A rat model of metabolic syndrome-related heart failure with preserved ejection fraction phenotype: pathological alterations and possible molecular mechanisms.

Background: Heart failure with preserved ejection fraction (HFpEF) represents a syndrome involving multiple pathophysiologic disorders and clinical phenotypes. This complexity makes it challenging to develop a comprehensive preclinical model, which presents an obstacle to elucidating disease mechanisms and developing new drugs. Metabolic syndrome (MetS) is a major phenotype of HFpEF. Thus, we produced a rat model of the MetS-related HFpEF phenotype and explored the molecular mechanisms underpinning the observed pathological changes. Methods: A rat model of the MetS-related HFpEF phenotype was created by feeding spontaneously hypertensive rats a high-fat-salt-sugar diet and administering streptozotocin solution intraperitoneally. Subsequently, pathological changes in the rat heart and their possible molecular mechanisms were explored. Results: The HFpEF rats demonstrated primary features of MetS, such as hypertension, hyperglycemia, hyperlipidemia, insulin resistance, and cardiac anomalies, such as left ventricular (LV) remodeling and diastolic impairment, and left atrial dilation. Additionally, inflammation, myocardial hypertrophy, and fibrosis were observed in LV myocardial tissue, which may be associated with diverse cellular and molecular signaling cascades. First, the inflammatory response might be related to the overexpression of inflammatory regulators (growth differentiation factor 15 (GDF-15), intercellular adhesion molecule-1 (ICAM-1), and vascular endothelial cell adhesion molecule-1 (VCAM-1)). Secondly, phosphorylated glycogen synthase kinase 3ß (GSK-3ß) may stimulate cardiac hypertrophy, which was regulated by activated -RAC-alpha serine/threonine-protein kinase (AKT). Finally, the transforming growth factor-ß1 (TGF-ß1)/Smads pathway might regulate collagen production and fibroblast activation, promoting myocardial fibrosis. Conclusion: The HFpEF rat replicates the pathology and clinical presentation of human HFpEF with MetS and may be a reliable preclinical model that helps elucidate HFpEF pathogenesis and develop effective treatment strategies.

Targeting epicardial adipose tissue: A potential therapeutic strategy for heart failure with preserved ejection fraction with type 2 diabetes mellitus.

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various comorbidities, multiple cardiac and extracardiac pathophysiologic abnormalities, and diverse phenotypic presentations. Since HFpEF is a heterogeneous disease with different phenotypes, individualized treatment is required. HFpEF with type 2 diabetes mellitus (T2DM) represents a specific phenotype of HFpEF, with about 45%-50% of HFpEF patients suffering from T2DM. Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM, which is intimately related to the expansion and dysfunction (inflammation and hypermetabolic activity) of epicardial adipose tissue (EAT). EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms. Therefore, suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM. Although there is no treatment specifically for EAT, lifestyle management, bariatric surgery, and some pharmaceutical interventions (anti-cytokine drugs, statins, proprotein convertase subtilisin/kexin type 9 inhibitors, metformin, glucagon-like peptide-1 receptor agonists, and especially sodium-glucose cotransporter-2 inhibitors) have been shown to attenuate the inflammatory response or expansion of EAT. Importantly, these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF. Accordingly, well-designed randomized controlled trials are needed to validate the efficacy of current therapies. In addition, more novel and effective therapies targeting EAT are needed in the future.

Ling-Gui-Qi-Hua formula alleviates left ventricular myocardial fibrosis in rats with heart failure with preserved ejection fraction by blocking the transforming growth factor-ß1 /Smads signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ling-Qui-Qi-Hua (LGQH) decoction, composed of Poria cocos (Schw.) Wolf, Cinnamomum cassia (L.) J. Presl, Paeonia veitchii Lynch, and Atractylodes macrocephala Koidz., is a compound formula derived from Ling-Gui-Zhu-Gan decoction recorded in the Treatise on Febrile and Miscellaneous. It has shown cardioprotective effects on patients or rats with heart failure with preserved ejection fraction (HFpEF). Nevertheless, the active ingredients of LGQH and its anti-fibrotic mechanism remain unknown. AIM OF THE STUDY: To determine the active ingredients in LGQH decoction and verify that LGQH decoction may inhibit left ventricular (LV) myocardial fibrosis in HFpEF rats by blocking the transforming growth factor-ß1 (TGF-ß1)/Smads signaling pathway from the perspective of animal experiments. MATERIALS AND METHODS: First, liquid chromatography-mass spectrometry (LC-MS) technology was used to identify active components in the LGQH decoction. Secondly, a rat model of the metabolic syndrome-associated HFpEF phenotype was established and subsequently received LGQH intervention. The mRNA and protein expression of targets in the TGF-ß1/Smads pathway were detected by quantitative real-time polymerase chain reaction and western blot analysis. Finally, molecular docking was conducted to examine the interactions between the active ingredients in the LGQH decoction and key proteins of the TGF-ß1/Smads pathways. RESULTS: According to LC-MS analysis, the LGQH decoction contained 13 active ingredients. In animal experiments, LGQH attenuated LV hypertrophy, enlargement, and diastolic function in HEpEF rats. Mechanically, LGQH not only down-regulated TGF-ß1, Smad2, Smad3, Smad4, α-SMA, Coll I, and Coll III mRNA expressions and TGF-ß1, Smad2, Smad3, P-Smad2/Smad3, Smad4, α-SMA, and Coll I protein expressions, but also up-regulated Smad7 mRNA and protein expressions, which ultimately led to myocardial fibrosis. Furthermore, molecular docking confirmed that 13 active ingredients in the LGQH decoction have excellent binding activities to the critical targets of the TGF-ß1/Smads pathway. CONCLUSION: LGQH is a modified herbal formulation with multiple active ingredients. It might alleviate LV remodeling and diastolic dysfunction and inhibit LV myocardial fibrosis by blocking TGF-ß1/Smads pathways in HFpEF rats.

Effects and mechanism of Compound Qidan Formula on rats with HFpEF induced by hypertension and diabetes mellitus based on Ang â ¡/TGF-ß1/Smads signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Qidan Formula is composed of traditional Chinese herbs and has a good curative effect in the clinical application of cardiovascular diseases such as heart failure. However, its potential molecular mechanisms of action remain highly unknown. AIM OF THE STUDY: To observe the effect of Compound Qidan Formula on cardiac function in rats with HFpEF induced by hypertension and diabetes mellitus, and to explore its mechanism from Ang Ⅱ/TGF-ß1/Smads signaling pathway. MATERIALS AND METHODS: A total of 50 SPF-grade spontaneously hypertensive rats (SHR) aged 14 weeks, fed with a high-fat and high-sucrose diet for 16 weeks, and after 2 weeks of a high-fat and high-sucrose diet, 1% streptozotocin (25 mg/kg body weight)was injected intraperitoneally to establish a rat model of HFpEF induced by hypertension and diabetes mellitus. After 8 weeks of intragastric administration, the changes in cardiac morphology and function were evaluated by echocardiography after anesthesia; the heart tissue was taken and embedded in paraffin for Masson staining, and the pathomorphological changes of left atrial tissue were observed under the optical microscope; the mRNA transcription levels of Ang Ⅱ, AT1R, TGF-ß1, Smad2, Smad3, MMP-9 and TIMP-1in left atrial tissue of rats were detected by RT-PCR; and the protein expressions were detected by Western blot. RESULTS: Compared with the SHR-DM group, the QD-Low and QD-High groups significantly decreased the left atrial (LA) anteroposterior diameter and interventricular septal thickness (IVST) and improved the peak velocity of mitral valve blood flow in early diastolic period (E), maximum mitral valve blood flow in systolic period (A), mitral ring myocardial movement velocity in early diastolic period (e') and E/e' ratio; the QD-High group significantly improved the E/A ratio, left atrial ejection fraction (LAEF) and left ventricular ejection fraction(LVEF). Masson staining showed that compared with the WKY group, the SHR-DM group had obvious myocardial histomorphological lesions. Compared with the SHR-DM group, the Compound Qidan Formula groups significantly improved cardiomyocyte hypertrophy and disordered arrangement and inhibited myocardial fibrosis; the mRNA expression levels of Ang Ⅱ, AT1R, TGF-ß1, Smad2, Smad3, and MMP-9 in myocardial tissue of Compound Qidan Formula groups were significantly decreased, and the mRNA expression level of TIMP-1 was significantly increased. The protein expression levels of Ang Ⅱ, TGF-ß1, P-Smad2/3, and MMP-9 were significantly decreased. CONCLUSION: Compound Qidan Formula, composed of traditional Chinese herbs, can significantly improve cardiac function, improve atrial and ventricular remodeling, and prevent myocardial fibrosis and hypertrophy in rats with HFpEF induced by hypertension and diabetes mellitus. The mechanism may be related to regulating the Ang Ⅱ/TGF-ß1/Smad2/3 signaling pathway.

Linggui Qihua Decoction Inhibits Atrial Fibrosis by Regulating TGF-ß1/Smad2/3 Signal Pathway.

Myocardial fibrosis is a critical factor in the development of heart failure with preserved ejection fraction (HFpEF). Linggui Qihua decoction (LGQHD) is an experienced formula, which has been proven to be effective on HFpEF in clinical and in experiments. Objective. This study aimed to observe the effect of LGQHD on HFpEF and its underlying mechanism. Methods. Spontaneously hypertensive rats (SHR) were induced with high-glucose and high-fat to establish HFpEF models and were treated with LGQHD for 8 weeks. The heart structure was detected by echocardiography, and the histopathological changes of the myocardium were observed by hematoxylin-eosin (HE) and Masson staining. Reverse transcription PCR (RT-PCR) and western blot were used to detect mRNA and protein expression of the target gene in rat myocardium. Results. In this study, LGQHD improved cardiac morphology and atrial fibrosis in HfpEF rats, decreased tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA expression, up-regulated matrix metalloproteinase-9 (MMP-9) mRNA expression, and inhibited the expression of angiotensin II (Ang II), angiotensin II type 1 receptor (AT1), transforming growth factor ß1 (TGF-ß1), Smad2/3 mRNA, and protein in myocardial tissue of HFpEF rats. Conclusion. LGQHD can suppress atrial fibrosis in HFpEF by modulating the TGF-ß1/Smad2/3 pathway.

The effectiveness and safety of Chinese Patent Medicines based on syndrome differentiation in patients following percutaneous coronary intervention due to acute coronary syndrome (CPM trial): A nationwide Cohort Study.

BACKGROUND: The incidence of cardiovascular events remains not unusual in patients following percutaneous coronary intervention (PCI) due to acute coronary syndrome (ACS). Chinese patent medicine (CPM) therapy based on syndrome differentiation in addition to conventional medicine (CM) had been expected to further reduce the risk of cardiovascular events. PURPOSE: To assess the effectiveness and safety of CPM based on syndrome differentiation in patients following PCI due to ACS. STUDY DESIGN: Nationwide prospective cohort study. METHODS: CPM study was conducted in 40 centers in mainland China. Patients following PCI due to ACS entered to syndrome differentiation-based CPM (SDCPM) or CM group according to whether they received CPM or not. The CPM comprised Guanxin Danshen dripping pills, Qishen Yiqi dripping pills, or Danlou tablets, and was used correspondingly with the syndrome differentiation of traditional Chinese medicine. The follow-up time was 36 months. The primary endpoint was composed of cardiac death, non-fatal myocardial infarction and urgent revascularization. The secondary endpoint included rehospitalization due to ACS, heart failure, stroke, other thrombotic events. Seattle Angina Questionnaire (SAQ) was used to evaluate quality of life. RESULTS: Between February 2012 and December 2018, ascertainment of the primary endpoint was completed in 2,724 patients of follow-up. 1,380 patients were in SDCPM group. At a median follow-up of 541 (interquartile range 513 - 564) days, the primary endpoint occurred in 126 (8.61%) patients in SDCPM group and 167 (11.62%) patients in CM group (adjusted hazard ratio [HR] = 0.70; [95% confidence interval [CI] 0.55 - 0.89]; p = 0.003). The secondary endpoint occurred in 144 (9.84%) patients in SDCPM group and 197 (13.71%) patients in CM group (adjusted HR = 0.66; [95% CI 0.53 - 0.82]; p < 0.001). The SAQ score in SDCPM group was higher than CM group (366.78 ± 70.19 vs 356.43 ± 73.80, p < 0.001). There were no significant differences of adverse events between two groups. CONCLUSION: In patients following PCI due to ACS, SDCPM in addition to CM treatment reduced the primary and secondary endpoints, as well as improved the quality of life without adverse events.

Diagnostic and prognostic value of serum soluble suppression of tumorigenicity-2 in heart failure with preserved ejection fraction: A systematic review and meta-analysis.

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) is a growing public health burden, with mortality and rehospitalization rates comparable to HF with reduced ejection fraction (HFrEF). The evidence for the clinical usefulness of soluble suppression of tumorigenicity 2 (sST2) in HFpEF is contradictory. Therefore, we conducted the following systematic review and meta-analysis to assess the diagnostic and prognostic value of serum sST2 in HFpEF. Methods: PubMed and Scopus were searched exhaustively from their inception until March 15, 2022. In diagnostic analysis, we compared the diagnostic value of serum sST2 in HFpEF to NT pro-BNP. We separately pooled the unadjusted and multivariate-adjusted hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) in prognostic analysis. Results: A total of 16 publications from 2008 to 2021 were examined. The results of this analysis were as follow: Firstly, compared with NT pro-BNP, sST2 obtains poor diagnostic performance in independently identifying HFpEF from healthy controls, hypertensive patients, and HFrEF patient. Nevertheless, it may provide incremental value to other biomarkers for diagnosing HFpEF and deserves further investigation. Secondly, log sST2 was independently associated with adverse endpoints on multivariable analysis after adjusting for variables such as age, sex, race, and NYHA class. Per log unit rise in sST2, there was a 2.76-fold increased risk of all-cause death [HR:2.76; 95% CI (1.24, 6.16); p = 0.516, I 2 = 0%; P = 0.013] and a 6.52-fold increased risk in the composite endpoint of all-cause death and HF hospitalization [HR:6.52; 95% CI (2.34, 18.19); p = 0.985, I 2 = 0%; P = 0.000]. Finally, the optimal threshold levels of serum sST2 need further determined. Conclusions: Higher sST2 was strongly linked to an increased risk of adverse outcomes in HFpEE. Especially, log sST2 independently predicted all-cause death and the composite endpoint of all-cause death and HF hospitalization. However, prospective and multicenter studies with large-sample and extended follow-up periods are required to validate our results due to limitations in our research.

Clinical Implications of Plasma Galectin-3 in Heart Failure With Preserved Ejection Fraction: A Meta-Analysis.

Background: Heart failure with preserved ejection fraction (HFpEF) is an increasing public health concern. Currently, data regarding the clinical application value of plasma Galectin-3 (Gal-3) in HFpEF are contradictory. Therefore, we performed the following meta-analysis to appraise the clinical implications of serum Gal-3 in HFpEF, including its capacity to predict new-onset disease, long-term unfavorable endpoints, and the degree of cardiac structural abnormality and left ventricular diastolic dysfunction (LVDD). Methods: PubMed, Embase, Scopus, and Web of Science were retrieved exhaustively from their inception until November 30, 2021, to obtain studies assessing the correlation between plasma Gal-3 and the clinical features of HFpEF (new-onset HFpEF, adverse outcomes, and echocardiographic parameters related to abnormal cardiac structure and LVDD). Results: A total of 24 papers containing 27 studies were ultimately included in the present research. The results of the meta-analysis revealed that high plasma Gal-3 levels are strongly associated with the following clinical characteristics of HFpEF: (i) the increased risk of new-onset HFpEF (HR: 1.11; 95% CI: 1.04-1.19; p = 0.910, I2 = 0%; P = 0.002); (ii) the high risk of adverse outcomes of HFpEF patients [all-cause death (HR: 1.55; 95% CI: 1.27-1.87; p = 0.138, I2 = 42%; P = 0.000) and the composite events [all-cause death and HF hospitalization (HR: 1.50; 95% CI: 1.30-1.74; p = 0.001, I2 = 61%; P = 0.000) or cardiovascular (CV) death and HF hospitalization (HR: 1.71; 95% CI: 1.51-1.94; p = 0.036, I2 = 58%; P = 0.000)]; (iii) echocardiographic indices [E/e ratio (r: 0.425, 95% CI: 0.184-0.617; p = 0.000, I2 = 93%; P = 0.001) and DT (r: 0.502, 95% CI: 0.061-0.779; p = 0.001 I2 = 91%; P = 0.027)]. Conclusions: Plasma Gal-3 might be employed as an additional predictor for new-onset HFpEF, the adverse prognosis in HFpEF patients (all-cause death, the composite endpoints of all-cause death and HF hospitalization or CV death and HF hospitalization), and the severity of LVDD in HFpEF populations.

Chinese Medicine Formula Huashibaidu Granule Early Treatment for Mild COVID-19 Patients: An Unblinded, Cluster-Randomized Clinical Trial.

Background: Previous research suggested that Chinese Medicine (CM) Formula Huashibaidu granule might shorten the disease course in coronavirus disease 2019 (COVID-19) patients. This research aimed to investigate the early treatment effect of Huashibaidu granule in well-managed patients with mild COVID-19. Methods: An unblinded cluster-randomized clinical trial was conducted at the Dongxihu FangCang hospital. Two cabins were randomly allocated to a CM or control group, with 204 mild COVID-19 participants in each cabin. All participants received conventional treatment over a 7 day period, while the ones in CM group were additionally given Huashibaidu granule 10 g twice daily. Participants were followed up to their clinical endpoint. The primary outcome was worsening symptoms before the clinical endpoint. The secondary outcomes were cure and discharge before the clinical endpoint and alleviation of composite symptoms after the 7 days of treatment. Results: All 408 participants were followed up to their clinical endpoint and included in statistical analysis. Baseline characteristics were comparable between the two groups (P > 0.05). The number of worsening patients in the CM group was 5 (2.5%), and that in the control group was 16 (7.8%) with a significant difference between groups (P = 0.014). Eight foreseeable mild adverse events occurred without statistical difference between groups (P = 0.151). Conclusion: Seven days of early treatment with Huashibaidu granule reduced the likelihood of worsening symptoms in patients with mild COVID-19. Our study supports Huashibaidu granule as an active option for early treatment of mild COVID-19 in similar well-managed medical environments. Clinical Trial Registration:www.chictr.org.cn/showproj.aspx?proj=49408, identifier: ChiCTR2000029763.

Combination of Hua Shi Bai Du granule (Q-14) and standard care in the treatment of patients with coronavirus disease 2019 (COVID-19): A single-center, open-label, randomized controlled trial.

OBJECTIVE: To evaluate the efficacy and safety of Hua Shi Bai Du Granule (Q-14) plus standard care compared with standard care alone in adults with coronavirus disease (COVID-19). STUDY DESIGN: A single-center, open-label, randomized controlled trial. SETTING: Wuhan Jinyintan Hospital, Wuhan, China, February 27 to March 27, 2020. PARTICIPANTS: A total of 204 patients with laboratory-confirmed COVID-19 were randomized into the treatment group and control group, consisting of 102 patients in each group. INTERVENTIONS: In the treatment group, Q-14 was administered at 10 g (granules) twice daily for 14 days, plus standard care. In the control group, patients were provided standard care alone for 14 days. MAIN OUTCOME MEASURE: The primary outcome was the conversion time for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral assay. Adverse events were analyzed in the safety population. RESULTS: Among the 204 patients, 195 were analyzed according to the intention-to-treat principle. A total of 149 patients (71 vs. 78 in the treatment and control groups, respectively) tested negative via the SARS-CoV-2 viral assay. There was no statistical significance in the conversion time between the treatment group and control group (Full analysis set: Median [interquartile range]: 10.00 [9.00-11.00] vs. 10.00 [9.00-11.00]; Mean rank: 67.92 vs. 81.44; P = 0.051). The recovery time for fever was shorter in the treatment group than in the control group. The disappearance rate of symptoms like cough, fatigue, and chest discomfort was significantly higher in the treatment group. In chest computed tomography (CT) examinations, the overall evaluation of chest CT examination after treatment compared with baseline showed that more patients improved in the treatment group. There were no significant differences in the other outcomes. CONCLUSION: The combination of Q-14 and standard care for COVID-19 was useful for the improvement of symptoms (such as fever, cough, fatigue, and chest discomfort), but did not result in a significantly higher probability of negative conversion in the SARS-CoV-2 viral assay. No serious adverse events were observed. TRIAL REGISTRATION: ChiCTR2000030288.

Efficacy and safety of Chinese herbal medicine versus Lopinavir-Ritonavir in adult patients with coronavirus disease 2019: A non-randomized controlled trial.

BACKGROUND: Treatments for coronavirus disease 2019 (COVID-19) are limited by suboptimal efficacy. METHODS: From January 30, 2020 to March 23, 2020, we conducted a non-randomised controlled trial, in which all adult patients with laboratory-confirmed COVID-19 were assigned to three groups non-randomly and given supportive treatments: Group A, Lopinavir-Ritonavir; Group B, Huashi Baidu Formula (a Chinese medicineformula made by the China Academy of Chinese Medical Sciences to treat COVID-19, which is now in the clinical trial period) and Lopinavir-Ritonavir; and Group C, Huashi Baidu Formula. The use of antibiotics, antiviruses, and corticosteroids was permitted in Group A and B. Traditional Chinese medicine injections were permitted in Group C. The primary outcomes were clinical remission time (interval from admission to the first time the patient tested negatively for novel coronavirus or an obvious improvement was observed from chest CT) and clinical remission rate (number of patients whose clinical time was within 16 days/total number of patients). RESULTS: A total of 60 adult patients with COVID-19 were enrolled at sites in Wuhan, China, and the sample size of each group was 20. In Groups A, B and C, the clinical remission rates were 95.0%%(19/20), 100.0%%(20/20) and 100.0%%(20/20), respectively. Compared with Groups A and B, the clinical remission time of Group C was significantly shorter (5.9 days vs. 10.8 days, p < 0.05; 5.9 days vs. 9.7 days, p < 0.05). There was no significant difference among Groups A, B, and C in terms of the time taken to be released from quarantine. The clinical biochemical indicators and safety indexes showed no significant differences among the three groups. CONCLUSIONS: Our findings suggest that Lopinavir-Ritonavir has some efficacy in the treatment of COVID-19, and the Huashi Baidu Formula might enhance this effect to an extent. In addition, superiority was displayed in the treatment of COVID-19 through a combination of the Huashi Baidu Formula and traditional Chinese medicine injection. In future, well-designed prospective double-blinded randomised control trials are required to confirm our findings.

Effect of Kuanxiong Aerosol () on Patients with Angina Pectoris: A Non-inferiority Multi-center Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris. METHODS: Block randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina. RESULTS: The 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01). CONCLUSIONS: KA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).

Traditional formula, modern application: chinese medicine formula sini tang improves early ventricular remodeling and cardiac function after myocardial infarction in rats.

SINI TANG (SNT) IS A TRADITIONAL CHINESE HERBAL FORMULA CONSISTING OF FOUR DIFFERENT HERBS: the root of Aconitum carmichaelii, the bark of Cinnamomum cassia, the rhizome of Zingiber officinale, and the root of Glycyrrhiza uralensis. This study aims to evaluate the improvement of early ventricular remodeling and cardiac function in myocardial infarction (MI) rats by SNT. A MI model was established by ligation of the left anterior descending coronary artery. Following treatment for 4 weeks, ultrasonic echocardiography was performed. Myocardial histopathological changes were observed using haematoxylin and eosin staining. Collagens (type I and type III), transforming growth factor- ß 1 (TGF- ß 1), and Toll-like receptors (TLR-2 and TLR-4) were measured in plasma, serum, and myocardial tissue. SNT treatment decreased the infarct size, the left ventricular cavity area/heart cavity area ratio, and the left ventricle dimension at end systole and increased the left ventricular ejection fraction. SNT reduced the levels of TLR-2 and TLR-4 in myocardial tissue significantly and decreased the collagens content in serum and in myocardial tissue. SNT could partially reduce the level of TGF- ß 1 in serum and in myocardial tissue. Our data suggest that the Chinese medicine formula SNT has the potential to improve early ventricular remodeling and cardiac function after MI.

[Effect of Kuanxiong aerosol on coronary heart disease angina patients: a multicenter randomized controlled clinical study].

OBJECTIVE: To evaluate the anginal attack-relieving efficacy and safety of Kuanxiong Aerosol (KA) in patients with coronary heart disease (CHD). METHODS: A total of 780 patients confirmatively diagnosed as CHD angina from November 2011 to December 2012 in 13 medical centers in the mainland area were assigned to 2 groups by blocked randomization, the treatment group (376 cases) and the control group (374 cases). When the angina attacked, patients in the treatment group received sublingual spray three times, 0.6 mL each time, while those in the control group sublingually dissolved Nitroglycerin Tablet (NT), 0.5 mg each tablet. The effective rate of angina relief, efficacy of electrocardiogram (ECG), and the incidence of adverse reactions were observed. RESULTS: The 3 min and 5 min remission rates of angina attack were 53.72% (202/376) and 94.41% (355/376) in the treatment group, and 47.86% (179/374) and 90.64% (339/374) in the control group. The 95% confidence interval (CI) of the difference between the 2 groups of 3 min and 5 min remission rates of angina attacks were [(-1.84%, 12.32%) and (-1.33%, 6.85%) respectively, P > 0.05]. The total improvement rates of ST-T changes in the treatment group and the control group after treatment were 74.07% and 73.13% respectively (P > 0.05). The adverse reaction rate was 9.31 (35/376 cases) in the treatment group and 22.46% (84/374 cases) in the control group (P < 0.01). CONCLUSION: KA was not inferior to NT in relieving anginal attacks and improving ischemic ECG changes, and had obviously less adverse reaction.

Anti-inflammatory effects of the chinese herbal formula sini tang in myocardial infarction rats.

The aim of this study was to evaluate the anti-inflammatory profiling of the Chinese herbal formula Sini Tang (SNT) in myocardial infarction (MI) rats. SNT, a decoction consisting of four herbs: Aconitum carmichaelii, Cinnamomum cassia, Zingiber officinale, and Glycyrrhiza uralensis, was characterized as a remedy to treat syndromes corresponding to heart failure and MI in China. Potential biomarkers, which reflect the extent of myocardial necrosis and correlate with cardiac outcomes following MI, such as atrial natriuretic peptide (ANP), high sensitivity C-reactive protein (hs-CRP), and proinflammatory cytokines such as tumor necrosis factor- α , interleukin-6, and interleukin-1 ß (TNF- α , IL-6, and IL-1 ß ) were determined in plasma, serum, and in myocardial tissue of MI rats after treatment with SNT. Our data indicate that SNT decreased significantly the levels of hs-CRP, TNF- α , IL-6, and IL-1 ß in MI rats. SNT decreased the expression of ANP levels in plasma and increased the vascular active marker nitric oxide, which limits vascular inflammation. In addition, SNT could decrease the expression of endothelin-1 levels in rat plasma post-MI. Our data suggest that the Chinese herbal formula SNT has the potential to improve cardiac function after MI. SNT may be a candidate for treating MI and its associated inflammatory responses.

[Application of patient-reported outcome in Chinese medical therapeutic efficacy assessment of cardiovascular diseases and some considerations on it].

Patient-reported outcome (PRO) is one of the important measures for clinical therapeutic efficacy assessment. The current application and development of PRO in China and abroad were introduced in this paper, put stress on the application of PRO in Chinese medical therapeutic efficacy assessment of cardiovascular diseases. Moreover, some suggestions on its further application were offered.

[Effects of water extractives of a qi and blood regulating prescription on early atherosclerosis of apolipoprotein E-deficient mice].

OBJECTIVE: To investigate whether the water extractives of regulating qi and blood prescription (WQBP) had effects on early atherosclerosis of apolipoprotein E-deficient mice (ApoE-mice) at the age of 19 weeks or not, and to explore the possible mechanisms. METHODS: Forty ApoE-mice, six weeks of age, were given high-fat diet and randomly divided into four groups: high-dose WQBP-treated group (360 mg/kg), low-dose WQBP-treated group (72 mg/kg), simvastatin-treated group (25 mg/kg) and untreated group, with ten mice in each group. Meanwhile, ten C57BL/6 mice of same genetic background were allocated to normal control group. Mice in the high- and low-dose WQBP-treated groups and simvastatin-treated group were administered with corresponding drugs from the 15 to 19 weeks. Mice in the untreated and normal control groups were administered with isovolumic water. Sacrificed at 19 weeks, the level of blood-lipid, the plaque construction, plaque integral, and the contents of plaque macrophages and vessel smooth muscle cells of the mice were analyzed by immunohistochemical method and a computer picture processing system. RESULTS: Compared to the untreated group, high-dose WQBP group could obviously decrease the level of low-density lipoprotein cholesterol (LDL-C). Simvastatin group could decrease the levels of LDL-C and total cholesterol (TC) (P<0.01). In high-dose WQBP-treated group and simvastatin-treated group, the thickness of fiber cap and the quantities of vessel smooth muscle cells increased (P<0.05), the quantities of plaque macrophages and the ratio of lipid and plaque reduced (P<0.01). CONCLUSION: WQBP and simvastatin can interfere in early atherosclerosis of ApoE-mice, attenuate and stabilize plaque in some extent. The mechanisms may include adjusting blood lipid, decreasing macrophage number and increasing the quantities of vessel smooth muscle cells.

[Effect of purified xuefu capsule on ultrasonographic figures in patients with carotid atherosclerosis].

OBJECTIVE: To investigate the effect of Purified Xuefu Capsule (PXC) on ultrasonographic figures in patients with carotid atherosclerosis (CAS). METHODS: Ninety-two patients with CAS were randomly divided into two groups, the 45 patients in the treated group were treated by conventional western medicine with additional PXC, the 47 patients in the control group were given conventional western medicine alone. One month's treatment was regarded as one course, and three courses of treatment were given successively to both groups. Carotid ultrasonography was performed before and after treatment, and the figures were compared. RESULTS: The thickness of endangium, average number of plaques, plaque scores, plaque volume index and length of the biggest soft plaque or mixed plaques, stenosis rate of vascular area, and the resistant index of blood vessels were decreased after treated with PXC for 3 months in the treated group. The differences of these indexes in the treated group before and after treatment, and that between the treated group and the control group after treatment were significant (P < 0.01). CONCLUSION: PXC can improve hemodynamics and eliminate atherosclerotic plaque to a certain degree, so it has definite effect for prevention and treatment of CAS.