the problems including adverse reactions, poor compliance due to long-term medication, and ineffective mitigation in clinical symptoms related to hypertension remain to be addressed. In the last decade, the research on traditional Chinese medicine(TCM) treatment of hypertension has received much attention and achieved remarkable progress. The TCM treatment of hypertension is the most active area of research with integrated Chinese and western medicine in China. In addition to lowering blood pressure smoothly, TCM can alleviate clinical symptoms, reverse risk factors, improve the quality of life, and protect target organs from the damage caused by hypertension. This article systematically reviews the research progress of TCM in treating hypertension in the last decade from the following four aspects: consensus on guideline, clinical trial, experimental study, and systematic review/Meta-analysis. It summarized the evidence of TCM in reducing blood pressure and clarified the mechanism of TCM in reducing blood pressure, aiming to provide a reference for the TCM diagnosis and treatment of hypertension and the development of new drugs.

Traditional Chinese medicine method of tonifying kidney for hypertension: Clinical evidence and molecular mechanisms.

Hypertension is the most common chronic disease. A large amount of evidence showed that traditional Chinese medicine (TCM) method of tonifying kidney (TK) combined with routine treatment is more effective and safer in the treatment of hypertension. This study integrated meta-analysis, data mining, and network pharmacology to explore the efficacy and potential mechanisms of TK in the treatment of hypertension. Meta-analysis was performed to explore the efficacy and safety of TK combined with routine treatment in the treatment of hypertension. Data mining was used to screen the core herbs of the TK. Network pharmacology was used to predict the antihypertensive mechanism of TK core herbs. A total of 18 studies with 2,024 patients were included in this study. Meta-analysis showed that TK combined with routine treatment was superior to routine treatment alone in lowering blood pressure (systolic and diastolic blood pressures), lowering blood lipids (total cholesterol, triglyceride, low-density lipoprotein cholesterol), improving vascular endothelial functions (nitric oxide, endothelin) and TCM symptoms (headache dizziness, soreness, and weakness of waist and knees). In addition, TK was safe and has no obvious adverse reactions. Data mining showed that the core herbs of TK were Eucommia ulmoides Oliv. (Duzhong), Vitex negundo L. (Huangjing), Taxillus chinensis (DC.) Danser (Sangjisheng), Ligustrum lucidum W.T.Aiton (Nuzhenzi), Astragalus mongholicus Bunge (Huangqi), Rehmannia glutinosa (Gaertn.) DC. (Shudihuang). Network pharmacology predicted that core herbs antihypertensive components were oleanolic acid, ursolic acid, and civetone, and the antihypertensive targets were NOS3, NOS2, MMP9, TNF, PTGS2, HMOX1. In addition, the antihypertensive targets were enriched in cGMP-PKG signaling pathway, calcium signaling pathway, aldosterone-regulated sodium reabsorption, HIF-1 signaling pathway. In conclusion, TK combined with routine treatment for hypertension is effective and safe. The mechanism of TK may be related to GMP-PKG signaling pathway, calcium signaling pathway, aldosterone-regulated sodium reabsorption. On the premise of syndrome differentiation and treatment, it is promising to treat hypertension with TK. Systematic review registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022358276].

Banxia baizhu tianma decoction, a Chinese herbal formula, for hypertension: Integrating meta-analysis and network pharmacology.

Hypertension is a major cardiovascular risk factor, which seriously affects the quality of life of patients. Banxia Baizhu Tianma Decoction (BXD) is a Chinese herbal formula that is widely used to treat hypertension in China. This study aimed to evaluate the efficacy and potential mechanism of BXD for hypertension by meta-analysis and network pharmacology. Meta-analysis was performed to explore the efficacy and safety of BXD combined with conventional treatment for hypertension. Network pharmacology was used to explore the molecular mechanism of BXD in antihypertension. A total of 23 studies involving 2,041 patients were included. Meta-analysis indicated that compared with conventional treatment, combined BXD treatment was beneficial to improve clinical efficacy rate, blood pressure, blood lipids, homocysteine, endothelial function, inflammation, and traditional Chinese medicine symptom score. In addition, meta-analysis indicated that BXD is safe and has no obvious adverse reactions. Network pharmacology showed that the antihypertensive targets of BXD may be AKT1, NOS3, ACE, and PPARG. The antihypertensive active ingredients of BXD may be naringenin, poricoic acid C, eburicoic acid, and licochalcone B. Due to the poor methodological quality of the Chinese studies and the small sample size of most, the analysis of this study may have been affected by bias. Therefore, the efficacy and safety of BXD for hypertension still need to be further verified by high-quality clinical studies. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022353666.

Mitochondrial Dynamics and Mitophagy in Cardiometabolic Disease.

Mitochondria play a key role in cellular metabolism. Mitochondrial dynamics (fusion and fission) and mitophagy, are critical to mitochondrial function. Fusion allows organelles to share metabolites, proteins, and mitochondrial DNA, promoting complementarity between damaged mitochondria. Fission increases the number of mitochondria to ensure that they are passed on to their offspring during mitosis. Mitophagy is a process of selective removal of excess or damaged mitochondria that helps improve energy metabolism. Cardiometabolic disease is characterized by mitochondrial dysfunction, high production of reactive oxygen species, increased inflammatory response, and low levels of ATP. Cardiometabolic disease is closely related to mitochondrial dynamics and mitophagy. This paper reviewed the mechanisms of mitochondrial dynamics and mitophagy (focus on MFN1, MFN2, OPA1, DRP1, and PINK1 proteins) and their roles in diabetic cardiomyopathy, myocardial infarction, cardiac hypertrophy, heart failure, atherosclerosis, and obesity.

Integrated Gut-Heart Axis and Network Pharmacology to Reveal the Mechanisms of the Huoxue Wentong Formula Against Myocardial Ischemia.

Background: Myocardial ischemia (MI) is a major public health problem with high mortality and morbidity worldwide. Huoxue Wentong formula (HX), a traditional Chinese medicine (TCM) formula, exhibits unambiguous effects on treating MI and preventing cardiovascular diseases. However, the molecular mechanism of the therapeutic effects of HX on MI remains largely unknown. Objective: This study combined microbiology, metabolomics, and network pharmacology to explore the relationship between the gut microbiota and its metabolites in MI rats and the efficacy of HX. Methods: First, the MI rat model was established by ligation of left anterior descending. Echocardiography, Masson's staining, and hematoxylin and eosin staining were used to evaluate the effect of HX on MI. Then, fecal metabolomics and 16S rRNA sequencing were used to obtain the microbial and metabolic characteristics of HX on MI. After that, network pharmacology was used to predict the target and action pathway of HX in treating MI. Finally, the relationship between fecal metabolites and target was explored through bioinformatics. Results: HX can improve the cardiac function and ameliorated myocardial fibrosis in MI rats. Moreover, HX can affect the gut microbiota community and metabolites of MI rats, especially Bacteroides, Deferribacteres, Ruminococcus_sp._zagget7, Acidobacteria, daidzein, L-lactic acid, and malate. Network pharmacology found that HX can function through tumor necrosis factor (TNF), tumor protein p53 (TP53), interleukin 6 (IL6), vascular endothelial growth factor A (VEGFA), fos proto-oncogene (FOS), bcl2-associated X (BAX), myeloperoxidase (MPO), PI3K-Akt signaling pathways, and HIF-1 signaling pathway. The mechanism study showed that the anti-MI effect of HX was related to valine, leucine, and isoleucine biosynthesis, fatty acid biosynthesis, and arachidonic acid metabolism. Conclusion: This study demonstrates that HX treated MI rats in a multitarget and multipathway manner. Its mechanism is related to the change of gut microbiota and the regulation of valine, leucine and isoleucine biosynthesis, fatty acid biosynthesis, and arachidonic acid metabolism.

Tetramethylpyrazine: A review on its mechanisms and functions.

Ligusticum chuanxiong Hort (known as Chuanxiong in China, CX) is one of the most widely used and long-standing medicinal herbs in China. Tetramethylpyrazine (TMP) is an alkaloid and one of the active components of CX. Over the past few decades, TMP has been proven to possess several pharmacological properties. It has been used to treat a variety of diseases with excellent therapeutic effects. Here, the pharmacological characteristics and molecular mechanism of TMP in recent years are reviewed, with an emphasis on the signal-regulation mechanism of TMP. This review shows that TMP has many physiological functions, including anti-oxidant, anti-inflammatory, and anti-apoptosis properties; autophagy regulation; vasodilation; angiogenesis regulation; mitochondrial damage suppression; endothelial protection; reduction of proliferation and migration of vascular smooth muscle cells; and neuroprotection. At present, TMP is used in treating cardiovascular, nervous, and digestive system conditions, cancer, and other conditions and has achieved good curative effects. The therapeutic mechanism of TMP involves multiple targets, multiple pathways, and bidirectional regulation. TMP is, thus, a promising drug with great research potential.

Effects of Bushen-Jiangya granules on blood pressure and pharmacogenomic evaluation in low-to-medium-risk hypertensive patients: study protocol for a randomized double-blind controlled trial.

INTRODUCTION: Hypertension is one of the most important risk factors for cardiovascular disease, and its control rates remain low worldwide. The most effective strategy is that patients with hypertension should be diagnosed and treated early. Preliminary studies showed that the Bushen Jiangya granule (BSJY) could suppress ventricular hypertrophy and inflammatory responses, lower blood pressure, and protect the target organs of hypertension. We designed a randomized, double-blind, placebo-controlled trial to evaluate the efficacy of BSJY in patients with low-to-medium risk hypertension. METHODS AND ANALYSIS: This trial is a one-center, randomized, double-blind, placebo-controlled study. A total of 260 participants will be randomized in a 1:1 ratio to an experimental group (BSJY plus amlodipine) and a control group (placebo plus amlodipine). The trial cycle will last 8 weeks. The primary outcome is the change in 24-h average systolic and diastolic blood pressure. The secondary outcomes include heart rate variability, pharmacogenomic evaluation, improvement in TCM syndrome, and serum pro-inflammatory/anti-inflammatory cytokines between the two groups. The safety of medication will also be evaluated. All the data will be recorded in electronic case report forms and analyzed by SPSS V.22.0. ETHICS AND DISSEMINATION: This study has been approved by the Research Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (No. 2019-186-KY-01). The participants are volunteers, understand the process of this trial, and sign an informed consent. The results of this study will be disseminated to the public through peer-reviewed journals and academic conferences. DISCUSSION: We hypothesize that patients with low-to-medium-risk hypertension will benefit from BSJY. If successful, this study will provide evidence-based recommendations for clinicians. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiMCTR1900002876. Registered in November 2019.

Efficacy and Safety of Xue-Fu-Zhu-Yu Decoction for Patients with Coronary Heart Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: To systematically evaluate the efficacy and safety of XFZYD for coronary heart disease (CHD). METHODS: A comprehensive literature search of randomized controlled trials using XFZYD for CHD was conducted in 10 electronic databases from their establishment to December 20, 2020. The researchers screened the relevant trials in NoteExpress, extracted the data in duplicate independently, assessed the risk of bias in the trials using the Cochrane collaboration tool, and then used Rev Man 5.3 for data analysis. RESULTS: 30 trials with 3126 participants were included for meta-analysis. The results showed that the clinical effects of XFZYD and its combination with chemical drugs (CD) were 1.13 (RR; 1.13; 95% CI, 1.03 to 1.24) and 1.26 (RR; 1.26; 95% CI, 1.20 to 1.32) times those of CD, respectively. And, it could also improve electrocardiogram effect, which was 1.63 (RR; 1.63; 95% CI, 1.04 to 2.53) times that of CD. XFZYD could not only decrease duration of angina pectoris and improve vascular endothelial function but also obviously reduce the TCM syndrome score. When used in combination with CD, it could also lower AF, correct the dyslipidemia, and reduce the blood viscosity. CONCLUSION: These results demonstrated that XFZYD had great advantages in treating CHD with no obvious adverse reactions. Therefore, it is believed that XFZYD is more suitable for CHD patients with clinical indicators of dyslipidemia, high blood viscosity, or vascular endothelial dysfunction. This study is the first systematic review and meta-analysis with some unique ways, including its comprehensiveness, large-scale search, the novelty of findings, and transparent approach.

[Mechanism of Xuefu Zhuyu Decoction in treatment of myocardial infarction based on network pharmacology and molecular docking].

To explore the action mechanism of Xuefu Zhuyu Decoction in treating myocardial infarction based on network pharmaco-logy and molecular docking. Active components and corresponding targets of Xuefu Zhuyu Decoction were obtained through Traditional Chinese Medicine Systems Pharmacology Database(TCMSP), and related targets of myocardial infarction were obtained through GeneCards, DisGeNET, and OMIM databases. Then the intersection targets were obtained by integrating the drug targets and disease targets. The "active component-target" network was constructed by Cytoscape software, and protein-protein interaction(PPI) network was drawn using STRING platform. Protein cluster analysis was carried out using MCODE. GO enrichment analysis and KEGG pathway analysis were carried out using DAVID database and ClueGO, and molecular docking was carried out using Autodock Vina and Pymol. Finally, 226 active components of Xuefu Zhuyu Decoction were obtained, 257 corresponding targets, 1 340 targets of myocardial infarction, and 109 drug and disease intersection targets were obtained. From GO enrichment analysis, 208 biological process terms, 38 molecular function terms, and 33 cellular component terms were obtained. From KEGG pathway analysis, NF-κB signaling pathway, IL-17 signaling pathway, HIF-1 signaling pathway, and other related pathways were obtained. The molecular docking results showed that the main active components(quercetin, kaempferol, ß-sitosterol, luteolin, stigmasterol and baicalein) of Xuefu Zhuyu Decoction in the treatment of myocardial infarction had good binding properties with the core proteins IL6, ALB, VEGFA, TNF, MAPK3 and CASP3. The results suggested that Xuefu Zhuyu Decoction may play a role in the treatment of myocardial infarction by reducing the inflammatory response, reducing oxidative stress, inhibiting cell apoptosis, and promoting angiogenesis.

Huoxue Wentong Formula ameliorates myocardial infarction in rats through inhibiting CaMKII oxidation and phosphorylation.

BACKGROUND: The Chinese medicine Huoxue Wentong Formula (HXWTF) was used to treat thoracic obstruction and angina pectoris in clinic, which has not been investigated in myocardial ischemia-induced apoptosis and angiogenic function. Here we aimed to investigate the roles of HXWTF in rats with myocardial ischemia-induced apoptosis and angiogenesis disorders, as well as to reveal the potential mechanisms. METHODS: Male SD rats were subjected to coronary artery ligation followed by HXWTF (420, 840 and 1680 mg/kg/day, p.o.) or isosorbide mononitrate (6.3 mg/kg/day, p.o.) treatment for 4 weeks. Electrocardiogram (ECG) and Echocardiography (ECHO) were used to measure cardiac function. Hematoxylin and eosin (H&E) staining and CD34/α-SMA immunohistochemical staining were performed to observe the ischemic heart sections pathological changes and angiogenesis. Then, the effects on cardiomyocyte apoptosis of H9c2 and tube formation of HCMECs were observed, as well as the changes in the levels of total calmodulin dependent protein kinase II (t-CaMKII), phosphorylated CaMKII (p-CaMKII), oxidized CaMKII (ox-CaMKII), CD34, and Bcl-2/Bax ratio were detected. RESULTS: Rats with coronary artery ligation exhibited abnormal cardiac function, enlarged myocardial space, disorderly arranged myocardial fibers, inflammatory cells infiltrated, and aggravated myocardial cell apoptosis, along with angiogenesis dysfunction. The expressions of CD34, p-CaMKII, and ox-CaMKII were elevated and Bcl-2/Bax ratio was diminished in ischemic hearts and H/SD-treated H9c2 or HCMECs, while HXWTF treatment completely rescued angiogenic dysfunction, inhibited cardiomyocyte apoptosis, and down-regulated cardiac CaMKII oxidation and phosphorylation activities. CONCLUSION: Our study demonstrates that HXWTF improves myocardial infarction possibly through inhibiting CaMKII oxidation and phosphorylation levels, facilitating angiogenic function and alleviating cardiomyocyte apoptosis. Thus, therapeutics targeting CaMKII activities may be a promising strategy for rescuing ischemic cardiomyopathy.

Xuefu Zhuyu Oral Liquid () Prevents Apoptosis of Ischemic Myocardium Cells in Rats by Regulating SIRT1 and Its Pathway-Related Genes.

OBJECTIVE: To observe the changes of ischemic myocardial cells apoptosis in rats following intervention with Xuefu Zhuyu Oral Liquid (, XFZY), as well as changes of protein expression of silent information regulator 1 (SIRT1) and SIRT1 pathway-related genes. METHODS: H9c2 rat myocardial cells were divided into 6 groups: control group, oxygen glucose deprivation (OGD) group, SIRT1 siRNA group, OGD+SIRT1 siRNA group, OGD+XFZY group, and OGD+SIRT1 siRNA+XFZY group. Quantitative fluorescent polymerase chain reaction (PCR) and Western blot were used to detect the concentration variations of SIRT1 and its pathway-related genes and corresponding protein expression after XFZY intervention and SIRT1 transfection. RESULTS: Compared with the control group, the mRNA and protein expressions of SIRT1 were decreased obviously, while the mRNA and protein levels of P53, FoxO1, FoxO3, FoxO4 and nuclear factor kappa B (NF-ΚB) were increased in the OGD group, SIRT1 siRNA group, and OGD+SIRT1 siRNA group (P<0.01). Compared with the OGD group and OGD+SIRT1 siRNA group, the treatment of XFZY inhibited the decline in SIRT1 mRNA and protein expressions (P<0.01), and down-regulated the mRNA and protein levels of P53, FoxO1, FoxO3, FoxO4 and NF-ΚB, respectively (P<0.05 or P<0.01). CONCLUSION: XFZY could prevent myocardial cells apoptosis probably by increasing the mRNA and protein expressions of SIRT1 and inhibiting the mRNA and protein expressions of P53, NF- K B, FoxO1, FoxO3 and FoxO4.

Effectiveness and safety of Chinese herbal medicine xuanbi antong granules for the treatment of borderline coronary lesions: study protocol for a randomised, double-blinded, placebo-controlled, multicentre clinical trial.

INTRODUCTION: As the early stage of coronary heart disease (CHD), borderline coronary lesion (BCL) is defined as a 30%-70% diameter stenosis. Previous studies have demonstrated that BCL may progress to acute coronary syndrome easily. However, routine medications available for the treatments of BCL have some limitations. Xuanbi antong granule (XAG) has been used for the treatment of BCL in China for many years. Previous studies have shown that XAG has effectiveness in improving clinical symptoms and quality of life in patients with CHD. This study aims to evaluate the effectiveness and safety of XAG in patients with BCL. METHODS AND ANALYSIS: This is a multicentre, randomised, double-blinded, placebo-controlled clinical trial. A total of 300 participants will be randomly assigned to the intervention group and the placebo group. Based on routine medications, the intervention group will be treated with XAG and the placebo group will be treated with XAG placebo. All participants will receive a 6-month treatment and then be followed-up for another 6 months. The primary outcomes are the changes of target plaque characteristics (including target plaque volume, degree of stenosis, CT value and calcification score) measured by dual source CT angiography. The secondary outcomes include blood lipid indicators, efficacy of angina symptoms, Seattle Angina Questionnaire, high-sensitivity C-reactive protein and occurrence of major adverse cardiac events. All the data will be recorded in electronic case report forms and analysed by SPSS V.20.0. ETHICS AND DISSEMINATION: This study has been approved by Research Ethics Committee of Guang'anmen Hospital, China Academy of Chinese Medical Sciences in Beijing, China (No. 2017-083-KY-01). Written informed consent will be obtained from all participants. The results of this study will be disseminated to the public through academic conferences and peer-reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-17013189; Pre-results.

[Pharmacological effects and clinical applications of Zingiber officinale and its processed products].

Zingiberis Rhizoma Recens, Zingiberis Rhizoma, ginger juice, Zingiberis Rhizoma Praeparatum and roasted ginger are derived from the rhizome of Zingiber officinale. They are commonly used herbs in clinical application, but their processing methods are completely different, leading to different properties and flavors, meridian distributions, and efficacy characteristics from the perspective of traditional Chinese medicine (TCM). In order to distinguish the clinical applications of different processed gingers, it's advisable to learn from Treatise on Febrile and Miscellaneous Diseases. Almost half of the prescriptions in the book contain Zingiber officinale, involving Zingiberis Rhizoma Recens, Zingiberis Rhizoma, ginger juice, Zingiberis Rhizoma Praeparatum and other species. In addition, many researches have confirmed that the contents of chemical compositions contained in different processed gingers were not exactly the same, and their pharmacological effects were also different, thus their applications could not be confused. However, physicians often encounter drug shortage or improper processing in clinical practice, contributing to the current chaotic use of different processed gingers. Therefore, this paper aims at sorting out the sources, processing methods, and chemical compositions, comparing their properties, flavors, meridian distributions, and pharmacological effects, and summarizing the efficacy characteristics and application rules in TCM theory of different processed products, with the hope to provide theoretical foundations for their reasonable use.

[Pharmacological mechanism analysis of oligopeptide from Pinctada fucata based on in silico proteolysis and protein interaction network].

Thoracic obstruction is mainly attributed to the scope of coronary heart disease in modern medicine, and traditional Chinese medicine(TCM) shows a significant effect in the treatment of thoracic obstruction. In this research, a network pharmacology method was carried out to systemically study the underlying mechanism of the core herbal compatibility in TCM on the thoracic obstruction. First, we collected the literature about TCM prescriptions for treating thoracic obstruction from CNKI. Then, a prescription database was establish by TCM inheritance support platform system(V2.5) to determine the medication rules and core herbal compatibility in TCM. Finally, to obtain the potential signaling pathways, KEGG pathway analysis was performed by BATMAN-TCM online analysis tool. Results showed that the potential signal pathway of core herbal compatibility in TCM for the clinical treatment of thoracic obstruction was calcium ion and cGMP-PKG signaling pathway. This study provided a new research strategy for the study of the medication rules and mechanism of traditional Chinese medicine in the treatment of thoracic obstruction.

Application of Traditional Chinese Medicine in Treatment of Atrial Fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, which is related to many cardiac and cerebral vascular diseases, especially stroke. It can therefore increase cardiovascular mortality and all-cause death. The current treatments of AF remain to be western drugs and radiofrequency ablation which are limited by the tolerance of patients, adverse side effects, and high recurrence rate, especially for the elderly. On the contrary, traditional Chinese medicine (TCM) with long history of use involves various treatment methods, including Chinese herbal medicines (CHMs) or bioactive ingredients, Chinese patent medicines, acupuncture, Qigong, and Tai Chi Chuan. With more and more researches reported, the active roles of TCM in AF management have been discovered. Then it is likely that TCM would be effective preventive means and valuable additional remedy for AF. The potential mechanisms further found by numerous experimental studies showed the distinct characteristics of TCM. Some CHMs or bioactive ingredients are atrial-selective, while others are multichannel and multifunctional. Therefore, in this review we summarized the treatment strategies reported in TCM, with the purpose of providing novel ideas and directions for AF management.