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The incidence of diabetes and related mortality rate increase yearly in modern cities. Additionally, elevated glucose levels can result in an increase of reactive oxygen species (ROS), ferroptosis, and the disruption of protective pathways in the heart. These factors collectively heighten the vulnerability of diabetic individuals to myocardial ischemia. Reperfusion therapies have been effectively used in clinical practice. There are limitations to the current clinical methods used to treat myocardial ischemia-reperfusion injury. As a result, reducing posttreatment ischemia/reperfusion injury remains a challenge. Therefore, efforts are underway to provide more efficient therapy. Salvia miltiorrhiza Bunge (Danshen) has been used for centuries in ancient China to treat cardiovascular diseases (CVD) with rare side effects. Salvianolic acid is a water-soluble phenolic compound with potent antioxidant properties and has the greatest hydrophilic property in Danshen. It has recently been discovered that salvianolic acids A (SAA) and B (SAB) are capable of inhibiting apoptosis by targeting the JNK/Akt pathway and the NF-kB pathway, respectively. This review delves into the most recent discoveries regarding the therapeutic and cardioprotective benefits of salvianolic acid for individuals with diabetes. Salvianolic acid shows great potential in myocardial protection in diabetes mellitus. A thorough understanding of the protective mechanism of salvianolic acid could expand its potential uses in developing medicines for treating diabetes mellitus related myocardial ischemia-reperfusion. [ABSTRACT FROM AUTHOR]

Objective: This meta-analysis aimed to determine the efficacy of curcumin in preventing myocardial ischemia/reperfusion (I/R) injury in animal models. Methods: Studies published from inception to January 2023 were systematically searched in databases including PubMed, Web of Science, Embase, China's National Knowledge Infrastructure (CNKI), Wan-Fang database, and VIP database (VIP). The SYRCLE's RoB tool was used to determine methodological quality. Sensitivity analysis and subgroup analysis were performed when there was high heterogeneity. Publication bias was assessed using a funnel plot. Results: Thirty-seven studies involving 771 animals were included in this metaanalysis with methodology quality scores ranging from 4 to 7. The results indicated that curcumin treatment significantly improved myocardial infarction size standard mean difference (SMD) = -5.65; 95% confidence interval (CI): 6.94, -4.36; p < 0.01; I2 = 90%). The sensitivity analysis for infarct size showed that the results were stable and reliable. However, the funnel plot was asymmetric. The subgroup analysis included species, animal model, dose, administration, and duration. The results showed that the subgroup dose was statistically significant between subgroups. In addition, curcumin treatment improved cardiac function, myocardial injury enzymes, and oxidative stress levels in animal models of myocardial I/R injury. The funnel plot revealed that there is publication bias for creatine kinase and lactate dehydrogenase. Finally, we performed a meta-analysis of inflammatory cytokines and apoptosis index. The results showed that curcumin treatment downregulated serum inflammatory cytokine levels and myocardial apoptosis index. Conclusion: This meta-analysis suggests that curcumin has excellent potential for the treatment of myocardial I/R injury in animal models. However, this conclusion needs to be further discussed and verified in large animal models and human clinical trials. [ABSTRACT FROM AUTHOR]

Aim: The Shexiang Baoxin Pill (SBP) has been extensively used to treat cardiovascular diseases in China for four decades, and its clinical efficacy has been widely approved. However, the mechanism by which this is achieved remains largely unexplored. Research attempting to understand the underlying mechanism is ongoing, but the findings are controversial. Here, we aimed to explore the possible mechanism of SBP in myocardial ischemia-reperfusion (I/R) injury using heart single-nucleus and spatial ribonucleic acid (RNA) sequencing. Methods: We established a murine myocardial I/R injury model in C57BL/6 mice by ligating and recanalizing the left coronary artery anterior descending branch. Subsequently, single-nucleus RNA-seq and spatial transcriptomics were performed on mice cardiac tissue. We initially assessed the status of cell types and subsets in the model administered with or without SBP. Results: Weused single-nucleus RNA sequencing to comprehensively analyze cell types in the cardiac tissue of sham, I/R, and SBP mice. Nine samples from nine individuals were analyzed, and 75,546 cells were obtained. We classified the cells into 28 clusters based on their expression characteristics and annotated them into seven cell types: cardiomyocytes, endothelial cells, fibroblasts, myeloid cells, smooth muscle cells, B cells, and T cells. The SBP group had distinct cellular compositions and features than the I/R group. Furthermore, SBP-induced cardioprotection against I/R was associated with enhanced cardiac contractility, reduced endocardial cell injury, increased endocardial-mediated angiogenesis, and inhibited fibroblast proliferation. In addition, macrophages had active properties. Conclusion: SBP improves the early LVEF of I/R mice and has a cardioprotective effect. Through sequencing analysis, we observed that SBP can increase the gene expression of Nppb and Npr3 in the infarct area of the heart. Npr3 is related to vascular generation mediated by endocardial cells and requires further research. In addition, SBP increases the number of fibroblasts, inhibits the expression of genes related to fibroblast activation and proliferation, and increases the transformation of endothelial cells into fibroblasts. These findings will help to indicate directions for further research. [ABSTRACT FROM AUTHOR]

Background. Infectious mononucleosis (IM) is a common viral infection that typically presents with fever, pharyngitis and cervical lymphadenopathy. Our aim was to identify the different pathogens causing IM in children admitted to our hospital and to analyze the differences in features of infection with different organisms. Methods. We retrospectively analyzed the data of children aged 0-17 years admitted to Wuhan Children's Hospital during 2013-2022 with IM. We compared symptoms, physical findings, blood counts, and serum biomarkers between patients with IM due to Epstein-Barr virus (EBV) and IM due to other pathogens. Results. Among 1480 enrolled children, 1253 (84.66%) had EBV infection, 806 (54.46%) had M. pneumoniae infection, 796 (53.78%) had cytomegalovirus infection, 159 (10.74%) had parvovirus infection, 38 (2.57%) had influenza virus infection, and 25 (1.69%) had adenovirus infection. Receiver operating characteristic curves were used to determine the area under the curve for alanine transaminase (ALT), aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin (TBil), indirect bilirubin (IBil) levels to assess liver damage, and for creatine kinase (CK), CK-MB, and lactate dehydrogenase (LDH) levels to assess myocardial damage. The optimal cutoff values of these biomarkers were then determined. In multivariate analysis, elevated ALT, AST, ALP, TBil, and IBil were independently associated with liver damage, and age <3 years, CK, CK-MB, and LDH with myocardial damage. Conclusion. Evaluation of biomarkers and pathogen detection may help physicians to take preventive actions to avoid serious complications in children with infectious mononucleosis. [ABSTRACT FROM AUTHOR]

Purpose. Myocardial ischemia-reperfusion (MIR) injury is a common stimulus for cardiac diseases like cardiac arrhythmias and heart failure and may cause high mortality rates. Salviae miltiorrhizae liguspyragine hydrochloride and glucose injection (SGI) has been widely used to treat myocardial and cerebral infarctions in China even though its pharmacological mechanisms are not completely clear. Methods. The protective effect and mechanism of SGI on MIR injury and heart failure were investigated through the H9c2 cell model induced by hypoxia/reoxygenation (H/R) and rapamycin, zebrafish model induced by H/R and isoprenaline, and rat MIR model. Results. SGI significantly reduced the infarct size and alleviated the impairment of cardiac functions in the MIR rat model and H/R zebrafish model and promoted cell viability of cardiomyocyte-like H9c2 cells under H/R condition. Consistently, SGI significantly downregulated the serum level of biomarkers for cardiac damage and attenuated the oxidative damage in the MIR and H/R models. We also found that SGI could downregulate the increased autophagy level in those MIR and H/R models since autophagy can contribute to the injurious effects of ischemia-reperfusion in the heart, suggesting that SGI may alleviate MIR injury via regulating the autophagy pathway. In addition, we demonstrated that SGI also played a protective role in the isoproterenol-induced zebrafish heart failure model, and SGI significantly downregulated the increased autophagy and SP1/GATA4 pathways. Conclusion. SGI may exert anti-MIR and heart failure by inhibiting activated autophagy and the SP1/GATA4 pathway. [ABSTRACT FROM AUTHOR]

Ischemic heart diseases are responsible for more than one-third of all deaths worldwide. Radix notoginseng is widely used to treat ischemic heart disease in China and other Asian countries, and notoginsenoside R1 (NGR1) is its characteristic and large-amount ingredient. However, the potential molecular mechanisms of NGR1 in improving ischemic heart diseases are unclear. In this study, we combined pharmacological evaluation with network pharmacology, myocardial proteomics, and conventional molecular dynamics (MD) simulation to explore the cardio-protection mechanisms of NGR1. Our results revealed that NGR1 improved the echocardiographic, tissue pathological, and serum biochemical perturbations in myocardial ischemic rats. The network pharmacology studies indicated that NGR1 mainly regulated smooth muscle cell proliferation, vasculature development, and lipid metabolism signaling, especially in the PI3K/AKT pathway. Myocardial proteomics revealed that the function of NGR1 was focused on regulating metabolic and energy supply processes. The research combined reverse-docked targets with differential proteins and demonstrated that NGR1 modulated lipid metabolism in ischemic myocardia by interacting with mTOR and AKT. Conventional MD simulation was applied to investigate the influence of NGR1 on the structural stabilization of the mTOR and AKT complex. The results suggested that NGR1 can strengthen the affinity stabilization of mTOR and AKT. Our study first revealed that NGR1 enhanced the affinity stabilization of mTOR and AKT, thus promoting the activation of the AKT/mTOR pathway and improving lipid metabolic abnormity in myocardial ischemic rats. [ABSTRACT FROM AUTHOR]

Background: Magnolol is a component of the bark of Magnolia officinalis , which is a traditional herbal remedy used in China. In this study, we investigated whether magnolol can reduce myocardial injury induced by renal ischemia and reperfusion (I/R). Methods: Renal I/R was elicited by a 60-minute occlusion of the bilateral renal arteries and a 24-hour reperfusion in Sprague-Dawley rats. Magnolol was administered intravenously 10 minutes before renal I/R to evaluate its effects on myocardial injury induced by renal I/R. Results: Renal I/R significantly increased the serum levels of creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and cardiac troponin I and caused myocardial damage. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling–positive nuclei and caspase-3 activation was significantly increased in the myocardium, indicating increase of apoptosis. Echocardiography revealed left ventricular dysfunction, as evidenced by reduction of left ventricular ejection fraction and left ventricular fractional shortening. Furthermore, serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-6 were significantly elevated, while the IL-10 level was suppressed. However, intravenously, pretreatment with magnolol at doses of 0.003 and 0.006 mg/kg 10 minutes before renal I/R significantly prevented the increases of CPK, LDH, and cardiac troponin I levels, as well as the histological damage and the apoptosis in the myocardium. Echocardiography showed significant improvement of left ventricular function. Furthermore, the increases in TNF-α, IL-1β, and IL-6 and the decrease in IL-10 were significantly limited, while Bcl-2 was increased and Bax was decreased in the myocardium. Phosphorylation of Akt and extracellular signal-regulated kinases 1 and 2 was increased, while phosphorylation of p38 and c-Jun N-terminal kinase was reduced. Conclusion: Magnolol reduces myocardial injury induced by renal I/R. The underlying mechanisms for this effect might be related to modulation of the production of pro- and anti-inflammatory cytokines and the limiting of apoptosis. [ABSTRACT FROM AUTHOR]

Higenamine, a natural product with multiple targets in heart diseases, is originally derived from Aconitum , which has been traditionally used in China for the treatment of heart disease, including heart failure, arrhythmia, bradycardia, cardiac ischemia/reperfusion injury, cardiac fibrosis, etc. This study is aimed to clarify the role of higenamine in heart diseases. Higenamine has effects on improving energy metabolism of cardiomyocytes, anti-cardiac fibroblast activation, anti-oxidative stress and anti-apoptosis. Accumulating evidence from various studies has shown that higenamine exerts a wide range of cardiovascular pharmacological effects in vivo and in vitro , including alleviating heart failure, reducing cardiac ischemia/reperfusion injury, attenuating pathological cardiac fibrosis and dysfunction. In addition, several clinical studies have reported that higenamine could continuously increase the heart rate levels of healthy volunteers as well as patients with heart disease, but there are variable effects on systolic blood pressure and diastolic blood pressure. Moreover, the heart protection and therapeutic effects of higenamine on heart disease are related to regulating LKB1/AMPKα/Sirt1, mediating the β2-AR/PI3K/AKT cascade, induction of heme oxygenase-1, suppressing TGF-β1/Smad signaling, and targeting ASK1/MAPK (ERK, P38)/NF-kB signaling pathway. However, the interventional effects of higenamine on heart disease and its underlying mechanisms based on experimental studies have not yet been systematically reviewed. This paper reviewed the potential pharmacological mechanisms of higenamine on the prevention, treatment, and diagnosis of heart disease and clarified its clinical applications. The literature shows that higenamine may have a potent effect on complex heart diseases, and proves the profound medicinal value of higenamine in heart disease. [ABSTRACT FROM AUTHOR]

Objective: Shenfu injection (SFI) is commonly used for cardiac dysfunction in China. Adenosine receptors have been reported to exert anti-fibrosis effects. The intent of this study was to evaluate that SFI attenuates cardiac fibrosis through activating of adenosine A2a receptor (A2aR) in rats with myocardial ischemia-reperfusion (MI/R). Methods: Sprague Dawley male rats were randomly divided into five groups, nine rats in each group. Injections in all rat groups were carried out prior to reperfusion, and in the sham and MI/R groups, only vehicle was injected. Injections in the remaining group were as follows: 5 mL/kg in the SFI group; 15 mg/kg nicorandil in the A2R agonist group; and 5 mL/kg SFI plus 5 mg/kg MSX-3 in the SFI + A2aR antagonist group. Changes in cyclic adenosine monophosphate (cAMP) and the development of myocardial infarction and cardiac fibrosis were documented among the groups. Additionally, the levels of A2aR, collagen Ⅰ, collagen Ⅲ, fibronectin, and matrix metalloproteinase-9 (MMP-9) were measured. Results: Following injection with SFI or nicorandil, the cAMP concentration, infarct area, and cardiac fibrosis induced by MI/R injury were significantly decreased (p < 0.05). Additionally, the levels of collagen Ⅰ, collagen Ⅲ, fibronectin, and MMP-9 were clearly suppressed by SFI or nicorandil when compared with the MI/R group (p <0.01). However, the protective effects of SFI were counteracted by MSX-3. A negative correlation between A2aR and collagen I and collagen III was found (p = 0.00). Conclusion: SFI activated the A2aR to reduce myocardial fibrosis caused by MI/R injury, which provided an underlying mechanism of action of SFI. [ABSTRACT FROM AUTHOR]

Tea is prepared from the young leaves, buds, stalks of the plant Camellia sinensis. The cultivation process of tea plants and the habit of tea drinking were initiated in China from ancient times. Now, the consumption of tea is very popular throughout the world and it is an integral part of our social culture. Tea contains polyphenolic compounds (catechins and epicatechins), theaflavins, flavonol glycosides, L-theanine, caffeine, theobromine, and volatile organic substances. These bioactive components are responsible for the astringency, flavor, aroma, and taste of the tea as well as its health beneficial effects. Moreover, tea has several medicinal values. The phytochemical components are involved in the prevention and cure of many illnesses like cardiovascular diseases, malignancy, digestive dysfunction, and metabolic disorders like obesity, diabetes. Tea flavonoids show strong antioxidant properties. Caffeine and other methylxanthine regulate the intracellular second messenger levels. Additionally, catechins exhibit anti-inflammatory effects. All these multidimensional actions make some positive attributes in favor of neuroprotection, cardioprotection, and cancer prevention. Various approaches are also taken to use tea ingredients as an adjuvant in cancer therapy. This review emphasizes the importance of bioactive components, and their health promotional activities. [ABSTRACT FROM AUTHOR]

[Display omitted] Longxuetongluo Capsule (LTC) is wildly applied to treat ischemic stroke in clinical practice in China. However, the pharmacological mechanism of LTC on ischemic stroke is still unstated. Our research was designed to study the protective effect of LTC against cerebral ischemia–reperfusion (I/R) injury and reveal the underlying mechanism both in vivo and in vitro. PC12 cells treated with glucose deprivation/reperfusion (OGD/R) were used to simulate in vitro ischemia/reperfusion (I/R) injury. The cell viability, apoptosis rate, and protein expressions of PC12 cells were evaluated. In vivo validation of the protective effect of LTC was carried out by middle cerebral artery occlusion (MCAO)/reperfusion treatment, and the underlying mechanism of its anti-apoptosis ability was further revealed by immunohistochemistry staining and Western blotting. In the current study, we observed that LTC effectively inhibited oxygen-glucose deprivation/reperfusion (OGD/R) induced apoptosis of PC12 cells through suppressing the cleavage of poly ADP-ribose polymerase (PARP), caspase-3, and caspase-9. Further investigation revealed that OGD/R insult remarkably triggered the endoplasmic reticulum stress responses (ER stress) to induce PC12 cell apoptosis. LTC treatment alleviated OGD/R induced ER stress by inhibiting the activation of protein kinase RNA (PKR)-like ER kinase (PERK)/eukaryotic translation initiation factor 2 (eIF2α) and inositol requiring enzyme 1 (IRE1)/tumor necrosis factor receptor-associated factor 2 (TRAF2) pathways. Additionally, LTC also restrained the OGD/R-induced PC12 cell apoptosis by reversing the activated mitogen-activated protein kinase (MAPK) through IRE1/TRAF2 pathway. Animal studies demonstrated LTC significantly restricted the infarct region induced by middle cerebral artery occlusion (MCAO)/reperfusion, the activation of ER stress and apoptosis of neuronal cells had also been suppressed by LTC in the penumbra region. LTC protects the cerebral neuronal cell against ischemia/reperfusion injury through ER stress and MAPK-mediated mechanisms. [ABSTRACT FROM AUTHOR]

Background: Trimetazidine (TMZ) pretreatment protects cardiomyocytes during cardiac surgery. TMZ may protect elderly patients with ischaemic heart disease (IHD) undergoing non-cardiac surgery.Methods: This was a randomized, double-blind, placebo-controlled trial (registration #ChiCTR1900025018) of patients with IHD scheduled to undergo non-cardiac surgery at Shenzhen People's Hospital (Shenzhen, Guangdong Province, China) between June 2014 and September 2015, randomized to 60 mg TMZ or placebo 12 h before surgery. The primary endpoint was the occurrence of in-hospital cardiovascular events. The secondary endpoints were myocardial ischaemia on five-lead electrocardiogram (cECG), cardiac troponin I (cTnI) elevation, cardiac death, acute coronary events, heart failure, and arrhythmia requiring treatments.Results: Compared with the placebo group, the TMZ group showed a lower occurrence of in-hospital cardiovascular events (primary endpoint, 20.0% vs. 37.5%, P = 0.02), myocardial ischaemia (15.0% vs. 32.5%, P < 0.01), cTnI elevation (2.5% vs. 10%, P < 0.01), acute coronary events (10.0% vs. 20.0%, P < 0.05), heart failure (0% vs. 2.5%, P < 0.05), and arrhythmia requiring treatment (17.5% vs. 35.0%, P < 0.05). There was no acute myocardial infarction during the 30-day postoperative period.Conclusions: In elderly patients with IHD undergoing non-cardiac surgery, TMZ pretreatment was associated with myocardial protective effects. Trial registration The trial was prospectively registered at http://www.chictr.org.cn/showproj.aspx?proj=41909 with registration number [ChiCTR1900025018] (7/8/2019). [ABSTRACT FROM AUTHOR]

Background: Cerebral infarction and cerebral hemorrhage, also known as "stroke", is one of the leading cause of death. At present, there is no real specific medicine for stroke. Crinis Carbonisatus (named Xue-yu-tan in Chinese), produced from carbonized hair of healthy human, and has been widely applied to relieve pain and treat epilepsy, stroke and other diseases in China for thousands of years. Results: In this work, a new species of carbon dots derived from Crinis Carbonisatus (CrCi-CDs) were separated and identified. And the neuroprotective effect of carbon dots from CrCi were evaluated using the middle cerebral artery occlusion (MCAO) model. Neurological deficit score and infarction volume was assessed, evans blue content of ischemic hemispheres was measured, the concentrations of inflammatory factors, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) in the cortex were measured, and the levels of neurotransmitters in the brain were determined. Preconditioning of CrCi-CDs significantly reduced ischemic lesion volume and blood–brain-barrier (BBB) permeability, improved neurologic deficits, decreased the level of TNF-α and IL-6 in MCAO rats, inhibited excitatory neurotransmitters aspartate (Asp) and glutamate (Glu), and increased the level of 5-hydroxytryptamine (5-HT). The RNA-Sequencing results reveal that further potential mechanisms behind the activities may be related to the anti-inflammation effects and inhibition of neuroexcitatory toxicity. Conclusion: CrCi-CDs performs neuroprotective effect on cerebral ischemia and reperfusion injury, and the mechanisms may correlate with its anti-inflammatory action, which suggested that CrCi-CDs have potential value in clinical therapy on the acute apoplexy cases in combination with thrombolytic drugs. [ABSTRACT FROM AUTHOR]

Dioscin has been widely used in clinics for coronary artery disease (CAD) treatment for years in China. However, the underlying mechanism for Dioscin‐mediated cardioprotective effect has not been elucidated. Here, we showed that Dioscin significantly rescues the cardiac function in mouse model of myocardial infarction (MI), accompanied by the reduction of cardiac fibrosis and apoptosis, resulting from elevated angiogenesis. Mechanistically, Dioscin promotes the proliferation and migration of hypoxic endothelial cells via the up‐regulation of lncRNA MANTIS, which serves as a scaffolding lncRNA within a chromatin remodeling complex. Meanwhile, it enables pol II binding to the transcription start sites, which leads to induced expression of angiogenesis‐related genes, including SOX18, SMAD6, and COUP‐TFII. Conversely, IncRNA MANTIS silencing prevents Dioscin‐induced migration and angiogenesis in hypoxic endothelial cells. Taken together, these data provide new insights that clarifies the cardioprotective effects of Dioscin against myocardial infarcted injury and confirms the effect on angiogenic activity of endothelial cells. This will build a solid theoretical basis for clinical therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: To investigate the predictive value of low-density lipoprotein cholesterol (LDL-C), total stent length and number of implanted stents in patients with unstable angina (UA) regarding myocardial injury and infarction during perioperative period. Methods: Three hundred and fifteen consecutive UA patients between January 2015 and June 2018 were retrospectively recruited from two cardiac centers of Hebei Province, China. These patients had normal preprocedural cardiac troponin I (cTnI) and underwent uneventful revascularizations. The predictive value of baseline LDL-C level and total stent length was investigated by linking to post procedural cTnI value in this cohort. Meanwhile, other related clinical and procedural variables were analyzed. Results: Baseline LDL-C level or LDL-C grade was correlated with post percutaneous coronary intervention (PCI) cTnI levels (r = 0.120, P = 0.01; r = 0.157, P = 0.004). LDL-C grade was an independent risk factor of perioperative myocardial injury and infarction (P < 0.05) after multivariable adjustment. The risk increased with the elevation of baseline LDL-C level. Compared to the lowest level group (< 70 mg/dl), the group with 70– 99 mg/dl carried three times higher risk (OR = 3.318; 95% CI: 1.167– 9.436; P < 0.05). And, patients with LDL-C level ≥ 100 mg/dl had the worst prognosis (OR = 4.783; 95% CI: 1.736– 13.180; P = 0.002). Besides, the study also found that the total length of stent was predictive of perioperative myocardial injury and infarction independently (OR = 1.037; 95% CI: 1.017– 1.058; P = 0.001). Conclusion: Baseline LDL-C level and total stent length were independent predictors of periprocedural myocardial injury and infarction in UA patients undergoing elective PCI. [ABSTRACT FROM AUTHOR]

Traditionally, Clematis tangutica Korsh. (Ranunculaceae) is used as a Tibetan herb for treating indigestion and blood stasis in China. Recently, a flavonoid glycoside, apigenin-7-O-β-d-(6″-p-coumaroyl)-glucopyranoside (APG), was isolated from the whole plant of C. tangutica. To investigate the cardioprotective effects of APG against myocardial ischaemia/reperfusion injury (MI/RI) and the possible mechanism. Animals were subjected to 30 min/3 h MI/RI model. At the end of reperfusion, infarct size (IS), histopathology, serum levels CK-MB, LDH, TNF-α, IL-6 and MPO activities were detected. Phospho-IκB-α, ICAM-1 and NF-κB were assessed in vivo. Neonatal rat cardiomyocytes were pre-treated with or without APG, followed by stimulation with 8 h/2 h oxygen and glucose deprived/reoxygenation (OGD/R) model. Cell viability, LDH and cardiomyocyte apoptosis were assessed. The expression levels of phospho-IκB-α and NF-κB were measured in vitro. Treatment with APG significantly reduced the following indicators in vivo (p < 0.05): (1) the IS (16.2%); (2) morphology score (1.67); (3) myocardial injury enzymes: CK-MB (26.2 ng/mL) and LDH (688 U/L); (4) pro-inflammatory cytokines: TNF-α (31.5 pg/mL) and IL-6 (163.8 pg/mL); (5) MPO activity (2.75 U/mg); (6) expression levels of phospho-IκB-α (0.47), NF-κB (2.87) and ICAM-1 (10.2). Moreover, treatment with APG also remarkably (p < 0.05) attenuated the following indicators in vitro: (1) LDH level (206 U/L); (2) cardiomyocyte apoptosis; (3) phospho-IκB-α (1.37) and NF-κB (2.50). APG possesses protective effects against MI/RI injury in rats and OGD/R-induced injury in cardiomyocytes by suppressing translocation of NF-κB and reducing inflammatory response; consequently, APG is helpful for treatment of ischaemic heart disease. [ABSTRACT FROM AUTHOR]

Background: We are currently faced with an increasing burden of cardiovascular disease in China and the inadequacy of the application of guidelines in clinical practice. In the past decade, China has been strengthening the healthcare system, but it still lacked a national performance measurement system and an appropriate quality improvement strategy. Therefore, in order to improve the implementation of guideline recommendations in clinical practice, China has learnt from the successful experience of Get With The Guidelines project in 2014. Under the guidance of the Medical and Health Hospital of the National Health and Family Planning Commission, the Chinese Society of Cardiology and the American Heart Association jointly launched the Improving Care for Cardiovascular Disease in China (CCC) project. The project team provided an analysis report on the completion of key medical quality evaluation indicators of each hospital every month, supplied guidance through education, training, experience exchange and on-site investigation for problems, and certified hospitals with outstanding performance and obvious progress. The circle pattern, including evaluation, training, improvement and re-evaluation, will boost the guidelines compliance on clinical practice in China and improve the quality of medical services.Methods: This study was conducted in a centre of the Third Xiangya Hospital of Central South University. It included patients with ACS from December 2009 to December 2011 (n=225), patients with ACS in the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome project coming from the Third Xiangya Hospital of Central South University (n=665), 12 hospitals in Hunan Province (n=4333) and 150 hospitals in China (n=63 641) from November 2014 to April 2017. It assessed the situation of drug therapy, hospitalisation day, mortality during hospitalisation, median of door-to-needle (D-to-N) time and median of door-to-balloon (D-to-B) time of patients with ST-segment elevation myocardial infarction (STEMI), the proportion of D-to-N within 30 min and D-to-B within 90 min, and the proportion of reperfusion therapy. Patients with ACS from the centre from November 2014 to April 2017 were divided into five groups (every 6 months as a group according to time). The study observed change trends in all the above-mentioned indexes.Results: Compared with before participating in the CCC project, there were increases after participating in the CCC project in the drug usage rates of aspirin, P2Y12 inhibitor (clopidogrel or ticagrelor), β-blocker, statin and angiotensin converting enzyme inhibitor (ACEI)/angiotensin-receptor blocker (ARB). Hospitalisation day and mortality during hospitalisation were shortened. D-to-N and D-to-B times of patients with STEMI were shorter. Compared with Hunan Province and China, the drug usage rates were higher; hospitalisation day and D-to-N time were shorter; D-to-B time was longer; and the proportion of reperfusion therapy was higher. The trend of drug usage rates was on the rise. There was no significant change in the hospitalisation day and D-to-N and D-to-B times. The mortality during hospitalisation showed a downward trend. The proportion of D-to-N within 90 min and reperfusion therapy showed upward trends.Conclusion: Quality of care for patients with ACS improved over time in the CCC project, including taking medicine following the guidelines, increased use of reperfusion therapy and faster time to treatment. Although overall mortality has improved, we also should attach importance to high-risk patients. The influence of the CCC project, which is based on guidelines on prognosis of ACS in the centre, presents an important clinical implication that it is necessary to enhance adherence to the guidelines in the treatment of ACS. [ABSTRACT FROM AUTHOR]

Aim: Heart failure (HF) post-acute myocardial infarction (AMI) leads to a large number of hospitalizations and deaths worldwide. Danqi pill (DQP) is included in the 2015 national pharmacopoeia and widely applied in the treatment of HF in clinics in China. We examined whether DQP acted on glucose metabolism to protect against HF post-AMI via hypoxia inducible factor-1 alpha (HIF-1α)/peroxisome proliferator-activated receptor α co-activator (PGC-1α) pathway. Methods and Results: In this study, left anterior descending (LAD) artery ligation induced HF post-AMI rats and oxygen-glucose deprivation-reperfusion (OGD/R)-induced H9C2 cell model were structured to explore the efficacy and mechanism of DQP. Here we showed that DQP protected the heart against ischemic damage as evidenced by improved cardiac functions and attenuated inflammatory infiltration. The expressions of critical proteins involved in glucose intake and transportation such as GLUT4 and PKM2 were up-regulated, while negative regulatory proteins involved in oxidative phosphorylation were attenuated in the treatment of DQP. Moreover, DQP up-regulated NRF1 and TFAM, promoted mitochondrial biogenesis and increased myocardial adenosine triphosphate (ATP) level. The protection effects of DQP were significantly compromised by HIF-1α siRNA, suggesting that HIF-1α signaling pathway was the potential target of DQP on HF post-AMI. Conclusions: DQP exhibits the efficacy to improve myocardial glucose metabolism, mitochondrial oxidative phosphorylation and biogenesis by regulating HIF-1α/PGC-1α signaling pathway in HF post-AMI rats. [ABSTRACT FROM AUTHOR]

Background: Coronary heart disease is a leading cause of mortality among women. Systematic evaluation of the quality of care and outcomes in women hospitalized for acute coronary syndrome (ACS), an acute manifestation of coronary heart disease, remains lacking in China.Methods: The CCC-ACS project (Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome) is an ongoing nationwide registry of the American Heart Association and the Chinese Society of Cardiology. Using data from the CCC-ACS project, we evaluated sex differences in acute management, medical therapies for secondary prevention, and in-hospital mortality in 82 196 patients admitted for ACS at 192 hospitals in China from 2014 to 2018.Results: Women with ACS were older than men (69.0 versus 61.1 years, P<0.001) and had more comorbidities. After multivariable adjustment, eligible women were less likely to receive evidence-based acute treatments for ACS than men, including early dual antiplatelet therapy, heparins during hospitalization, and reperfusion therapy for ST-segment-elevation myocardial infarction. With respect to strategies for secondary prevention, eligible women were less likely to receive dual antiplatelet therapy, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, statins at discharge, and smoking cessation and cardiac rehabilitation counseling during hospitalization. In-hospital mortality rate was higher in women than in men (2.60% versus 1.50%, P<0.001). The sex difference in in-hospital mortality was no longer observed in patients with ST-segment-elevation myocardial infarction (adjusted odds ratio, 1.18; 95% CI, 1.00 to 1.41; P=0.057) and non-ST-segment elevation ACS (adjusted odds ratio, 0.84; 95% CI, 0.66 to 1.06; P=0.147) after adjustment for clinical characteristics and acute treatments.Conclusions: Women hospitalized for ACS in China received acute treatments and strategies for secondary prevention less frequently than men. The observed sex differences in in-hospital mortality were mainly attributable to worse clinical profiles and fewer evidence-based acute treatments provided to women with ACS. Specially targeted quality improvement programs may be warranted to narrow sex-related disparities in quality of care and outcomes in patients with ACS.Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02306616. [ABSTRACT FROM AUTHOR]

Background: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) had beneficial effects on clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI) in the pre-reperfusion or thrombolytic era. It is unknown if the benefits persist in the contemporary reperfusion era., Aims: We sought to determine if ACEI/ARB improve clinical outcomes for STEMI patients in the contemporary reperfusion era according to the reperfusion strategy., Methods: In total, we analyzed 12 596 patients from the prospective, nationwide, multicenter China Acute Myocardial Infarction Registry. These patients were classified into the no-reperfusion group (n = 6004) and the primary percutaneous coronary intervention (PCI) group (n = 6592). Two-year all-cause mortality and major adverse cardiac and cerebrovascular events (MACCE) were compared., Results: In the no-reperfusion group, ACEI/ARB therapy on discharge may reduce the incidence of 30-day MACCE (4.7% vs. 7.4%; adjusted hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.53-0.85; P <0.001), stroke (0.5% vs. 1.1%; adjusted HR, 0.41; 95% CI, 0.21-0.83; P = 0.01), and revascularization (2.1% vs. 3.1%; adjusted HR, 0.66; 95% CI, 0.46-0.94; P = 0.02), compared to patients not treated with ACEI/ARB. Patients treated with ACEI/ARB also showed a lower rate of 2-year MACCE (17.0% vs. 19.1%; adjusted HR, 0.87; 95% CI, 0.76-0.99; P = 0.04). No differences were observed in the remaining outcomes. In the primary PCI group, no differences were observed for all examined outcomes before and after multivariate adjustments., Conclusions: Initiating ACEI/ARB treatment on discharge may reduce cardiovascular events in STEMI patients not receiving reperfusion, while no significant benefits were observed in those receiving primary PCI.

Objective: To probe into the effect of ticagrelor on myocardial reperfusion injury in patients with myocardial infarction undergoing percutaneous coronary intervention! PCI). METHODS: 152 patients with myocardial infarction undergoing PCI admitted into Danjiangkou the First Hospital from Mar. 2015 to Jul. 2016 were selected and divided into observation group and control group via random number table, with 76 cases in each group. The control group was treated with clopidogrel combined with aspirin, while the observation group was given ticagrelor combined with aspirin. The incidence of adverse cardiac events, levels of coagulation indices and coronary artery thrombolysis in myocardial infarction (TIMI) flow grades before and after treatment were observed. RESULTS: During hospital slays, the incidence of adverse cardiac events of observation group was 13. 16% (10/76) , which was significantly lower than that of the control group[34. 21 % (26/76)] , with statistically significant difference (P<0. 05). After treatment, the rale of platelet aggregation of observation group was significantly lower than that of the control group, with statistically significant difference (P<0. 05) ; there were no statistical significances in differences of the platelet count, thrombin time and activated partial thromboplastin time between two groups (P >0. 05). After treatment, the number of patients at the 3rd grade in TIMI flow grades of the observation group accounting for 36.84% (28 cases), with significantly higher than that of the control group [15. 79% (12 cases)] , with statistically significant difference 0.05). CONCLUSIONS: The application of ticagrelor on patients with myocardial infarction undergoing PCI can effectively inhibit the platelet aggregation, reduce myocardial reperfusion injury and the incidence of adverse events. [ABSTRACT FROM AUTHOR]

The author reflects on translational medical research. He discusses the role of "Clinical & Experimental Pharmacology & Physiology (CEPP)" in serving translational medicine through publishing research, examples of previous articles on translational medicine research appearing in "CEPP," such as one by and Lv et al. on the use of the plant compound 2,3,5,6-tetramethylpyrazine (TMP) to treat myocardial ischaemia reperfusion (IR), and a chart of translational medical research centers in China.

Vascular remodeling and neuroprotection are two major adaptable methods for treating ischemic stroke. Edaravone is a protective agent for the treatment of stroke and was used as a positive control in the present study. Sodium tanshinone IIA sulfonate (STS) has demonstrated therapeutic clinical effects in cerebral infarction in China, while its mechanisms of action in ischemic stroke have remained elusive. The angiogenesis and neuroprotective effects of STS were evaluated in a rat model induced by middle cerebral artery occlusion and 3 days of reperfusion. When used at the same dose, the magnitude of the therapeutic effect of STS was similar to that of edaravone in terms of decreased blood-brain barrier damage as indicated by reduced Evans blue leakage, improved neurological deficits, alleviated cerebral edema and inhibition of histopathological changes caused by ischemia/reperfusion. The TUNEL assay demonstrated that the ability of STS to inhibit neuronal apoptosis was equivalent to that of edaravone. Immunofluorescence detection of CD31 and α-smooth muscle actin indicated that the vascular density was significantly reduced in the vehicle group compared with that in the sham operation group, STS increased the microvessel density in the ischemic area. Furthermore, in the vehicle group the protein expression of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR) as determined by fluorescence microscopy and immunohistochemistry was significantly reduced compared with that in the sham group. However, STS promoted their expression compared to the vehicle group respectively, and increaed the mRNA expression of VEGF, VEGFR, CD31 and angiopoietin-1 as determined by reverse transcription-quantitative PCR, but these changes were not significant or not present for edaravone apart from Ang-1. In conclusion, STS protected against ischemic brain injury by promoting angiogenesis in ischemic areas and inhibiting neuronal apoptosis. These results provide a potential treatment for stroke recovery. [ABSTRACT FROM AUTHOR]

Stroke is among the most common causes of disability and death in highly developed countries and China. We sought to study the role of oleanolic acid in cerebral ischemia-reperfusion injury. Middle cerebral artery occlusion (MCAO) was performed to induce cerebral ischemia-reperfusion injury in mice. For the short-term effects of oleanolic acid (OA) against MCAO, mice administrated with OA (6 mg/kg /d) for 3 days before the injury were evaluated the infarct volume, neurological scores, blood brain barrier permeability and oxidative stress level, while for the long-term effects, MCAO mice were injected daily with OA for 6 weeks, followed by assessments of motor function, behavior and cerebral infarction area. Pretreatment of oleanolic acid alleviated MCAO-induced ischemia-reperfusion injury as indicated by the significant decreases in cerebral infarction area and neurological symptom score at 24 h post injury, Evans blue leakage, expression of matrix metalloproteinase 9 (MMP9) and occludin, dihydroethidium fluorescence, and block malonaldehyde generation. In the long run, OA significantly reduced brain loss, enhanced the motor function, promoted the recovery of nerve function, and improved the learning and memory ability 9 weeks after the ischemia-reperfusion injury. OA also inhibited astrocytes proliferation and microglia activation, promoted the expression of synapse-related proteins, and increased the number of DCX+ cells in the hippocampus. OA exhibits both short-term and long-term protective effects against the cerebral ischemia-reperfusion injury in mice. The short-term protective mechanism is related to the anti-oxidation of blood-brain barrier, while the long-term protective effect lies in neuroglia modulation, promotion of synaptic connection and neuroregeneration. • Oleanolic acid shows protective and therapeutic effects against MCAO. • The short-term protective mechanism is related to antioxidant protection of the blood-brain barrier. • The long-term protective effect might be due to neuroglia modulation, promotion of synaptic connection and neuroregeneration. [ABSTRACT FROM AUTHOR]

Danshen (Radix Salviae Miltiorrhizae) and Honghua (Flos Carthami) (Danhong) are two drugs commonly prescribed together, which are often used in the treatment of cerebrovascular diseases in China. Due to the complexity of the ingredients of Danhong, the present study focused on performing the orthogonal compatibility method on the primary effective molecules of this drug: Tanshinol, salvianolic acid A, salvianolic acid B and hydroxysafflor yellow A. These four molecules were studied to determine their protective effects and to screen for the most compatible ingredients to improve cerebral ischemia-reperfusion injury (IR) in rats. Focal middle cerebral artery occlusion was performed to establish the cerebral IR model in rats. Male Sprague-Dawley rats were randomly divided into sham operation group, IR group and nine orthogonal administration groups with different ratios of Danhong effective ingredients and Danhong injection group. Neurological deficit score and cerebral infarction volume were measured postoperatively. Morphological pathological alterations were observed via H&E staining. Bcl-2 and Bax were quantified using ELISA. Immunohistochemistry was conducted to analyze the expression of caspase-3 in the hippocampus. The expression levels of cytochrome c, apoptotic peptidase activating factor 1 (apaf-1), caspase-9, caspase-3 and p53 mRNA in the hippocampus were assessed via reverse transcription-quantitative PCR. The results demonstrated that different compatibility groups significantly reduced the neurological function score and decreased the volume of cerebral infarct compared with the IR group. These groups were also indicated to improve the pathological damage to the brain tissue. In addition, certain compatibility groups significantly decreased the number of caspase-3 positive cells in the hippocampus and the expression levels of cytochrome c, apaf-1, caspase-9, caspase-3 and p53 mRNA in the brain tissue. Orthogonal group 4 (30 mg/kg tanshinol; 2.5 mg/kg salvianolic acid A; 16 mg/kg salvianolic acid B; 8 mg/kg hydroxysafflor yellow A) was indicated to be the most effective. The four effective ingredients of Danhong exhibited a protective effect on rats with cerebral IR injury, potentially through the inhibition of apoptosis via the downregulation of key targets upstream of the caspase-3 pathway. In addition, the present study provided novel insights for the continued study of the drug compatibility rules of TCM. [ABSTRACT FROM AUTHOR]

Shengmai injection (SMI), a traditional Chinese medicine formula with the nature of multicomponent and multi-target, has been widely used in clinic for treating cardiovascular diseases in China; however, its comprehensive mechanism of action remains unclear. In this study, a TMT-based quantitative serum proteomics was performed to explore SMI's global mechanism and help identify serum biomarkers of its effect on isoproterenol (ISO)-induced myocardial ischemia rats. The results of TMT-based proteomic analysis identified 227, 100, and 228 differentially expressed proteins (DEPs) for the model compared to the control group, SMI pretreatment + model compared to the model group, and SMI pretreatment + model compared to the control group, respectively. Based on bioinformatics analyses of gene ontology (GO), KEGG pathways, and the protein-protein interaction (PPI) networks for the DEPs, it is concluded that the comprehensive mechanism of SMI's effect on ISO-induced myocardial ischemia injury includes regulation of energy metabolism, reducing endothelial cell permeability, regulation of vessel and cardiac contractility, anti-inflammation, and prevention of cell apoptosis. Furthermore, 10 common DEPs were found, and six of them were regulated in model vs. control group, while back-regulated in SMI pretreatment + model vs. model group. Among them, three functional proteins of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), Fas apoptotic inhibitory molecule 3 (FAIM3), and uncharacterized protein (M0R5J4), which were verified by the PRM analysis, might be the potential serum biomarkers on SMI's effects. Overall, this serum proteomics of SMI not only provides insights into the comprehensive mechanism underlying SMI's effects on ischemic heart disease but also helps identify serum biomarkers for directing SMI's cardioprotective effects. [ABSTRACT FROM AUTHOR]

Background : Guan-Xin-Shu-Tong capsule (GXSTC) is a traditional Chinese medicine (TCM) that has been used to treat coronary heart disease (CHD) for many years in China. However, the holistic mechanism of GXSTC against CHD is still unclear. Therefore, the purpose of this paper was to systematically explore the mechanism of action GXSTC in the treatment of CHD rats using a metabolomics strategy. Methods : A CHD model was induced by ligation of the left anterior descending coronary artery (LAD). In each group, echocardiography was performed; the contents of creatine kinase (CK), lactate dehydrogenase (LDH) and aspartate transaminase (AST) in serum were determined; and the myocardial infarct size was measured. The metabolites in plasma were analyzed by UHPLC-MS/MS-based untargeted metabolomics. Then, multivariate statistical analysis was performed to screen potential biomarkers associated with the GXSTC treatment in the LAD-induced rat CHD model. Finally, the MetaboAnalyst 4.0 platform was used for metabolic pathway enrichment analysis. Results : GXSTC was able to regulate the contents of CK, LDH and AST; restore impaired cardiac function; and significantly reduce the myocardial infarction area in model rats. Twenty-two biomarkers and nine metabolic pathways of GXSTC in the treatment of CHD were identified through UHPLC-MS/MS-based untargeted metabolomics analysis. Conclusion : GXSTC regulates metabolic disorders of endogenous components in LAD-induced CHD rats. The anti-CHD mechanism of GXSTC is mainly related to the regulation of amino acid, lipid and hormonal metabolism. This study provides an overall view of the mechanism underlying the action of GXSTC against CHD. [ABSTRACT FROM AUTHOR]

• Hongjingtian injection (HJT) is efficient in treating myocardial ischemia reperfusion as an antioxidant and autophagy regulator. • HJT scavenges ROS and protects mitochondrial function against excessive oxidative stress injury in cardiomyocytes. • HJT reduces autophagic-flux and protects cardiomyocytes from apoptosis might partially through AMPK/mTOR pathway. Hongjingtian injection (HJT) has been widely used in the clinic to treat coronary heart disease in China. However, the underlying mechanisms of therapies still need to be illustrated. The present study aims to determine whether HJT protects against myocardial ischemia reperfusion injury via Reactive Oxygen Species (ROS)-induced autophagic flux and apoptosis and, if so, to explore the underlying mechanisms. In vivo myocardial protection and autophagy regulation of HJT in myocardial ischemia reperfusion injury in C57BL/6 J and CAG-RFP-EGFP-LC3 transgenic C57BL/6 J mice were investigated. In vitro, the effects of HJT on apoptosis, autophagic flux, oxidative stress and mitochondrial function were observed in H 2 O 2 -induced H9c2 cells. In addition, apoptosis-related proteins and autophagy-related proteins were assessed to explore the underlying mechanisms. HJT significantly decreased the infarct area and cell apoptosis after myocardial ischemia reperfusion injury in C57BL/6 J mice. Autophagic flux was reduced by HJT treatment after myocardial ischemia reperfusion injury in CAG-RFP-EGFP-LC3 transgenic C57BL/6 J mice. HJT inhibited H 2 O 2 -induced cell apoptosis by significantly decreasing the levels of cleaved caspase 3 and increasing the Bcl-2/Bax ratio. HJT inhibited autophagic flux after H 2 O 2 stimulation by significantly decreasing LC3-Ⅱ and p-AMPK expression and increasing p-mTOR. HJT inhibited ROS production and improved mitochondrial function in H 2 O 2 -induced cells by significantly increasing the mitochondrial membrane potential, intracellular ATP contents and oxygen consumption. The beneficial effects of HJT in treating myocardial ischemia reperfusion are partially due to improved mitochondrial function and regulated autophagy to inhibit cell apoptosis through the AMPK/mTOR pathway. [ABSTRACT FROM AUTHOR]

Background: Myocardial ischaemia/reperfusion (I/R) results in myocardial injury via excessive autophagy. Huoxue Jiedu Formula (HJF) has been widely applied in China for the treatment of ischaemic heart disease. However, the mechanisms of HJF are still poorly understood. Thus, the present experiment was designed to observe the effects of HJF on myocardial I/R injury and explore the possible mechanism. Methods: Myocardial injury in rats subjected to myocardial I/R was reflected by nitrotetrazolium blue chloride staining, thioflavin S staining, serum creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT). Autophagy was determined by electron microscopy, laser confocal microscopy, Q-PCR and western blot. The possible pathway was predicted by network pharmacology and validated in vivo and in vitro. Results: Pretreatment of HJF decreased the no-reflow area, infarcted area, serum CK-MB levels and serum cTnT levels in I/R rat model. In addition, pretreatment of HJF decreased autophagy in heart tissues (decrease in Beclin-1 and LC3-II, and increase in Bcl-2, p62 and ratio of LC3-I/LC3-II). In the vivo study, pretreatment of HJF significantly decreased hypoxia/reoxygenation (H/R)-induced autophagy in H9C2 cells. Network pharmacology was applied to predict the possible mechanism by which HJF affects cardiac autophagy, and the PI3K/AKT/mTOR signalling pathway was the most significantly enriched pathway. And experimental studies demonstrated that pretreatment of HJF increased the phosphorylation of AKT and mTOR, and the effects of HJF on autophagy would be offset by PI3K inhibitor LY294002. Conclusion: Pretreatment of HJF ameliorates myocardial I/R injury by decreasing autophagy through activating PI3K/AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

• The vaccine candidate strain (rGtVarVP2) of novel variant IBDV was developed. • The rGtVarVP2 induced a good immune response. • The rGtVarVP2 was safe and effective. Infectious bursal disease (IBD), caused by infectious bursal disease virus (IBDV), is the most important immunosuppressive disease threatening the poultry industry worldwide. Recently, the novel variant IBDV has been emerging in large-scale in Asia including China and is becoming a new threat to the healthy development of the poultry industry, but no ideal vaccine is available. Therefore, it is necessary and urgent to develop a new vaccine against the novel variant IBDV. In this study, based on the skeleton of an attenuated vaccine strain Gt, a reassortment virus strain rGtVarVP2 was constructed for the first time, which could express the main protective antigen VP2 of the novel variant IBDV and replicate well in cell culture. Subsequently, the safety and effectiveness of rGtVarVP2 were further evaluated using animal experiments. The rGtVarVP2 is nonpathogenic to specific-pathogen-free (SPF) chicken. The immunization of rGtVarVP2 could induce the specific neutralizing antibodies against the novel variant IBDV. The challenge protection tests further confirmed the effectiveness of the IBDV reassortment virus rGtVarVP2. No atrophy and obvious lesions were observed in the immunization group while the bursae of non-immunization control group were severely destroyed after challenge, which showed that rGtVarVP2 could provide complete protection against the novel variant IBDV. These data indicate that the vaccine candidate (rGtVarVP2 strain) is safe and effective, which is of great significance for comprehensive control of IBD and healthy breeding. [ABSTRACT FROM AUTHOR]

Danhong injection (DHI) is used widely against cardiovascular disease in China. Recent studies have demonstrated its mitochondria-protection effect as being pivotal in treatment of myocardial ischemia/reperfusion (I/R) injury, but the underlying mechanism of action is incompletely understood. We aimed to identify the effect and mechanism of action of DHI on mitochondrial integrity and cardiomyocyte apoptosis after I/R. An I/R rat model was induced to detect the effect of DHI on myocardial repair by infarct size, apoptosis and oxidative stress. In vitro , H9C2 cells or H9C2 cells with nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown were injured under hypoxia-reoxygenation (H/R). The effects of DHI on apoptosis, antioxidant capacity and mitochondrial integrity were evaluated by mitochondrial morphology, apoptosis rate, reactive oxygen species (ROS) generation, ATP levels, mitochondrial membrane potential, and oxygen consumption in H9C2 cells treated with H/R. The underlying mechanism of action of DHI in maintenance of mitochondrial integrity and anti-apoptosis was detected in H9C2 cells with or without Nrf2 knockdown. DHI treatment significantly decreased the infarct size, inhibited apoptosis and suppressed oxidative stress in the hearts of I/R rats. Also, DHI promoted cell survival by: an anti-apoptosis action; inhibiting ROS generation; maintaining mitochondrial morphology with increased mitochondrial length; alleviating mitochondrial dysfunction with a decreased mitochondrial membrane potential; increasing ATP levels and the oxygen-consumption rate. Moreover, the Keap1/Nrf2/JNK pathway was found to be involved in DHI reducing oxidative stress and maintaining mitochondrial integrity. We revealed a novel mechanism by which DHI protected H9C2 cells against H/R injury via the Keap1/Nrf2/JNK pathway and provided a mitochondrial protectant for the treatment of myocardial I/R injury. [ABSTRACT FROM AUTHOR]

• HXP improves cardiac function in myocardial infarction (MI) mice. • HXP treatment ameliorates cardiac apoptosis partly via suppression of the p53 signaling pathway. • HXP treatment alleviates cardiac fibrosis by inhibiting the activation of TGF-β1/Smad2/3 pathway. Huoxin Pill (HXP), a Traditional Chinese Medicine, is used widely to treat patients with coronary heart disease and angina pectoris in China. However, the underlying protective mechanism of HXP on cardiac apoptosis and fibrosis has never been evaluated. Therefore, the aim of this study was to investigate the role of HXP in a myocardial infarction (MI) mouse model. The mice were randomly divided into 3 groups and subjected to surgical ligation of the left anterior descending (LAD) coronary artery or sham surgery (n = 6 for each group) and treated with HXP (50 mg/kg/day) or saline by gavage for 2 weeks. At 2 weeks post MI, we found that HXP significantly enhanced myocardial function and attenuated the increase of heart weight index (HWI) and pathological changes in MI mice. RNA-sequencing and KEGG pathway analyses identified 660 differentially expressed genes and multiple enriched signaling pathways including p53 and TGF-β. In support of these findings, HXP attenuated cardiac apoptosis and decreased p53 and Bax protein expression, while increasing Bcl-2 protein expression in cardiac tissues of MI mice. Furthermore, HXP treatment inhibited cardiac fibrosis and significantly down-regulated TGF-β1 protein expression and Smad2/3 phosphorylation in cardiac tissues. In summary, HXP can improve cardiac function in mice after MI by attenuating cardiac apoptosis and fibrosis partly via supression of the p53/Bax/Bcl-2 and TGF-β1/Smad2/3 pathways. [ABSTRACT FROM AUTHOR]

• This study combined chemometrics, HPLC, bioactivity validation and molecular docking to identify antiplatelet aggregation quality markers of SY. The inhibitory effect of SY extract on platelet aggregation was measured to evaluate its biological activity in vitro. Chemical composition differences were determined by HPLC. Molecular docking methods assessed the action mechanism of potential active compounds and target protein. The results of multivariate statistical analysis was in accordance with the molecular docking result. This study provided a feasible method for screening the quality markers for the effect of SY on promoting blood circulation for removing, and provided preliminary scientific information basis for the antithrombotic effect. • The study of the combination of fingerprint and pharmacological effects can not only correlate fingerprints with its pharmacodynamic effects, but also locate the fingerprint peak closely related to the pharmacological activity, so as to construct a more effective pharmacodynamic fingerprint for the quality control of TCM. • Salvia yunnanensis (SY), native to Yunnan, belongs to genus salvia of the labiatae. Historically, SY is commonly used by folks, such as the Yi and Miao peoples in southwestern China for activating blood and removing stasis. According to modern pharmacological studies, extracts of SY can inhibit platelet aggregation, significantly decrease arteriolar and microvascular spasm and facilitate blood flow, which means that thrombosis is less likely to be formed when whole blood viscosity and fibrinogen content are significantly reduced, and that creased abnormal blood flow state in myocardial ischemia rats improves. Previous studies have shown that extracts of SY has antiplatelet aggregation effect, but the material basis for conferring this effect is uncertain. In this study, a comprehensive evaluation method based on chemical fingerprints and bioactivity was framed through measurement of different batches of SY, and analysis of antiplatelet aggregation rate. • On the basis of traditional spectrum-effect relationships, this study combined molecular docking as a new strategy to perform high-throughput screening of activity. The advantage of virtual screening was not only to save costs, but also to make the experimental results more intuitive. The pocket binding of compound molecules and target proteins, its binding energy and binding morphology can be displayed intuitively. It makes the experimental results more visible and scientific. This study aimed to identify the antiplatelet aggregation quality markers of Salvia yunnanensis (SY) based on an integrated approach. The effects of SY methanol extracts on platelet aggregation were measured to evaluate their in vitro biological activity. Chemical composition differences were determined by HPLC. Molecular docking methods were used to assess the action mechanism of the potential active compounds and target proteins in SY. The results showed that 12 batches of SY samples inhibited platelet aggregation. Sodium danshensu, protocatechuic aldehyde, rutin, rosmarinic acid, salvianolic acid B, dihydrotanshinone I, tanshinone I, cryptotanshinone, and tanshinone IIA components were identified using chemical fingerprints. Multivariate statistical analysis indicated that cryptotanshinone, dihydrotanshinone I, tanshinone I, tanshinone IIA, and rosmarinic acid may have been the active components for antiplatelet aggregation, and molecular docking showed that these five components could combine with P2Y 12 protein on platelets. Furthermore, platelet aggregation inhibition activity of the five monomers was verified separately and it was obvious that cryptotanshinone and rosmarinic acid inhibited platelet aggregation. Therefore, cryptotanshinone and rosmarinic acid may be the quality markers of SY. This report describes a comprehensive, scientific, and feasible method for SY quality evaluation and provides a preliminary scientific basis for applying the antithrombotic activity of SY. [ABSTRACT FROM AUTHOR]

Oridonin is a diterpenoid isolated from Rabdosia rubescens (Hemsl.) Hara, a well-known herbal tea in China with many health benefits. To provide a better understanding of the potential cardioprotective effect of Oridonin, we investigated the metabolic alterations in heart tissue and serum of rat subjected to myocardial ischemia/reperfusion (MI/R) injury with or without pretreatment of Oridonin by UPLC-MS/MS metabolomics approach. Rats were randomly divided into groups as follows: Control, Sham, MI/R and pretreated with Oridonin (10 mg/kg)+MI/R. After 24 h of reperfusion, heart tissue and serum were collected for biochemical and metabolomic analysis. Pretreatment with Oridonin significantly decreased infarct size and reversed the abnormal elevated myocardial zymogram in serum. Moreover, Oridonin regulated several metabolic pathways, including glycolysis, branched chain amino acid, kynurenine, arginine, glutamine and bile acid metabolism. Our results suggest that Oridonin indeed displays outstanding cardioprotective effect mainly by regulating energy and amino acid metabolism. Scheme summarizing the potential mechanisms of Oridonin against MI/R injury by regulating several host metabolic pathways, including glycolysis, branched chain amino acid, kynurenine, arginine and bile acid metabolism. Image 1 [ABSTRACT FROM AUTHOR]

QiShenYiQi Pills (QSYQ) is a compound Chinese medicine widely used in China for treatment of cardiovascular disease. However, limited data are available regarding the anti-fibrotic role of QSYQ after ischemia/reperfusion (I/R) injury. This study aimed to investigate the effect of post-treatment with QSYQ on myocardial fibrosis after I/R-induced myocardium injury, and the role of different compounds of QSYQ, focusing especially on the involvement of chemokine ribosomal protein S19 (RP S19) dimer and monocyte migration. Male Sprague-Dawley rats were subjected to left anterior descending coronary artery occlusion for 30 min followed by reperfusion with or without administration of QSYQ (0.6, 1.2, or 1.8 g/kg) once daily by gavage for 6 days. Post-treatment with QSYQ diminished I/R-induced infarct size, alleviated myocardium injury, attenuated myocardial fibrosis after 6 days of reperfusion, and restored heart function and myocardial blood flow after I/R. In addition, the drug significantly inhibited monocyte infiltration and macrophage polarization towards M2, which was attributable to chemokine RP S19 dimer. Moreover, Western blots revealed that QSYQ blocked I/R-induced increase in TGFβ1 and TGFβRⅡ and reversed its relevant gene expression, such as Smad3,4,6,7, and inhibited the increase of MMP 2,9 expression. As the major components of QSYQ, astragaloside IV (AsIV), 3,4-dihydroxy-phenyl lactic acid (DLA), and notoginsenoside R1 (R1) were assessed as to the contribution of each of them to the expression of the proteins concerned. The results showed that the effect of AsIV was similar to QSYQ, while DLA and R1 only partly simulated the effect of QSYQ. The results provide evidence for the potential role of QSYQ in treating myocardial fibrosis following I/R injury. This effect may be associated with QSYQ's inhibition effect on monocyte chemotaxis and TGFβ1/Smads signaling pathway with different component targeting distinct link (s) of the signaling. [ABSTRACT FROM AUTHOR]

Objective: Insufficient myocardial reperfusion for patients with acute myocardial infarction (AMI) during primary percutaneous coronary intervention (PPCI) has a great influence on prognosis. The aim of this study was to investigate the association of the platelet-to-lymphocyte ratio (PLR) with myocardial reperfusion and in-hospital major adverse cardiac events (MACEs) in patients with AMI undergoing PPCI., Design: Retrospective cohort study., Setting: Patients and researchers from two tertiary hospitals., Participants: A total of 445 consecutive AMI patients who underwent PPCI between January 2015 and December 2017 were enrolled. Patients were divided into two groups based on the PLR value: patients with PLR values in the third tertile were defined as the high-PLR group (n=150), and those in the lower two tertiles were defined as the low-PLR group (n=295). Explicit criteria for inclusion and exclusion were applied., Interventions: No interventions., Primary and Secondary Outcome Measures: Primary outcome measures were defined as cardiovascular death, reinfarction or target vessel revascularisation. Secondary outcome measures were defined as stroke, non-lethal myocardial infarction, ventricular tachycardia/ventricular fibrillation and in-hospital mortality., Results: The high-PLR group had insufficient myocardial perfusion (23% vs 13%, p=0.003), greater postprocedural thrombolysis in myocardial infarction flow grade (0-2) (17% vs 10%, p=0.037), greater myocardial blush grade (0-1) (11% vs 4%, p=0.007) and higher B-type natriuretic peptide (BNP) (614±600 vs 316±429, p<0.001) compared with the low-PLR group. Multivariate logistic regression analysis indicated that the independent risk factors for impaired myocardial perfusion were high PLR (OR 1.256, 95% CI 1.003 to 1.579, p=0.056) and high BNP (OR 1.328, 95% CI 1.056 to 1.670, p=0.015). The high-PLR group had significantly more MACEs (43% vs 32%, p=0.029)., Conclusions: This study suggested that high PLR and BNP were independent risk factors for insufficient myocardial reperfusion in patients with AMI. Higher PLR was related to advanced heart failure and in-hospital MACEs in patients with AMI undergoing PPCI., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study was to investigate the value of initial serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations in ST-segment elevation myocardial infarction (STEMI) patients for predicting ST-segment resolution (STR) after primary percutaneous coronary intervention (pPCI)., Patients and Methods: Consecutive STEMI patients (n = 218) who underwent pPCI were assigned to an STR group (≥ 50 % resolution) or a non-STR group (< 50 % resolution). All patients were followed up for 12 months, and major adverse cardiac events were recorded. Data related to the pPCI procedure, biochemical parameters, and cardiac markers were compared between the two groups. Predictive factors of non-STR were also identified., Results: STR at 180 min after pPCI occurred in 202 patients (92.7 %). Compared to the STR group, patients in the non-STR group had a significantly lower left ventricular ejection fraction, a larger left ventricular end-diastolic dimension, and significantly higher serum concentrations of glycosylated hemoglobin and NT-proBNP. Multivariate logistic regression analysis indicated that a high serum NT-proBNP level in STEMI patients on hospital admission was the only independent predictive factor of non-STR after pPCI. An NT-proBNP concentration of ≥ 2,563.6 pg/ml had a sensitivity of 81.2 % and a specificity of 65.8 %., Conclusions: Serum NT-proBNP concentrations in STEMI patients on hospital admission were useful in predicting non-STR after pPCI.

Several studies have demonstrated the association between elevated admission glycaemia (AG) and the occurrence of some arrhythmias such as atrial fibrillation, ventricular tachycardia, and ventricular fibrillation after myocardial infarction. However, the impact of elevated AG on the high grade atrioventricular block (AVB) occurrence after ST-segment elevation myocardial infarction (STEMI) remains unclear. Included were 3359 consecutive patients with STEMI who received reperfusion therapy. The primary endpoint was the development of high grade AVB during hospital course. Patients were divided into non-diabetes mellitus (DM), newly diagnosed DM, and previously known DM according to the hemoglobin A1c level. The optimal AG value was determined by receiver operating characteristic curves analysis with AG predicting the high grade AVB occurrence. The best cut-off value of AG for predicting the high grade AVB occurrence was 10.05 mmol/L by ROC curve analysis. The prevalence of AG ≥ 10.05 mmol/L in non-DM, newly diagnosed DM, and previously known DM was 15.7%, 34.1%, and 68.5%, respectively. The incidence of high grade AVB was significantly higher in patients with AG ≥ 10.05  mmol/L than <10.05  mmol/L in non-DM (5.7% vs. 2.1%, P < 0.001) and in newly diagnosed DM (10.2% vs.1.4%, P < 0.001), but was comparable in previously known DM (3.6% vs. 0.0%, P = 0.062). After multivariate adjustment, AG ≥ 10.05  mmol/L was independently associated with increased risk of high grade AVB occurrence in non-DM (HR = 1.826, 95% CI 1.073-3.107, P = 0.027) and in newly diagnosed DM (HR = 5.252, 95% CI 1.890-14.597, P = 0.001). Moreover, both AG ≥ 10.05  mmol/L and high grade AVB were independent risk factors of 30-day all cause-mortality (HR = 1.362, 95% CI 1.006-1.844, P = 0.046 and HR = 2.122, 95% CI 1.154-3.903, P = 0.015, respectively). Our study suggested that elevated AG level (≥10.05  mmol/L) might be an indicator of increased risk of high grade AVB occurrence in patients with STEMI.

Background: In cardiology, it is controversial whether gender influences prognosis after acute myocardial infarction (MI). We examined the 30-day and 1-year prognosis for female patients with ST-elevation myocardial infarction (STEMI) in Liaoning province, and we analyzed factors that influenced these outcomes., Methods: This was a prospective, multicenter, observational study in which patient data were collected by questionnaire at the time of diagnosis and at approximately 30 days and 1 year later by telephone inquiries. Patients were diagnosed with STEMI between June 1, 2009 and June 1, 2010 at any of the 20 hospitals that gave treatment representative of current STEMI treatment in Liaoning Province. Unified follow-up questionnaire was used to visit the STEMI patients., Results: We analyzed data from a total of 1429 consecutive patients with STEMI in Liaoning province. Female patients were older (70.0 vs. 60.3, P < 0.001) and were less likely to receive emergency reperfusion therapy than male ones (39.2% vs. 58.0%, P < 0.001). Female gender was associated with higher unadjusted 30-day mortality rates (HR = 2.118, 95%CI: 1.572 - 2.854, P < 0.001) and higher unadjusted 1-year mortality rates (HR = 2.174, 95%CI: 1.659 - 2.848, P < 0.001). Multivariate Cox regression analysis showed that female gender was not an independent predictor of 30-day mortality rates (HR = 1.273, 95%CI: 0.929 - 1.745, P = 0.133) nor of 1-year mortality rates (HR = 1.112, 95%CI: 0.831 - 1.487, P = 0.475)., Conclusions: Women with STEMI appear to be at increased risk of 30-day and 1-year mortality compared with male STEMI patients, but this difference may be explained by older age and less frequent receipt of reperfusion therapy among the women.

Objective: To analyze the current use of reperfusion strategies and the outcomes of patients with ST elevation acute coronary syndromes (ACS) in China., Methods: A total of 518 consecutive patients (371 male and 147 females, mean age 65 +/- 11) with ST elevation ACS or newly discovered left bundle branch block were registered from 20 hospitals from 5 regions (ranging from large regional centre hospitals to small county hospitals) in China. Patient general characteristics, reperfusion patterns and outcomes were analyzed. Patients were followed up for 3 months., Results: The median time from pain onset to presentation at the hospital was 4 hours. Pre-hospital delay > 12 hours was found in 20% patients. Fifty-six percent patients (292/518) underwent reperfusion therapy (134 with primary percutaneous coronary intervention and 158 with fibrinolysis). The median time from admission to reperfusion (door-to-needle) was 65 min in fibrinolysis group and 110 min (door-to-cath) in primary PCI group respectively. Urokinase was used in 67% (106/158) patients underwent fibrinolysis. Multivariate logistic regression analysis showed that age >/= 75 years (P < 0.01), previous myocardial infarction (P < 0.01) and history of congestive heart failure (P < 0.05) were associated with no reperfusion therapy. Mortality and congestive heart failure rates were significantly higher in patients with no reperfusion therapy not only at discharge (P < 0.01) but also at 3 months (P < 0.01) compared to patients underwent reperfusion. The incidence of combined outcomes (death or MI, and death, MI or Strobe) was also higher in patients without reperfusion therapy at 3 months (all P < 0.01) compared to patients underwent reperfusion. There were no differences on combined outcomes between fibrinolysis and primary PCI subgroups., Conclusion: Reperfusion therapy was the primary treatment of choice to improve the outcomes of patients with ST elevation ACS. Strategies to increase reperfusion therapy rate for ST elevation ACS are urgently needed in China.