Traditional Chinese Medicine Compound (Tongxinluo) and Clinical Outcomes of Patients With Acute Myocardial Infarction: The CTS-AMI Randomized Clinical Trial.

Importance: Tongxinluo, a traditional Chinese medicine compound, has shown promise in in vitro, animal, and small human studies for myocardial infarction, but has not been rigorously evaluated in large randomized clinical trials. Objective: To investigate whether Tongxinluo could improve clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled clinical trial was conducted among patients with STEMI within 24 hours of symptom onset from 124 hospitals in China. Patients were enrolled from May 2019 to December 2020; the last date of follow-up was December 15, 2021. Interventions: Patients were randomized 1:1 to receive either Tongxinluo or placebo orally for 12 months (a loading dose of 2.08 g after randomization, followed by the maintenance dose of 1.04 g, 3 times a day), in addition to STEMI guideline-directed treatments. Main Outcomes and Measures: The primary end point was 30-day major adverse cardiac and cerebrovascular events (MACCEs), a composite of cardiac death, myocardial reinfarction, emergent coronary revascularization, and stroke. Follow-up for MACCEs occurred every 3 months to 1 year. Results: Among 3797 patients who were randomized, 3777 (Tongxinluo: 1889 and placebo: 1888; mean age, 61 years; 76.9% male) were included in the primary analysis. Thirty-day MACCEs occurred in 64 patients (3.4%) in the Tongxinluo group vs 99 patients (5.2%) in the control group (relative risk [RR], 0.64 [95% CI, 0.47 to 0.88]; risk difference [RD], -1.8% [95% CI, -3.2% to -0.6%]). Individual components of 30-day MACCEs, including cardiac death (56 [3.0%] vs 80 [4.2%]; RR, 0.70 [95% CI, 0.50 to 0.99]; RD, -1.2% [95% CI, -2.5% to -0.1%]), were also significantly lower in the Tongxinluo group than the placebo group. By 1 year, the Tongxinluo group continued to have lower rates of MACCEs (100 [5.3%] vs 157 [8.3%]; HR, 0.64 [95% CI, 0.49 to 0.82]; RD, -3.0% [95% CI, -4.6% to -1.4%]) and cardiac death (85 [4.5%] vs 116 [6.1%]; HR, 0.73 [95% CI, 0.55 to 0.97]; RD, -1.6% [95% CI, -3.1% to -0.2%]). There were no significant differences in other secondary end points including 30-day stroke; major bleeding at 30 days and 1 year; 1-year all-cause mortality; and in-stent thrombosis (<24 hours; 1-30 days; 1-12 months). More adverse drug reactions occurred in the Tongxinluo group than the placebo group (40 [2.1%] vs 21 [1.1%]; P = .02), mainly driven by gastrointestinal symptoms. Conclusions and Relevance: In patients with STEMI, the Chinese patent medicine Tongxinluo, as an adjunctive therapy in addition to STEMI guideline-directed treatments, significantly improved both 30-day and 1-year clinical outcomes. Further research is needed to determine the mechanism of action of Tongxinluo in STEMI. Trial Registration: ClinicalTrials.gov Identifier: NCT03792035.

A Photothermal Therapy Strategy for Monitoring Real-Time Temperature in Kidney Cancers by Injecting Gold Nanorods with Phosphors.

Photothermal ablation therapy (PTA) has been widely reported; however, it is not possible to predict the internal temperature of the tumor in real time that causes ineffective treatment and normal tissue burns. Here, we have designed a photothermal therapy strategy under real-time temperature monitoring by injecting gold nanorods (AuNRs) and NaYF4: Yb3+ /Er3+ into the tumor site where AuNRs are used for PTA of cancer cells by converting the absorbed energy into heat and using Yb3+ , Er3+-NaYF 4 phosphors to monitor the temperature inside the tumor. Our experiments confirm the effectiveness of this strategy, which is expected to be an aid in the development of real-time temperature monitoring and effective photothermal therapy for the treatment of cancers.

Structural characterization and antioxidant activities of one neutral polysaccharide and three acid polysaccharides from Ziziphus jujuba cv. Hamidazao: A comparison.

A neutral polysaccharide (HJP-1a) and three acid polysaccharides (HJP-2, HJP-3 and HJP-4) were obtained from Z. jujuba cv. Hamidazao. HJP-1a was mainly composed of arabinose and galactose in a ratio of 56.9:20.0, with an average molecular weight of 3.115 × 104 g/mol. HJP-2, HJP-3 and HJP-4 were homogeneous heteropolysaccharides mainly containing galacturonic acid, arabinose and galactose, with average molecular weights of 4.590 × 104, 6.986 × 104 and 1.951 × 105 g/mol, respectively. Structural characterization indicated that the backbone of HJP-3 appeared to be mainly composed of →4)-α-d-GalpA (1→ and →2,4)-α-l-Rhap (1→ residues with some branches consisting of →5)-α-l-Araf (1→ residues and terminals of T-α-l-Araf (1→ and T-ß-d-Galp residues. The four purified fractions displayed dose-dependent radical scavenging activity on ABTS+ radicals and reducing capacity, as well as excellent protective effect on H2O2-induced HepG2 cells and metronidazole-damaged zebrafish embryos, especially HJP-2 in vitro and HJP-1a in vivo. Therefore, the polysaccharides from Z. jujuba cv. Hamidazao could be used as a potential antioxidant in functional foods.

China Tongxinluo Study for myocardial protection in patients with Acute Myocardial Infarction (CTS-AMI): Rationale and design of a randomized, double-blind, placebo-controlled, multicenter clinical trial.

Acute ST-segment elevation myocardial infarction (STEMI) remains a serious life-threatening event. Despite coronary revascularization, patients might still suffer from poor outcomes caused by myocardial no-reflow and ischemic/reperfusion injury. Tongxinluo (TXL), a traditional Chinese medicine, has been preliminarily demonstrated to reduce myocardial no-reflow and ischemic/reperfusion injury. We further hypothesize that TXL treatment is also effective in reducing clinical end points for the patients with STEMI. METHODS AND RESULTS: The CTS-AMI trial is a prospective, randomized, double-blind, placebo-controlled, multicenter clinical study in China. An estimated 3,796 eligible patients with STEMI from about 120 centers are randomized 1:1 ratio to TXL or placebo groups. All enrolled patients are orally administrated a loading dose of 8 capsules of TXL or placebo together with dual antiplatelet agents on admission followed by 4 capsules 3 times a day until 12 months. The primary end point is 30-day major adverse cardiovascular and cerebrovascular events, a composite of cardiac death, myocardial reinfarction, emergency coronary revascularization, and stroke. Secondary end points include each component of the primary end point, 1-year major adverse cardiovascular and cerebrovascular events, and other efficacy and safety parameters. CONCLUSIONS: Results of CTS-AMI trial will determine the clinical efficacy and safety of traditional Chinese medicine TXL capsule in the treatment of STEMI patients in the reperfusion era.

Meta-Analysis of Efficacy and Safety of New Oral Anticoagulants Compared With Uninterrupted Vitamin K Antagonists in Patients Undergoing Catheter Ablation for Atrial Fibrillation.

Anticoagulation in catheter ablation (CA) of atrial fibrillation (AF) is of paramount importance for prevention of thromboembolic events, and recent studies favor uninterrupted vitamin K antagonists (VKAs). We aimed to compare the efficacy and safety of new oral anticoagulants (NOACs) to uninterrupted VKAs for anticoagulation in CA by performing a meta-analysis. PubMed, EMBASE, the Cochrane Library, and Clinicaltrials.gov databases were searched for studies comparing NOACs with uninterrupted VKAs in patients who underwent CA for AF from January 1, 2000, to August 31, 2015. Odds ratio (OR) and Peto's OR (POR) were used to report for event rates >1% and <1%, respectively. A total of 11,686 patients with AF who underwent CA in 25 studies were included in this analysis. There was no significant difference between NOACs and uninterrupted VKAs in occurrence of stroke or transient ischemic attacks (POR 1.35, 95% CI 0.62 to 2.94) and major bleeding (POR 0.87, 95% CI 0.58 to 1.31), which were consistent in subgroup analysis of interrupted and uninterrupted NOACs. A lower risk of minor bleeding was observed with NOACs (OR 0.80, 95% CI 0.65 to 1.00), and no major differences were observed for the risk of thromboembolic events, cardiac tamponade or pericardial effusion requiring drainage, and groin hematoma. NOACs, whether interrupted preprocedure or not, were associated with equal rates of stroke or TIA and major bleeding complications and less risk of minor bleeding compared with uninterrupted VKAs in CA for AF.

An in-vitro evaluation of direct thrombin inhibitor and factor Xa inhibitor on tissue factor-induced thrombin generation and platelet aggregation: a comparison of dabigatran and rivaroxaban.

Dabigatran and rivaroxaban may simultaneously inhibit coagulation and platelet activation. This study aimed to reveal the in-vitro effects of dabigatran and rivaroxaban on thrombin generation and platelet aggregation (PAg) derived via tissue factor (TF) pathway. Citrated blood was obtained from six healthy adults (26-60 years old) and pretreated with increasing concentrations of dabigatran or rivaroxaban. Plasmatic endogenous thrombin potential (ETP) was measured by the calibrated automated thrombogram method. The whole blood PAg was evaluated via a kinetic counting method. TF produced an ETP of 1904.69 ±â€Š121.42 nmol min and a PAg of 78 ±â€Š5%. Dabigatran and rivaroxaban concentration-dependently reduced ETP with half-maximal inhibitory concentrations of 460.1 ±â€Š1.4 and 678.1 ±â€Š1.4 nmol/l, and inhibited PAg with half-maximal inhibitory concentrations of 119.5 ±â€Š1.5 and 77.5 ±â€Š1.6 nmol, respectively. Dabigatran and rivaroxaban significantly inhibit TF-induced hypercoagulation and platelet activation in vitro in a concentration-dependent manner. Rivaroxaban displays stronger inhibition on thrombin generation and PAg than dabigatran.

Role of pseudolaric acid B in A549 lung cancer cell proliferation and apoptosis.

Recently, traditional Chinese medicine has gained attention for its potential use as a chemotherapeutic agent. Pseudolaric acid B (PAB) is a diterpene acid isolated from Pseudolarix kaempferi and possesses antifungal, antimicrobial, antifertility and antiangiogenic properties. It was also reported that PAB may inhibit proliferation and induce apoptosis in various types of cancer. However, its effects on A549 lung cancer cells remain to be determined. The present study aimed to determine the potential roles of PAB in the proliferation and apoptosis of A549 cells. The results showed that PAB inhibited A549 cell proliferation in a time­ and dose­dependent manner. Fluorescence microscopy results showed that cells treated with 20 µmol/l PAB for 24 h exhibited karyorrhexis and apoptotic body formation. In addition, A549 cells were treated with 5, 10, 20, 40 or 80 µmol/l PAB for 24 h and apoptosis was analyzed using Annexin­V/propidium iodide kit. The apoptosis rates were 8.95, 18.71, 24.66, 35.02 and 43.64%, respectively, in PAB­treated cells and 0.80% in the control group. Furthermore, western blot analysis showed that PAB treatment upregulated the protein levels of Bax, Bad and downregulated Bcl­2 and Bcl­xl expression. In conclusion, PAB may serve as a potent chemotherapeutic agent against human lung cancer.

Comparative effects of Guanfu base A and Guanfu base G on HERG K+ channel.

BACKGROUND: Guanfu base A (GFA) and Guanfu base G (GFG) are chemicals isolated from Aconitum coreanum. The potassium channel encoded by the human ether-a-go-go related gene (HERG) plays an important role in repolarization of the cardiac action potential. The purpose of the present study was to investigate the effects of GFA and GFG on the HERG channel and its structure-function relationship. METHODS: The effects of GFA and GFG were investigated in human embryonic kidney 293 (HEK293) cells transiently transfected with HERG complementary DNA using a whole-cell patch clamp technique. RESULTS: GFA and GFG inhibited HERG channel current in concentration-, voltage-, and time-dependent manners. The IC50 for GFA and GFG was 1.64 mM and 17.9 µM, respectively. Both GFA and GFG shifted the activation curve in a negative direction and accelerated channel inactivation but showed no effect on the inactivation curve. Moreover, GFG also accelerated channel recovery from inactivation. CONCLUSIONS: Both GFA and GFG blocked HERG channel current. This effect was stronger after GFG treatment rather than GFA treatment. This blockade was dependent on open and inactivated channel states. These results indicate that GFA could be a rather promising antiarrhythmic drug without severe side effects, whereas GFG could cause QT prolongation and requires further research.

[Clinical characteristics of 52 patients with torsade de points associated with acquired QT prolongation].

OBJECTIVE: Risk factors, ECG characteristics and treatment options of patients with Torsade de Points associated with acquired QT prolongation are summarized in this study. METHOD: Using "torsade de points" and "QT prolongation" as the keywords to search the inpatients database from 1990 - 2010 of Fuwai hospital, 52 eligible patients were included in this analysis. RESULTS: Structural heart diseases were found in 67.3% and electrolyte disorders in 59.6% patients, 36.5% patients received diuretic therapy and 28.8% received antiarrhythmic drugs which might induce prolonged QT interval. The mean QTc was (571 ± 93) ms and (456 ± 50) ms before and after treatment. All patients received potassium and magnesium supplement. Isoproterenol was used in 32.7% patients. 13.5% patients received temporary pacing therapy. CONCLUSIONS: Torsade de points and acquired QT interval prolongation was often associated with electrolyte disorders and drugs causing QT prolongation. ECG and QTc should be intensively monitored for high risk patients. Early awareness of the warning signs might contribute to early recognition and proper treatment of patients with Torsade de Points associated with acquired QT prolongation.

[Effect of high dose glucose-insulin-potassium infusion in patients with acute ST-segment elevation myocardial infarction: analysis of 7510 patients in China as part of CREATE-ECLA study].

OBJECTIVE: To investigate the effect of high-dose glucose-insulin-potassium (GIK) infusion on the outcomes of ST-elevation myocardial infarction (STEMI) in China. METHODS: As part of the international multicentre CREATE-ECLA study, 7510 patients with STEMI, aged (62 +/- 12), presenting their symptoms within 12 hours of onset who were hospitalized in 274 centers throughout China from July 2001 through July 2004 were randomized to receive GIK intravenous infusion for 24 hours plus routine treatment (3739) or control group (n=3771) receiving routine treatment alone. The patients were flowed up in the out-patient department 30 days after the randomization to assess the rates of mortality, cardiac arrest, cardiogenic shock and re-infarction. RESULTS: The median time from symptom onset to randomization was 5.8 hours. The mortality of the control group was 10.4%, not significantly different from that of the GIK group (11.2%, hazard ratio = 1.05, 95% CI: 0.916-1.207, P = 0.476). There rates of cardiac arrest, cardiogenic shock, and re-infarction of the GIK group were 0.8%, 6.8%, and 2.0% respectively, all not significantly different from those of the control group (1.0%, 6.4%, and 1.9% respectively, all P > 0.05). At the Day 7 the heart failure rate of the GIK group was 19.7%, not significantly different from that of the control group (18.3%, P = 0.102). The symptomatic hypotension rate of the GIK group was 3.7%, significantly higher than that of the control group (1.2%, P < 0.01). The phlebitis rate of the GIK group was 2.2%, significantly higher than that f the control group (0.1%, P < 0.01). The net increased fluid volume of the control group wasl3 584 ml. more than that of the GIK group (1036 ml). CONCLUSIONS: High dose GIK infusion has neutral effect on mortality, cardiac arrest or cardiogenic shock in patients with acute STEMI in China.

Continuous pulmonary infusion of L-arginine during deep hypothermia and circulatory arrest improves pulmonary surfactant integrity in piglets.

BACKGROUND: The integrity of pulmonary surfactant (PS) is impaired during deep hypothermia and circulatory arrest (DHCA), a preferred bypass strategy for infants undergoing complex cardiac operations, due mainly to bypass-induced systemic inflammation. The requirement of L-arginine, a precursor of nitric oxide, is elevated during acute pulmonary inflammation. We hypothesized that continuous intrapulmonary supplementation of L-arginine during DHCA can maintain the integrity of PS metabolism and thus protect the pulmonary function. METHODS: Sixteen piglets underwent 90-minute circulatory arrest at 18 degrees C before rewarming. During circulatory arrest, antegrade infusion of Ringer's lactate solution alone (n = 8) or containing L-arginine (1 mg/kg/min, n = 8) was initiated into the pulmonary circulation. Disaturated phosphatidylcholine, total phospholipids, and total proteins from tracheal aspirates were measured serially until the experiment ended (4 hours after rewarming). Various variables of pulmonary function were also monitored. RESULTS: L-arginine led to less decrement of disaturated phosphatidylcholine/total phospholipids and disaturated phosphatidylcholine/total proteins after DHCA. At 4 hours after rewarming, L-arginine had significantly mitigated the deterioration of pulmonary static compliance (3.6 +/- 0.5 vs 3.3 +/- 0.3 mL/cm H2O) and partial pressure of arterial oxygen/fraction of inspired oxygen (330 +/- 48 vs 296 +/- 32 mm Hg). Pulmonary retention of water (6.2 +/- 1.0 vs 5.5 +/- 1.2) was significantly reduced. The L-arginine-treated group showed an increase in NO metabolites (NO2-/NO3-) from the pulmonary circulation, the extent of which is correlated to PS content. CONCLUSIONS: Continuous L-arginine supplementation during DHCA attenuated PS depletion and, therefore, ameliorated postoperative pulmonary dysfunction.

[Efficacy of intravenous Acehytisine Hydrochloride versus propafenone on terminating paroxysmal supraventricular tachycardia: a double-blinded, randomized multi-center study].

OBJECTIVE: In this double-blinded, randomized, parallel study, we investigated the clinical efficacy of intravenous Acehytisine Hydrochloride (AHH) and propafenone on terminating paroxysmal supraventricular tachycardia (PSVT). METHODS: Patients (18 - 70 years old) with either spontaneous or induced sustained supraventricular tachycardia lasted at least 15 min were recruited in this study. Exclusion criteria included sick sinus syndrome, atrial ventricular block or intraventricular block, etc. Eligible patients were randomly assigned to receive intravenously AHH (n=101) or propafenone (n=100) according to a proportion of 1:1 in a double-blinded manner. AHH (4 mg/kg, iv.) or propafenone (PRO, 1 mg/kg, iv.) was administered in 5 min followed by the same dose if no response was observed. Conversion times, vital signs, electrocardiograms were documented before and after drug administration. RESULTS: Except for age, the demographic characteristics and clinical features were comparable between the two groups. Efficacy on PSVT termination was comparable between AHH (72/101, 71.3%) and PRO group (73/100, 73.0%, P=0.6368). The average time from drug administration to conversion was also similar [AHH: (9.62 +/- 8.39) min vs. PRO: (10.61 +/- 9.47) min, P=0.5035]. In the AHH group, 59/72 episodes of PSVT were terminated by the first dose, and 66/72 were terminated prematurely. The average AHH dose in the 72 converted patients was (273.7 +/- 111.2) mg. In the PRO group, 54/73 episodes of PSVT were terminated by the first dose. The electrocardiographic parameters, such as sinus recovery time, longest PP and RR interval, PR interval, QRS interval, QT interval after conversion were similar between the two groups. Transient adverse events were reported in 11/101 (10.9%) patients in the AHH group and in 18/100 (18.0%,) in the PRO group (P=0.1653). CONCLUSION: With the dosage used in the present study, the efficacy on terminating PSVT was comparable between AHH and PRO.

[Effect of Guanfu Base A in patients with ventricular arrhythmias].

OBJECTIVE: To investigate the effect and safety of intravenous Guanfu Base A hydrochloride (GFA) in the treatment of ventricular arrhythmias. METHODS: Patients without severe structural heart disease presenting with equal or more than 150 premature ventricular contractions per hour and/or non sustained ventricular tachycardia in drug-free holter monitoring were recruited in this double blind randomized active-controlled study. Eligible patients were randomly assigned to receive GFA or propafenone intravenously by a proportion of 1:1 in a double-blind manner. Intravenous bolus of the study medicine was given, followed by maintenance infusion for 6 hours. 24 hours continuous electrocardiographic recordings were performed to evaluate the efficacy. Vital signs, electrocardiograms and adverse events were documented before, during and after drug administration. RESULTS: A total of 201 patients came from eight centres were randomized to GFA or propafenone group. The demographic characteristics, the extent of ventricular arrhythmias and baseline clinical findings were comparable between the two groups. There were no significant differences in the percentage of reducing premature ventricular contractions and the accumulated efficacy between two groups. GFA had tendency to be more effective than propafenone in reducing the number of ventricular ectopy (P = 0.0609). There were no significant differences in the onset of action after drug administration between two drugs. The tolerance of GFA was better than propafenone. The adverse events in GFA group were less severe than those in propafenone group. CONCLUSIONS: Intravenous GFA in controlling the premature ventricular contraction has comparable effect to IV propafenone. Tolerance of GFA was better than propafenone.

[Electrophysiological effects of acehytisine hydrochloride in a porcine model of acute coronary occlusion].

OBJECTIVE: To observe the electrophysiological effect of Acehytisine Hydrochloride (AHH) in Wu Zhi Shan (WZS) micropigs with experimental acute coronary occlusion. METHODS: Adult WZS micropigs were randomized into group A: coronary ligation with AHH infusion (n = 9); group B: AHH infusion without coronary ligation (n = 9) and group C: coronary ligation with saline (NS) infusion (n = 9). Surface ECGs and cardiac electrophysiological data including atrium, atrium-ventricle junction and ventricle electrograms were collected by programmed electrical stimulation at ischemic baseline and after AHH (or NS) infusion. RESULTS: Compared to animals treated with AHH without ischemia, VARC-ERP was significantly increased while QT, QTc intervals, VRRP and VFRP were significantly reduced in ischemic animals treated with AHH. Compared to ischemic animals treated with saline, AHH prolongs the P-wave duration and PR interval, shortens QTc interval, prolongs ARP and AEP, also prolongs V-A reverse conduction time and VARC-ERP but shortens VFRP. No proarrhythmia effect was found in both AHH treated groups. CONCLUSION: AHH resulted in significant electrophysiological effects on this porcine acute coronary ischemic model.