[Treatment of Chronic Heart Failure with Carotid Plaque Patients by Yiqi Huoxue Tongyang Xezhuo Recipe].

OBJECTIVE: To evaluate the clinical effectiveness of Yiqi Huoxue Tongyang Xiezhuo Recipe (YHTXR, capable of supplementing qi, activating blood, warming yang, and discharge turbidity) in treating coronary atherosclerotic heart disease (CAHD). and chronic heart failure (CHF) with carotid plaque patients, and to explore new ways of Chinese medicine (CM). METHODS: Totally 69 CAHD-CHF patients of qi deficiency phlegm stasis syndrome (QDPSS) with carotid plaque were recruited in this study using parallel cohort method. They were assigned to the treatment group (35 cases) and the control group (34 cases). Patients in the control group received routine treatment of Western medicine, while those in the treatment group were additionally treated with YHTXR (twice daily). The therapeutic course for all was three months. Cardiac function levels, echocardiography, carotid plaque, blood lipids and safety indicators were observed before and after treatment. RESULTS: After treatment the improvement of cardiac function levels was better in the treatment group than in the control group (P < 0.05). Decreased LDL-C levels were higher in the treatment group than in the control group (P < 0.01). There was statistical difference in left ventricular ejection fraction (LVEF), carotid intima-media thickness (IMT), LDL-C, TC, TG in the treatment group between before and after treatment (P < 0.05). LDL-C and TG also decreased in the control group after treatment (P <0.05). There was no significant difference in the left ventricular ejection fraction, carotid IMT, or TC in the control group between before and after treatment (P > 0.05). There was no significant difference in stroke volume, left ventricular end-diastolic diameter, the area of carotid artery plaque, or HDL-C in the two groups between before and after treatment (P > 0.05). CONCLUSIONS: YHTXR could effectively improve cardiac functions of CAHD-CHF patients of QDPSS with carotid plaque, reduce blood lipids and IMT. It had no significant adverse reactions for elderly patients in short term.

Multimodal imaging of bilateral retinal pigment epithelial immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition.

OBJECTIVE: To describe multimodal imaging of peculiar bilateral globular subretinal deposits and acquired serous retinal detachment in patients with systemic immunoglobulin light chain deposition. DESIGN: A retrospective observational case series. PARTICIPANTS: We examined six eyes in three patients (one with multiple myeloma, one with membranous nephropathy, and one with immunoglobulin A nephropathy) at the Eye and ENT Hospital of Fudan University. The patients presented with peculiar globular subretinal deposits along the retinal pigment epithelium (RPE)‒Bruch's membrane complex and acquired serous retinal detachment. METHODS: Fundus appearance was documented with multimodal imaging, which included fundus photography, fundus autofluorescence, spectral domain optical coherence tomography (OCT), swept-source OCT (SS-OCT), en-face OCT, and SS-OCT angiography. Additional evaluations included serum protein electrophoreses, positron emission tomography computed tomography, and renal and bone biopsies to assess the primary diseases. MAIN OUTCOME MEASURES: Multimodal imaging, course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. RESULTS: Bilateral, multiple, speckled, or patchy RPE changes in the posterior fundus that corresponded to striking multifocal hyperautofluorescence on fundus autofluorescence and lumpy, globular hyperreflective deposits along the RPE‒Bruch's membrane complex were identified as characteristic features of bilateral RPE light chain deposition. These features may be accompanied by dense light chain deposits in the choriocapillaris and choroid vessels, diffuse choroidal thickening, and "angiographically silent" serous retinal detachment in patients with systemic immunoglobulin light chain deposition. CONCLUSIONS: We have documented the characteristic features, clinical course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. Appropriate evaluations, including serum protein electrophoresis and hematologic consultation, are recommended to manage patients with this fundus abnormality.

A double-blinded, placebo-controlled randomized trial evaluating the efficacy and safety of Zhigancao Tang granules for treating HFpEF: study protocol for a randomized controlled trial.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a clinical syndrome characterized by diastolic dysfunction. Despite the increasing incidence of HFpEF, there is no available therapy that reduces the mortality rate of HFpEF. Zhigancao Tang has been used traditionally for the treatment of cardiovascular diseases in China. The use of traditional Chinese medicine (TCM) is associated with improvements in clinical syndromes and quality of life of patients. A randomized clinical trial should be conducted to provide clear evidence regarding the efficacy and safety of Zhigancao Tang granules for the treatment of HFpEF. METHODS: A randomized, double-blinded, placebo-controlled clinical trial was proposed. A total of 122 patients with HFpEF will be randomly assigned to receive Zhigancao Tang granules or placebo for 12 weeks. The primary outcome measure is cardiac function. The secondary outcomes include measurement of the integral TCM syndrome score, echocardiography, 6-min walk test, N-terminal-pro hormone B-type natriuretic peptide level, atrial natriuretic peptide level, Minnesota Living with Heart Failure scale, and Lee's scale. The outcome measures will be evaluated at baseline, 4 weeks, and 12 weeks. Adverse events will be evaluated from baseline till the 12-week follow-up period. DISCUSSION: The results of this trial will demonstrate whether Zhigancao Tang granules are effective and safe for treating HFpEF. TRIAL REGISTRATION: ClinicalTrials.gov NCT04317339 . Registered on 23 March 2020.

Huatan Dingji Decoction intervening in atrial fibrillation: protocol for a randomized double-blind single-simulated placebo-controlled clinical trial.

BACKGROUND: Atrial fibrillation (AF) is one of the most common cardiac arrhythmias and can lead to heart failure (HF), stroke, pulmonary embolism (PE), and other complications, seriously affecting people's quality of life and health. Western medicine is limited in the treatment of AF, while Traditional Chinese Medicine (TCM) has unique advantages, such as less side effects, low toxicity, long effect duration, and high compliance. The prescription of HTDJ is a common prescription for the treatment of atrial fibrillation in Longhua Hospital, Shanghai University of Traditional Chinese Medicine. It has been used for many years and has a large number of clinically effective cases. It has a good clinical application prospect, but there is a lack of effective evaluation of its clinical efficacy. METHOD: This study adopts a randomized double-blind, single-simulated, placebo-controlled research method. Participants were randomly assigned in a 1:1 ratio through a centrally controlled, computer-generated, simple randomization schedule. Participants would take the medicine for 1 month, and the curative effect would be evaluated. Subsequently, the participants would not take TCM and only receive western medicine treatment. They would be followed up for another 8 weeks, and a clinical evaluation would be conducted. The secondary outcomes include echocardiography, Hamilton Anxiety Scale, Hamilton Depression Scale, rate of increase and decrease of anti-arrhythmia western medicine, the MOS 36-item short-form health survey, N-terminal-pro hormone B-type natriuretic peptide level, and integral TCM syndrome score. Adverse events will be monitored throughout the trial. Cases are from outpatient and inpatient with atrial fibrillation in the Cardiology Department of Longhua Hospital. Evaluations will be conducted at baseline and at weeks 4 and 12 after randomization. DISCUSSION: In this study, the efficacy and safety of HTDJ plus western medicine in the treatment of atrial fibrillation (qi deficiency and phlegm opacities) will be evaluated, so as to provide medical evidence of short-term and medium-term clinical efficacy for the treatment of atrial fibrillation with integrated traditional and western medicine and lay a foundation for further clinical development and application. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2000030517 . Registered on March 5, 2020, with the Chinese Clinical Trial Registry.

Efficacy and Safety of Different Aerobic Exercise Intensities in Patients With Heart Failure With Reduced Ejection Fraction: Design of a Multicenter Randomized Controlled Trial (HF-EI Trial).

Background: Heart failure (HF) is one of the major causes of mortality worldwide, representing the terminal stage of several cardiovascular diseases. Exercise-based rehabilitation is a beneficial therapy for patients with chronic heart failure (CHF). However, there is a lack of specific guidance on clinical decision-making regarding optimal exercise intensity. It is necessary to optimize the clinical recommendations for HF exercises. We will evaluate the efficacy and safety of different aerobic exercise intensities in patients with heart failure with reduced ejection fraction (HFrEF): the HF-EI trial. This trial aims to assess the appropriate exercise intensity for patients with HFrEF. Methods: After a baseline assessment to determine the safety of exercise, 180 patients will be randomly assigned to supervised high-intensity exercise training (ET) group, supervised moderate intensity training (MIT) group, and control group at a ratio of 1:1:1. Patients randomly receiving high intensity training (HIT) undergo supervised ET (3 times/week, 30 min) for aerobic endurance at 70% peak oxygen consumption (peak VO2) intensity for 12 weeks. The MIT patients will perform supervised aerobic ET (3 times/week, 35-42 min) at the anaerobic threshold (AT) intensity for 12 weeks. The control group will continue to maintain their daily activities and will not receive ET. During the baseline and follow-up period, physical examination, laboratory tests, cardiology diagnostic tests, cardiopulmonary exercise tests (CPET), 6-min walk distance (6MWD), scale scores, exercise steps, medications, and clinical events will be monitored. Throughout the research, sport bracelets and patient diaries will be used to monitor and record overall physical activity, training courses, and compliance. Discussion: The HF-EI trial will evaluate the effects of different aerobic exercise intensities on peak VO2, quality of life (QoL), and clinical events among patients with HFrEF. The findings of this trial will provide a basis for formulating exercise prescriptions for patients with HFrEF. Clinical Trial Registration:http://www.chictr.org.cn/, identifier: ChiCTR2000036381.

Pro-angiogenesis effect and transcriptome profile of Shuxinyin formula in zebrafish.

BACKGROUND: Angiogenesis plays a critical role in ischemia disease like coronary heart disease. Shunxinyin formula has been developed for treating coronary heart disease according to the principle of traditional Chinese medicine while its underlying mechanism is not fully elucidated. PURPOSE: Here, we hypothesize Shuxinyin formula could promote angiogenesis and microcirculation, and the underlying mechanism is also investigated. METHODS: We established the chemical profile of Shuxinyin (SXY) extract utilizing a UHPLC-Q/Exactive analysis system and evaluated its pro-angiogenesis effect in zebrafish model. The underlying mechanisms were investigated by combination of pharmacological experiments with transcriptome analysis in zebrafish. Zebrafish treated with VEGF was served as the positive control in present study. RESULTS: We found SXY significantly enhanced the sub-intestinal vessel plexus (SIVs) growth in zebrafish. Co-treatment and post-treatment SXY attenuated VEGF receptor tyrosine kinase inhibitor II (VRI)-induced deficiency of intersegmental vessels (ISVs) in a concentration dependent manner. Post-treatment VEGF, which is a well-known angiogenesis driver, also partially ameliorated VRI-induced ISVs deficiency. In addition, SXY inhibited the down-regulation of VEGF receptors, including kdr, flt1 and kdrl, induced by VRI in zebrafish. The pro-angiogenesis effect of SXY on VRI-induced ISVs deficiency was suppressed by PI3K and JNK inhibitors, and Akt inhibitor abolished the pro-angiogenesis effect of SXY. The transcriptome profile of SXY preventing from VRI-induced vascular growth deficiency revealed that the underlying mechanisms were also co-related to cell junction, apoptosis and autophagy. CONCLUSION: We could conclude that SXY presented pro-angiogenesis effect and the action mechanisms were involved in VEGF/PI3K/Akt/MAPK signaling pathways, cell junction, apoptosis and autophagy.

Spatholobi Caulis extracts promote angiogenesis in HUVECs in vitro and in zebrafish embryos in vivo via up-regulation of VEGFRs.

ETHNOPHARMACOLOGICAL RELEVANCE: Spatholobi Caulis is a traditional blood-activating and stasis-dispelling herb medicine, which has been used to treat diseases related to blood stasis syndrome (BSS) by inhibiting platelet aggregation, stimulate hematopoiesis, etc. It has been demonstrated that pro-angiogenesis could improve BSS. However, the pro-angiogenic activity of Spatholobi Caulis was not well elucidated AIM OF STUDY: To determine the potential pro-angiogenic activity of Spatholobi Caulis and elucidate its underlying mechanism. The active fractions of Spatholobi Caulis were further screened. MATERIAL AND METHODS: Gelatin precipitation and reversed-phase liquid chromatography (RPLC) were used to purify the methanol extracts of Spatholobi Caulis, respectively. The RPLC was also used to prepare fractions. Total flavonoids of purified methanol extracts of Spatholobi Caulis (PSC) were determined using ultraviolet spectrophotometry. The morphological observation of subintestinal vessel plexus (SIVs) and tyrosine kinase inhibitor II (VRI)-induced intersegmental blood vessels (ISVs) loss in transgenic zebrafish Tg(fli-1a: EGFP)y1 were selected to evaluate the pro-angiogenic activity of PSC in vivo. Cell proliferation by MTT assay and cell migration assay were used to evaluate the pro-angiogenesis effect of PSC in human umbilical vein endothelial cells (HUVECs) in vitro. Both zebrafish and HUVECs were used in screening active fractions of PSC. The mechanism of PSC promoting angiogenesis were studied by real-time PCR in zebrafish and western blotting in HUVECs. RESULTS: Co-treatment PSC dramatically rescued VRI-induced ISVs loss in zebrafish embryos in a dose-dependent manner and 80% of the defective vascular recovered at the concentration of 30µg/ml compared with VRI-only group. PSC also concentration-dependently increased average sprouting number and diameter of SIVs in zebrafish embryo. Real-time PCR assay proved that PSC significantly restored the down regulation of VEGFRs including Flt-1, Kdr and Kdrl induced by VRI in zebrafish (P<0.001). Furthermore, PSC not only promoted proliferation and migration of normal HUVECs but also ameliorated VRI-induced HUVECs cytotoxicity. Western blotting assay showed that co-treatment of PSC increased the expression of VEGFRs and phosphorylation of MAPKs which decreased by VRI treatment. In addition, quality evaluation experiments showed that the content of total flavonoids of PSC reached 56.36% and the main pro-angiogenic fractions of PSC were F3, F4 and F5 both in zebrafish and HUVECs. CONCLUSIONS: Our data demonstrated that PSC presented pro-angiogenic activity both in zebrafish and HUVECs, and principal pro-angiogenic active components were likely flavonoids. Thus, the current study provided evidence for the clinical usage of Spatholobi Caulis in promoting blood circulation and removing stasis in traditional Chinese medicine (TCM).

Ferulic acid relaxed rat aortic, small mesenteric and coronary arteries by blocking voltage-gated calcium channel and calcium desensitization via dephosphorylation of ERK1/2 and MYPT1.

Ferulic acid, a natural ingredient presents in several Chinese Materia Medica such as Radix Angelicae Sinensis, has been identified as an important multifunctional and physiologically active small molecule. However, its pharmacological activity in different blood vessel types and underlying mechanisms are unclear. The present study was to investigate the vascular reactivity and the possible action mechanism of FA on aorta, small mesenteric arteries and coronary arteries isolated from Wistar rats. We found FA dose-dependently relieved the contraction of aorta, small mesenteric arteries and coronary arteries induced by different contractors, U46619, phenylephrine (Phe) and KCl. The relaxant effect of FA was not affected by L-NAME (eNOS inhibitor), ODQ (soluble guanylate cyclase inhibitor), and mechanical removal of endothelium in thoracic aortas. The contraction caused by 60mM KCl (60K) was concentration-dependently hindered by FA pretreatment in all three types of arteries. In Ca2+-free 60K solution, FA weakened Ca2+-related contraction in a concentration dependent manner. And FA relaxed both fluoride and phorbol ester which were PKC, ERK and Rho-kinase activators induced contraction in aortic rings with or without Ca2+ in krebs solution. Western blotting experiments in A7r5 cells revealed that FA inhibited calcium sensitization via dephosphorylation of ERK1/2 and MYPT1. Furthermore, the relaxation effect of FA was attenuated by verapamil (calcium channel blocker), ERK inhibitor, and fasudil (ROCK inhibitor). These results provide evidence that FA exhibits endothelium-independent vascular relaxant effect in different types of arteries. The molecular mechanism of vasorelaxation activity of FA probably involved calcium channel inhibition and calcium desensitization.