[Mechanisms of NLRP3 inflammasome-mediated pyroptosis in chronic heart failure and research progress in traditional Chinese medicine].

Chronic heart failure(CHF) is a severe cardiovascular disease characterized by a complex pathogenesis involving myocardial structural and functional abnormalities and the activation of inflammatory responses. The NOD-like receptor thermal protein domain-associated protein 3(NLRP3) inflammasome, acting as a sensor for inflammatory cells, plays a pivotal role in the development of CHF. Research indicates that the activation of the NLRP3 inflammasome can induce inflammatory responses, leading to cardiac inflammation and impairing myocardial function, and it is correlated with the severity of CHF. Traditional Chinese medicine(TCM) has garnered increasing attention as a traditional therapeutic approach in recent years. Various TCM drugs and treatment methods have exhibited potential efficacy in suppressing inflammatory responses, alleviating myocardial cell pyroptosis, improving myocardial structure and function, and inhibiting myocardial fibrosis. Several TCM drugs and their extracts have been utilized in CHF treatment, with mechanisms potentially involving the inhibition of NLRP3 inflammasomes and the mitigation of inflammatory responses. The article provided an overview of the composition, structural characteristics, initiation, and activation modes of the NLRP3 inflammasome, its mechanisms in CHF, and the research progress of TCM in CHF treatment. It aims to offer references and foundations for a deeper understanding of CHF pathogenesis and subsequent development of new therapeutic strategies.

[Shenfu Injection improves chronic heart failure by regulating pyroptosis based on NLRP3/caspase-1 pathway].

This study investigated the mechanisms and targets of Shenfu Injection in the intervention in chronic heart failure(CHF) through the NOD-like receptor thermal protein domain associated protein 3(NLRP3)/caspase-1 signaling pathway. A CHF model was induced in rats by subcutaneous injection of isoproterenol. Model rats were randomly divided into a model group, a Shenfu Injection group, and a MCC950(NLRP3 inhibitor) group, and a blank group was also set up as a control. After 15 days of treatment, echocardiography was performed to measure cardiac function parameters [left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS)]. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of N-terminal pro-brain natriuretic peptide(NT-proBNP), interleukin(IL)-1ß, and IL-18. Hematoxylin-eosin(HE) and Masson staining were used to observe morphological changes in myocardial tissues, and Western blot was used to measure the expression levels of NLRP3/caspase-1 pathway-related proteins [NLRP3, caspase-1, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), IL-1ß, and IL-18]. The study found that isoproterenol-induced CHF in rats resulted in decreased cardiac function, worsened myocardial fibrosis, increased expression levels of NLRP3, ASC, caspase-1, GSDMD-N, IL-1ß, and IL-18 in myocardial tissues, elevated serum inflammatory factors, and induced myocardial cell pyroptosis. Following Shenfu Injection intervention, the Shenfu Injection group showed significantly improved LVEF and LVFS, a significant decrease in NT-proBNP, a marked downregulation of NLRP3, ASC, caspase-1, GSDMD-N, IL-1ß, and IL-18 protein expression levels, reduced serum inflammatory factors IL-1ß and IL-18 expression in CHF rats, and a decrease in the rate of TUNEL-positive cells. Shenfu Injection can significantly improve cardiac function in CHF, inhibit myocardial fibrosis, and alleviate the progression of myocardial cell pyroptosis through the inhibition of the NLRP3/caspase-1 pathway.

[Protective effect of Shenfu Injection on regulation of autophagy in rats with chronic heart failure based on PI3K/Akt/mTOR pathway].

This study aimed to investigate the mechanism and target sites of Shenfu Injection in the intervention of chronic heart fai-lure based on the PI3K/Akt/mTOR autophagy signaling pathway. The chronic heart failure model was induced in rats by subcutaneous injection of isoproterenol. The model rats were randomly divided into model group, Shenfu Injection group, and 3-methyladenine autophagy inhibitor(3-MA) group. A normal group was also set up. After 15 days of administration, cardiac function indexes of the rats were detected by echocardiography. The serum N-terminal pro-B-type natriuretic peptide(NT-proBNP) levels were measured using the ELISA. HE and Masson staining was performed to observe the morphological changes in myocardial tissues, and electron microscopy was used to observe the autophagosomes in myocardial tissues. Western blot was conducted to measure the changes in autophagy-related proteins(LC3 Ⅱ/Ⅰ and p62), PI3K, Akt, mTOR, and phosphorylation levels. The results showed that compared with normal group, model group in rats led to reduced cardiac function, significant activation of cardiac autophagy, increased fibrotic lesions in myocardial tissues, structural disorder of the myocardium, increased autophagosomes, and cytoplasmic vacuolization. Compared with model group, Shenfu Injection group in rats led to cardiac function significantly improved, myocardial fibrosis decreased, and the number of autophagosomes and cytoplasmic vacuolization decreased. The phosphorylation levels of PI3K, Akt, and mTOR were significantly increased(P<0.01). In the 3-MA group, autophagy was inhibited through the activation of the PI3K/Akt/mTOR signaling pathway, resulting in improved cardiac function, reduced myocardial fibrosis, and no significant cytoplasmic vacuolization. The findings suggest that Shenfu Injection can activate the PI3K/Akt/mTOR signaling pathway and inhibit autophagy, thereby improving cardiac function.

[Protective effect of Shenfu Injection on rats with chronic heart failure based on HMGB1/TLR4/NF-κB signaling pathway].

The study aimed to explore the mechanism and targets of Shenfu Injection in the regulation of inflammatory injury in chronic heart failure rats based on the high mobility group box-1/Toll like receptor 4/nuclear factor kappa-B(HMGB1/TLR4/NF-κB) signaling pathway. The rat model of chronic heart failure was established using isoproterenol. The modeled rats were divided into three groups by random number table: the model group, Shenfu group and glycopyrrolate group, and the normal group was also set. The rats were administrated for 15 consecutive days, and on the following day after the last administration, they were sacrificed for sample collection. The cardiac mass index and left ventricular mass index of the rats in each group were measured, and the echocardiogram was used to analyze the cardiac function indices, and ELISA to test the inflammatory indices in rat serum. The pathological morphology and fibrosis status of rat heart tissues were observed by HE staining and Masson staining, respectively. The content of HMGB1 was determined by immunofluorescence staining. The protein and mRNA expression of HMGB1/TLR4/TLR4 signaling pathway was detected by Western blot and RT-qPCR, respectively. The results showed that the chronic heart failure rat model was successfully prepared. The rats in the model group had reduced cardiac function, increased levels of HMGB1 and inflammatory factors(P<0.05), and elevated protein and mRNA expression of HMGB1, TLR4, MyD88, and NF-κB P65 in myocardial tissue(P<0.05), with fibrous connective tissue hyperplasia, inflammatory cell infiltration and severe fibrosis. Shenfu Injection improved cardiac function, decreased the levels of HMGB1 and inflammatory factors(P<0.05) and the protein and mRNA expression of HMGB1, TLR4, MyD88, and NF-κB P65 in myocardial tissue(P<0.05), ameliorated interstitial fibrous connective tissue hyperplasia and inflammatory cell infiltration, and reduced fibrosis. In conclusion, Shenfu Injection can reduce inflammatory damage and improve cardiac function in chronic heart failure rats by regulating the HMGB1/TLR4/NF-κB signaling pathway.

[Animal model analysis of rheumatoid arthritis based on clinical characteristics of Chinese and Western medicine].

Rheumatoid arthritis(RA) is an autoimmune disease involving multiple joints bilaterally with symmetrical polyarthritis as the main symptom. The high disability rate of this disease seriously affects the quality of life of patients and even threatens their lives. The establishment of a good animal model is of great significance for the diagnosis and clinical prevention of RA. Based on the clinical characteristics of RA in traditional Chinese and Western medicine, the common animal models of RA were summarized, including drug-induced, gene-related, and syndrome and disease combined models. Joint swelling, pain, redness, nodules, and joint deformity are the main criteria for model evaluation, which have certain differences from the clinical diagnostic criteria of RA. From the perspective of syndrome differentiation, the animal model combining syndrome and disease only simulates the syndrome of traditional Chinese medicine and has no direct causal relationship with the formation of RA. In this paper, we analyzed the advantages and disadvantages of animal models of RA and the coincidence degree of the models with the clinical characteristics and then put forward the corresponding recommendations for the evaluation and improvement of these models, aiming to make the animal models of RA closer to the clinical symptoms and play an important role in the clinical diagnosis and treatment of RA.

[Analysis of animal models of hypertension based on characteristics of clinical symptoms of Chinese and western medicine].

Hypertension, a cardiovascular disease with main clinical manifestations of dizziness and elevated blood pressure, especially elevated arterial pressure, features high prevalence rate and low control rate, which affects patients' quality of life. Therefore, establishing a good animal model of hypertension is of great significance for its diagnosis and clinical prevention and treatment. Based on the clinical characteristics of hypertension in traditional Chinese and western medicine, this study summarized the advantages and disadvantages of current hypertension animal models: gene-related model, surgery-caused model, drug-induced model, and environment-induced model, and investigated the similarity to the clinical symptoms in traditional Chinese medicine and Western medicine. Among them, spontaneously hypertensive rats, models established with the surgical two-kidney one-clip, one-kidney one-clip, two-kidney two-clip, and abdominal aorta constriction methods, models induced with the drug deoxycorticosterone acetate, and models induced with the high-fat high-purine diet showed symptoms highly similar to the clinical manifestations. Then, the corresponding evaluation and improvement methods of hypertension animal models were proposed. This study provides suggestions for the establishment of hypertension animal model so that the symptoms are more similar to the clinical characteristics of hypertension in traditional Chinese and Western medicine, which is important for the clinical diagnosis and treatment of hypertension.

The Efficacy of the Yasmin[Ethinylestradiol-Drospirenone (0.03/3 mg)] Treatment for Postoperative Abortion: A Protocol of Meta-Analysis.

Background: Induced abortion is a universal phenomenon and about 25% of pregnancies in the world end in induced abortion. Induced abortion refers to the use of artificial or drug methods to terminate the pregnancy in the early stage of pregnancy, which is a remedy for failed contraception and accidental pregnancy. Induced abortion means surgical abortion. There are two commonly used methods: negative pressure suction abortion and forceps curettage for induced abortion. Abortion is invasive and it will cause great harm to women's reproductive function. Clinically, there are also cases of re-pregnancy within 3 months after abortion or even re-pregnancy without recovery of menstruation. To improve symptoms and reduce these complications, antibiotics, motherwort, and Yasmin[Ethinylestradiol-Drospirenone (0.03/3 mg)] are clinically used alone or in combination after induced abortion. Methods: Data were collected from six databases, including three English databases of Cochrane Library, PubMed and Embase, and three Chinese databases of CNKI, Wanfang, and Weipu. The original indicators of vaginal bleeding, menstrual recovery time, bleeding time, endometrial thickness 21 days after surgery and so on were included, and the incidence of postoperative bleeding less than menstrual volume, menstrual re-fluid time ≤ 37 days, bleeding time ≤ 7 days, re-pregnancy without menstruation, re-pregnancy within 3 months after the operation, the total incidence of postoperative complications were based on the ratio of the number of events in the group to the total number of people in the group reported in the literature. Review Manager 5.4 software was downloaded from the Cochrane website to evaluate the quality of the literature and analyze the results using random or fixed-effects models. The outcome of index data is divided into two types, one is dichotomy, and the other is measurement data. The binary data is expressed by odds ratio (OR), and the measurement data is expressed by mean difference (MD), and the confidence interval of both is 95%. Results: After completing this meta-analysis, the results will be available. Conclusion: The results will provide reliable data basis for the value of Yasmin combined with antibiotics and Motherwort in postoperative induced abortion. PROSPERO Registration Number: CRD42021246764.

The efficacy of mifepristone combined with methotrexate for the treatment of ectopic pregnancy: a systematic review and meta-analysis.

OBJECTIVE: Systematically evaluate the clinical efficacy of mifepristone combined with methotrexate therapy for ectopic pregnancy (EP), analyze the experimental designs, put forward improvement ideas. METHODS: RCTs of mifepristone combined with mifepristone for EP until January 2022 in six databases were searched. The primary outcome indicator was the cure rate. RevMan 5.4 was used to analyse and the online GRADEpro tool was used to assess the certainty of the evidence. RESULTS: Twenty-five RCTs involved 2263 patients. The cure rate was higher in the investigational group (OR = 4.09, 95%CI: [3.20, 5.22]), time of vagina stopped bleeding (MD = -11.21, 95%CI: [-11.85, -10.57]) and time of abdominal pain disappeared (MD = -6.24, 95%CI: [-6.63, -5.86]) were shorter in the investigational group, ß-HCG level (MD = -585.32, 95%CI: [-609.62, -561.03]) was lower and diameter of the mass (MD = -1.23, 95%CI: [-1.40, -106]) was smaller in the investigational group. The certainty of the evidence for most outcomes was moderate or high, and only one was low. CONCLUSIONS: The combination of mifepristone and methotrexate can improve the efficacy of ectopic pregnancy without amplifying the toxic side effects. Larger scale and better design of the randomized controlled trials are needed.KEY MESSAGESIn recent years, the increase in ectopic pregnancies and their impacts on female fertility makes physicians have to find an effective medical treatment as soon as possible that can avoid surgery.The mifepristone combined with methotrexate therapy for EP has better curative effects on improving the cure rate, lowering ß-HCG level, reducing the mass, and alleviating symptoms of abdominal pain and bleeding, without amplifying the toxic side effects.Literature with high quality is lacking, and well-designed, large-scale and high-quality multicenter randomized controlled trials are needed.

Acupuncture against the metabolic risk factors for stroke: A systematic review of systematic reviews.

OBJECTIVE: This systematic review (SR) of SRs aims aimed to evaluate the current evidence of rehabilitation interventions in stroke patients after acupuncture treatment. METHODS: Full-text SRs published in Chinese and English up to December 15, 2021 were searched in PubMed, Embase, Cochrane Library, CNKI, VIP, and Wanfang databases. The PRISMA statement and the assessment of multiple systematic reviews 2 (AMSTAR 2) scale were used to evaluate the quality of the included articles. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was employed to assess the outcome indicators for evidence quality evaluation. RESULTS: A number of 42 publications were identified in this study. According to these articles, 4 metabolic areas were identified: systolic blood pressure, weight loss, glycemic index and cholesterol. The acupuncture is beneficial to improve the systolic blood pressure of patients, and the effect of acupuncture on diastolic blood pressure is better than that of sham acupuncture. The weight loss effect of acupuncture is better than that of lifestyle and western medicine. The improvement effect of acupuncture on body mass index (BMI) is also better than that of sham acupuncture. In the study of glycemic index of stroke patients, acupuncture significantly improved glycosylated hemoglobin and insulin sensitivity index compared with western medicine. In cholesterol-related research, acupuncture can effectively improve the content of triglycerides. However, studies on HDL and LDL show that acupuncture can significantly improve HDL, but has no significant effect on LDL. CONCLUSION: This review summarizes the available evidence and underpins findings of the acupuncture exhibited the therapeutic role in eliminating metabolic risk factors for stroke, including systolic blood pressure, weight loss, glycemic index and cholesterol. Acupuncture could have positive effects on a specific symptom, and the effects depend not only on intervention type but also on how and when the intervention is provided. And more prioritizing high-quality research in this field in the future is conducive to guiding clinical practice.

Test-Retest Reliability of the Coronary Heart Disease Damp Phlegm and Blood Stasis Pattern Questionnaire: Results from a Multicenter Clinical Trial.

BACKGROUND: Damp phlegm and blood stasis pattern (DPBSP) is the main pattern in coronary heart disease (CHD) patients. To quantify and standardize the diagnosis of DPBSP, questionnaires are usually administered. The CHD Damp Phlegm and Blood Stasis Pattern Questionnaire (CHD-DPBSPQ) is the standard metric for measuring CHD-DPBSP signs and symptoms in practice and clinical research. The CHD-DPBSPQ has moderate diagnostic efficiency, as evidenced by its receiver operating characteristic curves. Furthermore, and high reliability and validity have been shown in some studies but not in a multicenter clinical trial. Our purpose was to evaluate the test-retest reliability of a proprietary CHD-DPBSPQ. METHODS: The CHD-DPBSPQ uses a standard procedure for measuring symptoms. The (interrater) reliability and validity of this questionnaire have been previously studied. Here, we evaluated the test interval and weighted kappa value of items of test-retest (intrarater) reliability of the CHD-DPBSPQ. The test-retest reliability was evaluated by the intraclass correlation coefficient (ICC) for the total CHD-DPBSPQ score and the phlegm domain and blood stasis domain scores. Weighted kappa statistics were calculated for the individual CHD-DPBSPQ items. RESULTS: Using the CHD-DPBSPQ, 79 patients with late-stage CHD who were participating in a multicenter clinical trial were assessed twice. The ICCs for the CHD-DPBSPQ score were as follows: 0.827 for the total CHD-DPBSPQ, 0.778 for the phlegm domain score, and 0.828 for the blood stasis domain score. The reliability was slightly better in patients whose test interval was ≤14 days. The weighted kappa values of individual items showed moderate consistency. CONCLUSIONS: The CHD-DPBSPQ was found to have excellent test-retest reliability in this sample of patients.

A novel approach to devise the therapy for ventricular fibrillation by epicardial delivery of lidocaine using active hydraulic ventricular attaching support system: An experimental study in rats.

Active hydraulic ventricular attaching support system (ASD) placed around the heart is not only a novel, nontransplant surgical device used for epicardial administration of drugs like lidocaine, but also a promising treatment option for ventricular fibrillation (VF) and arrhythmias. We hypothesize that lidocaine in 5 mg/kg dose released by ASD significantly improves the VF in the rat model. Sprague-Dawley (SD) rats were selected and were divided into four groups, intravenous injection (IV), epicardial infusion (EI), ASD, and control. ASD group was further divided into four subgroups for different lidocaine doses (i) ASD+A group (10 mg/kg), (ii) ASD+B group (5 mg/kg), (iii) ASD+C group (1 mg/kg), and (iv) ASD+D group (0.1 mg/kg). VF was induced with calcium chloride injection and was confirmed by electrocardiogram (ECG) in all the groups. VF was treated with different doses of lidocaine using different modes of administration. Data were analyzed using the SPSS 19.0 Chi-square tests and one-way analysis of variance (ANOVA). The Kaplan-Meier curve for OS was compared to the Logrank test based on the survival time. P < 0.05 was considered as statistically significant. ASD + B group (5 mg/kg) showed significantly reduced sgroup. The time of first sinus rhythm recovered (15.96 ± 21.77 min) and ▵T-SOD in plasma (-42.02 ± 26.99 U/mL) was significantly different than that of control, IV, and EI groups. ▵T-SOD in plasma for all ASD-treated groups was smaller than the control and IV groups. This study proves that ASD with 5 mg/kg lidocaine dose appears as a promising therapeutic platform for treating VF in rats. Furthermore, ASD may also have potential for treating VF or other cardiovascular disease with different therapeutic agents. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1722-1731, 2019.

Role of oxidative stress in pathology of chronic prostatitis/chronic pelvic pain syndrome and male infertility and antioxidants function in ameliorating oxidative stress.

Oxidative stress (OS) is a result of the imbalance between reactive oxygen species (ROS) and antioxidants in the body that can cause tissue damage. Oxidative stress has a significant involvement in the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and male infertility. CP/CPPS is a major risk factor for male infertility due to generation of excessive ROS that damage sperm DNA, lipids, and proteins, resulting in compromised vitality and decreased sperm motility. Here we present a comprehensive review of oxidative stress relevance in CP/CPPS and male infertility, and embody the protective effects of antioxidants against ROS. An online literature was searched using the following keywords/terms: oxidative stress, ROS, Oxidative stress and chronic prostatitis, oxidative stress and male infertility and antioxidants. Original and review articles, clinical trials, and case reports of human and animal studies published till 2017 were searched using the PubMed and MEDLINE.

A novel mouse model of chronic prostatitis/chronic pelvic pain syndrome induced by immunization of special peptide fragment with aluminum hydroxide adjuvant.

OBJECTIVES: CP/CPPS is a commonly observed distress in male patients. Because of its little-known etiology, no effective therapy has been developed which has promising outcomes. Therefore, there is a need to develop a valid model which can mimic the etiology of CP/CPPS. MATERIALS AND METHODS: Fifty male C57BL/6 mice were randomly and averagely divided into 5 groups of 10 mice each. The control group was injected with 0.9% NaCl solution. Aluminum hydroxide and T2 groups were injected with aluminum hydroxide adjuvant and T2 peptide. T2 plus complete Freund adjuvant (CFA) with aluminum hydroxide group was injected with a mixture of T2, CFA and aluminum hydroxide adjuvant. At the same time, CFA group was injected with complete Freund adjuvant. Hematoxylin-eosin stain and immunohistochemistry were used to investigate inflammatory lesion and expression of IL-ß1. Furthermore, TNF-α and CRP protein levels were evaluated by using commercially available ELISA kits. The ANOVA test was used to compare the statistical differences among groups. RESULTS: Prostates from a mixture of T2 plus CFA with aluminum hydroxide immunized mice showed elevated lesions and high level of inflammatory cells infiltration compared to the other groups. In addition, the levels of TNF-α, IL-ß1, and CRP were also higher in the T2 plus CFA with aluminum hydroxide group as compared to the other groups. CONCLUSION: Our results showed that T2 with CFA plus aluminum hydroxide adjuvant injection could successfully induce CP/CPPS in mice. This autoimmune novel model provides a useful, economic, safer, and easy tool for exploring the etiology and pathophysiology of CP/CPPS which will improve the therapeutic outcomes.

Exo-organoplasty interventions: A brief review of past, present and future directions for advance heart failure management.

Heart failure (HF) is a debilitating disease in which abnormal function of the heart leads to imbalance of blood demand to tissues and organs. The pathogenesis of HF is very complex and various factors can contribute including myocardial infarction, ischemia, hypertension and genetic cardiomyopathies. HF is the leading cause of death and its prevalence is expected to increase in parallel with the population age. Different kind of therapeutic approaches including lifestyle modification, medication and pacemakers are used for HF patients in NYHA I-III functional class. However, for advance stage HF patient's (NYHA IV), ventricle assist devices are clinically use and stem cells are under active investigation. Most of these therapies leads to modest symptoms relief and have no significant role in long-term survival rate. Currently there is no effective treatment for advance HF except heart transplantation, which is still remain clinically insignificant because of donor pool limitation. As HF is a result of multiple etiologies therefore multi-functional therapeutic platform is needed. Exo-organoplasty interventions are studied from almost one century. The major goals of these interventions are to treat various kind of heart disease from outside the heart muscle without having direct contact with blood. Various kind of interventions (devices and techniques) are developed in this arena with the passage of time. The purpose of this review is to describe the theory behind intervention devices, the devices themselves, their clinical results, advantages and limitations. Furthermore, to present a future multi-functional therapeutic platform (ASD) for advance stage HF management.

A novel ventricular restraint device (ASD) repetitively deliver Salvia miltiorrhiza to epicardium have good curative effects in heart failure management.

A novel ventricular restraint is the non-transplant surgical option for the management of an end-stage dilated heart failure (HF). To expand the therapeutic techniques we design a novel ventricular restraint device (ASD) which has the ability to deliver a therapeutic drug directly to the heart. We deliver a Traditional Chinese Medicine (TCM) Salvia miltiorrhiza (Danshen Zhusheye) through active hydraulic ventricular support drug delivery system (ASD) and we hypothesize that it will show better results in HF management than the restraint device and drug alone. SD rats were selected and divided into five groups (n=6), Normal, HF, HF+SM (IV), HF+ASD, HF+ASD+SM groups respectively. Post myocardial infarction (MI), electrocardiography (ECG) showed abnormal heart function in all groups and HF+ASD+SM group showed a significant therapeutic improvement with respect to other treatment HF, HF+ASD, and HF+SM (IV) groups on day 30. The mechanical functions of the heart such as heart rate, LVEDP, and LVSP were brought to normal when treated with ASD+SM and show significant (P value<0.01) compared to other groups. BNP significantly declines in HF+ASD+SM group animals compared with other treatment groups. Masson's Trichrome staining was used to study histopathology of cardiac myocytes and quantification of fibrosis was assessed. The large blue fibrotic area was observed in HF, HF+ASD, and HF+SM (IV) groups while HF+ASD+SM showed negligible fibrotic myocyte at the end of study period (30days). This study proves that novel ASD device augments the therapeutic effect of the drug and delivers Salvia miltiorrhiza to the cardiomyocytes significantly as well as provides additional support to the dilated ventricle by the heart failure.