Berberine Decreases Thrombosis Potential Induced by a High-choline Diet by Inhibiting CutC Enzyme.

INTRODUCTION: Gut microbes influence thrombosis potential by generating trimethylamine N-oxide (TMAO). However, whether the antithrombotic effect of berberine is associated with TMAO generation remains unclear. OBJECTIVE: The present study was designed to explore whether berberine decreases the TMAO-induced thrombosis potential and the possible mechanism underneath it. METHODS: C57BL/6J female mice under a high-choline diet or standard diet were treated with/without berberine for 6 weeks. The TMAO level, carotid artery occlusion time following FeCl3 injury and platelet responsiveness were measured. The binding of berberine to the CutC enzyme was analysed with molecular docking, and molecular dynamics simulations were verified with enzyme activity assays. Results：The results showed that berberine increased the carotid artery occlusion time following FeCl3 injury and decreased the platelet hyperresponsiveness induced by a high-choline diet, both offset by intraperitoneal injection of TMAO. The effect of berberine on thrombosis potential was associated with decreasing the generation of TMAO by inhibiting the CutC enzyme. CONCLUSION: Targeting TMAO generation with berberine might be a promising therapy for ischaemic cardiac-cerebral vascular diseases.

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.

Lingbao Huxin Pill Alleviates Apoptosis and Inflammation at Infarct Border Zone through SIRT1-Mediated FOXO1 and NF- κ B Pathways in Rat Model of Acute Myocardial Infarction.

OBJECTIVE: To investigate whether Lingbao Huxin Pill (LBHX) protects against acute myocardial infarction (AMI) at the infarct border zone (IBZ) of myocardial tissue by regulating apoptosis and inflammation through the sirtuin 1 (SIRT1)-mediated forkhead box protein O1 (FOXO1) and nuclear factor-κ B (NF-κ B) signaling pathways. METHODS: Six-week-old Wistar rats with normal diet were randomized into the sham, the model, Betaloc (0.9 mg/kg daily), LBHX-L (0.45 mg/kg daily), LBHX-M (0.9 mg/kg daily), LBHX-H (1.8 mg/kg daily), and LBHX+EX527 (0.9 mg/kg daily) groups according to the method of random number table, 13 in each group. In this study, left anterior descending coronary artery (LADCA) ligation was performed to induce an AMI model in rats. The myocardial infarction area was examined using a 2,3,5-triphenyltetrazolium chloride solution staining assay. A TdT-mediated dUTP nick-end labeling (TUNEL) assay was conducted to assess cardiomyocyte apoptosis in the IBZ. The histopathology of myocardial tissue at the IBZ was assessed with Heidenhain, Masson and hematoxylineosin (HE) staining assays. The expression levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1 ß, and intercellular adhesion molecule-1 were measured using enzyme-linked immunosorbent assays (ELISAs). The mRNA expressions of SIRT1 and FOXO1 were detected by real-time qPCR (RT-qPCR). The protein expressions of SIRT1, FOXO1, SOD2, BAX and NF- κ B p65 were detected by Western blot analysis. RESULTS: The ligation of the LADCA successfully induced an AMI model. The LBHX pretreatment reduced the infarct size in the AMI rats (P<0.01). The TUNEL assay revealed that LBHX inhibited cardiomyocyte apoptosis at the IBZ. Further, the histological examination showed that the LBHX pretreatment decreased the ischemic area of myocardial tissue (P<0.05), myocardial interstitial collagen deposition (P<0.05) and inflammation at the IBZ. The ELISA results indicated that LBHX decreased the serum levels of inflammatory cytokines in the AMI rats (P<0.05 or P<0.01). Furthermore, Western blot analysis revealed that the LBHX pretreatment upregulated the protein levels of SIRT1, FOXO1 and SOD2 (P<0.05) and downregulated NF- κ B p65 and BAX expressions (P<0.05). The RT-qPCR results showed that LBHX increased the SIRT1 mRNA and FOXO1 mRNA levels (P<0.05). These protective effects, including inhibiting apoptosis and alleviating inflammation in the IBZ, were partially abolished by EX527, an inhibitor of SIRT1. CONCLUSION: LBHX could protect against AMI by suppressing apoptosis and inflammation in AMI rats and the SIRT1-mediated FOXO1 and NF- κ B signaling pathways were involved in the cardioprotection effect of LBHX.

Prognostic Significance of Triglyceride-Glucose Index for Adverse Cardiovascular Events in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis.

Background: Insulin resistance (IR) represents a critical regulator in the development and progress of coronary artery disease (CAD). Triglyceride-glucose (TyG) index, a novel surrogate biomarker of IR, has been implicated in several cardiovascular diseases. Accordingly, we conduct a meta-analysis to elucidate the relationship between TyG index and adverse cardiovascular events in patients with CAD. Methods: To identify the studies examining the predictive capacity of the TyG index for adverse cardiovascular events in the setting of CAD, we performed a comprehensive literature retrieval of Scopus, PubMed, EMBASE, and Web of Science, from the inception of databases to October 5, 2021. We pooled the adjusted hazard ratio (HR) along with 95% CI using a random-effects model. The primary outcome was a composite of major adverse cardiovascular events (MACEs), including all-cause death, cardiovascular death (CV death), myocardial infarction (MI), stroke, hospitalization for unstable angina or heart failure, and revascularization. The secondary outcomes were all-cause death, CV death, MI, stroke, and revascularization. Additionally, we conducted subgroup analyses stratified by diabetes status, age, body mass index (BMI), low-density lipoprotein cholesterol (LDL-C), category of TyG index, sample size, follow-up duration, and study design. Results: About 12 studies involving 28,795 patients with CAD were finally taken into the quantitative analysis. Our findings showed that there was a 2.14-fold higher risk of MACEs among CAD populations in the highest TyG group compared with those in the lowest TyG group (HR: 2.14, 95% CI: 1.69-2.71, P < 0.001). A greater risk of MACEs was observed in participants with higher BMI than those with lower BMI (P = 0.03 for interaction). In the analysis of secondary outcomes, we also observed a markedly increased risk of MI, stroke, and revascularization in the highest TyG group compared with the lowest TyG group. No evidence of a significant association between TyG index and CV mortality or all-cause mortality in patients with CAD was identified. Conclusions: The elevated TyG index is a promising predictive factor of adverse cardiovascular events in patients with CAD. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021228521.

A Meta-Analysis of Growth Differentiation Factor-15 and Prognosis in Chronic Heart Failure.

Background: Previous studies had reported increased circulating concentrations of growth differentiation factor-15 (GDF-15) in chronic heart failure (CHF), suggesting the potential prognostic significance of GDF-15 in this setting. To verify the relationship between the circulating GDF-15 levels and prognosis of CHF patients, we conducted an updated evidence-based meta-analysis. Methods: A comprehensive literature retrieval of PubMed, EMBASE, and Cochrane library was performed to collect the qualified studies that analyzed the prognostic value of GDF-15 in CHF from the inception of these online databases to September 25, 2021. The hazard ratio (HR) calculated for logGDF-15 of all-cause death and the related 95% confidence interval (CI) in multivariate analysis were used to measure the effect size. Additionally, subgroup analyses stratified by characteristics of the study participants were conducted for incremental evidence of GDF-15 in CHF with different clinical status. Results: A total of ten eligible studies involving 6,244 CHF patients were finally taken into the quantitative analysis. Results in the random-effects model indicated that there was an increased risk of 6% in all-cause mortality with a per 1LnU increase in baseline GDF-15 concentration (HR: 1.06, 95% CI: 1.03-1.10, P < 0.001). In stratified analyses, the association of GDF-15 with risk of all-cause mortality was found among chronic ischemic HF patients (HR:1.75, 95%CI: 1.24-2.48, P = 0.002), while the association was not found among chronic nonischemic HF patients (HR:1.01, 95%CI: 1.00-1.02, P = 0.219). Conclusion: The elevated GDF-15 is associated with an increased risk of all-cause mortality in CHF, especially, among CHF patients with ischemic etiology. The circulating GDF-15 might be a prognostic indicator in CHF patients. Registration Number: https://www.crd.york.ac.uk/PROSPERO; CRD42020210796.

Combination of Activating Blood Circulation and Detoxifying Chinese Medicines Played an Anti-Inflammatory Role in Unstable Angina Patients after Percutaneous Coronary Intervention: A Multicenter, Open-Labeled, Randomized Controlled Trial.

OBJECTIVE: To investigate the combined anti-inflammatory effect of activating blood circulation and detoxifying Chinese medicines in unstable angina (UA) patients. METHODS: This study was an open-labeled, randomized controlled trial conducted in 5 centers in Beijing. A total of 154 patients were randomized into two groups at a 1:1 ratio by random numbers. Based on the conventional treatment, patients in the activating blood circulation (ABC) group were treated with Guanxin Danshen Droping Pill (, 0.4 g, thrice daily), and patients in the activating blood circulation and detoxifying (ABCD) group were treated with Guanxin Danshen Droping Pill (0.4 g, thrice daily) and Andrographis tablet (0.2 g, thrice daily) for 4 weeks. The primary outcome was the serum level of high sensitive C reaction protein (hs-CRP), and the secondary outcome index included the serum levels of tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), soluble CD40 ligand (sCD40L), thrombomodulin (TM), the score of angina pectoris, the score of blood stasis syndrome, and the score of Chinese medicine symptoms, observed at week 0 and week 4. RESULTS: A total of 144 patients completed the trial (ABC group, n=70; ABCD group, n=74). There were no significant differences in the clinical baseline characteristics between the two groups. When compared with the ABC group, ABCD group showed better performance in reducing the level of inflammatory factors, especially hs-CRP (P<0.05), IL-6 (P<0.01) and TNF-α (P<0.01). In term of clinical symptoms, ABCD group played a better role in improving the scores of angina pectoris and blood stasis syndrome than ABC group (all P<0.05). CONCLUSIONS: The combination of Guanxin Danshen Dropping Pill and Andrographis tablet exert significant anti-inflammatory effect on UA patients, which is superior to single Guanxin Danshen Dropping Pill. (Registration No. ChiCTR-TRC-13004072).

Panax Notoginseng Saponin Attenuates Gastric Mucosal Epithelial Cell Injury Induced by Dual Antiplatelet Drugs through COX and PI3K/Akt/ VEGF-GSK-3ß-RhoA Network Pathway.

OBJECTIVE: To elucidate the underlying mechanism of Panax notoginseng saponin (PNS) on gastric epithelial cell injury and barrier dysfunction induced by dual antiplatelet (DA). METHODS: Human gastric mucosal epithelial cell (GES-1) was cultured and divided into 4 groups: a control, a DA, a PNS+DA and a LY294002+PNS+DA group. GES-1 apoptosis was detected by flow cytometry, cell permeability were detected using Transwell, level of prostaglandins E2 (PGE2), 6-keto-prostaglandin F1α (6-keto-PGF1α) and vascular endothelial growth factor (VEGF) in supernatant were measured by enzyme linked immunosorbent assay (ELISA), expression of phosphatidylinositide 3-kinase (PI3K), phosphorylated-PI3K (p-PI3K), Akt, phosphorylated-Akt (p-Akt), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), glycogen synthase kinase-3ß (GSK-3ß) and Ras homolog gene family member A (RhoA) were measured by Western-blot. RESULTS: DA induced apoptosis and hyper-permeability in GES-1, reduced supernatant level of PGE2, 6-keto-PGF1α and VEGF (P<0.05). Addition of PNS reduced the apoptosis of GES-1 caused by DA, restored the concentration of PGE2, 6-keto-PGF1α and VEGF (P<0.05). In addition, PNS attenuated the alteration of COX-1 and COX-2 expression induced by DA, up-regulated p-PI3K/p-Akt, down-regulated RhoA and GSK-3ß. LY294002 mitigated the effects of PNS on cell apoptosis, cell permeability, VEGF concentration, and expression of RhoA and GSK-3ß significantly. CONCLUSIONS: PNS attenuates the suppression on COX/PG pathway from DA, alleviates DA-induced GES-1 apoptosis and barrier dysfunction through PI3K/Akt/ VEGF-GSK-3ß-RhoA network pathway.

Berberine Protects against TNF-α-Induced Injury of Human Umbilical Vein Endothelial Cells via the AMPK/NF-κB/YY1 Signaling Pathway.

Endothelial injury, characterized by an inflammatory response and increased permeability, is an initial stage of atherosclerosis (AS). Adenosine 5'-monophosphate (AMP), activated protein kinase (AMPK), and Nuclear Factor kappa B (NF-κB)/Yin Yang 1(YY1) signaling pathways play important roles in the process of endothelial injury. Berberine (BBR), a bioactive alkaloid isolated from several herbal substances, possesses multiple pharmacological effects, including anti-inflammatory, antimicrobial, antidiabetic, anticancer, and antioxidant activities. Previous studies showed a protective effect of berberine against endothelial injury. However, the underlying mechanism remains unclear. We explored the potential effect of BBR on TNF- (tumor necrosis factor-) α-induced injury of human umbilical endothelial cells (HUVECs) and studied its possible molecular mechanism. In the present study, HUVECs were divided into three groups. HUVEC viability was measured with Cell Counting Kit-8 assay. Extracellular lactic dehydrogenase (LDH) concentration was measured with LDH leakage assay. Endothelial microparticle (EMP) numbers were evaluated by flow cytometry analysis assay. The expression of proinflammatory cytokines was evaluated by Enzyme-Linked Immunosorbent Assay (ELISA). The mRNA expression of NF-κB and YY1 was detected by Real-Time PCR (RT-PCR). The protein expression of NF-κB, YY1, and AMPK was detected by immunofluorescence microscopy assay or western blot analysis. The results showed that LDH concentration, EMPs numbers, and the expression of proinflammatory cytokines (IL-6, IL-8, and IL-1ß) increased in TNF-α-induced injured HUVECs, but ameliorated by BBR pretreatment. BBR pretreatment upregulated the expression of phosphorylated AMPK and downregulated the expressions of NF-κB and YY1 in injured HUVECs induced by TNF-α, which were offset by the AMPK inhibitor Compound C (CC). The results indicated that BBR protected against TNF-α-induced endothelial injury via the AMPK/NF-κB/YY1 signaling pathway.

The Effect of Prebiotic Products on Decreasing Adiposity Parameters in Overweight and Obese Individuals: A Systematic Review and Meta- Analysis.

BACKGROUND: Prebiotics are substrates selectively utilized by host microorganisms to confer health benefits. The potential of prebiotics to decrease body weight in overweight/obese individuals was suggested by some clinical and animal studies. However, these studies were based on relatively small sample sizes and the precise effects of prebiotic products have not yet been evaluated. Therefore, the present meta-analysis of Randomized Controlled Trials (RCTs) was designed to comprehensively assess the effects of prebiotic products on overweight and obese individuals. METHODS: PubMed, EMBASE and Cochrane Library were searched to identify RCT investigating the effects of prebiotic products on overweight and obese individuals. We calculated the pooled weighted mean difference (WMD) to assess the effects of prebiotic products on Body Mass Index (BMI), body weight, fat mass and inflammatory biomarkers. RESULTS: Twelve RCTs with a total of 535 overweight and obese individuals were enrolled. Compared with placebo, prebiotic products decreased C reactive protein (WMD, -1.06 mg/L; 95%CI, -1.72 to - 0.40; p=0.002), tumour necrosis factor-α(WMD, -0.64 pg/mL; 95%CI, -1.11 to -0.18; p=0.006) and other inflammatory markers, such as interleukin-1ß，lipopolysaccharide (p<0.05); whereas no reductions in BMI (WMD, -0.20 kg/m2; 95%CI, -0.58 to 0.19; p=0.32), body weight (WMD, -0.51 kg; 95%CI, -1.18 to 0.16; p=0.14) and fat mass (WMD, 0.11 kg; 95%CI, -0.04 to 0.25; p=0.15) were observed. CONCLUSION: In the present analysis, comprehensive evidence suggested that prebiotic products did not decrease adiposity parameters (BMI, body weight and body fat mass), but they could decrease the levels of systemic inflammatory biomarkers, implying adherence to prebiotic products might be a promising complementary approach to managing inflammatory states in overweight and obese individuals.

A Multicenter Randomized Controlled Pilot Trial Testing the Efficacy and Safety of Pterygopalatine Fossa Puncture Using One Acupuncture Needle for Moderate-to-Severe Persistent Allergic Rhinitis.

OBJECTIVE: To compare the efficacy and safety of pterygopalatine fossa puncture using one acupuncture needle inserted through the temporal fossa (intervention) and Chinese verum acupuncture (VA) in patients with moderate-to-severe persistent allergic rhinitis. METHODS: The patients were randomized to an intervention group receiving pterygopalatine fossa puncture with one acupuncture needle for 4 weeks (once or twice weekly, 4-8 sessions in total, with a second course performed if required) or to a control group receiving individualized VA for 4 weeks (twice weekly, eight sessions in total). Patients were followed up 4 weeks later. RESULTS: Ninety-six participants were assigned to intervention (n = 48) or VA (n = 48) or VA (P > 0.05 in all cases). Compared with the VA, the time to onset of effect in the intervention group was shorter and the duration of effectiveness was longer. The mean clinical waiting time was significantly shorter in the intervention group than in the control group (6.640 ± 3.035 min and 31.19 ± 10.216 min, respectively). The total number of sessions in the VA group was 384; 7 episodes of subcutaneous bleeding occurred but did not require treatment. The total number of sessions in the intervention group was 185. Two cases of subcutaneous bleeding (one of local hematoma during the intervention and the other one of bruising in the palpebra inferior on the day after intervention) resolved upon withdrawal from the study. CONCLUSIONS: Pterygopalatine fossa puncture using one acupuncture needle resulted in a shorter time to onset of effect, a longer duration of effectiveness, and less clinical waiting time when compared with VA. Though the significant differences for TNSS and TNNSS were shown within intervention and VA groups, there were no differences between the two groups. Although the rate of subcutaneous bleeding was low, these adverse events may influence patient compliance. This trial is registered with ISRCTN21980724.

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.

[Expert consensus statement on Diemailing~® Kudiezi Injection in clinical practice].

Diemailing~® Kudiezi Injection( DKI) is widely used in the treatment of cerebral infarction,coronary heart disease and angina pectoris. Long-term clinical application and related research evidence showed that DKI has a good effect in improving the clinical symptoms of cardiovascular and cerebrovascular diseases. However,this injection has not been included in any clinical practice guideline. It has been found that the use of DKI is in wrong way in clinical practice in recent years. Therefore,clinical experts from the field of cardiovascular and cerebrovascular diseases nationwide are invited to compile this expert consensus in order to guide clinicians.GRADE system is used to grade the quality of evidence according to different outcomes according to degrading factors. Then it forms the recommendation or consensus suggestion through the nominal group method. The formation of expert consensus mainly considers six factors: quality of evidence,economy,efficacy,adverse reactions,patient acceptability and others. Based on these six aspects,if the evidence is sufficient,a " recommendation" supported by evidence is formed,and GRADE grid voting rule is adopted. If the evidence is insufficient,a " consensus suggestions" will be formed,using the majority voting rule. In this consensus,the clinical indications,efficacy,safety evidences and related preliminary data of DKI were systematically and comprehensively summarized in a concise and clear format,which could provide valuable reference for the clinical use of DKI. This consensus has been approved by China association of Chinese medicine which is numbered GS/CACM 202-2019.

[Editorial explanation for Expert consensus statement on Diemailing Kudiezi Injection in clinical practice].

Expert consensus statement on Diemailing Kudiezi Injection in clinical practice was approved on April 17,2019 by the Standardadization Office of the Chinese Association of Chinese Medicine. This project,which started in November 2017,has been developed and completed in accordance with the standard developing procedure. This paper will give a detailed introduction to the compilation process about the consensus. The aim is to enable readers to understand the background,purpose and basis of this consensus in a timely manner. Readers can learn about diffferent stages of develping process,including project management system,drafting,consulting,expert consensus,as well as current problems and shortcomings. Such an editorial explanation is just a dynamic follow-up of the whole consensus-making process. It also plays a good supervisory role in the whole consensus-making. It could be a guarantee for the quality of the consensus. There is no doubts that the editorial explanation is an important auxiliary document in the process of consensus-making. It is the extension and supplement of consensus content and a basis for fully understanding the technical content of this consensus. Therefore it is an indispensable document in the process of consensus-making.

Asymmetric Dimethylarginine Predicts One-year Recurrent Cardiovascular Events: Potential Biomarker of "Toxin Syndrome" in Coronary Heart Disease.

OBJECTIVE: To examine the prognostic value of serum levels of asymmetric dimethylarginine (ADMA) in patients with stable coronary heart disease (CHD) thus explore a potential biomarker of "toxin syndrome" in CHD. METHODS: In this prospective nested case-control study, 36 of 1,503 Chinese patients with stable CHD experienced at least 1 recurrent cardiovascular event (RCE) during 1-year follow-up. Serum levels of ADMA at the start of follow-up were compared between these 36 cases and 36 controls which matched to cases in terms of gender, age, history of hypertension, and myocardial infarction. RESULTS: Based on the crude model, subjects in the 2 highest ADMA quartiles showed significantly higher risk of developing RCE than those in the lowest ADMA quartile [odds ratio (OR) 4.09, 95% confidence interval (CI) 1.01 to 16.58; OR 6.76, 95% CI 1.57 to 29.07]. This association was also observed in the case-mix model (OR 5.51, 95% CI 1.23 to 24.61; OR 7.83, 95% CI 1.68 to 36.41) and multivariable model (OR 6.64, 95% CI 1.40 to 31.49: OR 13.14, 95% CI 2.28 to 75.71) after adjusting for confounders. The multivariable model which combined ADMA and high-sensitivity C-reactive protein (hsCRP) showed better predictive power with areas under the receiver operator characteristic curves (0.779) than the model of either ADMA (0.694) or hsCRP (0.636). CONCLUSION: Serum ADMA level may be a potential biomarker of "toxin syndrome" in CHD which shows favorable prognostic value in predicting 1-year RCE in patients with stable CHD. [The registration number is ChiCTR-PRNRC-07000012].

Effects of microbiota-driven therapy on inflammatory responses in elderly individuals: A systematic review and meta-analysis.

Current evidence suggests that age-associated inflammation, a strong risk factor for the health status of elderly individuals, is closely associated with gut microbiota. Previous animal studies have demonstrated a benefit of microbiota-driven therapy in decreasing low-grade chronic inflammation in elderly individuals; however, it remains controversial in clinical studies. Therefore, the present systematic review and meta-analysis were designed to assess the effects of microbiota-driven therapy on inflammatory markers in elderly individuals. PubMed, EMBASE, and the Cochrane Library were searched with no language restrictions from the inception of the database to November 11th, 2018 to identify all existing literature. We calculated pooled standard mean difference (SMD) using fixed effect model or random effect model to assess the effects of microbiota-driven therapy on elderly individuals. The methodological quality of the studies was determined according to the Cochrane Handbook. The publication bias was evaluated by funnel plot and Egger regression test. Ten randomized controlled studies, with 689 elderly individuals (347 individuals in the microbiota-driven therapy group and 342 individuals in the placebo group), were included in the analysis. Compared with placebo, microbiota-driven therapy did not decrease the levels of tumor necrosis factor-α (SMD, -0.24; 95% CI, -0.69 to 0.21; p = 0.30; I2 = 82.7%), interleukin-6 (SMD, -0.13; 95% CI, -0.74 to 0.49; p = 0.69; I2 = 90.7%) and interleukin-10 (SMD, 1.00; 95% CI, -0.15 to 2.15; p = 0.09; I2 = 96.3%). In addition, the microbiota-driven therapy also did not decrease the levels of C reactive protein (SMD, -1.28; 95% CI, -2.62 to 0.06; p = 0.06; I2 = 96.2%), interleukin-1ß (SMD, -0.22; 95% CI, -0.81 to 0.37; p = 0.46; I2 = 73.8%), interleukin-8 (SMD, -0.03; 95% CI, -0.67 to 0.61; p = 0.93; I2 = 88.0%) and monocyte chemoattractant protein-1 (SMD, -0.11; 95% CI, -0.41 to 0.20; p = 0.49; I2 = 0%) when compared with placebo. No obvious publication bias was observed (p>0.05). In conclusion, the present meta-analysis of available randomized controlled studies did not suggest any significant benefit of microbiota-driven therapy in decreasing the inflammatory responses of elderly individuals.

The effect of statin treatment on circulating coenzyme Q10 concentrations: an updated meta-analysis of randomized controlled trials.

BACKGROUND: The effect of statin treatment on circulating coenzyme Q10 (CoQ10) has been studied in numerous randomized controlled trails (RCTs). However, whether statin treatment decreases circulating CoQ10 is still controversial. METHODS: PubMed, EMBASE, and the Cochrane Library were searched to identify RCTs to investigate the effect of statin treatment on circulating CoQ10. We calculated the pooled standard mean difference (SMD) using a fixed effect model or random effect model to assess the effect of statin treatment on circulating CoQ10. The methodological quality of the studies was determined according to the Cochrane Handbook. Publication bias was evaluated by a funnel plot, the Egger regression test, and the Begg-Mazumdar correlation test. RESULTS: Twelve RCTs with a total of 1776 participants were evaluated. Compared with placebo, statin treatment resulted in a reduction of circulating CoQ10 (SMD, - 2.12; 95% CI, - 3.40 to - 0.84; p = 0.001), which was not associated with the duration of statin treatment (Exp, 1.00; 95% CI, 0.97 to 1.03; p = 0.994). Subgroup analysis demonstrated that both lipophilic statins (SMD, - 1.91; 95% CI, - 3.62 to 0.2; p = 0.017) and hydrophilic statins (SMD, - 2.36; 95% CI, - 4.30 to - 0.42; p = 0.028) decreased circulating CoQ10, and no obvious difference was observed between the two groups (SMD, - 0.20; 95% CI, - 0.208 to 0.618; p = 0.320). In addition, both low-middle intensity statins (SMD, - 2.403; 95% CI, - 3.992 to - 0.813; p < 0.001) and high intensity statins (SMD, - 1.727; 95% CI, - 2.746 to - 0.709; p < 0.001) decreased circulating CoQ10. Meta-regression showed that the effect of statin on decreasing circulating CoQ10 was not closely associated with the duration of statin treatment (Exp, 1.00; 95% CI, 0.97 to 1.03; p = 0.994). CONCLUSIONS: Statin treatment decreased circulating CoQ10 but was not associated with the statin solution, intensity, or treatment time. The findings of this study provide a potential mechanism for statin-associated muscle symptoms (SAMS) and suggest that CoQ10 supplementation may be a promising complementary approach for SAMS.

Effects of Coenzyme Q10 on Statin-Induced Myopathy: An Updated Meta-Analysis of Randomized Controlled Trials.

Background Previous studies have demonstrated a possible association between the induction of coenzyme Q10 (CoQ10) after statin treatment and statin-induced myopathy. However, whether CoQ10 supplementation ameliorates statin-induced myopathy remains unclear. Methods and Results PubMed, EMBASE , and Cochrane Library were searched to identify randomized controlled trials investigating the effect of CoQ10 on statin-induced myopathy. We calculated the pooled weighted mean difference ( WMD ) using a fixed-effect model and a random-effect model to assess the effects of CoQ10 supplementation on statin-associated muscle symptoms and plasma creatine kinase. The methodological quality of the studies was determined, according to the Cochrane Handbook. Publication bias was evaluated by a funnel plot, Egger regression test, and the Begg-Mazumdar correlation test. Twelve randomized controlled trials with a total of 575 patients were enrolled; of them, 294 patients were in the CoQ10 supplementation group and 281 were in the placebo group. Compared with placebo, CoQ10 supplementation ameliorated statin-associated muscle symptoms, such as muscle pain ( WMD , -1.60; 95% confidence interval [ CI ], -1.75 to -1.44; P<0.001), muscle weakness ( WMD , -2.28; 95% CI , -2.79 to -1.77; P=0.006), muscle cramp ( WMD , -1.78; 95% CI , -2.31 to -1.24; P<0.001), and muscle tiredness ( WMD , -1.75; 95% CI , -2.31 to -1.19; P<0.001), whereas no reduction in the plasma creatine kinase level was observed after CoQ10 supplementation ( WMD , 0.09; 95% CI , -0.06 to 0.24; P=0.23). Conclusions CoQ10 supplementation ameliorated statin-associated muscle symptoms, implying that CoQ10 supplementation may be a complementary approach to manage statin-induced myopathy.

Panax quinquefolius saponins combined with dual antiplatelet drug therapy alleviate gastric mucosal injury and thrombogenesis through the COX/PG pathway in a rat model of acute myocardial infarction.

OBJECTIVES: Previous studies have found that Panax quinquefolius saponins (PQS) combined with dual antiplatelet therapy (DAPT) of aspirin and clopidogrel enhances antithrombotic effects while reducing gastric mucosal injury induced by DAPT. We investigated the effects of the combined drug therapy (PQS+DAPT) through the COX/PG pathways. METHODS: Acute myocardial infarction (AMI) was induced in Wistar rats by ligation of the left anterior descending (LAD) coronary artery, and the animals were randomly divided into Model, DAPT, and PQS+DAPT groups. Rats in the sham group did not undergo artery ligation. They were intragastrically treated for 14 days. Myocardial infarct size; myocardial pathology; platelet aggregation rate, CD62p activation, concentrations of thromboxane B2 (TXB2), 6-keto-PGF1α, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor (PAI), the TXB2/6-keto-PGF1α ratio were measured. The ultrastructure of the gastric mucosa was observed by scanning electron microscopy. The expression of PGE2 and 6-keto-PGF1α in gastric mucosa was measured by radioimmunoassay, and levels of COX-1, COX-2, and VEGF in gastric mucosa were assessed using immunohistochemistry. RESULTS: The addition of Panax quinquefolius saponins (PQS+DAPT) to standard DAPT therapy significantly decreased the myocardial infarct area, degree of myocardial lesions, TXB2 and PAI levels, and the TXB2/6-keto-PGF1α ratio, while increasing 6-keto-PGF1α and t-PA levels and reducing the degree of gastric mucosal injury. Expression of PGE2, 6-keto-PGF1α, COX-2, and VEGF in the gastric mucosa was upregulated in the PQS+DAPT group compared with the standard DAPT group. CONCLUSION: PQS increases the degree of DAPT inhibition of myocardial necrosis and antiplatelet effects in AMI rats, as well as reducing damage to the gastric mucosa caused by DAPT. The mechanism may be related to inhibition of TXB2 and PAI activity and elevation of 6-keto-PGF1α and t-PA levels in blood, and may be associated with upregulated expression of COX-2, PGE2, PGI2, and VEGF in gastric tissue.

Effect of Kuanxiong Aerosol () on Patients with Angina Pectoris: A Non-inferiority Multi-center Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris. METHODS: Block randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina. RESULTS: The 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01). CONCLUSIONS: KA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).