Efficacy and safety of Panax notoginseng saponin injection in the treatment of acute myocardial infarction: a systematic review and meta-analysis of randomized controlled trials.

Purpose: This study aimed to assess the efficacy and safety of Panax notoginseng saponin (PNS) injection, when combined with conventional treatment (CT), for acute myocardial infarction (AMI). Methods: Comprehensive searches were conducted in seven databases from inception until 28 September 2023. The search aimed to identify relevant randomized controlled trials (RCTs) focusing on PNS injection in the context of AMI. This meta-analysis adhered to the PRISMA 2020 guidelines, and its protocol was registered with PROSPERO (number: CRD42023480131). Result: Twenty RCTs involving 1,881 patients were included. The meta-analysis revealed that PNS injection, used adjunctively with CT, significantly improved treatment outcomes compared to CT alone, as evidenced by the following points: (1) enhanced total effective rate [OR = 3.09, p < 0.05]; (2) decreased incidence of major adverse cardiac events [OR = 0.32, p < 0.05]; (3) reduction in myocardial infarct size [MD = -6.53, p < 0.05]; (4) lower ST segment elevation amplitude [MD = -0.48, p < 0.05]; (5) mitigated myocardial injury as indicated by decreased levels of creatine kinase isoenzymes [MD = -11.19, p < 0.05], cardiac troponin T [MD = -3.01, p < 0.05], and cardiac troponin I [MD = -10.72, p < 0.05]; (6) enhanced cardiac function, reflected in improved brain natriuretic peptide [MD = -91.57, p < 0.05], left ventricular ejection fraction [MD = 5.91, p < 0.05], left ventricular end-diastolic dimension [MD = -3.08, p < 0.05], and cardiac output [MD = 0.53, p < 0.05]; (7) reduced inflammatory response, as shown by lower levels of C-reactive protein [MD = -2.99, p < 0.05], tumor necrosis factor-α [MD = -6.47, p < 0.05], interleukin-6 [MD = -24.46, p < 0.05], and pentraxin-3 [MD = -2.26, p < 0.05]; (8) improved vascular endothelial function, demonstrated by decreased endothelin-1 [MD = -20.56, p < 0.05] and increased nitric oxide [MD = 1.33, p < 0.05]; (9) alleviated oxidative stress, evidenced by increased superoxide dismutase levels [MD = 25.84, p < 0.05]; (10) no significant difference in adverse events [OR = 1.00, p = 1.00]. Conclusion: This study highlighted the efficacy and safety of adjunctive PNS injections in enhancing AMI patient outcomes beyond CT alone. Future RCTs need to solidify these findings through rigorous methods. Systematic Review Registration: (https://www.crd.york.ac.uk/PROSPERO/), identifier (CRD42023480131).

Long-Term Immunogenicity and In Vitro Prophylactic Protective Efficacy of M. tuberculosis Fusion Protein DR2 Combined with Liposomal Adjuvant DIMQ as a Boosting Vaccine for BCG.

The resuscitation of dormant Mycobacterium tuberculosis is an important cause of adult tuberculosis (TB) transmission. According to the interaction mechanism between M. tuberculosis and the host, the latency antigen Rv0572c and region of difference 9 (RD9) antigen Rv3621c were selected in this study to prepare the fusion protein DR2. Stimulating clinically diagnosed active tuberculosis infections (i.e., TB patients), latent tuberculosis infections, and healthy controls confirmed that T lymphocytes could recognize DR2 protein in the peripheral blood of TB-infected individuals more than subcomponent protein. The DR2 protein was then emulsified in the liposome adjuvant dimethyl dioctadecyl ammonium bromide, and imiquimod (DIMQ) was administered to C57BL/6 mice immunized with Bacillus Calmette-Guérin (BCG) vaccine to evaluate their immunogenicity. Studies have shown that DR2/DIMQ, a booster vaccine for BCG primary immunization, can elicit robust CD4+ Th1 cell immune response and predominant IFN-γ+ CD4+ effector memory T cells (TEM) subsets. Furthermore, the serum antibody level and the expression of related cytokines increased significantly with the extension of immunization time, with IL2+, CD4+, or CD8+ central memory T cells (TCM) subsets predominant in the long term. This immunization strategy showed matched prophylactic protective efficacy by performing in vitro challenge experiment. This result provides robust evidence that the novel subunit vaccine prepared by fusion protein DR2 combined with liposomal adjuvant DIMQ is a promising TB vaccine candidate for further preclinical trials as a booster vaccine for BCG.

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

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

Predictive value of soluble suppression of tumorigenicity 2 in atrial fibrillation: a systematic review and meta-analysis.

Purpose: Atrial fibrosis is the main pathological basis for the pathogenesis and progression of atrial fibrillation (AF). Soluble suppression of tumorigenicity 2 (sST2) is involved in fibrosis. Recent studies have explored its predictive value in AF outcomes. We performed this study to assess whether sST2 is an independent biomarker of AF outcomes and explore the potential mechanism. Methods: PubMed, Web of Science, EMBASE, and Cochrane Library databases were searched systematically from inception through July 1, 2023, to identify relevant studies. Outcomes of interest included occurrence, recurrence, and major adverse cardiac events (MACEs) of AF. This meta-analysis was reported following the criteria outlined in PRISMA 2020, and the protocol was registered in PROSPERO (number: CRD42023459789). All statistical analyses were performed using the STATA version 16. Result: Twenty four studies with 14,755 patients were included in the meta-analysis. The meta-analyses found that sST2 was significantly associated with the risk of occurrence [HR:1.04, 95% CI: 1.02-1.07, P < 0.01; I2 = 67.8%], recurrence [HR:1.09, 95% CI: 1.02-1.16, P < 0.01; I2 = 89.5%], and MACEs (HR:1.60, 95% CI: 1.13-2.27, P < 0.01; I2 = 82.0%) of AF. Furthermore, patients with AF showed higher sST2 than controls without AF (SMD: 0.41, 95% CI: 0.27-0.54, P < 0.01; I2 = 0%), and AF patients with recurrence after catheter ablation (CA) showed significantly higher sST2 than those without recurrence (SMD: 0.81, 95% CI: 0.33-1.28, P < 0.01; I2 = 83.9%). Sensitivity analyses showed that the outcomes were stable. Conclusions: Higher sST2 was association with an increased risk of occurrence, recurrence, and MACEs of AF. Assessing sST2 can be used as a potential screening method to predict AF outcomes. Systematic Review Registration: PROSPERO (CRD42023459789).

Construction and expression of Mycobacterium tuberculosis fusion protein AR2 and its immunogenicity in combination with various adjuvants to form vaccine.

Tuberculosis (TB) is recognized as a highly infectious disease worldwide, and Bacille Calmette-Guerin (BCG) remains the only TB vaccine licensed for clinical use. As there is little evidence that BCG is effective in adults, there is an urgent need for a safe and effective vaccine to control TB in adults. In this study, we tested the immunomodulatory efficiency of the fusion protein AR2. whole blood IFN-γ release assay (WBIA) was used to detect antigen specificity. The immunogenicity of the vaccine was tested in C57BL/6 mice, and confirmed by enzyme-linked immunosorbent assay (ELISA), flow cytometry, and qRT-PCR. The fusion protein AR2 was successfully constructed and expressed. The level of IFN-γ in the peripheral blood of subjects stimulated by AR2 was significantly higher than in those induced by all subcomponent proteins. AR2-specific IgG and the Th1 cytokines IFN-γ, TNF-α, and iNOS were significantly increased in the group treated with the fusion protein and compound adjuvant (AR2+DMC). Likewise, the number of IFN-γ+ CD4+, IFN-γ+CD8+, and IL-4+ CD8+ T lymphocytes increased significantly. The combination of the fusion protein and the compound adjuvant (AR2+DMC) may be a suitable candidate for an enhanced TB vaccine. This study provides theoretical and experimental support for future research to enhance the effectiveness of TB vaccines and provides an experimental basis for evaluating the influence of different adjuvants on vaccine efficacy.

Catheter ablation and cognitive function in atrial fibrillation: A systematic review and meta-analysis.

Background: Atrial fibrillation (AF) is a risk factor for cognitive dysfunction. Although catheter ablation (CA) is one of the main treatments for AF, whether it can improve cognitive function in patients with AF remains unclear. We conducted a systematic review and meta-analysis to evaluate the cognitive outcome post-CA procedure. Methods: Two investigators independently searched the PubMed, EMBASE, Web of Science, CNKI, WanFang, and VIP databases from inception to September 2021 for all the potentially eligible studies. The outcomes of interest included dementia or cognitive disorder through scoring or recognized classification criteria. Heterogeneity was determined by using Cochrane's Q test and calculating the I 2. A random-effects model was used to incorporate the potential effects of heterogeneity. The Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of each included study, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was adopted to evaluate the quality of evidence. Result: Thirteen studies including 40,868 patients were included, among which 12,086 patients received AF ablation. Meta-analysis indicated that patients with AF ablation had a lower risk of dementia incidence in comparison to patients with AF without ablation [hazard ratio (HR): 0.60, 95% CI: 0.43 to 0.84, p = 0.003 I 2 = 40%]. Significant differences were observed in the incidence of new-onset dementia [risk ratio (RR): 0.43, 95% CI: 0.28 to 0.65, p < 0.0001 I 2 = 84%]; the changes in the Montreal Cognitive Assessment (MoCA) score [weighted mean difference (WMD): 1.00, 95% CI: 0.36 to 1.64, p < 0.005 I 2 = 0%] and Mini-Mental State Examination (MMSE) score (WMD: 0.98, 95% CI: 0.69 to 1.26, p < 0.00001 I 2 = 0%]. However, in subgroup analysis, we did not observe significant changes in MoCA score at < 3 months (WMD: 1.20, 95% CI: -0.19 to 2.58, p = 0.09 I 2 = 50%) and changes in cognitive function scores between the radiofrequency group and cryoballoon group [standard mean difference (SMD): 0.39, 95% CI: -0.47 to 1.24, p = 0.38 I 2 = 87%]. The NOS indicated that included studies were moderate to high quality, while the quality of evidence assessed by GRADE was low in 2 and very low in 2. Conclusion: We analyzed the related cognitive outcomes after AF ablation. In the overall population, AF ablation had a positive trend for improving cognitive function at >3 months post-procedure. However, AF ablation might not be related to the improvement of cognitive function at < 3 months. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42021285198.

Left atrial appendage flow velocity predicts recurrence of atrial fibrillation after catheter ablation: A systematic review and meta-analysis.

Purpose: There is increasing evidence that left atrial appendage flow velocity (LAAFV) is linked to the recurrence of atrial fibrillation (AF) after catheter ablation (CA), suggesting the potential predictable significance of LAAFV in this setting. We performed a systematic review and meta-analysis to assess whether LAAFV is association with AF recurrence after CA. Methods: Up to May 1, 2022, six databases (PubMed, EMBASE, Web of Science, Cochrane Library, Scopus, and CINAHL) were searched for literature reporting the association between LAAFV and AF recurrence after CA. All statistical analyses were carried out using STATA version 16 software. Heterogeneity was determined by the Cochrane's Q test and I2 statistics. The Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of each included study, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was adopted to evaluate the quality of evidence. Result: Sixteen studies with 5,006 AF patients after CA (1,479 patients with AF recurrence, 3,527 without AF recurrence) were included in the meta-analysis. The meta-analysis of 15 studies (16 data sets) showed that patients with recurrence exhibited lower LAAFV values than those without recurrence [standardized mean difference (SMD): -0.65, 95% CI: -0.88 to -0.42, P < 0.01]. Moreover, we evaluated the association of LAAFV and the risk of AF recurrence after CA. Nine studies (11 data sets) defined LAAFV as continuous variables, and the pooled analysis suggested that for every 1 cm/s rise in LAAFV values, the risk of AF recurrence after CA decreased by 3% [Odds Ratio (OR): 0.97, 95% CI: 0.95 to 0.99, P < 0.01]. Seven studies defined LAAFV as categorical variables, and the pooled analysis showed that lower LAAFV were associated with an increased risk of AF recurrence after CA [OR: 2.28, 95% CI: 1.46 to 3.57, P < 0.01]. The subgroup analyses showed that the association between LAAFV and AF recurrence after CA was not significantly affected by the AF type and ablation procedure. The NOS indicated that included studies were moderate to high quality, while the GRADE assessment suggested a low certainty of the evidence. Conclusion: Lower LAAFV may be associated with an increased risk of AF recurrence after CA. Further studies with well designed and randomized studies for LAAFV should be conducted. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022333627].

Use of DosR and Rpf antigens from Mycobacterium tuberculosis to screen for latent and relapse tuberculosis infection in a tuberculosis endemic community of Huainan City.

The dormancy survival regulator (DosR) antigens upgraded during latency and resuscitation-promoting factors (Rpfs) expressed over the reactivation from dormant Mycobacterium tuberculosis (M. tuberculosis) could be used to diagnose tuberculosis (TB) at different stages. We performed a retrospective cohort study based on four groups, including healthy controls (HCs), active tuberculosis infections (ATBs), latent tuberculosis infections (LTBIs), and relapse tuberculosis infections (RTBs) enrolled between November 2020 and June 2021. Compared to the fusion protein E6-C10, combined with early secreted antigenic target 6 kDa (ESAT-6) and culture filtrate of 10 kDa (CFP-10), the DosR- or Rpf-encoded antigens could not elicit significant IFN-γ concentration for the diagnosis of ATB. Of note, the DosR antigens produce significantly more antigen-specific IFN-γ in LTBIs than Rpfs, and the levels of antigen-specific IFN-γ elicited in RTBs stimulated by Rpfs were higher than the DosR antigens. Among the DosR antigens, Rv2003c was the most immunogenic in diagnosing LTBIs, followed by Rv2007c and Rv2005c. As far as Rpfs are concerned, Rv0867c was the best antigen to identify RTBs, followed by Rv2389c and Rv1009. Both Rv2450c and Rv1884c showed relatively limited IFN-γ concentration in RTBs. Besides, the selected DosR antigens and Rpfs showed ideal specificity and inadequate sensitivity, which could have been enhanced by the fusion antigens prepared by the DosR antigens or Rpfs, respectively. The results of this study can provide more accurate detection methods for LTBIs and RTBs and could be used for screening the dormant M. tuberculosis throughout reactivation.

Role and Mechanism of PKC-δ for Cardiovascular Disease: Current Status and Perspective.

Protein kinase C (PKC) is a protein kinase with important cellular functions. PKC-δ, a member of the novel PKC subfamily, has been well-documented over the years. Activation of PKC-δ plays an important regulatory role in myocardial ischemia/reperfusion (IRI) injury and myocardial fibrosis, and its activity and expression levels can regulate pathological cardiovascular diseases such as atherosclerosis, hypertension, cardiac hypertrophy, and heart failure. This article aims to review the structure and function of PKC-δ, summarize the current research regarding its activation mechanism and its role in cardiovascular disease, and provide novel insight into further research on the role of PKC-δ in cardiovascular diseases.

Enhanced immunogenicity of the tuberculosis subunit Rv0572c vaccine delivered in DMT liposome adjuvant as a BCG-booster.

COVID-19 has affected the progress made in the prevention and treatment of tuberculosis (TB); hence, the mortality of tuberculosis has risen. Different strategies-based novel TB vaccine candidates have been developed. This study identifies strategies to overcome the limitations of Bacille Calmette-Guérin (BCG) in preventing latent infection and reactivation of TB. The latency antigen Rv0572c was selected based on the mechanism of interaction between Mycobacterium tuberculosis and its host. The rRv0572c protein was used to stimulate whole blood samples derived from patients with clinically diagnosed active TB (ATBs) or latent TB infections (LTBIs) and healthy control (HCs) donors, confirming that this protein can be recognized by T cells in patients with TB, especially LTBIs. C57BL/6 mice were used to investigate the immunogenicity of the rRv0572c protein emulsified in the liposome adjuvant dimethyldioctadecylammonium [DDA], monophosphoryl lipid A [MPLA], trehalose-6, 6'-dibehenate [TDB] (DMT). The results demonstrated that rRv0572c/DMT could boost BCG-primed mice to induce antigen-specific CD4+ T cell production and generate functional T cells dominated by antigen-specific CD8+ T cells. The rRv0572c/DMT vaccine could also trigger limited Th2 humoral immune responses. These findings suggest that rRv0572c/DMT is a potential subunit vaccine candidate that can be used as a booster vaccine for BCG.

Effects of Microbiota-Driven Therapy on Circulating Trimethylamine-N-Oxide Metabolism: A Systematic Review and Meta-Analysis.

Aim: This study was designed to systematically evaluate the effects of microbiota-driven therapy on decreasing TMAO and its related metabolites. Methods and Results: PubMed, EMBASE and Cochrane Library databases were searched (up to July 2021). Randomized controlled trials (RCTs), compared microbiota-driven therapy (prebiotics, probiotics, or synbiotics) with placebo on decreasing TMAO and its related metabolites, were eligible. Two researchers extracted the data independently and the disagreement was resolved by a third researcher. The risk of bias of included study was evaluated using Cochrane tool (RoB 2.0). Meta-analysis, meta-regression analysis and publication bias analysis were performed by RevMan 5.3 or Stata 12.0 software. Ten studies (12 arms) involving 342 patients (168 patients in the intervention group and 174 patients in the control group) were included. Compared with the control group, microbiota-driven therapy did not reduce circulating TMAO [SMD = -0.05, 95% CI (-0.36, 0.26), P = 0.749], choline [SMD = -0.34, 95% CI (-1.09, 0.41), P = 0.373], betaine aldehyde [SMD = -0.704, 95% CI (-1.789, 0.382), P = 0.204], and L-carnatine [SMD = -0.06, 95% CI (-0.38, 0.25), P = 0.692]. Conclusion: Current evidence does not support that microbiota-driven treatment reduce circulating levels of TMAO, choline, betaine aldehyde, and L-carnitine. However, given the small sample size, this conclusion needs to be proved in the future. Systematic Review Registration: PROSPERO:CRD42019119107.

Serum Uric Acid and Risk of Chronic Heart Failure: A Systematic Review and Meta-Analysis.

Objectives: A systematic review and meta-analysis was performed to evaluate the potential prognostic role of serum uric acid (SUA) in patients with chronic heart failure (CHF). Methods: The Embase, PubMed, Web of Science and Cochrane Library databases were searched up to 5 April 2021 for relevant publications. Random effects model was used to pool data. STATA15.0 software was used to perform meta-analysis. Heterogeneity was assessed using the Cochran Q statistic (significance level of P < 0.10) and I 2 statistics (significance level of 50%). Results: Ultimately, 18 publications reporting adverse events in CHF patients were included. The results indicate reveal associations between a high level of SUA and the risk of all-cause mortality (HR 2.24, 95% CI 1.49-3.37), cardiovascular mortality (HR 1.14, 95% CI 1.06-1.23), and the composite of death or cardiac events (HR 1.26, 95% CI 1.01-1.56) in CHF patients. A 1 mg/dL increase in serum uric acid led to 4% (HR 1.04, 95% CI 1.02-1.05) and 9% (HR 1.09, 95% CI 1.03-1.17) increases in the risk of all-cause mortality and the composite endpoint of death or cardiac events in CHF patients, respectively. Conclusion: Serum uric acid is positively associated with the risk of adverse events in CHF patients. This study protocol has been registered at PROSPERO as CRD42021247084 (https://www.crd.york.ac.uk/PROSPERO). Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO.

Xinyue Capsule in patients with stable coronary artery disease after percutaneous coronary intervention: a multicenter, randomized, placebo-controlled trial.

BACKGROUND: Xinyue capsule, a patented Chinese herbal medicine, has been used to manage coronary artery disease (CAD) for over a decade in China, but whether it can further reduce risk of cardiovascular events beyond conventional treatment is unknown. METHODS: In this multicenter, randomized, placebo-controlled trial, we randomly assigned patients with stable CAD who underwent percutaneous coronary intervention (PCI) within the preceding 3-12 months to receive Xinyue capsule (100 mg panax quinquefolius saponins, three times a day) or placebo for 24 weeks in addition to conventional treatment. The primary endpoint was a composite that included cardiac death, nonfatal myocardial infarction and urgent revascularization with either PCI or coronary artery bypass grafting. The secondary composite endpoints included stroke, re-hospitalization due to acute coronary syndrome (ACS), pulmonary embolism, peripheral vascular events and all-cause mortality. Quality of life was assessed using a 36-item Short-Form Health Survey (SF-36). RESULTS: A total of 1054 participants were included in the analyses. The median follow up was 1 year. The primary endpoint events occurred in 16 patients (3.02%) in the Xinyue group and 34 patients (6.49%) in the placebo group (hazard ratio [HR] 0.455, 95% confidence interval [CI] 0.25 to 0.825; P = 0.009). Secondary end-point events occurred in 5.47% of patients in the Xinyue group and 10.31% in the placebo group (HR 0.515, 95% CI 0.328 to 0.809; P = 0.004). SF-36 subscale scores at 12 months were significantly higher in the Xinyue group than placebo group for general health (P = 0.048) and vitality (P = 0.008). CONCLUSIONS: In patients with stable CAD after PCI within the preceding 3 to 12 months, Xinyue capsule added on conventional treatment reduced the incidence of primary composite endpoint (cardiac death, nonfatal myocardial infarction and urgent revascularization).

The efficacy of Chinese herbal medicines on acute coronary syndrome with renal insufficiency after percutaneous coronary intervention.

ETHNOPHARMACOLOGICAL RELEVANCE: Fufang Chuanxiong capsule consists of Angelica sinensis radix and Chuanxiong rhizome, which are used in the traditional Chinese medicine for the treatment of coronary artery disease, and Xinyue capsule is composed of panax quinquefolius saponin extracted from leaves and stems of Panax quinquefolium L, which has the functions of anti-myocardial ischemia, improving myocardial energy metabolism and inhibiting apoptosis of cardiomyocytes. OBJECTIVE: To observe the role of Chinese herbal medicines in the cardiovascular outcome among patients with acute coronary syndrome (ACS) and renal insufficiency after percutaneous coronary intervention (PCI). METHODS: The subjects came from the 5C trial (chictr.org number: chictr-trc-07000021), post-PCI patients suffered from ACS with mild-to-moderate renal insufficiency (30 mL•min-1•1.73 m-2 < estimated glomerular filtration rate≤89 mL•min-1•1.73 m-2) included. The study population consisted of 215 subjects in the control group who were treated with western medicine standard therapy, and 211 subjects in the treatment group who were treated with Chinese herbal medicines (Fufang Chuanxiong Capsule and Xinyue Capsule) for 6 months on the basis of western medicine standard therapy. All were followed for 1 year. The primary endpoint included the composite of cardiac death, nonfatal recurrent myocardial infarction, and ischemia-driven revascularization. Secondary endpoint included the composite of stroke, congestive heart failure, and readmission for ACS. The serum creatinine and estimated glomerular filtration rate (eGFR) were evaluated. RESULTS: After 1 year follow-up of two groups, there were 16 cases of primary endpoint in the control group and 6 cases of primary endpoint in the treatment group [absolute risk reduction (ARR): 0.046, 95%CI: 0.004-0.088; relative risk (RR): 0.38, 95%CI: 0.15-0.96, P = 0.040]. There were 15 cases of secondary endpoint in the control group and 5 cases of secondary endpoint in the treatment (ARR: 0.041, 95%CI: 0.006-0.086; RR: 0.34, 95%CI: 0.13-0.92, P = 0.033). The eGFR in the treatment group was significantly higher than that in the control group (75.19 ±â€¯16.74 mL min-1·1.73 m-2 VS 72.03 ±â€¯14.96 mL min-1·1.73 m-2, P < 0.05). The eGFR in the treatment group was significantly higher after the intervention with Chinese herbal medicines than that before intervention (72.27 ±â€¯11.83 mL min-1·1.73 m-2 VS 75.19 ±â€¯16.74 mL min-1·1.73 m-2, P < 0.05). CONCLUSION: Chinese herbal medicines plus western medicine standard therapy improved clinical outcomes in patients with ACS and mild-to-moderate renal insufficiency. Additionally, this study also demonstrated Chinese herbal medicines were useful in deferring decline of renal function.

Qing-Xin-Jie-Yu Granule for patients with stable coronary artery disease (QUEST Trial): A multicenter, double-blinded, randomized trial.

BACKGROUND AND AIM: Despite optimal secondary preventive treatment, patients with stable coronary artery disease (SCAD) remain at high risk of cardiovascular events. This multicenter, double-blinded, randomized trial sought to determine whether the addition of Qing-Xin-Jie-Yu Granule (QXJYG), a traditional Chinese medicine prescription, to standard therapy would further reduce risk of cardiovascular events in patients with SCAD. METHODS: A total of 1500 patients with documented SCAD were randomly assigned in a 1:1 ratio to QXJYG or placebo for 6 months, and followed up for another 6 months. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction (MI) and coronary revascularization. Near the end of the trial, but before unblinding, a commonly used composite 'hard' endpoint composed of cardiovascular death, nonfatal myocardial infarction and ischemic stroke was additionally analyzed. RESULTS: During a median follow-up of 12 months, no significant difference of the primary outcome between the two groups was observed (1.59% vs. 1.62%; hazard ratio, 0.41; 95% CI, 0.13-1.28). However, absolute risk of the composite 'hard' endpoint was reduced by 0.99% (0.31% vs. 1.30%; hazard ratio, 0.06; 95%CI, 0.01 to 0.53). No difference of adverse events between the two groups was observed. CONCLUSION: In patients with SCAD, the addition of QXJYG to standard therapy was associated with reduced risk of nonfatal MI and the composite 'hard' endpoint of cardiovascular death, nonfatal MI and stroke. (http://www.chictr.org.cn/showproj.aspx?proj=5200, ChiCTR-TRC-13004370).

Panax quinquefolium saponin attenuates cardiac remodeling induced by simulated microgravity.

BACKGROUND: Cardiac atrophy and reduced cardiac distensibility have been reported following space flight. Cardiac function is correspondingly regulated in response to changes in loading conditions. Panax quinquefolium saponin (PQS) improves ventricular remodeling after acute myocardial infarction by alleviating endoplasmic reticulum stress and Ca2+overload. However, whether PQS can ameliorate cardiac atrophy following exposure to simulated microgravity remains unknown. PURPOSE: To explore the protective role of PQS in cardiac remodeling under unloading conditions and its underlying mechanisms. METHODS: Hindlimb unloading (HU) model was used to simulate unloading induced cardiac remodeling. Forty-eight male rats were randomly assigned to four groups, including control, PQS, HU and HU + PQS. At 8 weeks after the experiment, cardiac structure and function, serum levels of Creatine Kinase-MB (CK-MB), Cardiactroponin T (cTnT), ischemia modified albumin (IMA), and cardiomyocyte apoptosis were measured. Network pharmacology analysis was used to predict the targets of the six major constituents of PQS, and the signaling pathways they involved in were analyzed by bioinformatics methods. Changes in the key proteins involved in the protective effects of PQS were further confirmed by Western Blot. RESULTS: Simulated microgravity led to increases in serum levels of CK-MB, cTnT and IMA, remodeling of cardiac structure, impairment of cardiac function, and increased cardiomyocyte apoptosis as compared with control. PQS treatment significantly reduced serum levels of CK-MB, cTnT and IMA, improved the impaired cardiac structure and function, and decreased cardiomyocyte apoptosis induced by unloading. The activation of AMPK and inhibition of Erk1/2 and CaMKII/HDAC4 were demonstrated in the cardiocytes of HU rats after PQS treatment. CONCLUSION: PQS provides protection against cardiac remodeling induced by simulated microgravity, partly resulting from changes in the signaling pathways related to energy metabolism reduction, calcium overloading and cell apoptosis.

Zedoary Guaiane-Type Sesquiterpenes-Eluting Stents Accelerate Endothelial Healing Without Neointimal Hyperplasia in a Porcine Coronary Artery Model.

OBJECTIVE: The effects of zedoary guaiane-type sesquiterpenes (ZGS)-based eluting stent (ZES) in accelerating reendothelialization and inhibiting neointimal hyperplasia were examined in a porcine coronary artery model. METHODS: The ZES was prepared by polymer-free 316L stainless metal stents. Sirolimus-eluting stents (SES) and bare metal stents (BMS) with identical platforms were used as controls. Stents with 15 mm in length and 2.0 to 3.5 mm in diameter were implanted in porcine coronary arteries. Scanning electron microscopy (SEM) and histopathology were performed to assess the reendothelialization and neointimal hyperplasia. The 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl-2H-tetrazoliumbromide assay and flow cytometry were used to assess the influence of ZGS on human umbilical vascular endothelial cells (HUVECs). RESULTS: At 7 days, SEM showed that percentage of endothelial coverage area was 94.04% ± 5.01% for ZES, 47.59% ± 19.91% for SES ( P < .01 for ZES vs SES), and 59.58% ± 19.61% for BMS ( P < .05 for ZES vs BMS). At 28 days, the percentage of coverage area was 98.51% ± 1.86% for ZES, 86.18% ± 8.16% for SES ( P < .05 for ZES vs SES), and 94.26% ± 5.58% for BMS. Neointimal area and stenosis were significantly lower in ZES (1.07 ± 0.48 mm2, 27.66% ± 12.20%) compared to BMS (1.73 ± 0.69 mm2, 44.08% ± 15.03%, both P < .01, respectively), with no difference in SES (0.94 ± 0.12 mm2, 28.87% ± 6.00%, both P > .05, respectively). The ZGS also promoted HUVECs viability and improved HUVECs proliferation compared to sirolimus. CONCLUSION: The ZES accelerated reendothelialization and suppressed neointimal hyperplasia in a porcine coronary artery model, with beneficial effects on HUVECs.

Long-term follow-up of Chinese herbal medicines combined with conventional treatment in patients with acute coronary syndrome after percutaneous coronary intervention: A multicenter randomized controlled trial.

OBJECTIVE: To evaluate the prognosis effect of Chinese herbal medicines (CHMs) for benefiting qi and activating blood circulation adjunctive to conventional treatment in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). METHODS: A total of 702 patients with ACS who underwent PCI were enrolled and randomly assigned to receive conventional treatment plus CHMs for benefiting qi and activating blood circulation (treatment group, 351 cases) or conventional treatment alone (control group, 351 cases) for 6 months. Six months later, all patients received conventional treatment alone. Follow-ups were scheduled at 6th, 12th, 18th, 24th month after enrollment in April 2008, and the final follow-up visit was during September 2011 and November 2011. The primary endpoint was the composite of cardiac death, nonfatal myocardial infarction or revascularization (PCI or coronary artery bypass grafting); and the secondary endpoint was the composite of re-admission for ACS, congestive heart failure, nonfatal stroke or other thrombus events. RESULTS: A total of 621 (88.59%) patients completed 35.4±3.8 months follow-up, while 80 (11.41%) patients withdrew from the trial (41 in the treatment group and 39 in the control group). The incidence of primary endpoint was 5.7% (20 patients) in the treatment group versus 10.86% (38 patients) in the control group [relative risk (RR): 0.53; 95% confidence interval (CI): 0.30, 0.88; P=0.013; absolute risk reduction (ARR):-0.052, 95% CI: -0.06, 0.01]. The incidence of secondary endpoint was 5.98% (21 patients) in the treatment group versus 10.28% (36 patients) in control group (RR: 0.58, 95% CI: 0.33, 0.97, P=0.037; ARR: -0.043, 95% CI: 0.06, 0.01). Most of the primary and secondary endpoints were occurred in 18 months (84.50% in the treatment group versus 78.10% in the control group). CONCLUSION: CHMs for benefiting qi and activating blood circulation adjunctive to conventional treatment improved clinical outcomes for patients with ACS after PCI in long-term follow-up.

Resting heart rate associates with one-year risk of major adverse cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention.

The study was to access the association between resting heart rate (RHR) and one-year risk of major adverse cardiovascular events (MACE) in acute coronary syndrome (ACS) patients after percutaneous coronary intervention (PCI). Patients with ACS after PCI (n = 808) were prospectively followed-up for MACE. RHR was obtained from electrocardiogram. MACE was defined as a composite of cardiac death, nonfatal recurrent myocardial infarction, ischemic-driven revascularization, and ischemic stroke. The association between RHR and one-year risk of MACE was assessed using Cox proportional hazards regression model. Compared with patients with RHR >76 bpm, the adjusted hazard ratio (AHR) was 0.51 (95% confidence intervals [CI]: 0.23-1.14; P = 0.100) for patients with RHR < 61 bpm, and 0.44 (95%CI: 0.23-0.85; P = 0.014) for those with RHR 61-76 bpm. For patients with RHR ≥ 61 bpm, an increase of 10 bpm in RHR was associated with an increase by 38.0% in the risk of MACE (AHR: 1.38; 95% CI: 1.04-1.83; P = 0.026). ACS patients after PCI with RHR >76 bpm were at higher risk of MACE during one-year follow-up compared with patients with RHR 61-76 bpm. An elevated RHR ≥ 61 bpm was associated with increased risk of one-year MACE in ACS patients.

[Efficacy of Chinese Herbs for Supplementing Qi and Activating Blood Circulation on Patients with Acute Coronary Syndrome and Type 2 Diabetes Mellitus after Percutaneous Coronary Intervention: a Clinical Observation].

OBJECTIVE: To observe the efficacy of Chinese herbs for supplementing qi and activating blood circulation (CHSQABC) on patients with acute coronary syndrome (ACS) and type 2 diabetes mellitus (DM) after successful percutaneous coronary intervention (PCI). METHODS: In this ChiCTR-TRC-00000021, a total of 281 ACS patients complicated with type 2 DM after successful PCI were randomly assigned to the Western medicine treatment group (the control group, treated by routine Western medicine treatment) and the combined treatment group (the treatment group, treated by CHSQABC + routine Western medicine treatment). Patients in the combined treatment group took Xinyue Capsule (2 pills each time, 3 times per day) and Compound Chuanxiong Capsule (2 pills each time, 3 times per day for half a year and 1-year follow-ups). Primary endpoints covered incidence of death, nonfatal myocardial infarction (MI), ischemia-driven revascularization, and secondary endpoints included stroke, heart failure, and rehospitalization for ACS. At the same time scores for blood stasis syndrome (BSS) and the incidence of angina pectoris were evaluated before treatment, at month 1, 3, 6, 9, and 12 after treatment. RESULTS: The incidence of ischemia-driven revascularization was obviously less in the treatment group than in the control group (P < 0.05). No patient had nonfatal MI in the treatment group, while 5 patients in the control group had it. The incidence of non-fatal MI showed an obvious lowering tendency in the treatment group, but with no statistical difference when compared with that in the control group (P > 0.05). Four patients readmitted to hospital in the treatment group, while 12 patients readmitted. There existed obvious tendency in the treatment group, but with no statistical difference when compared with that in the control group (P > 0.05). The incidence of angina was significantly lower in the treatment group at month 6, 9, and 12 than that at month 1 , but it was lower in the control group at 9 months (P < 0.05). The incidence of angina was 15. 4% in the treatment group, obviously lower than that in the control group (26.2%, P < 0.05). Compared with before treatment, scores for BSS were obviously lowered in the treatment group at 1, 3, 6, 9, and 12 months of treatment and in the control group at 3, 6, 9, and 12 months of treatment (P < 0.05). It was obviously lower in the treatment group than in the control group at 3, 6, 9, and 12 months of treatment (P < 0.01). CONCLUSION: Administration of CHSQABC combined routine Western medicine treatment could reduce the event of revascularization and post-PCI recurrent angina, and improve scores for BSS of ACS patients complicated with DM after PCI.