L-theanine alleviates myocardial ischemia/reperfusion injury by suppressing oxidative stress and apoptosis through activation of the JAK2/STAT3 pathway in mice.

BACKGROUND: L-theanine is a unique non-protein amino acid in tea that is widely used as a safe food additive. We investigated the cardioprotective effects and mechanisms of L-theanine in myocardial ischemia-reperfusion injury (MIRI). METHODS: The cardioprotective effects and mechanisms of L-theanine and the role of Janus Kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling were investigated in MIRI mice using measures of cardiac function, oxidative stress, and apoptosis. RESULTS: Administration of L-theanine (10 mg/kg, once daily) suppressed the MIRI-induced increase in infarct size and serum creatine kinase and lactate dehydrogenase levels, as well as MIRI-induced cardiac apoptosis, as evidenced by an increase in Bcl-2 expression and a decrease in Bax/caspase-3 expression. Administration of L-theanine also decreased the levels of parameters reflecting oxidative stress, such as dihydroethidium, malondialdehyde, and nitric oxide, and increased the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD) in ischemic heart tissue. Further analysis showed that L-theanine administration suppressed the MIRI-induced decrease of phospho-JAK2 and phospho-STAT3 in ischemic heart tissue. Inhibition of JAK2 by AG490 (5 mg/kg, once daily) abolished the cardioprotective effect of L-theanine, suggesting that the JAK2/STAT3 signaling pathway may play an essential role in mediating the anti-I/R effect of L-theanine. CONCLUSIONS: L-theanine administration suppresses cellular apoptosis and oxidative stress in part via the JAK2/STAT3 signaling pathway, thereby attenuating MIRI-induced cardiac injury. L-theanine could be developed as a potential drug to alleviate cardiac damage in MIRI.

Application of AI-empowered scenario-based simulation teaching mode in cardiovascular disease education.

BACKGROUND: Cardiovascular diseases present a significant challenge in clinical practice due to their sudden onset and rapid progression. The management of these conditions necessitates cardiologists to possess strong clinical reasoning and individual competencies. The internship phase is crucial for medical students to transition from theory to practical application, with an emphasis on developing clinical thinking and skills. Despite the critical need for education on cardiovascular diseases, there is a noticeable gap in research regarding the utilization of artificial intelligence in clinical simulation teaching. OBJECTIVE: This study aims to evaluate the effect and influence of AI-empowered scenario-based simulation teaching mode in the teaching of cardiovascular diseases. METHODS: The study utilized a quasi-experimental research design and mixed-methods. The control group comprised 32 students using traditional teaching mode, while the experimental group included 34 students who were instructed on cardiovascular diseases using the AI-empowered scenario-based simulation teaching mode. Data collection included post-class tests, "Mini-CEX" assessments, Clinical critical thinking scale from both groups, and satisfaction surveys from experimental group. Qualitative data were gathered through semi-structured interviews. RESULTS: Research shows that compared with traditional teaching models, AI-empowered scenario-based simulation teaching mode significantly improve students' performance in many aspects. The theoretical knowledge scores(P < 0.001), clinical operation skills(P = 0.0416) and clinical critical thinking abilities of students(P < 0.001) in the experimental group were significantly improved. The satisfaction survey showed that students in the experimental group were more satisfied with the teaching scene(P = 0.008), Individual participation(P = 0.006) and teaching content(P = 0.009). There is no significant difference in course discussion, group cooperation and teaching style of teachers(P > 0.05). Additionally, the qualitative data from the interviews highlighted three themes: (1) Positive new learning experience, (2) Improved clinical critical thinking skills, and (3) Valuable suggestions and concerns for further improvement. CONCLUSION: The AI-empowered scenario simulation teaching Mode plays an important role in the improvement of clinical thinking and skills of medical undergraduates. This study believes that the AI-empowered scenario simulation teaching mode is an effective and feasible teaching model, which is worthy of promotion in other courses.

The value of serum Sema4D level in predicting the prognosis of patients with acute ST-segment elevation myocardial infarction and with high thrombus burden.

BACKGROUND: Acute ST-segment elevation myocardial infarction (STEMI) is a serious cardiovascular disease. High thrombus burden is an independent risk factor for poor prognosis of acute myocardial infarction. However, there is no study on the correlation between soluble semaphorin 4D (sSema4D) level and high thrombus burden in patients with STEMI. PURPOSE: This study aimed to investigate the relationship between sSema4D level and the thrombus burden of STEMI and further explore its effect on the main predictive value of the occurrence of major adverse cardiovascular events (MACE). METHODS: From October 2020 to June 2021, 100 patients with STEMI diagnosed in our hospital's cardiology department were selected. According to the thrombolysis in myocardial infarction(TIMI)score, STEMI patients were divided into high thrombus burden groups (55 cases) and non-high thrombus burden groups (45 cases) 0.74 patients with stable coronary heart disease (CHD) were selected as stable CHD group, and 75 patients with negative coronary angiography (CAG) were selected as control group. Serum sSema4D levels were measured in 4 groups. The correlation between serum sSema4D and high-sensitivity C-reactive protein (hs-CRP) in patients with STEMI was analyzed. The relationship of serum sSema4D levels between the high and non-high thrombus burden group was evaluated. The effect of sSema4D levels on the occurrence of MACE was explored in one year after percutaneous coronary intervention. RESULTS: Serum sSema4D level was positively correlated with hs-CRP level in STEMI patients (P < 0.05) with a correlation coefficient of 0.493. The sSema4D level was significantly higher in the high versus non-high thrombus burden group (22.54(20.82,24.17), P < 0.05). Moreover, MACE occurred in 19 cases in high thrombus burden group and 3 cases in non-high thrombus burden group. The results of Cox regression analysis showed that sSema4D was an independent predictor of MACE (OR = 1.497,95% CI: 1.213-1.847, P < 0.001). CONCLUSION: The sSema4D level is associated with coronary thrombus burden and is an independent risk factor for MACE.

Measurement of myocardial extracellular volume fraction in patients with heart failure with preserved ejection fraction using dual-energy computed tomography.

OBJECTIVES: To measure the myocardial extracellular volume (ECV) in patients with heart failure with preserved ejection fraction (HFpEF) using dual-energy computed tomography with late iodine enhancement (LIE-DECT) and to evaluate the relationship between ECV and risk of HFpEF and cardiac structure and function. METHODS: A total of 112 consecutive patients with HFpEF and 80 consecutive subjects without heart disease (control group) who underwent LIE-DECT were included. All patients were divided into ischaemic and non-ischaemic groups according to the LIE patterns detected using iodine maps. The ischaemic scar burden was calculated in the ischaemic HFpEF group. Iodine maps and haematocrit were used to measure ECV in the non-ischaemic HFpEF group and remote ECV of the non-scarred myocardium in the ischaemic HFpEF group, respectively. Cardiac structural and functional variables were collected. RESULTS: ECV in patients with non-ischaemic HFpEF (n = 77) and remote ECV in patients with ischaemic HFpEF (n = 35) were significantly higher than those in control subjects (p < 0.001). Multivariate logistic regression analysis revealed that after adjusting for age, sex, body mass index, smoking, and drinking, a higher ECV/remote ECV was still associated with non-ischaemic HFpEF and ischaemic HFpEF (p < 0.001). A positive correlation was established between ECV and cardiac structural and functional variables (p < 0.05) in all participants. Subgroup analysis showed that ECV/remote ECV and ischaemic scar burden positively correlated with heart failure classification in the HFpEF subgroup (p < 0.05). CONCLUSION: ECV/remote ECV elevation was significantly associated with non-ischaemic and ischaemic HFpEF. Remote ECV and LIE may have synergistic effects in the risk assessment of ischaemic HFpEF. KEY POINTS: • ECV/remote ECV elevation is associated not only with non-ischaemic HFpEF but also with ischaemic HFpEF. • ECV/remote ECV and ischaemic scar burden are correlated with cardiac structure and function.

Values of Radial Artery Provocation Tests at Different Doses of Ergonovine in the Diagnosis of Coronary Artery Spasm.

The intracoronary drug provocation test has been the gold standard for diagnosis of coronary artery spasm (CAS); however, it has been identified with severe complications. In this study, we investigated the sensitivity, specificity, and safety of radial artery provocation test at different doses of ergonovine in the diagnosis of CAS. This study enrolled 57 patients, which were then divided into CAS group (n = 24) and control group (n = 33) after intracoronary ergonovine provocation test. All patients underwent radial artery provocation test at different doses of ergonovine. The predictive values of radial artery provocation test for the diagnosis of CAS were analyzed using receiver operator characteristic curve. In the radial artery provocation test at different doses of ergonovine, radial artery stenosis degree was all found to be significantly higher in the CAS group than in the control group (all P < 0.001). In the control group, significant differences were noted in the radial artery stenosis degree between different doses of ergonovine (all P < 0.05). In the CAS group, the radial artery stenosis degree was significantly higher in 160 µg and 100 µg of ergonovine than in 60 µg of ergonovine (all P < 0.001). The radial artery provocation test at 60 µg and 100 µg of ergonovine did not cause CAS, chest pain, and ECG ischemic changes. In the radial artery provocation test at 160 µg of ergonovine, some patients had CAS, chest pain, and ECG ischemic changes. The specificity and sensitivity of radial artery provocation test were 90.91% and 50.00% at 60 µg of ergonovine, 96.97% and 66.67% at 100 µg of ergonovine, and 90.91% and 95.83% at 160 µg of ergonovine for the diagnosis of CAS. As per our findings, we can conclude that the basic tension of radial artery increases in the CAS group. With the increase of ergonovine doses, its sensitivity and specificity improve, but its safety decreases. We will explore the most optimal dose of ergonovine in future studies.

Ciliary Neurotrophic Factor (CNTF) Protects Myocardial Cells from Oxygen Glucose Deprivation (OGD)/Re-Oxygenation via Activation of Akt-Nrf2 Signaling.

BACKGROUND/AIMS: Oxygen glucose deprivation (OGD)/re-oxygenation (OGDR) exposure to myocardial cells mimics ischemia-reperfusion injuries. We studied the potential activity of ciliary neurotrophic factor (CNTF) on OGDR-treated myocardial cells. METHODS: CNTF and CNTFR expression were tested by RT-PCR assay and Western blotting assay. Cell viability and death were tested by MTT assay and LDH release assay, respectively. Akt-Nrf2 signalings were tested by Western blotting assay and qPCR assay. RESULTS: CNTF and its receptor CNTFR were functionally expressed in established H9c2 myocardial cells and primary murine myocardiocytes. Pretreatment of CNTF significantly attenuated OGDR-induced viability reduction and death in myocardial cells. Further studies show that in the myocardial cells CNTF activated NF-E2-related factor 2 (Nrf2) signaling to inhibit OGDR-induced reactive oxygen species (ROS) production and programmed necrosis, preventing adenine nucleotide translocator 1 (ANT-1)-p53-cyclophilin D (Cyp-D) mitochondrial association and mitochondrial depolarization. Nrf2 silencing or knockout almost abolished CNTF-induced H9c2 cytoprotection against OGDR. CNTF activated Akt in H9c2 cells and primary murine myocardiocytes. Conversely, Akt blockage by the pharmacological inhibitors not only blocked CNTF-induced Nrf2 Ser-40 phosphorylation and activation, but also nullified anti-OGDR actions by CNTF in myocardial cells. CONCLUSION: CNTF activates Akt-Nrf2 signaling to protect myocardial cells from OGDR.

Low-concentration of perifosine surprisingly protects cardiomyocytes from oxygen glucose deprivation.

Here we found that low-concentration of perifosine, an Akt inhibitor, surprisingly protected cardiomyocytes from oxygen glucose deprivation (OGD)/re-oxygenation. In H9c2 cardiomyocytes, non-cytotoxic perifosine (0.1-0.5 µM) suppressed OGD/re-oxygenation-induced reactive oxygen species (ROS) production, p53 mitochondrial translocation and cyclophilin D complexation, as well as mitochondrial membrane potential (MMP) reduction. Molecularly, perifosine activated AMP-activated kinase (AMPK) signaling to increase intracellular NADPH (nicotinamide adenine dinucleotide phosphate) content in H9c2 cells. On the other hand, AMPK inhibition by AMPKα1 shRNA-knockdown in H9c2 cells significantly reduced perifosine-induced NADPH production, and alleviated perifosine-mediated anti-oxidant and cytoprotective activities against OGD/re-oxygenation. In primary murine cardiomyocytes, perifosine similarly activated AMPK signaling, and offered significant protection against OGD/re-oxygenation, which was largely attenuated with siRNA knockdown of AMPKα1. We demonstrate an unexpected function of perifosine (low-concentration) in protecting cardiomyocytes from OGD/re-oxygenation.

Salidroside inhibits oxygen glucose deprivation (OGD)/re-oxygenation-induced H9c2 cell necrosis through activating of Akt-Nrf2 signaling.

Oxygen glucose deprivation (OGD)/re-oxygenation has been applied to cultured cardiomyocytes to create a cellular model of ischemic heart damage. In the current study, we explored the potential role of salidroside against OGD/re-oxygenation-induced damage in H9c2 cardiomyocytes, and studied the underlying mechanisms. We found that OGD/re-oxygenation primarily induced necrosis in H9c2 cells, which was inhibited by salidroside. Salidroside suppressed OGD/re-oxygenation-induced reactive oxygen species (ROS) production, p53 mitochondrial translocation and cyclophilin D (Cyp-D) association as well as mitochondrial membrane potential (MMP) decrease in H9c2 cells. Meanwhile, salidroside activated Akt and promoted transcription of NF-E2-related factor 2 (Nrf2)-regulated genes (heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO-1)). Significantly, Nrf2 shRNA knockdown or Akt inhibitors (LY 294002 and wortmannin) not only prevented salidroside-induced HO-1/NQO-1 transcription, but also alleviated salidroside-mediated cytoprotective effect against OGD/re-oxygenation in H9c2 cells. These observations suggest that salidroside activates Nrf2-regulated anti-oxidant signaling, and protects against OGD/re-oxygenation-induced H9c2 cell necrosis via activation of Akt signaling.

Nomogram for predicting cardiovascular mortality in patients with gastrointestinal stromal tumor: A population-based study.

This research aimed to develop and validate a clinical nomogram for predicting the probability of cardiovascular death (CVD) in patients with gastrointestinal stromal tumors (GIST). Information regarding patients diagnosed with GIST was extracted from the surveillance, epidemiology, and end results database. The multivariable competing risk model and multivariable Cox regression model were utilized to determine the independent predictive factors. A comparison was made between the results obtained from the 2 models. A nomogram was built to visualize the competing risk model. The nomogram's performance was assessed utilizing concordance index, calibrate curve, decision curve analysis, and risk stratification. A total of 9028 cases were enrolled for final analysis, with CVD accounting for 12.8% of all deaths since GIST diagnosis. The multivariate analysis of competing risks revealed that age, chemotherapy and marital status were identified as independent risk factors for CVD in GIST individuals. The nomogram model exhibited good calibration and strong discriminative ability, indicating its effectiveness in predicting outcomes, with a concordance index of 0.788 (95% confidence interval: 0.753-0.823) in the training set, and 0.744 (95% confidence interval: 0.673-0.815) in the validation set. Decision curve analysis indicated that the prediction model had good clinical practicability. Additionally, risk stratification analysis efficiently divided GIST individuals into high- and low-risk populations for CVD. This was the first research to construct and validate a predictive nomogram using a competing risk model to estimate the individual probabilities of CVD in GIST patients. The nomogram can assist clinicians in making personalized treatment and monitoring plans.

Loganin protects against myocardial ischemia-reperfusion injury by modulating oxidative stress and cellular apoptosis via activation of JAK2/STAT3 signaling.

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is a pathological process that follows immediate revascularization of myocardial infarction and is characterized by exacerbation of cardiac injury. Loganin, a monoterpene iridoid glycoside derived from Cornus officinalis Sieb. Et Zucc, can exert cardioprotective effects in cardiac hypertrophy and atherosclerosis. However, its role in ischemic heart disease remains largely unknown. METHODS: Considering that Janus kinase 2 (JAK2)/ signal transducer and activator of transcription 3 (STAT3) has a protective effect on the heart, we developed a mouse model of MIRI to investigate the potential role of this pathway in loganin-induced cardioprotection. RESULTS: Our results showed that treatment with loganin (20 mg/kg) prevented the enlargement of myocardial infarction, myocyte destruction, serum markers of cardiac injury, and deterioration of cardiac function induced by MIRI. Myocardium subjected to I/R treatment exhibited higher levels of oxidative stress, as indicated by an increase in malondialdehyde (MDA) and dihydroethidium (DHE) density and a decrease in total antioxidant capacity (T-AOC), glutathione (GSH), and superoxide dismutase (SOD), whereas treatment with loganin showed significant attenuation of I/R-induced oxidative stress. Loganin treatment also increased the expression of anti-apoptotic Bcl-2 and reduced the expression of caspase-3/9, Bax, and the number of TUNEL-positive cells in ischemic cardiac tissue. Moreover, treatment with loganin triggered JAK2/STAT3 phosphorylation, and AG490, a JAK2/STAT3 inhibitor, partially abrogated the cardioprotective effects of loganin, indicating the essential role of JAK2/STAT3 signaling in the cardioprotective effects of loganin. CONCLUSIONS: Our data demonstrate that loganin protects the heart from I/R injury by inhibiting I/R-induced oxidative stress and cellular apoptosis via activation of JAK2/STAT3 signaling.

The value of serum Sema4D level in reflecting the inflammatory state of acute ST-segment elevation myocardial infarction.

Background: This study sought to investigate the expression of soluble semaphorin 4D (sSema4D) in acute ST-segment elevation myocardial infarction (STEMI) and to explore its value in evaluating the inflammatory status of acute myocardial infarction (AMI). Methods: From October 2020 to June 2021, 100 patients with STEMI diagnosed at the Department of Cardiology of our hospital were selected as the STEMI group, 83 patients with unstable angina (UA) were selected as the UA group, and 78 patients with negative coronary angiography (CAG) were selected as the control group. The baseline data of the 3 groups of patients were recorded, the sSema4D levels were determined, the expression of sSema4D levels in AMI was analyzed, and the value of sSema4D levels in reflecting inflammatory state of AMI was explored. Results: Compared with UA group and control group, the expression of sSema4D in peripheral blood of STEMI group was significantly increased (P<0.001), which could better reflect the inflammatory status of patients with STEMI than traditional inflammatory indicators [hypersensitive c-reactive protein (hs-CRP)] (P<0.05). The receiver operating characteristic (ROC) curve showed that sSema4D (AUC =0.780, cut-off =19.62, 95% CI: 0.629, 0.837, P<0.001) was more specific than hs-CRP (AUC =0.697, cut-off =3.39, 95% CI: 0.629, 0.765, P<0.001) in reflecting the inflammatory status of STEMI patients. Conclusions: sSema4D levels have certain value in reflecting the inflammatory state of STEMI.

Down-regulation of Hrd1 protects against myocardial ischemia-reperfusion injury by regulating PPARα to prevent oxidative stress, endoplasmic reticulum stress, and cellular apoptosis.

The E3 ubiquitin ligase HMG-CoA reductase degradation protein 1 (Hrd1) is a key enzyme for ER-associated degradation of misfolded proteins. Its role in ischemic heart disease has not been fully elucidated. Here, we investigated its effect on oxidative status and cell survival in cardiac ischemia-reperfusion injury (MIRI). We found that virus-induced down-regulation of Hrd1 expression limited infarct size, decreased creatinine kinase (CK) and lactate dehydrogenase (LDH), and preserved cardiac function in mice subjected to left anterior descending coronary artery ligation and reperfusion. Silencing of the Hrd1 gene also prevented the ischemia/reperfusion (I/R)-induced (i) increase in dihydroethidium (DHE) intensity, mitochondrial production of reactive oxygen species (ROS), malondialdehyde (MDA), and nitric oxide (NO), (ii) decrease in total antioxidant capacity (T-AOC) and glutathione (GSH), (iii) disruption of mitochondrial membrane potential, and (iv) increase in the expression of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) in ischemic heart tissue. In addition, down-regulation of Hrd1 expression prevented the abnormally increased caspase-3/caspase-9/Bax expression and decreased Bcl-2 expression in ischemic heart tissue of I/R mice. Further analysis showed that the I/R stimulus reduced peroxisome proliferation activated receptor α (PPARα) expression in ischemic heart tissue, which was partially prevented by down-regulation of Hrd1. Pharmacological inhibition of PPARα was able to abolish the preventive effect of down-regulation of Hrd1 on oxidative stress, endoplasmic reticulum stress, and cellular apoptosis in ischemic heart tissue. These data suggest that down-regulation of Hrd1 protects the heart from I/R-induced damage by suppressing oxidative stress and cellular apoptosis likely through PPARα.

Correlation between serum laminin level and prognosis of acute heart failure.

OBJECTIVE: To investigate the correlation between serum laminin (LN) level and the prognosis of acute heart failure (AHF). METHODS: A total of 199 patients with AHF treated in Nantong First People's Hospital from March 2019 to November 2021 were included in this study. The patients were divided into the event group and the non-event group according to whether major adverse cardiovascular events (MACEs) occurred during hospitalization. We collected the baseline data of all patients and their LN levels were measured. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of LN for the occurrence of MACE in AHF patients during hospitalization. Multivariate Logistic regression analysis was used to screen the independent factors associated with the occurrence of MACE in patients with AHF. RESULTS: Among 199 patients with AHF, 43 were in the event group and 156 were in the non-event group. The area under ROC curve of LN to predict MACE in AHF patients during hospitalization was 0.8144, 95% confidence interval (CI): 0.7433-0.8855, p < .0001, cutoff point = 77.9, specificity 58.33%, and sensitivity 88.37%. Multivariate logistic regression analysis showed that the independent factors associated with the occurrence of MACE in AHF patients were the increase of LN level (odds ratio [OR]: 1.020, 95% CI: 1.012-1.028), the decrease of ejection fraction (OR: 0.007, 95% CI: 0.000-0.362) and diastolic blood pressure (OR: 0.946, 95% CI: 0.913-0.981; p < .05). CONCLUSION: The increase of LN level is independently correlated with the occurrence of MACE in AHF patients during hospitalization, which has the potential to be a serological indicator for poor prognosis in patients with AHF.

Measurement of myocardial extracellular volume using cardiac dual-energy computed tomography in patients with ischaemic cardiomyopathy: a comparison of different methods.

To clarify the consistency and efficiency of four methods for myocardial extracellular volume (ECV) measurement (manual method using dual-energy iodine [manual ECViodine], manual method using subtraction [manual ECVsub], automatic ECViodine, automatic ECVsub) in patients with ischaemic cardiomyopathy. Fifty patients with ischaemic cardiomyopathy who underwent coronary computed tomography angiography (CCTA) following dual-energy computed tomography (CT) with late iodine enhancement (LIE-DECT) were included. LIE with ischaemic patterns representing scarring could be detected using iodine maps in all patients. The global and remote ECVs of non-scarred myocardium were measured using four methods (manual ECViodine, automatic ECViodine, manual ECVsub, and automatic ECVsub). The consistency and time cost of the four methods were analysed. There were no significant differences in the mean global ECVs or remote ECVs among the four methods (p > 0.05). ECViodine resulted in a lower Bland-Altman limit of agreement than that of ECVsub for both global and remote measurements. Intraclass correlation coefficients of the automatic and manual ECViodine measurements demonstrated better concordance (0.804 and 0.859, respectively) than those of automatic and manual ECVsub (0.607 and 0.669, respectively) for both global and remote measurements. The measurement time for automatic ECV was less than that for manual ECV for both global and remote ECV measurements (all p < 0.001). ECV measurement using dual-energy iodine yielded good concordance, and the automatic method has the advantages of being simple and convenient, which can become a useful tool for quantification of myocardial fibrosis.

Indole-3-Carbinol (I3C) Protects the Heart From Ischemia/Reperfusion Injury by Inhibiting Oxidative Stress, Inflammation, and Cellular Apoptosis in Mice.

Strategies for treating myocardial ischemia in the clinic usually include re-canalization of the coronary arteries to restore blood supply to the myocardium. However, myocardial reperfusion insult often leads to oxidative stress and inflammation, which in turn leads to apoptosis and necrosis of myocardial cells, for which there are no standard treatment methods. The aim of this study was to determine the pharmacological effect of indole-3-carbinol (I3C), a phytochemical found in most cruciferous vegetables, in a mouse model of myocardial ischemia/reperfusion injury (MIRI). Our results showed that I3C pretreatment (100 mg/kg, once daily, i. p.) prevented the MIRI-induced increase in infarct size and serum creatine kinase (CK) and lactate dehydrogenase (LDH) in mice. I3C pretreatment also suppressed cardiac apoptosis in MIRI mice by increasing the expression levels of the anti-apoptotic protein Bcl-2 and decreasing the expression levels of several apoptotic proteins, including Bax, caspase-3, and caspase-9. In addition, I3C pretreatment was found to reduce the levels of parameters reflecting oxidative stress, such as dihydroethidium (DHE), malondialdehyde (MDA), reactive oxygen species (ROS), and nitric oxide (NO), while increasing the levels of parameters reflecting anti-oxidation, such as total antioxidant capacity (T-AOC) and glutathione (GSH), in MIRI-induced ischemic heart tissue. I3C pretreatment was also able to remarkably decrease the expression of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6) mRNA in ischemic heart tissue. These results demonstrate that administration of I3C protects the heart from MIRI through its anti-apoptotic, antioxidant, and anti-inflammatory effects.

Sinomenine Confers Protection Against Myocardial Ischemia Reperfusion Injury by Preventing Oxidative Stress, Cellular Apoptosis, and Inflammation.

Sinomenine (SIN), an alkaloid extracted from the root of S. acutum. sinomenine, has been shown to have antiarrhythmic, antioxidant, and anti-inflammatory effects in myocardial ischemia-reperfusion injury (MIRI) ex vivo. In this study, we investigated the cardioprotective effects of SIN in an in vivo mouse model of MIRI. Adult male C57BL/6J mice received SIN (80 mg/kg) for 5 days and underwent 30 min of percutaneous occlusion of the left anterior descending artery (LAD) followed by 24 h of reperfusion. Results showed that pretreatment with SIN significantly reduced myocardial infarct size and concentrations of markers of cardiac injury and improved left ventricular ejection fraction (EF) and shortening fraction (FS) in MIRI mice. The SIN pretreatment prevented the MIRI-induced decrease in the expression levels of Bcl-2, increase in the expression levels of caspase-3, caspase-9, and Bax, and increase in the number of TUNEL-positive cells in ischemic heart tissue. It was also found that pretreatment with SIN prevented the MIRI-induced oxidative stress imbalance in ischemic heart tissue, as shown by the increase in total antioxidant capacity (T-AOC) and glutathione (GSH) and the decrease in malondialdehyde (MDA), reactive oxygen species (ROS), and dihydroethidium (DHE) density. Further studies showed that the stimulus of cardiac ischemia/reperfusion caused a remarkable increase in the expression levels of interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) mRNA in ischemic heart tissue, which was effectively prevented by pretreatment with SIN. These results demonstrate that SIN can attenuate MIRI-induced cardiac injury in vivo by preventing oxidative stress, inflammation, and apoptosis.

A Four-MicroRNA Panel in Peripheral Blood Identified as an Early Biomarker to Diagnose Acute Myocardial Infarction.

Objective: This study aimed to evaluate suitable circulating microRNAs (miRNAs) as diagnostic biomarkers of acute myocardial infarction (AMI). Methods: Patients with AMI were enrolled as study participants. All patients with AMI coming from the Second Affiliated Hospital of Nantong University between October 1, 2017 and May 31, 2019 were screened. At the same time, 80 patients with coronary angiographic stenosis <50% during the same period were selected as the control group. Peripheral blood samples were collected at different time points (0, 6, 12, and 24 h after disease onset) to detect the expression of a previously identified promising four-microRNA panel. The expression levels of miRNAs were tested by real-time polymerase chain reaction (RT-PCR), and the receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of circulating miRNAs. Results: Based on the inclusion and exclusion criteria, 80 patients with AMI and 80 controls were enrolled in this study. The expression of circulating miR-1291, miR-217, miR-455-3p, and miR-566 was significantly downregulated in patients with AMI compared with controls. The area under the ROC curve (AUC) of circulating miR-1291, miR-217, miR-455-3p, and miR-566 were 0.82, 0.79, 0.82, and 0.83, respectively. The AUC of these four miRNAs was 0.87 with 83% sensitivity and 87% specificity. The expression peaks of these four miRNAs occurred earlier than those of cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB). Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the targets of these four miRNAs were significantly enriched in several signaling pathways associated with AMI progression. Conclusion: Circulating miR-1291, miR-217, miR-455-3p, and miR-566 expression levels were significantly lower in patients with AMI; and combined, this panel of four miRNAs acted as a novel and potential early diagnostic biomarker of AMI.

Relation of red cell distribution width with HAS-BLED score in patients with non-valvular atrial fibrillation.

BACKGROUND: Numerous researchers have shown that there is a close correlation between red cell distribution width (RDW) and cardiovascular disease such as heart failure, coronary heart disease, and atrial fibrillation. This study was designated to investigate the correlation between RDW and the Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly, Drugs/alcohol (HAS-BLED) score. METHODS: The HAS-BLED scores of 251 hospitalized patients with non-valvular atrial fibrillation were calculated and the receiver operating characteristics were used to evaluate the predictive value of RDW on high HAS-BLED score (≥3 scores). Multiple logistic regression analysis was used to analyze the independent predictor of high HAS-BLED scores. RESULTS: Correlation analysis between RDW and HAS-BLED scores showed the RDW was positively correlated with HAS-BLED score, with r=0.393 (P<0.0001). The RDW of the high HAS-BLED score group was higher than that of the no-high HAS-BLED score group. The area under the receiver operating characteristic curve of RDW was 0.796 (0.740-0.844, P<0.0001) to predict a high HAS-BLED score, and multiple logistic regression analysis showed that a high RDW value could be used as an independent predictor of high HAS-BLED. CONCLUSIONS: RDW value is associated with HAS-BLED value, and can be used as the independent predictive factor of high HAS-BLED scores.

Correlation between serum cartilage oligomeric matrix protein and major adverse cardiovascular events within 30 days in patients with acute coronary syndrome.

BACKGROUND: We studied the correlation between cartilage oligomeric matrix protein (COMP) and major adverse cardiovascular events in patients with acute coronary syndrome (ACS) within 30 days. METHODS: This study included 170 ACS patients who were hospitalized in the Second Affiliated Hospital of Nantong University from August 2017 to April 2019. Serum COMP level was measured at baseline. The enrolled patients were followed up for 30 days and grouped according to the occurrence of major adverse cardiovascular events (MACE) during follow-up. Among the 170 patients, 23 patients had MACE during hospitalization (MACE group), and 147 patients had no MACE (no MACE group). RESULTS: The serum COMP levels in the MACE group were significantly higher than those of the non-MACE group [84.85 (51.55, 141.75) vs. 20.65 (9.11, 46.31) ng/mL, respectively, P<0.05]. The area under the receiver operating characteristic (ROC) curve for COMP in predicting the occurrence of MACE within 30 days was 0.839, with a cutoff level of 39.9 ng/mL [95% confidence interval (CI): 0.774-0.890], 86.96% sensitivity, and 72.79% specificity (P<0.0001). Multivariate logistic regression analysis showed that serum COMP could be used as an independent predictor of MACE within 30 days in ACS patients [odds ratio (OR): 1.024, 95% CI: 1.0133-1.0349, P=0.0001]. CONCLUSIONS: Serum COMP is associated with the short-term prognosis of ACS patients. High serum COMP levels can be used as a predictor of MACE within 30 days in ACS patients.

Diagnosis of coronary artery spasm by ergonovine provocation test of radial artery.

We investigated the sensitivity, specificity and safety of ergonovine provocation test of radial artery in the diagnosis of coronary artery spasm (CAS). The patients who came to our hospital for chest pain from January to June 2020 as well as had coronary stenosis < 50% and no radial artery stenosis, were enrolled in this study. These patients were divided into CAS group and control group after intracoronary ergonovine provocation test. All patients underwent ergonovine provocation test of radial artery, the inner diameter (D0 and D1) and the peak systolic velocities (PSV0 and PSV1) of the radial artery were measured by ultrasound before and after ergonovine provocation. The predictive value of ergonovine provocation test of radial artery for the diagnosis of CAS was analyzed using receiver operator characteristic (ROC) curve. There were 19 patients in the CAS group and 28 patients in the control group. Low density lipoprotein cholesterol and smoking rate were significantly higher in the CAS group than in the control group (all P < 0.05), but there were no significant differences in other items (P > 0.05) between the two groups. In the ergonovine provocation test of radial artery, degree of radial artery stenosis was significantly higher in the CAS group [41.50% (35.60%, 50.00%)] than in the control group [11.25% (5.15%, 23.00%)] (P = 0.000), but there were no siginificant differences in D0, PSV0 and PSV1 between the two groups (P > 0.05). The area under ROC curve of ergonovine (120 µg) provocation test of radial artery for the diagnosis of CAS was 0.912 with 95%CI: 0.792-0.975, P = 0.001, cut-off of 31%, specificity of 92.86% and sensitivity of 84.21%. The ergonovine (120 µg) provocation test of radial artery did not cause any adverse reactions. We concluded that the ergonovine provocation test of radial artery has high sensitivity, specificity and safety in the diagnosis of CAS.