Blood urea nitrogen to creatinine ratio and long-term survival in patients with chronic heart failure.

OBJECTIVES: To explore the correlation between Blood urea nitrogen to creatinine ratio (BUN/Scr ratio) and prognosis of patients with chronic heart failure complicated with renal injury. METHODS: A retrospective analysis of 504 patients hospitalized in Guang 'anmen Hospital, Chinese Academy of Traditional Chinese Medicine from March 2006 to June 2014 was conducted. The baseline data were analyzed, and the cutoff value was obtained by receiver operator characteristic curve (ROC) analysis, according to the cutoff value, all the participants were divided into two groups, BUN/Scr < 19.37 group (280 cases) and BUN/Scr ≥ 19.37 group (224 cases). The main end point was defined as all-cause death. The long-term mortality of the two groups was evaluated, and Kaplan-Meier survival curve was drawn. Univariate analysis was performed on all the variables affecting the patient's prognosis, and the variables with P < 0.05 were put into Cox regression model, and subgroup analysis was performed on the variables that might affect the patient's prognosis. RESULTS: The baseline data of 504 patients were analyzed and found that the median follow up was 683. Through ROC analysis of 504 subjects, the cutoff value of BUN/Scr was 19.37. The results of Kaplan-Meier survival curve showed that the mortality rate of patients with ratio ≥ 19.37 was higher than that of patients with ratio < 19.37. After multivariate analysis, COX regression model showed that the mortality of patients with BUN/Scr ≥ 19.37 was 1.885 times that of patients with BUN/Scr < 19.37 [HR = 1.885 (1.298-2.737), P = 0.001]. Subgroup analysis showed that the relationship between BUN/Scr and the prognosis of CHF was influenced by NYHA and eGRF (P < 0.05). CONCLUSIONS: BUN/Scr ratio is related to the poor prognosis of patients with CHF, and is an independent predictor of all-cause death.

Tanshinone IIA inhibits cardiomyocyte pyroptosis through TLR4/NF-κB p65 pathway after acute myocardial infarction.

Background: Tanshinone IIA, derived from Radix Salviae Miltiorrhizae (Salvia miltiorrhiza Bunge), constitutes a significant component of this traditional Chinese medicine. Numerous studies have reported positive outcomes regarding its influence on cardiac function. However, a comprehensive comprehension of the intricate mechanisms responsible for its cardioprotective effects is still lacking. Methods: A rat model of heart failure (HF) induced by acute myocardial infarction (AMI) was established via ligation of the left anterior descending coronary artery. Rats received oral administration of tanshinone IIA (1.5 mg/kg) and captopril (10 mg/kg) for 8 weeks. Cardiac function was assessed through various evaluations. Histological changes in myocardial tissue were observed using staining techniques, including Hematoxylin and Eosin (HE), Masson, and transmission electron microscopy. Tunel staining was used to detect cell apoptosis. Serum levels of NT-pro-BNP, IL-1ß, and IL-18 were quantified using enzyme-linked immunosorbent assay (ELISA). Expression levels of TLR4, NF-κB p65, and pyroptosis-related proteins were determined via western blotting (WB). H9C2 cardiomyocytes underwent hypoxia-reoxygenation (H/R) to simulate ischemia-reperfusion (I/R) injury, and cell viability and apoptosis were assessed post treatment with different tanshinone IIA concentrations (0.05 µg/ml, 0.1 µg/ml). ELISA measured IL-1ß, IL-18, and LDH expression in the cell supernatant, while WB analysis evaluated TLR4, NF-κB p65, and pyroptosis-related protein levels. NF-κB p65 protein nuclear translocation was observed using laser confocal microscopy. Results: Tanshinone IIA treatment exhibited enhanced cardiac function, mitigated histological cardiac tissue damage, lowered serum levels of NT-pro-BNP, IL-1ß, and IL-18, and suppressed myocardial cell apoptosis. Moreover, tanshinone IIA downregulated the expression of TLR4, NF-κB p65, IL-1ß, pro-IL-1ß, NLRP3, Caspase-1, and GSDMD-N pyroptosis-related proteins in myocardial tissue. Additionally, it bolstered H/R H9C2 cardiomyocyte viability, curbed cardiomyocyte apoptosis, and reduced the levels of TLR4, NF-κB p65, IL-1ß, pro-IL-1ß, NLRP3, Caspase-1, and GSDMD-N pyroptosis-related proteins in H/R H9C2 cells. Furthermore, it hindered NF-κB p65 protein nuclear translocation. Conclusion: These findings indicate that tanshinone IIA enhances cardiac function and alleviates myocardial injury in HF rats following AMI. Moreover, tanshinone IIA demonstrates potential suppression of cardiomyocyte pyroptosis. These effects likely arise from the inhibition of the TLR4/NF-κB p65 signaling pathway, presenting a promising therapeutic target.

Qi-Po-Sheng-Mai granule ameliorates Ach-CaCl2 -induced atrial fibrillation by regulating calcium homeostasis in cardiomyocytes.

BACKGROUND: Atrial fibrillation (AF) is one of the most common arrhythmias encountered in clinical settings. Currently, the pathophysiology of AF remains unclear, which severely limits the effectiveness and safety of medical therapies. The Chinese herbal formula Qi-Po-Sheng-Mai Granule (QPSM) has been widely used in China to treat AF. However, its pharmacological and molecular mechanisms remain unknown. PURPOSE: The purpose of this study was to investigate the molecular mechanisms and potential targets of QPSM for AF. STUDY DESIGN AND METHODS: The AF model was induced by Ach (66 µg/ml) and CaCl2 (10 mg/kg), and the dose of 0.1 ml/100 g was injected into the tail vein for 5 weeks. QPSM was administered daily at doses of 4.42 and 8.84 g/kg, and amiodarone (0.18 g/kg) was used as the positive control. The effect of QPSM on AF was assessed by electrocardiogram, echocardiography, and histopathological analysis. Then, we employed network pharmacology with single nucleus RNA sequencing (snRNA-Seq) to investigate the molecular mechanisms and potential targets of QPSM for AF. Furthermore, high performance liquid chromatography (HPLC) method was used for component analysis of QPSM, and molecular docking was used to verify the potential targets. Using the IonOptix single cell contraction and ion synchronization test equipment, single myocyte length and calcium ion variations were observed in real time. The expression levels of calcium Transporter-related proteins were detected by western blot and immunohistochemistry. RESULTS: Based on an Ach-CaCl2-induced AF model, we found that QPSM treatment significantly reduced atrial electrical remodeling-related markers, such as AF inducibility and duration, and attenuated atrial dilation and fibrosis. Network pharmacology identified 52 active ingredients and 119 potential targets for QPSM in the treatment of AF, and 45 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched, among which calcium pathway had the greatest impact. Using single nucleus sequencing (snRNA-seq), we identified cardiomyocytes as the most differentially expressed in response to drug treatment, with nine differentially expressed genes enriched in calcium signaling pathways. High performance liquid chromatography and molecular docking confirmed that the core components of QPSM strongly bind to the key factors in the calcium signaling pathway. Additional experiments have shown that QPSM increases calcium transients (CaT) and contractility in the individual cardiomyocyte. This was accomplished by increasing the expression of CACNA1C and SERCA2a and decreasing the expression of CAMK2B and NCX1. CONCLUSION: The present study has systematically elucidated the role of QPSM in maintaining calcium homeostasis in cardiomyocytes through the regulation of calcium transporters, which could lead to new drug development ideas for AF.

Effects of garlic supplementation on components of metabolic syndrome: a systematic review, meta-analysis, and meta-regression of randomized controlled trials.

BACKGROUND: Garlic (Allium sativum), the underground bulb of the Allium genus, has been consumed on Earth for thousands of years. Many clinical trials of garlic supplementation on components of metabolic syndrome (MetS) have emerged in recent years, but there is no consensus on the effect. This meta-analysis aimed at systematically evaluating the effect of garlic supplementation on components of MetS. METHODS: In this meta-analysis, we searched Pubmed, Embase, Cochrane, Medline, Web of Science databases, and clinical trials online sites from inception to November 1, 2022, with language restrictions to English. We engaged participants > 18 years and eligible for the clinical diagnosis of MetS or those with metabolic disorders and garlic was the only intervention. Outcomes included waist circumference, and body mass index, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, blood pressure, and fasting blood glucose. Meta-regression and subgroup analyses were conducted based on six covariates (total sample size, the mean age, the mean dose, the duration of intervention, the oral form of garlic, and the dietary intervention). RESULTS: Results from 19 RCTs were included engaging 999 participants. Compared to placebo, garlic significantly reduced TG [SMD (95%CI) = -0.66 (-1.23, -0.09)], TC [SMD (95%CI) = -0.43 (-0.86, -0.01)], LDL [SMD (95%CI) = -0.44(-0.88, -0.01)], DBP [SMD (95%CI) = -1.33 (-2.14, -0.53)], BMI [SMD (95%CI) = -1.10(-1.90, -0.20)], and WC [SMD (95%CI) = -0.78(-1.09, -0.47)]. Meta-regression showed age and sample size are potential effect modifiers. CONCLUSION: According to the results of meta-analysis, the modulatory effect of garlic on some MetS components is evident. More high-quality, large-scale RCTs are needed to confirm iat based on the high heterogeneity and potential publication bias of the current data. TRIAL REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=373228 , ID: CRD42022373228.

Circadian rhythm in cardiovascular diseases: a bibliometric analysis of the past, present, and future.

BACKGROUND: One of the most prominent features of living organisms is their circadian rhythm, which governs a wide range of physiological processes and plays a critical role in maintaining optimal health and function in response to daily environmental changes. This work applied bibliometric analysis to explore quantitative and qualitative trends in circadian rhythm in cardiovascular diseases (CVD). It also aims to identify research hotspots and provide fresh suggestions for future research. METHODS: The Web of Science Core Collection was used to search the data on circadian rhythm in CVD. HistCite, CiteSpace, and VOSviewer were used for bibliometric analysis and visualization. The analysis included the overall distribution of yearly outputs, top nations, active institutions and authors, core journals, co-cited references, and keywords. To assess the quality and efficacy of publications, the total global citation score (TGCS) and total local citation score (TLCS) were calculated. RESULTS: There were 2102 papers found to be associated with the circadian rhythm in CVD, with the overall number of publications increasing year after year. The United States had the most research citations and was the most prolific country. Hermida RC, Young ME, and Ayala DE were the top three writers. The three most notable journals on the subject were Chronobiology International, Hypertension Research, and Hypertension. In the early years, the major emphasis of circadian rhythm in CVD was hormones. Inflammation, atherosclerosis, and myocardial infarction were the top developing research hotspots. CONCLUSION: Circadian rhythm in CVD has recently received a lot of interest from the medical field. These topics, namely inflammation, atherosclerosis, and myocardial infarction, are critical areas of investigation for understanding the role of circadian rhythm in CVD. Although they may not be future research priorities, they remain of significant importance. In addition, how to implement these chronotherapy theories in clinical practice will depend on additional clinical trials to get sufficient trustworthy clinical evidence.

Andrographolide in atherosclerosis: integrating network pharmacology and in vitro pharmacological evaluation.

OBJECTIVE: Andrographis paniculata (Burm.f.) Nees is a medicinal plant that has been traditionally used as an anti-inflammatory and antibacterial remedy for several conditions. Andrographolide (AG), the active constituent of A. paniculata (Burm.f.) Nees, has anti-lipidic and anti-inflammatory properties as well as cardiovascular protective effects. The present study aimed to explore the effects of AG on the progression of atherosclerosis and to investigate related mechanisms via network pharmacology. MATERIALS AND METHODS: Compound-related information was obtained from the PubChem database. Potential target genes were identified using STITCH, SwissTargetPrediction, Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine, and Comparative Toxicogenomics Database. Genes involved in atherosclerosis were obtained from DisGeNet and compared with AG target genes to obtain an overlapping set. Protein-protein interactions were determined by STRING. Gene ontology (GO) analysis was performed at WebGestalt, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment was analyzed using Metascape. The final network showing the relationship between compounds, targets, and pathways was constructed using Cytoscape. After that, oxLDL-induced RAW264.7 cells were used to further validate a part of the network pharmacology results. RESULT: Eighty-one potential AG target genes were identified. PPI, GO, and KEGG enrichment revealed genes closely related to tumor progression, lipid transport, inflammation, and related pathways. AG improves the reverse cholesterol transport (RCT) through NF-κB/CEBPB/PPARG signaling in oxLDL-induced RAW264.7 cells. CONCLUSION: We successfully predict AG's potential targets and pathways in atherosclerosis and illustrate the mechanism of action. AG may regulate NF-κB/CEBPB/PPARG signaling to alleviate atherosclerosis.

Role of puerarin in pathological cardiac remodeling: A review.

Pathological cardiac remodeling normally involves changes in structure, function, and energy metabolism of the heart induced by cardiac injury or load, terminally leading to heart failure. Cardiac remodeling plays an essential role in the progression of cardiovascular disease, thus increasingly identified as an important therapeutic target for heart failure of all pathogenesis. Puerarin, as a natural isoflavone mainly from Pueraria lobata （Willd.）Ohwi, has been developed as injections, eye drops, microemulsions, etc., and is widely used in the clinical treatment of cardiovascular diseases in eastern Asia countries. In recent years, a growing number of studies have shown that puerarin significantly inhibits myocardial hypertrophic growth, myocyte death, fetal gene expression, fibroblast proliferation and activation, improves energy metabolism, promotes post-infarction angiogenesis, and suppresses inflammation and oxidative stress, consequently attenuating or preventing cardiac remodeling in response to multiple stimuli ( e.g., pressure overload, MIRI, MI, Iso, and Ang II stimulation). This review summarized the roles and underlying molecular mechanisms of puerarin in cardiac remodeling induced by diverse etiologies, aiming to help develop novel therapeutic strategies to prevent or reverse pathological ventricular remodeling.

Network Pharmacology and Molecular Docking Analysis on Molecular Mechanism of Qingzi Zhitong Decoction in the Treatment of Ulcerative Colitis.

Ulcerative colitis (UC) is a disease with complex pathological mechanisms. We explored the potential molecular mechanisms behind the therapeutic functions of Qingzi Zhitong decoction (QZZTD) in the treatment of UC by network pharmacology and molecular docking. QZZTD is a formula of Chinese traditional medicine consisting of 10 herbs. The potential active ingredients of QZZTD and their target genes were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and UC-related target genes were obtained from GeneCards and OMIM databases. A total of 138 co-identified target genes were obtained by plotting the intersection target Venn diagram, and then the STRING database and Cytoscape software were used to establish protein-protein interaction networks and herb-ingredient-target networks. Four key active compounds and nine key proteins were identified. Then, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the biological functions of potential target genes were associated with DNA transcription, signaling receptor and ligand activity, cytokine activity, cellular autophagy, and antioxidant pathways, with related pathways involving the phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, advanced glycosylation end product (AGE)-RAGE signaling pathway, tumor necrosis factor (TNF) signaling pathway, and IL-17 signaling pathway. Moreover, the binding activities of key target genes and essential active compounds of Chinese herbal medicines in QZZTD were further validated by molecular docking. This demonstrated that quercetin, luteolin, hyndarin, and beta-sitosterol had good binding to eight key proteins, and Akt1 was the target protein with the best binding activity, suggesting that Akt1 could be the essential mediator responsible for signaling transduction after QZZTD administration. The rat experiment verified that QZZTD inhibited PI3K-Akt pathway activation and reduced inflammation in UC. In conclusion, our study suggested four potential key active components, including quercetin, were identified in QZZTD, which could interact with Akt1 and modulate the activation of the PI3K-Akt pathway. The other three pathways may also be involved in the signaling transduction induced by QZZTD in the treatment of UC.

Use of Network Pharmacology to Explore the Mechanism of Gegen (Puerariae lobatae Radix) in the Treatment of Type 2 Diabetes Mellitus Associated with Hyperlipidemia.

Rapid increases in metabolic disorders, such as type 2 diabetes mellitus (T2DM) and hyperlipidemia, are becoming a substantial challenge to worldwide public health. Traditional Chinese medicine has a long history and abundant experience in the treatment of diabetes and hyperlipidemia, and Puerariae lobatae Radix (known as Gegen in Chinese) is one of the most prevalent Chinese herbs applied to treat these diseases. The underlying mechanism by which Gegen simultaneously treats diabetes and hyperlipidemia, however, has not been clearly elucidated to date. Therefore, we systematically explored the potential mechanism of Gegen in the treatment of T2DM complicated with hyperlipidemia based on network pharmacology. We screened the potential targets of Gegen, T2DM, and hyperlipidemia in several online databases. Then, the hub targets were analyzed by performing protein-protein interaction, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment assays, and finally, the complicated connections among compounds, targets, and pathways were visualized in Cytoscape. We found that isoflavones, including daidzein, genistein, and puerarin, as well as ß-sitosterol, are the key active ingredients of Gegen responsible for its antidiabetic and antihyperlipidemia effects, which mainly target AKR1B1, EGFR, ESR, TNF, NOS3, MAPK3, PPAR, CYP19A1, INS, IL6, and SORD and multiple pathways, such as the PI3K-Akt signaling pathway; the AGE-RAGE signaling pathway in diabetic complications, fluid shear stress, and atherosclerosis; the PPAR signaling pathway; insulin resistance; the HIF-1 signaling pathway; the TNF signaling pathway; and others. These active ingredients also target multiple biological processes, including the regulation of glucose and lipid metabolism, the maintenance of metabolic homeostasis, and anti-inflammatory and antioxidant pathways. In conclusion, Gegen is a promising therapeutic phytomedicine for T2DM with hyperlipidemia that targets multiple proteins, biological processes, and pathways.

Comparative efficacy and safety of wenxin granule combined with antiarrhythmic drugs for atrial fibrillation: A protocol for a systematic review and network meta-analysis.

BACKGROUND: The combination of Chinese patent medicine Wenxin Granules (WXG) and antiarrhythmic drugs has been widely used in the treatment of atrial fibrillation (AF), but the results are controversial. This study will conduct a network meta-analysis (NMA) based on data from randomized controlled trials to evaluate the efficacy and safety of WXG combined with ADDs (amiodarone, metoprolol, propafenone, bisoprolol, or other antiarrhythmic drugs) in the treatment of AF, which will perform comparisons or rankings of efficacy among the currently available therapeutic schemes in order to provide evidence to determine the optimal threshold and treatment regimen to AF patients. METHODS AND ANALYSIS: A comprehensive systematic literature search will be conducted in Cochrane Library, PubMed, Web of Science, EMBASE, Chinese Biomedical Literature Database (SinoMed), Chinese National Knowledge Infrastructure (CNKI), and WanFang database for randomized controlled trials about the WXG with ADDs. The NMA will be conducted following the PRISMA-NMA guidelines. Statistical analyses will be conducted by using Stata software (version 14.0) and RevMan software (version 5.3). RESULTS: The results of this NMA will provide a high-quality evidence for the efficacy of WXG combined with ADDs in the treatment of AF, and a ranking of the therapeutic classes will also be presented. CONCLUSION: The protocol will provide updated evidence for the application of WXG for AF.

Efficacy and safety of ShenSongYangXin Capsule combined with antiarrhythmic drugs for atrial fibrillation: A protocol for systematic review and network meta-analysis.

BACKGROUND: Shen-Song-Yang-Xin Capsule (SSYX), a Chinese patent medicine, combined with antiarrhythmic drugs (AADs) in the treatment of atrial fibrillation (AF) has been widely applied in clinical practice, but the results are controversial. This study aims to conduct a network meta-analysis (NMA) based on data from the randomized controlled trials (RCTs) to evaluate the efficacy and safety of SSYX combined with ADDs in the treatment of AF. METHODS AND ANALYSIS: A comprehensive systematic literature search will be conducted in Cochrane Library, PubMed, Web of Science, EMBASE, Chinese Biomedical Literature Database (SinoMed), Chinese National Knowledge Infrastructure (CNKI), and WanFang database for RCTs about SSYX combined with ADDs. The primary outcomes will be the frequency of AF attack and P-wave dispersion, and the secondary outcomes will be the symptom improvements, left atrial diameter, and adverse events. Statistical analyses will be conducted by using WinBUGS software (version 1.4.3), Stata software (version 14.0) and RevMan software (version 5.3). RESULTS: The results of this NMA will provide a high-quality evidence for the efficacy of SSYX combined with ADDs in the treatment of AF, and a ranking of the therapeutic classes will also be presented. CONCLUSION: The protocol will provide updated evidence for the application of SSYX for AF. INTERNATIONAL PLATFORM OF REGISTERED SYSTEMATIC REVIEW AND META-ANALYSIS PROTOCOLS (INPLASY) REGISTRATION NUMBER:: The protocol of this systematic review and meta-analysis was registered on the INPLASY website (https://inplasy.com/inplasy-2020-8-0075/) and INPLASY registration number is INPLASY202080075.

Effects of acupuncture on Luteinized Unruptured Follicle Syndrome: A meta-analysis of randomized controlled trials.

PURPOSE: This meta-analysis aimed to evaluate the comprehensive efficiency and safety of acupuncture on Luteinized Unruptured Follicle Syndrome based on Randomized Controlled Trials (RCTs). METHODS: Six electronic databases (i.e. Wanfang, VIP, China National Knowledge Infrastructure, Pubmed, Cochrane, and Embase) were searched from inception to July 2019. Randomized controlled trials were eligible to evaluate the effects of acupuncture alone or acupuncture as an adjunct. The primary outcomes were the ovulation rate and pregnancy rate. Two reviewers proceeded study selection and quality assessment of included trials and performed heterogeneity of included studies before meta-analysis.Trial Sequential Analysis was used to assess the risk of random error and estimate required information size. The Grading of Recommendations Assessment, Development and Evaluation was applied for assessing level of evidence. RESULTS: 10 studies involving 715 participants were included Meta-analysis showed acupuncture alone and acupuncture as an adjunct both could significantly improve ovulation, which were confirmed by Trial Sequential Analysis. The evidence of acupuncture improving pregnancy rate was insufficient. Improved serum luteinizing hormone and estradiol levels, and decreased pulsatility index and resistance index of ovary artery were shown in both two subgroups. Level of evidence of most outcomes was "low" or "very low", so the results should be cautiously interpreted. CONCLUSIONS: Acupuncture alone or be combined with drugs are effective on Luteinized Unruptured Follicle Syndrome especially for improving ovulation . While concurrent evidence is insufficient, and further studies of high quality are needed to strengthen the conclusion.