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.

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.

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.

Tongxinluo capsule as supplementation and cardiovascular endpoint events in patients with coronary heart disease: A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials.

ETHNOPHARMACOLOGICAL RELEVANCE: Tongxinluo Capsule(TXLC) is a well-known traditional Chinese medicine prescription with effects of tonifying Qi and activating blood based on the Chinese herbal medicine theory that has been recommended as routine adjuvant treatment in patients with coronary heart disease (CHD) in China. AIM OF THE STUDY: This meta-analysis aimed to evaluate the efficacy and safety of TXLC as supplementation in the prevention of adverse cardiovascular events in patients with CHD. MATERIALS AND METHODS: We performed a literature search in Pubmed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), Wan Fang Database, and Chinese Biomedical Database (CBM) from their inceptions to March 2020. Only randomized controlled trials (RCTs) that assessed supplementation with TXLC or placebo and with adverse cardiovascular outcomes, were included in this meta-analysis. Primary end points were myocardial infarction (MI), target vessel revascularization (TVR) or in-stent restenosis (ISR), and cardiovascular death. Secondary end points included cerebrovascular accidents, heart failure (HF), and unscheduled readmission for cardiovascular diseases (CVDs). Adverse drug events were also evaluated. Trial sequential analysis (TSA) was conducted to reduce random errors introduced by possible insufficient sample size. RESULTS: Eleven RCTs involving 1505 patients were analyzed. The mean(SD) age of included patients were 59.03(9.7) years. Treatment duration varied from 2 months to 12 months. Compared with placebo, TXLC supplementation showed significant effects on reducing the risk of MI (RR = 0.44, [95% CI, 0.24-0.80]), TVR or ISR (RR = 0.43, [95% CI, 0.31-0.58]), cerebrovascular accidents(RR = 0.17, [95% CI, 0.06-0.46]), HF (RR = 0.41, [95% CI, 0.21-0.79]), and unscheduled readmission for CVDs (RR = 0.72, [95% CI], P = 0.04), but did not have associations with incidence of cardiovascular death (RR = 0.53, [95% CI, 0.15-1.91]). Subgroups of trials with 2-month (MI: RR = 0.44, [95% CI, 0.13-1.53]; cardiovascular death: RR = 0.30, [95% CI, 0.01-7.67]; cerebrovascular accidents: RR = 0.04, [95% CI, 0.01-0.26]; unscheduled readmission for CVDs: RR = 0.43, [95% CI, 0.20-0.94]) and 12-month (MI: RR = 0.42, [95% CI, 0.20-0.89]; TVR or ISR: RR = 0.42, [95% CI, 0.31-0.58]; HF: RR = 0.34, [95% CI, 0.14-0.78]; unscheduled readmission for CVDs: RR = 0.85, [95% CI, 0.59-1.22]) intervention period were analyzed. The adverse drug reactions were mild with no significant difference between TXLC and placebo. CONCLUSIONS: This meta-analysis indicated that TXLC supplementation had beneficial effects on the prevention of cardiovascular adverse events, especially in TVR or ISR after coronary revascularization and may possibly lower the incidence of first or recurrent MI and HF within 12 months in patients with CHD, while insufficient sample size implied that these results lacked certain stability. And the effects of TXLC on cardiovascular mortality, cerebrovascular events, and unscheduled readmission for CVDs could not be confirmed due to insufficient cases. Clinical trials with large-sample sizes and extended follow-up time are of interest in the future researches.

Acupuncture as Adjuvant Therapy for Treating Stable Angina Pectoris with Moderate Coronary Artery Lesions and the Mechanism of Heart-Brain Interactions: A Randomized Controlled Trial Protocol.

Background. Stable angina pectoris with moderate coronary artery lesions is a syndrome caused by coronary artery stenosis, which endangers the quality of life. Previous acupuncture studies have shown effectiveness as a complementary therapy for ischaemic heart disease. However, more clinical evidence is needed for verification, and the mechanism should be investigated, especially involving the functional interactions between the heart and brain. Therefore, we designed a clinical trial to provide more evidence for acupuncture efficacy and its mechanism in ischaemic heart disease. Methods/Design. A total of 80 participants will be randomized to the electroacupuncture group and sham-electroacupuncture group at a ratio of 1 : 1. This trial will be conducted over 8 weeks, including a 2-week screening, 2-week treatment, and 4-week follow-up. All participants will continue to receive similar basic disease treatment procedures before the trial (including lifestyle changes and treatment for standard supportive medications, hypertension, and hyperlipidaemia, such as aspirin, metoprolol succinate, atorvastatin, and sodium fosinopril). Additionally, 12 sessions of acupuncture will be administered during the treatment period. The main outcome is Seattle Angina Questionnaire scores. The other observation indices are the heart rate variability and self-rating anxiety scale and self-rating depression scale scores. To explore mechanisms based on the hypothesis of a correlation between heart and brain function, fMRI scans will be used to detect functional brain changes in 15 patients from each group at baseline and at the end of treatment. Finally, the efficacy of acupuncture will be evaluated, and the HRV and imaging data will be correlated with clinical data to investigate the possible relationships between the brain and heart activity. Discussion. This trial will provide evidence for acupuncture as adjuvant therapy for the treatment of stable angina pectoris with moderate coronary artery lesions. The results will shed light on potential mechanisms of heart-brain interactions underlying acupuncture as an adjuvant therapy for treating ischaemic heart disease. Trials registration: Clinical Trial, https://clinicaltrials.gov/ct2/show/ChiCTR1900024937. Registered 4 August 2019, http://www.chictr.org.cn/.

Efficacy and safety of Linggui Zhugan decoction in the treatment of chronic heart failure with Yang deficiency: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic heart failure (CHF) is an advanced stage of various heart diseases and has become a major global health problem. In 2018, the Chinese guideline for the diagnosis and treatment of HF suggested adding traditional Chinese medicine (TCM) as an adjunct to the treatment of CHF, but also pointed out the need for more convincing clinical evidences. Linggui Zhugan decoction (LGZGD) is one of the widely used TCM for CHF treatment, especially for patients with Yang deficiency. Given that treatment based on syndrome differentiation is an important principle in TCM, we provide a protocol to systematically evaluate efficacy and safety of LGZGD for CHF with Yang deficiency. METHODS: We will search the following electronic databases from inception to April 30, 2021, including PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, VIP Information Database, Chinese Biomedical Literature Database (CBM), and Wanfang Database. Randomized controlled trials (RCT) examining the LGZGD on CHF patients with Yang deficiency will be included. Study selection, data extraction and quality assessment will be conducted by 2 researchers, respectively. The primary outcome measures will be n-terminal brain natriuretic peptide and left ventricular ejection fraction. The risk of bias will be evaluated by the Cochrane Collaboration tool. We will use the fixed-effects model or random-effects model of RevMan V.5.3 based on the results of heterogeneity assessment. The evidence quality of results will be assessed by Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: It will provide the results about efficacy and safety of LGZGD in the treatment of CHF with Yang deficiency by various comprehensive assessments. CONCLUSIONS: This study will provide reliable evidences about the efficacy and safety of LGZGD in the treatment of CHF with Yang deficiency. ETHICS AND DISSEMINATION: Ethical approval is not necessary for this study because the data extracted does not involve any individual privacy. We plan to presented the results of this review in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD 42019140797.

[Evaluation on effect of integrative medical treatment on quality of life of rehabilitation stage in 85 patients with SARS].

OBJECTIVE: To evaluate the effect of integrative medical treatment (IMT) with serial Chinese recipes on quality of life (QOF) of rehabilitation stage in SARS patients. METHODS: Eighty-five SARS patients of rehabilitation stage were enrolled in the clinical study. They were divided into the IMT group (62 patients received serial Chinese recipes and western medicine) and the control group (23 patients received western medicine alone). The serial Chinese recipes were given according to patients' syndrome, one dose per day for oral intake for 3 weeks. QOF scoring in patients was observed. RESULTS: QOF scoring in the IMT group before treatment was not significantly different from that in the control group. After 3 weeks treatment, it improved to some extent in both groups, but the improvement in the IMT group was superior to that in the control group in respect of total score and score of psychologic emotional factors. CONCLUSION: Serial Chinese recipe could improve QOF of rehabilitation stage in SARS patients.