To examine the role of CITED2 in myocardial ischemia/reperfusion injury (MIRI) in a cell model and uncover the mechanism, hypoxia/reoxygenation (H/R) -stimulated H9C2 cell model was utilized as a MIRI cell model. Quantitative polymerase chain reaction (qPCR) as well as immunoblot assays were carried out to determine the expression of CITED2 in the MIRI cell model. MTT as well as lactate dehydrogenase assays were employed to detect the survival of H/R-stimulated H9C2 cells. Immunoblot, flow cytometry, qPCR, and enzyme-linked immunosorbent assay were carried out to assess the pyroptosis and inflammation in H9C2 cells. Immunoblot assays were used to confirm the mechanism. The expression of CITED2 was low in H/R-stimulated H9C2 cells. CITED2 can increase the survival of H/R-stimulated H9C2 cells. Additionally, CITED2 restrained H/R-stimulated pyroptosis of H9C2 cells. It also restrained the release of H/R-induced inflammatory factors. Mechanically, CITED2 inhibited HIF-1α expression, thereby suppressing MIRI progression. CITED2 attenuates MIRI in cardiomyocytes via mediating HIF-1α expression.

Atrial fibrillation (AF) pharmaceutical treatment strategy on when to start rhythm control has been debated for decades. In early studies, these 2 strategies exhibited equivalent efficacy; however, more recent studies based on CHADS-VASc score indicated that early rhythm control (ERC) is more beneficial than UC. We hypothesized that ERC might benefit persons with AF in other cardiovascular outcomes, regardless of the CHADS-VASc score. To elucidate this, we conducted the present study.A retrospective cohort study was conducted using the Yinzhou Regional Health Care Database. We included all patients diagnosed with AF within 1 year and excluded those without age/sex information, without ERC/UC treatment prescription, or with ongoing cancer. The primary outcome was major cardiovascular events (MACE). We used inverse probability of treatment weighting (IPTW) for covariate weighting.A total of 7,161 patients diagnosed with early-stage AF were included in this study. Of them, 2,248 and 4,913 were included in the ERC and UC groups, respectively. During the mean follow-up period of 3.2 years (27,945 person-year), and after IPTW, ERC showed significantly lower risk for MACE (HR: 0.75 [0.61, 0.96], P = 0.02) and heart failure (HF; HR: 0.71 [0.54, 0.95], P = 0.01). No significant results were obtained for stroke, cardiovascular death, or all-cause mortality.ERC is more beneficial to early-stage Persons with AF than UC for MACEs, particularly HF.

Pulmonary hypertension (PH) is a serious prognostic complication in patients with systemic sclerosis (SSc). Deep learning models can be applied to detect PH in the chest X-ray images of these patients. The aim of the study was to investigate the performance and prognostic implications of a deep learning algorithm for the diagnosis of PH in SSc patients using chest X-ray images.Chest X-ray images were acquired from 230 SSc patients with suspected PH who underwent chest X-ray and right heart catheterization (RHC). A convolutional neural network was trained to identify the data of patients with PH (mean pulmonary arterial pressure > 20 mmHg). Kaplan-Meier analysis was used to evaluate survival. The area under the receiver operating characteristic curve (AUC) obtained with the deep learning algorithm was 0.826 while the AUC obtained with cardiologist assessments of the same images was 0.804. The 5-year prognosis was 83.4% in patients with PH detected by RHC, and 85% in those with PH detected by the model.The deep learning model developed in this study can detect PH from the chest X-ray data of SSc patients. The prognostic accuracy of the model was demonstrated as well.

Ivabradine is indicated as a new treatment option for heart rate reduction in patients with reduced ejection fraction heart failure. This study aims to assess the cost-effectiveness of ivabradine on top of standard therapy in patients with chronic heart failure in Japan.A two-state Markov model was used to analyze the cost-effectiveness of ivabradine from a Japanese health-care payer perspective. The Quality-Adjusted Life Year (QALY) was set as an outcome measure. Two study population cohorts were included in this analysis: patients with chronic heart failure with a resting heart rate ≥ 75 beats per min (bpm) and those with a resting heart rate ≥ 70 bpm.The incremental cost-effectiveness ratio for ivabradine with standard therapy compared to standard therapy alone was estimated as JPY 2,460,952 per QALY gained for the ≥ 75 bpm population and JPY 2,556,899 per QALY for the ≥ 70 bpm population. With a willingness-to-pay threshold of JPY 5,000,000 per QALY, ivabradine with standard therapy was 90% more likely to be cost-effective for the ≥ 75 bpm cohort in Japan. These findings were found to be robust in both the sensitivity and scenario analyses.This study suggests that adding ivabradine to standard therapy represents a cost-effective treatment option for chronic heart failure patients with reduced ejection fraction in Japan.

The prognosis in patients with acute myocardial infarction-related cardiogenic shock (AMI-CS) remains unsatisfactory even in the era of Impella, especially among the patients who receive concomitant veno-arterial extracorporeal membrane oxygenation (ECMO) support (i.e., ECPELLA). The prognostic impact of Impella device type in patients with AMI-CS receiving ECPELLA support remains uncertain.Patients with AMI-CS who had received Impella-incorporated temporary mechanical circulatory support between 2020 and 2022 were prospectively registered in the Japanese Registry for Percutaneous Ventricular Assist Device (J-PVAD). The prognostic impact of Impella device type on the 30-day mortality in patients receiving ECPELLA therapy was retrospectively investigated.A total of 996 patients receiving ECPELLA therapy (median 69 years; out-of-hospital cardiac arrest 36.8%; lactate 8.2 mmol/L) were included. The device type of Impella 5.0/5.5 (n = 73) was associated with a lower 30-day mortality with an adjusted hazard ratio of 0.575 (95% confidence interval 0.369-0.895, P = 0.0143) and a lower 30-day cumulative mortality (35.6% versus 56.8%, P = 0.0002) compared with the Impella 2.5/CP (n = 923).Among the patients with AMI-CS receiving ECPELLA support, Impella 5.0/5.5 use was significantly associated with a lower 30-day mortality compared with smaller Impella devices. Implementing an Impella 5.5 or Impella upgrade from CP to 5.5 may improve the short-term prognosis in patients with advanced AMI-CS who are receiving ECPELLA support.

In patients with acute cardiovascular disease, treatment aimed at reducing lactate levels is crucial for improving prognosis. Trends in blood lactate levels for each specific cardiovascular disease can provide an accurate evaluation of the patient's condition. We used functional data analysis with nonlinear mixed effects models to estimate the timeframe of lactate reduction in 3 cardiovascular diseases (acute heart failure, aortic dissection, and ischemic heart disease) by analyzing lactate trends.Among 1,816 patients admitted to the intensive care unit (ICU) or intensive cardiovascular care unit (ICCU) of St. Luke's International Hospital for cardiology or cardiovascular surgery from December 31, 2010, to June 31, 2020, 1,249 adults with a diagnosis of acute heart failure (39%), aortic dissection (24%), or ischemic heart disease (37%) were included in the present study. Using functional data analysis with nonlinear mixed effects models, our study estimated the timeframe of lactate reduction based on blood lactate level trends. Lactate reduction took 30 hours (95% CI, 23-37 hours) in patients with acute heart failure, 40 hours (95% CI, 33-47 hours) in patients with aortic dissection, and 95 hours (95% CI, 49-failed estimate) in patients with ischemic heart disease.We were able to estimate the timeframe of lactate reduction with different cardiovascular diseases. Recognizing the differences in lactate reduction may be useful in developing treatment plans tailored to each disease.

This study aimed to summarize our experience using a systematic approach to reduce blood transfusions in acute type A aortic dissection (ATAAD) surgery.From August 2016 to June 2020, 326 patients underwent ATAAD surgery in our center employing a systematic approach, which primarily included the following: Liu's aortic root repair technique, Liu's aortic arch inclusion technique with a frozen elephant trunk, moderate-to-mild hypothermia circulatory arrest, and application of centrifugal pump in cardiopulmonary bypass circuit. Patients were divided into two groups based on whether they had blood product transfusion during their hospital stay: transfusion group and transfusion-free group. Preoperative, intraoperative, and postoperative outcomes were compared between the 2 groups.In the transfusion group, 152 patients were included, and in the transfusion-free group, 174 patients were involved; the transfusion-free rate was 53.37%. Patients in the transfusion group were significantly older than those in the transfusion-free group, and there were more patients with preoperative anemia and malperfusion in the transfusion group. Overall in-hospital mortality was 5.21% (17/326), with 3 mortalities (1.72%) in the transfusion-free group and 14 mortalities (9.21%) in the transfusion group (P = 0.0025). At tested time points, the Hb levels of patients between the 2 groups were similar.In ATAAD patients, the transfusion group showed significantly older patient age, more incidences of preoperative anemia and malperfusion, and higher in-hospital mortality than the transfusion-free group. Through Liu's systematic approach, ATAAD surgery can be achieved and safely carried out in ATAAD patients without blood product transfusion in selected patients.

Stroke poses a serious risk to human health. The incidence of stroke is increasing year by year. In this study, a rat cerebral ischemiareperfusion (middle cerebral artery occlusion) model was established, and the reliability of this model was determined.The expression changes of key proteins of the BDNF TrkB pathway and synaptic plasticity markers (SYP, PSD-95, and MAP-2) were detected at different time points.The results showed that BDNF expression increased rapidly in the acute phase, and the expression of synaptic plasticity markers decreased, and blocking the BDNF-TrkB pathway with the specific blocker K252a also had a significant effect.This suggests that changes in the BDNF-TrkB signaling pathway can affect the synaptic plasticity in nerve cells of stroke patients.

Sepsis-induced myocardial injury (SIMI) is a vital pathological component of severe sepsis and septic shock. As a prevalent internal mRNA modification in eukaryotic cells, N6-methyladenosine (m6A) modification is implicated in sepsis and immune disorders. Methyltransferase-like 14 (METTL14), a core subunit of the methyltransferase complex that catalyzes messenger RNA m6A modification, is involved in the regulation of human cardiomyocyte cell line (AC16) injury. This study aimed to explore the role and mechanism of METTL14 in lipopolysaccharide (LPS) -induced myocardial injury.Cell viability and apoptosis were analyzed via 3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide (MTT), flow cytometry, and TdT-mediated dUTP nick-end labeling (TUNEL) assay. The Tumor necrosis factor alpha (TNF-α) and Interleukin-1beta (IL-1β) levels were analyzed via Enzyme linked immunosorbent assay (ELISA). Caspase-3 activity, reactive oxygen species activity, malondialdehyde level, and glutathione level were assessed using special assay kits. The levels of transient receptor potential melastatin 7 (TRPM7) and METTL14 mRNA were determined via Real-time quantitative polymerase chain reaction (RT-qPCR). Meanwhile, the protein levels of TRPM7, METTL14, phospho-p65 (p-p65), total p65 (p65), p-IκBα, and total IκBα (IκBα) were examined via western blot assay.LPS treatment repressed AC16 cell viability and induced cell apoptosis, inflammatory response, oxidative stress, and ferroptosis in vitro. METTL14 and TRPM7 were upregulated in LPS-treated AC16 cells. At the molecular level, METTL14 could increase the stability of TRPM7 mRNA via m6A methylation. Moreover, METTL14 deficiency could abolish LPS-triggered AC16 cell injury and ferroptosis via TRPM7 regulation.METTL14 knockdown reversed LPS-caused myocardial cell damage mainly by regulating the stability of TRPM7 mRNA, providing a novel therapeutic target for septic cardiomyopathy treatment.

An error appeared in the article entitled "Evaluation of Myocardial Microcirculation in Rats under a High-Altitude Hypoxic Environment by Computed Tomography Myocardial Perfusion Imaging" by Chunlong Yan, Jinfeng Ma, Dengfeng Tian, Chenhong Zhang, Fengjuan Zhang, Yuchun Zhao, Shihan Fu, Yanqiu Sun, and Qiang Zhang. (Vol. 64, No. 5, 928-934, 2023). Figure 3 on page 931 should be replaced by the following figure.

The study aims to examine the effect of FABP4 on inflammatory response and angiogenesis in the cell model of atherosclerosis and to explore its potential mechanism.Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting, the mRNA and protein levels of FABP4 in human umbilical vein endothelial cells (HUVECs) treated with lipopolysaccharide (LPS) or oxidized low-density lipoprotein for 6, 12, 24, or 48 hours were measured. To silence FABP4 expression and NF-κB signaling in HUVECs, FABP4 inhibitor and NF-κB inhibitor were utilized. To assess cell survival rate and apoptosis, methyl thiazolyl tetrazolium assays and flow cytometry analysis were conducted. Genes related to cholesterol metabolism, including LOX-1, ABCA1, and ABCG1, were subjected to RT-qPCR and western blotting. Moreover, protein levels of apoptotic markers (Bcl-2 and Bax), PPARγ, the phosphorylated levels of NF-κB p65, and angiogenetic markers (ICAM1, VCAM1, and VEGF) were quantified via western blotting. Using an enzyme-linked immunosorbent assay, concentrations of inflammatory cytokines in HUVECs were measured.FABP4 expression was upregulated in LPS-stimulated HUVECs. The silencing of FABP4 lowered LOX-1 and p65 levels while upregulating ABCA1 and ABCG1 expression in the context of LPS. Furthermore, the inhibition of FABP4 or NF-κB signaling promoted the growth of HUVECs, upregulated Bcl-2 and PPARγ protein levels, and reduced Bax levels, angiogenetic markers, and inflammatory cytokines in the context of LPS. The combination of FABP4 inhibitor and NF-κB inhibitor treatment amplified the above-mentioned effects on cell growth, angiogenesis, and inflammation.Inhibition of FABP4 reduces LPS-induced HUVEC cell damage via the inactivation of NF-κB p65 and activation of PPARγ signaling.

Obstructive sleep apnea (OSA) is characterized by repetitive pharyngeal collapses during sleep, which leads to intermittent hypoxia, a risk factor of OSA-related cardiovascular morbidity.In this work, exosome isolation and identification with ultracentrifugation, transmission electron microscopy, nanoparticle tracking analysis, and Western blot assay were carried out. H9C2 cells were subjected to chronic intermittent hypoxia (CIH) treatment, which was followed by bone marrow mesenchymal stem cell (BMSC) -derived exosome treatment. Through reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the expression of miR-744-5p was determined. Using corresponding commercial kits, the levels of oxidative stress indicators and inflammatory factors were measured. The potential target genes of miR-744-5p were predicted using four publicly target-predicting databases. To verify the interaction between miR-744-5p and NFIX, RNA pulldown and luciferase reporter assays were conducted.Significant upregulated expression of miR-744-5p in BMSC-derived exosomes was observed. The exosomes derived from miR-744-5p-overexpressing BMSCs (miR-744-5p mimics/Exo) promoted cell viability and reduced excessive inflammation and oxidative stress. Additionally, the intermolecular interaction between miR-744-5p and NFIX was determined. The exosomes derived from BMSCs cotransfecting with NFIX overexpression plasmid and miR-744-5p mimics reversed the miR-744-5p mimics/Exo-induced inhibitory effects on CIH-caused cardiomyocyte injury.BMSC-derived exosomal miR-744-5p suppressed OSA-induced cardiomyocyte damage by targeting NFIX.

An 18-year-old man experienced refractory cardiogenic shock due to dilated cardiomyopathy of unknown aetiology, and was referred to our hospital to undergo a paracorporeal left ventricular assist device (LVAD) implantation. After surgery, the patient lost consciousness, with subsequent head computed tomography revealing low-density areas in the bilateral basal ganglia. Metabolic acidosis and hyperammonaemia also appeared. Metabolic evaluation and genetic tests led to a diagnosis of propionic acidemia. Following appropriate management of heart failure and propionic acidemia, his neurological and cardiac functions gradually recovered, and the paracorporeal LVAD was successfully explanted. Dilated cardiomyopathy and heart failure are rare manifestations of adult-onset propionic acidemia. This is the first reported case of cardiogenic shock due to propionic acidemia-associated cardiomyopathy successfully treated with a combination of mechanical circulatory support and medical therapy for heart failure and propionic acidemia.

Congenital antithrombin (AT) deficiency is a congenital coagulopathy that predisposes to venous thromboembolism (VTE), although the number of reported patients is limited; thus, large-scale data on the efficacy of direct oral anticoagulants (DOACs) in this population are lacking. There have been case reports of DOAC use in the treatment of VTE in patients with AT deficiency; however, it remains unclear whether rivaroxaban is effective in resolving thrombus and preventing long-term recurrence in pulmonary thromboembolism (PE) associated with massive deep vein thrombosis (DVT). The patient was a 39-year-old man with a family history of thrombosis who presented with lower limb pain and was diagnosed with PE and massive DVT. Continuous treatment with rivaroxaban resulted in a relatively rapid thrombus resolution and no recurrence for 15 months. This case suggests that rivaroxaban may be useful for the treatment and long-term prevention of VTE in patients with AT deficiency with massive thrombosis.

In this study, a retrospective analysis was conducted to investigate the associations between systemic inflammation markers and persistent atrial fibrillation (pAF), intending to identify potential biomarkers for early detection of pAF.In the analysis, a total of 207 patients were included, with 109 in the pAF group and 98 in the non-pAF group. The associations between three systemic inflammation markers were investigated, namely, the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), and pAF.The proportion of pAF showed a gradual increase with increasing logSII, logSIRI, and logAISI tertiles. Compared with those in the lowest tertiles, those in the highest logSII and logSIRI tertiles had 3.196- and 2.884-fold higher risks of developing pAF, respectively. Nonetheless, no significant correlation between logAISI and pAF risk was observed in the highest tertile of logAISI. The restricted cubic spline analysis revealed a nonlinear relationship between the elevation of systemic inflammation markers and the risk of pAF, with logSII ≥ 2.56, logSIRI ≥ -0.10, and logAISI ≥ 2.28 identified as significant predictors. The receiver operating characteristic analysis of logSII, logSIRI, and logAISI showed AUC values of 0.629, 0.721, and 0.646, respectively. It also presented favorable sensitivity and specificity of these systemic inflammation markers in detecting the presence of pAF.To conclude, our cross-sectional study shows significant positive correlations between the SII, SIRI, and AISI with the incidence of pAF.

Aortic arch plaque (AAP) morphology and complexity can serve as markers of atherosclerotic cardiovascular disease. This study investigated 1) the diagnostic value of the thoracic aortic calcification (TAC) score for detecting AAP and large complex AAP and 2) the prognostic significance of TAC in patients with chronic coronary syndrome (CCS). The predictors of AAPs with large (≥ 4 mm in thickness) and complex (ulcerated or protruded) morphologies were evaluated in 412 symptomatic patients with CCS who underwent coronary computed tomography angiography and simultaneous assessment of the aortic arch. Receiver operating curve analysis was performed to determine whether the TAC score can improve the diagnostic value of complex large AAP compared with clinical parameters. Multivariate logistic regression analyses revealed that the TAC score was an independent predictor of complex large AAP (odds ratio, 1.46; P = 0.0074). The area under the curve (AUC) for the base model comprising clinical parameters (age ≥ 70 years + current smoking status + systolic blood pressure) was 0.707 (P = 0.0177). The addition of a TAC score of ≥ 978 Agatston units (AUC, 0.744) significantly improved the AUC (AUC, 0.751, P < 0.001) for patients aged ≥ 70 years (AUC, 0.638). The multivariable Cox hazard model revealed that TAC of ≥ 432.4 (hazard ratio [HR], 4.312; P = 0.01) and large complex AAP are independently associated with the incidence of major adverse cardiovascular events (HR, 3.108; P = 0.011). This study demonstrated that TAC and AAP morphology serve as markers of major adverse cardiovascular events. The combination of advanced age, TAC score, and obstructive CAD exhibited robust diagnostic accuracy in detecting complex large AAP.

Diabetic cardiopathy is a common clinical complication of diabetes and is one of the main causes of mortality in type 2 diabetes mellitus patients. In this study, we examined the effect and mechanism of integrin β1 (ITGB1) on high glucose-induced myocardial cell injury. High glucose exposure inhibits the expression of ITGB1 in myocardial cells. ITGB1 inhibited the apoptosis and growth inhibition induced by high glucose. Additionally, the high glucose-induced expression of HSPA5, IRE1α, XBP1, CHOP, ATF6, and cleaved-caspase12 was downregulated significantly when ITGB1 was overexpressed in the presence of high glucose, showing that ITGB1 alleviated endoplasmic reticulum (ER) stress triggered by high glucose. Mechanistically, ITGB1 activated the FAK/ERK singling pathway in high glucose-treated myocardial cells. In the rescue experiment conducted using a signaling pathway inhibitor, overexpression of ITGB1 could not alleviate the effect of high glucose on cell activity and apoptosis in the presence of an inhibitor. In conclusion, ITGB1 alleviates high glucose-induced myocardial cell injury by activating the FAK/ERK singling pathway in myocardial cells. This research contributed to the understanding of the pathogenesis of diabetic cardiopathy and the development of novel drugs and therapeutic targets for it.

In this study, the expression and clinical value of miR-191-5p in sepsis and sepsis-induced left ventricular systolic dysfunction are explored, and the effects of miR-191-5p on inflammation and cardiac function in rats are examined by establishing a septic rat model.The expression level of serum miR-191-5p was detected via reverse transcription quantitative polymerase chain reaction. To evaluate the diagnostic efficacy of miR-191-5p in sepsis, the receiver operator characteristic curve was established. To evaluate the relationship between the expression level of miR-191-5p and the clinical biochemical indicators, Pearson analysis was employed. Multivariate logistic regression was utilized to analyze the risk factors of cardiac dysfunction. The rat model was reproduced via cecal ligation and puncture. FDP-1 HRV-BRS analysis system was utilized to detect the cardiac function. To determine the myocardial enzymes and cytokines, blood samples from rats were collected.Compared with healthy individuals. the expression of miR-191-5p in the serum of sepsis patients was lower, and the miR-191-5p level in the serum of patients with cardiac dysfunction was lower than in that of those with normal cardiac function. MiR-191-5p demonstrated good accuracy in distinguishing cardiac dysfunction from normal cardiac function. Decreased levels of miR-191-5p are a risk factor for developing normal cardiac function in sepsis into cardiac dysfunction. In septic rats, upregulating the miR-191-5p expression by injecting miR-191-5p agomir can significantly enhance cardiac function and inhibit the inflammatory response.MiR-191-5p has shown clinical value in distinguishing patients with sepsis associated with left ventricular systolic dysfunction and has the potential as a diagnostic marker for sepsis.

Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity worldwide. Thus, a simple and practical method to identify it is urgently needed. This study aims to explore the correlation between the Reynolds and Framingham risk scores and the Gensini score (GS), along with their utility in predicting the presence and severity of CAD.This research represents a single-center retrospective study. A total of 13,824 Chinese patients were enrolled in our study. GS was used to assess and group the presence and severity of CAD. The Spearman rank test and the logistic regression analysis were then performed to explore the correlation between the Reynolds/Framingham risk scores and the GS. The receiver-operating characteristic curve analysis was used to evaluate the performance of the Reynolds and Framingham risk stratification models.Both the Reynolds and Framingham risk scores showed statistically significant positive correlations with the presence (r (Reynolds): 0.179; r (Framingham): 0.182) and severity (r (Reynolds): 0.232; r (Framingham): 0.259) of CAD. Both scores had statistically significant powers of predicting the presence (cut-off value [Reynolds]: 4.20%; cut-off value [Framingham]: 12.33%) and severity (cut-off value [Reynolds]: 8.94%; cut-off value [Framingham]: 20.59%) of CAD. The Reynolds risk score showed a better performance compared to the Framingham risk score for both the presence (Reynolds area under the curve (AUC): 0.649 versus Framingham AUC: 0.637 P < 0.05) and severity (Reynolds AUC: 0.656 versus Framingham AUC: 0.645 P < 0.05) of CAD.Our study suggests that the Reynolds and Framingham risk scores can be used to predict the presence and severity of CAD in the Chinese population. The Reynolds risk score showed great superiority in the women's group, while the Framingham risk score had a better performance in predicting severity as a whole.