Integrated network pharmacology and metabolomics to explore the mechanisms of Shenzao dripping pill against chronic myocardial ischemia

Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic effects.The objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat model.Methods:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of SZDP.The integration of network pharmacology and metabolomics was conducted to investigate the mechanisms.Molecular docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated targets.Results:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart damage.Metabolomics results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for CMI.Integrating network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl formamidocarboxamide.Conclusion:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.

Liqi Huoxue dripping pill protects against myocardial ischemia-reperfusion injury via the PI3K/Akt/GSK-3β signaling pathway in rats

Background:Liqi Huoxue dripping pill(LQHXDP),a traditional Chinese drug for coronary heart disease,has a protective effect on the heart of rats with myocardial ischemia-reperfusion injury(MIRI)in previous studies;however,its mechanism of action remains unclear.The purpose of this study was to investigate the protective mechanism of LQHXDP on MIRI in rats and its relationship with the PI3K/Akt signaling pathway.Methods:In this study,Sprague-Dawley rats were pre-infused with LQHXDP(175 mg/kg/d)for 10 days.PI3K inhibitor LY294002(0.3 mg/kg)was intravenously injected 15 minutes before ischemia.The rat model of MIRI was established by ligating the left anterior descending coronary artery.Subsequently,cardiac hemodynamics,serum myocardial injury markers,inflammatory factors,myocardial infarct size,antioxidant indexes,myocardial histopathology,and phosphorylation levels of key proteins of PI3K/Akt signaling pathway were assessed in rats.Results:LQHXDP was found to improve cardiac hemodynamic indexes,reduce serum creatine kinase MB isoenzyme activity and cardiac troponin and heart-type fatty acid binding protein levels,lower serum interleukin-1 beta,interleukin-6 and tumour necrosis factorαlevels,reduce the myocardial infarct size and enhance the antioxidant capacity of myocardial tissue in MIRI rats.Pathological analysis revealed that LQHXDP attenuated the extent of myocardial injury and protected mitochondria from damage in MIRI rats.Immunoblot analysis revealed that LQHXDP increased the expression levels of p-Akt and p-GSK-3βin MIRI rat cardiomyocytes.PI3K inhibitor LY294002 could impair these effects of LQHXDP.Conclusion:LQHXDP attenuated myocardial injury,attenuated oxidative stress injury and reduced inflammatory response in MIRI rats,and its protective effects were mediated by activating of PI3K/Akt/GSK-3βsignaling pathway.

Formation of mono-dispersed droplets with electric periodic dripping regime in electrohydrodynamic(EHD) atomization

The formation of controllable size and dripping frequency in electrohydrodynamic(EHD)atomization with electric periodic dripping regime are of much interest and importance because of significant and wide applications,such as micro-encapsulation and ink-printing.In the present study,the experimental and theoretical works were carried out to explore droplet formation in periodic dripping regime in presence of an electric field.The dimensionless electric charge carried by each droplet produced is smaller than the 50%of critical value of the Rayleigh limit,where charge-to-mass ratio of droplets was obtained through the deflection distance in the presence of an electric field.The droplet in electric periodic dripping regime usually undergoes oscillating deformation,and finally forms a spherical droplet below the tip no more than ten times out diameter of tube.The droplet size tens of microns to one hundreds of microns decreases with an increase in applied potential.In the electric dripping mode,droplets size is independent of flow rate and affected by flow rate due to adsorption of surface active species in micro-dripping.The simplified model to predict droplets size was derived from the balance of electric,surface tension and gravity forces.The droplets size calculated in good agreement with the experiments.Meanwhile,the dripping frequency of droplets with rang of a few to several hundred hertz obtained from timeresolved images is highly dependent of liquid flow rate and electric potential.The largest dripping frequency was predicted and in reasonable agreement with the experimental results.In electric periodic dripping regime drop-on-demand droplets in size and dripping frequency further our understanding on the formation of identical droplets and are beneficial to many practical applications.

Development of a physiologically relevant dripping analytical method using simulated nasal mucus for nasal spray formulation analysis

Current methods for nasal spray formulations have been elementary evaluating the dripping characteristics of a formulation and have not assessed the behavior of the nasal formulation in the presence of varying types of mucus depending on the indication or diseased state. This research investigated the effects of nasal mucus on the dripping behavior of nasal formulations and focused on developing an improved in vitro analytical test method that is more physiologically relevant in characterizing nasal formulation dripping behavior. Method development was performed using simulated nasal mucus preparations for both healthy and diseased states as coatings for the dripping experiment representing a wide range of viscosity. Factors evaluated during development of this in vitro test method included amount of mucus, application of mucus, drying times, and compatibility of the mucus on a C18 Thin Layer Chromatography(TLC) substrate. The dripping behavior of nasal formulations containing a range of 1%Avicel to 3.5% Avicel was assessed by actuating the nasal spray on a perpendicular TLC plate coated with either healthy or diseased simulated nasal mucus. After actuation of the nasal spray, the dripping of the formulation on the coated TLC plate was measured after the plate was repositioned vertically. The method that was developed generated reproducible results on the dripping behavior of nasal formulations and provided critical information about the compatibility of the formulation with the nasal mucus for different diseased states, aiding in nasal spray formulation development and physical characterization of the nasal spray.

Research on droplet formation and dripping behavior during the electroslag remelting process

A better understanding of droplet formation and dripping behavior would be useful in the efficient removal of impurity elements and nonmetallic inclusions from liquid metals. In the present work, we developed a transparent experimental apparatus to study the mechanisms of droplet formation and the effects of filling ratio on droplet behavior during the electroslag remelting（ESR） process. A high-speed camera was used to clearly observe, at small time scales, the droplet formation and dripping phenomenon at the slag/metal interface during a stable ESR process. The results illustrate that a two-stage process for droplet formation and dripping occurs during the ESR process and that the droplet diameter exhibits a parabolic distribution with increasing filling ratio because of the different shape and thermal state of the electrode tip. This work also confirms that a relatively large filling ratio reduces electricity consumption and improves ingot quality.

Dripping and evolution behavior of primary slag bearing TiO2 through the coke packed bed in a blast-furnace hearth

To investigate the flow of primary slag bearing TiO2 in the cohesive zone of blast furnaces, experiments were carded out based on the laboratory-scale packed bed systems. It is concluded that the initial temperature of slag dripping increases with decreasing FeO content and increasing TiO2 content. The slag holdup decreases when the FeO content is in the range of 5wt%-10wt%, whereas it increases when the FeO content exceeds 10wt% . Meanwhile, the slag holdup decreases when the TiO2 content increases from 5wt% to 10wt% but increases when the TiO2 content exceeds 10wt%. Moreover, slag/coke interface analysis shows that the reaction between FeO and TiO2 occurs be- tween the slag and the coke. The slag/coke interface is divided into three layers： slag layer, iron-rich layer, and coke layer. TiO2 in the slag is reduced by carbon, and the generated Ti diffuses into iron.

The Protective Effect of Compound Danshen Dripping Pills on Oxidative Stress after Retinal Ischemia/Reperfusion Injury in Rats

Objective: To investigate the effect of Compound Danshen Dripping Pills (CDDP) on oxidative stress after ischemia/reperfusion (I/R) injury in the rat retina. Methods: Adult male SD rats were randomly divided into 3 groups: sham (group A), I/R (group B), and I/R plus CDDP (group C). Retinal ischemia/reperfusion injury (RIRI) was introduced by increasing the intraocular pressure (IOP) to 110 mmHg for 60 min via cannulation into the anterior chamber. Right after the insult, CDDP was administered intragastrically (450 mg/kg/d) for 7 days. The levels of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) in the retinal tissues were determined on d1 and d7 after the ischemic insult. Results: Following ischemia, the MDA levels in group B and group C were significantly higher than those in group A (p < 0.01). CDDP significantly lowered MDA levels in group C when compared with group B (p < 0.01). The activities of SOD, GSH-Px and CAT were higher in group A than in group B and group C (p < 0.01). CDDP could increase the activities of SOD, GSH-Px and CAT remarkably in group C when compared with group B (p < 0.01). Conclusion: CDDP can protect the retina from I/R injury through reducing oxidative stress, and thus may be a promising method for the treatment of ischemic retinal disorders.

Integrated UHPLC-MS and network pharmacology to explore the active constituents and pharmacological mechanisms of Shenzao dripping pills against coronary heart disease

Background:Shenzao dripping pills(SZDP)is an empirical prescription of traditional Chinese medicine that is mainly used to treat coronary heart disease.However,the chemical composition and pharmacological mechanisms of SZDP are unknown.Methods:In this study,ultra-high performance liquid chromatography-quadruple-Exactive Orbitrap mass spectrometry was used to identify the chemical components in extracts and medicated plasma of SZDP.Subsequently,we performed network pharmacology methods,including target prediction by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine,protein-protein interaction network via STRING database;further,the key targets and compounds were screened using Cytoscape.Finally,the key targets and compounds were validated by molecular docking.Results:72 chemical constituents were identified from SZDP by high performance liquid chromatography and mass spectrometry technology.Among the components absorbed into plasma by SZDP,24 prototype components and 9 metabolized components were identified.The network pharmacology analysis of the prototype components showed that there are 13 key compounds(including ginsenoside Rc,Rb1,Rb2,ferulic acid,etc.),90 proteins(including proto-oncogene tyrosine-protein kinase Src,nuclear receptor subfamily 3 group C member 1,caspase-3,etc.),and 10 pathways(including estrogen,IL-17 and VEGF signaling pathway,etc.)that play an essential role in the treatment of coronary heart disease with SZDP.In addition,the results of molecular docking revealed that ginsenosides Rc,Rb2 and Rb1 have strong binding activities to the caspase-3,as well as ginsenoside Rb2 to the nuclear receptor subfamily 3 group C member 1.Conclusion:This study showed that SZDP might act through multiple chemical constituents and targets against coronary heart disease.

Effect of Qishen Yiqi dripping pills combined with trimetazidine on the treatment of chronic heart failure: A meta-analysis

Objective:To systematically evaluate the safety and effectiveness of Qishen Yiqi dripping pills combined with trimetazidine in the treatment of chronic heart failure.Methods:A total of four English and Chinese electronic databases were searched:CNKI,VIP,CBM,PUBMED.Cochrane bias risk tools were used to assess the methodological quality of qualified studies.Meta-analysis was conducted by Review Manager 5.3.A total of 9 articles were included,with a total sample size of 855 cases,443 cases in the observation group and 412 cases in the treatment group.Results:Qishen Yiqi dripping pills combined with trimetazidine in the treatment of chronic heart failure has a total effective rate(RR=1.22,95%CI[1.15-1.30];p<0.00001),LVEF(MD=6.03,95%CI[5.39,6.67],P<0.00001),BNP(MD=-101.87,95%CI[-109.90,-93.83],P<0.00001),E/A(MD=-4.32,95%CI[-5.70,-2.93],P<0.00001),SYP(MD=-10.32,95%CI[-13.32,-7.32],P<0.00001),LVESD(MD=-5.50,95%CI[-6.03,-4.96],P<0.00001),6-MWT(MD=110.13,95%CI[96.89,123.36],P<0.00001)Adverse reactions occurred less frequently and did not affect treatment.Conclusion:This study shows that QYDP combined with TMZ can improve various indicators of CHF patients.However,due to the small sample size and the generally low quality of research,a more rigorous and reasonably designed RCT is needed to confirm these findings.

Drag-induced breakup mechanism for droplet generation in dripping within flow focusing microfluidics

Based on viscous drag-induced breakup mechanism, a simple model was proposed to predict the dripping droplet size as a function of controllable parameters in flow focusing micro devices. The size of thread before breakup was also investigated through laminar flow theory. Experiments and numerical simulations by VOF are carried out simultaneously to validate the theoretical analysis, showing that droplet size decreases rapidly with the increase of the flow rate ratio and capillary number.

Fabrication of W@Cu Composite Powders by Direct Electroless Plating Using a Dripping Method

A direct electroless copper （Cu） coating on tungsten powders method requiring no surface treatment or stabilizing agent and using glyoxylic acid （C2H203） as a reducing agent was reported. The effects of copper sulfate concentration and the pH of the plating solution on the properties of the prepared W@Cu composite powders were assessed. The content of Cu in the composite powders was controlled by adjusting the concentration of copper sulfate in the electroless plating solution. A uniform, dense, and consistent Cu coating was obtained under the established optimum conditions （flow rate of C2H203 = 5.01 mL/min, solution pH = 12.25 and reaction temperature 45.35℃） by using central composite design method. In addition, the crystalline Cu coating was evenly dispersed within the W@Cu composite powders and Cu element in the coating existed as Cu~. The formation mechanism for the W@Cu composite powders by electroless plating in the absence of surface treatment and stabilizing agent was also proposed.

Anti-asthmatic mechanism of the Huashanshen dripping pill via suppressing contraction of the airway smooth muscle

Background:The Huashanshen(HSS)dripping pill has been widely used in asthma for a long time in China.However,the relaxant mechanism of HSS is not well understood.Methods:In this report,high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry was used to identify the constituents in rat plasma after oral administration of HSS.Ovalbumin-sensitized allergic asthma and isolated trachea were studied for the anti-asthmatic mechanism of HSS.Results:D-anisodamine,L-anisodamine,scopolamine and atropine were detected in the rat plasma containing HSS.It was clear that the HSS inhibited the release of inflammatory mediators,regulated the balance of T-helper 1 and T-helper 2 to reduce the airway inflammation,and relaxed the tracheal smooth muscle by controlling the KCa channel,Ca^(2+)influx and release to reduce the airway hyperresponsiveness.Conclusion:Atropine,anisodamine and scopolamine might be active compounds of HSS which inhibited the release of inflammatory mediators,regulated the balance of Th1/Th2,and relaxed the tracheal smooth muscle to reduce airway hyperresponsiveness.

Clinical Intervention Effect of Compound Danshen Dripping Pills on Aspirin Resistant Patients with Coronary Heart Disease

[Objectives]To study the clinical intervention effect of Compound Danshen Dripping Pills on aspirin-resistant patients with coronary heart disease(CHD).[Methods]240 patients with coronary heart disease who took Aspirin were selected to measure thrombocytopenia by sonoclot.They were randomly divided into four groups:group A(n=60),Compound Danshen Dripping Pills and aspirin.group B(n=60),aspirin;group C(n=60),high dose aspirin;group D(n=60),Compound Danshen Dripping Pills.CR and PF were determined by sonoclot after one month.The incidence of angina pectoris,acute myocardial infarction,sudden cardiac death and hemorrhage were observed.[Results]After treatment,the CR and PF levels of group A and C were significantly lower than those before treatment,and there was no significant difference between group B and D and before treatment.After treatment,the levels of CR and PF in group A and C were significantly lower than those in group B and D,and there was a significant difference.Angina pectoris and myocardial infarction events in group D were significantly higher than the other four groups;hemorrhage events in group C were significantly higher than the other three groups.[Conclusions]Compound Danshen Dripping Pills combined with aspirin can be used as an economical,effective,and more dependent alternative to inhibit platelet activity in aspirin resistance,and can further reduce the occurrence of acute coronary events.

Effects of compound danshen dripping pills on the levels of serum inflammatory factors, brain natriuretic peptide and blood lipid in CABG postoperative patients

Objective:To explore the effects of compound danshen dripping pills on the levels of serum inflammatory factors,brain natriuretic peptide(BNP)and blood lipid in CABG postoperative patients.Methods:156 cases of patients who were given CABG from January 2015 to January 2018 in Baogang Hospital were chosen and randomly divided into the observation group(n=78)and the control group(n=78).Both groups were given conventional drugs,simultaneously,the observation group was given compound danshen dripping pills.The treatment lasted 3 months.The clinical efficacy was compared between two groups of patients,and the levels of serum inflammatory factors,plasma BNP and blood lipid before and after treatment in two groups of patients were detected in order to make a comparison in the incidence of adverse cardiac events between two groups of patients.Results:After treatment,the total effective rate of treatment in the observation group was significantly higher than that in the control group;in the two groups,the levels of serum interleukin-6(IL-6),interleukin-8(IL-8),C-reactive protein and plasma BNP after treatment were obviously lower than those before treatment,and these indicators in the observation group were lower than those in the control group(p<.05);the levels of TG,TC and LDL-C in two groups were obviously lower(p<.05)with the level of HDL-C significantly higher(all p<.05),and the descending or ascending range of each indicator in the observation group was obviously larger than that in the control group(p<.05);in the follow-up visit,the incidence of adverse cardiac events in the observation group of patients was significantly lower than that in the control group of patients(p<.05).Conclusions:Compound danshen dripping pills can effectively reduce the levels of serum inflammatory factors and BNP,regulate blood lipid metabolism and reduce the incidence of adverse cardiac events in CABG postoperative patients.

Research survey and review of the effect of Compound Danshen Dripping Pills on the uric acid metabolism of patients with coronary heart disease

A growing number of studies have reported that serum uric acid（SUA） is associated with coronary heart disease（CHD）, which has been increasingly recognized and valued by the medical community. This paper surveys the epidemiological studies of hyperuricemia and CHD and summarizes the clinical study discussing the association between hyperuricemia and coronary heart disease with a prospect of exploring the possible mechanisms of compound Danshen dripping pills in reducing SUA in patients with coronary heart disease.

Effect of Guanxin Danshen Dripping Pills on Coronary Heart Disease Comorbid with Depression or Anxiety: The ADECODE-Real World Study

Objective: To evaluate the efficacy of Guanxin Danshen Dripping Pill(GXDSDP) in treating anxiety and depression in patients with coronary heart disease(CHD). Methods: A total of 1,428 patients diagnosed with CHD screened for anxiety, depression, and quality of life(QOL) at baseline received 0.4 g of GXDSDP treatment 3 times per day and returned for monthly reassessment. Patients were recruited after stable treatment for CHD and received assessment of General Anxiety Disorder-7(GAD-7), Patient Health Questionnaire-9(PHQ-9), and Seattle Angina Questionnaire(SAQ) for evaluating anxiety, depression, and QOL.Patients were followed up 3 times, once every 4 weeks, during outpatient visits for 12 weeks. Results: At the third follow-up(F3), the anxiety symptom of 63.79%(673/1,055) of the patients improved to sub-clinical level, and the GAD-7 score improved significantly(8.11 vs. 3.87, P<0.01);57.52%(585/1,017) patients' depressive symptoms improved to sub-clinical level, with a significant improvement in PHQ-9 score(8.69 vs. 4.41, P<0.01) at F3. All aspects of QOL significantly improved at the end of treatment compared to those at baseline(all P<0.01) as assessed by SAQ: physical limitation(31.17 vs. 34.14), anginal stability(2.74 vs. 4.14), anginal frequency(8.16vs. 9.10), treatment satisfaction(13.43 vs. 16.29), and disease perception(8.69 vs. 11.02). Conclusions: A fixed dosage of GXDSDP may be a potential treatment option for CHD patients comorbid with anxiety or depression.(Registration No. ChiCTR2100051523)

Effectiveness and Safety of Qishen Yiqi Dripping Pill in Patients with Acute Coronary Syndrome after Percutaneous Coronary Intervention:3-Year Results from a Multicentre Cohort Study

Objectives:To evaluate the effectiveness and safety of Qishen Yiqi Dripping Pill(QSYQ)in patients with acute coronary syndrome(ACS)after percutaneous coronary intervention(PCI).Methods:This multicentre prospective cohort study was conducted at 40 centers in China.Patients with ACS after PCI entered either the QSYQ or Western medicine(WM)groups naturally based on whether they had received QSYQ before enrollment.QSYQ group received QSYQ(0.52 g,3 times a day for 12 months)in addition to WM.The primary endpoint included cardiac death,non-fatal myocardial infarction,and urgent revascularization.The secondary endpoint included rehospitalization due to ACS,heart failure,stroke,and other thrombotic events.Quality of life was assessed by the Seattle Angina Questionnaire(SAQ).Results:A total of 936 patients completed follow-up of the primary endpoint from February 2012 to December 2018.Overall,487 patients received QSYQ and WM.During a median follow-up of 566 days(inter quartile range,IQR,517–602),the primary endpoint occurred in 46(9.45%)and 65(14.48%)patients in QSYQ and WM groups respectively[adjusted hazard ratio(HR)0.60,95%confidence interval(CI)0.41–0.90;P=0.013].The secondary endpoint occurred in 61(12.53%)and 74(16.48%)patients in QSYQ and WM groups,respectively(adjusted HR 0.76,95%CI 0.53–1.09;P=0.136).In sensitivity analysis,the results still demonstrated that WM combined with QSYQ reduced the risk of the primary endpoint(HR 0.67,95%CI 0.46–0.98;P=0.039).Moreover,QSYQ improved the disease perception domain of the SAQ(P<0.05).Conclusions:In patients with ACS after PCI,QSYQ combined with WM reduced the incidence of the primary endpoint.These findings provide a promising option for managing ACS after PCI and suggest the potential treatment for reducing the risk of primary endpoint included cardiac death,non-fatal myocardial infarction,and urgent revascularization through intermittent administration of QSYQ.(Registration No.Chi CTR-OOC-14005552).

Compound Danshen Dripping Pill inhibits hypercholesterolemia/atherosclerosis-induced heart failure in ApoE and LDLR dual deficient mice via multiple mechanisms

Heart failure is the leading cause of death worldwide.Compound Danshen Dripping Pill(CDDP)or CDDP combined with simvastatin has been widely used to treat patients with myocardial infarction and other cardiovascular diseases in China.However,the effect of CDDP on hypercholesterolemia/atherosclerosis-induced heart failure is unknown.We constructed a new model of heart failure induced by hypercholesterolemia/atherosclerosis in apolipoprotein E(ApoE)and LDL receptor(LDLR)dual deficient(ApoE^(–/–)LDLR^(–/–))mice and investigated the effect of CDDP or CDDP plus a low dose of simvastatin on the heart failure.CDDP or CDDP plus a low dose of simvastatin inhibited heart injury by multiple actions including anti-myocardial dysfunction and anti-fibrosis.Mechanistically,both Wnt and lysine-specific demethylase 4A(KDM4A)pathways were significantly activated in mice with heart injury.Conversely,CDDP or CDDP plus a low dose of simvastatin inhibited Wnt pathway by markedly up-regulating expression of Wnt inhibitors.While the anti-inflammation and anti-oxidative stress by CDDP were achieved by inhibiting KDM4A expression and activity.In addition,CDDP attenuated simvastatin-induced myolysis in skeletal muscle.Taken together,our study suggests that CDDP or CDDP plus a low dose of simvastatin can be an effective therapy to reduce hypercholesterolemia/atherosclerosis-induced heart failure.

Qishen Yiqi Dripping Pills for Cardiovascular Diseases: Effects and Mechanisms

Qishen Yiqi Dripping Pills(QSYQ) is a compound of Chinese medicine, which has been used to treat coronary heart disease and cardiac dysfunction. Its natural components include astragaloside Ⅳ, flavonoids, danshensu, protocatechualdehyde, salvianolic acid B, salvianolic acid A, ginsenosides Rg1, ginsenosides Rb1, and essential oils, etc. It exerts effects of nourishing qi and promoting blood circulation to relieve pain. In this review, the bioactive components of QSYQ and its effects for treating cardiovascular diseases and possible mechanism were summarized, providing references for further study and clinical application of QSYQ.

Effects of Compound Danshen Dripping Pills on Ventricular Remodeling and Cardiac Function after Acute Anterior Wall ST-Segment Elevation Myocardial Infarction(CODE-AAMI):Protocol for a Randomized Placebo-Controlled Trial

Background:Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction(AAMI)is an important factor in occurrence of heart failure which additionally results in poor prognosis.Therefore,the treatment of ventricular remodeling needs to be further optimized.Compound Danshen Dripping Pills(CDDP),a traditional Chinese medicine,exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction.Objective:This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale.Methods:This study is a multi-center,randomized,doubleblind,placebo-controlled,parallel-group clinical trial.The total of 268 patients with AAMI after primary percutaneous coronary intervention(pPCI)will be randomly assigned 1:1 to the CDDP group(n=134)and control group(n=134)with a follow-up of 48 weeks.Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction(STEMI),with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI,and the control group treated with a placebo simultaneously.The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction(LVEF),left ventricular end-diastolic volume index(LVEDVI),and left ventricular end-systolic volume index(LVESVI).The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide(NT-proBNP)level,arrhythmias,and cardiovascular events(death,cardiac arrest,or cardiopulmonary resuscitation,rehospitalization due to heart failure or angina pectoris,deterioration of cardiac function,and stroke).Investigators and patients are both blinded to the allocated treatment.Discussion:This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI.Patients in the CDDP group will be compared with those in the control group.If certified to be effective,CDDP treatment in AAMI will probably be advised on a larger scale.(Trial registration No.NCT05000411)