A risk predictive model for determining the severity of coronary artery lesions in older postmenopausal women with coronary heart disease.

OBJECTIVE: To determine the risk factors affecting the severity of coronary artery disease (CAD) in older postmenopausal women with coronary heart disease (CHD) and to construct a personalized risk predictive model. METHODS: In this cohort study, clinical records of 527 female patients aged ≥60 with CHD who were hospitalized in the First Affiliated Hospital of the University of Science and Technology of China from March 2018 to February 2019 were analyzed retrospectively. The severity of CAD was determined using the Gensini scores that are based on coronary angiography findings. Patients with Gensini scores ≥40 and <40 were divided into high-risk (n=277) and non-high-risk groups (n=250), respectively. Logistic regression analysis was used to assess independent predictors of CAD severity. The nomogram prediction model of CAD severity was plotted by the R software. The area under the receiver operating characteristic (ROC) and calibration curves were used to evaluate the predictive efficiency of the nomogram model, and the decision curve analysis (DCA) was used to assess the clinical applicability of the nomogram model. RESULTS: Multivariate analysis showed that high-sensitivity C-reactive protein, RBC count, WBC count, BMI, and diabetes mellitus were independent risk factors associated with CAD severity in older menopausal women (P<0.05); the area under the ROC curve of the nomogram constructed based on the independent risk factors was 0.846 (95% CI: 0.756-0.937). The area under the ROC curve after internal validation of the nomogram by the Bootstrap method after resampling 1000 times was 0.840 (95% CI: 0.741-0.923). The calibration curve suggested that the nomogram had an excellent predictive agreement, and the DCA curve indicated that the net benefit of applying the nomogram was significantly higher than that of the "no intervention" and "all intervention" methods when the risk probability of patients with high-risk CAD severity was 0.30-0.81. CONCLUSION: A personalized risk assessment model was constructed based on the risk factors of severe CAD in older menopausal women with CHD, which had good prediction efficiency based on discrimination, calibration, and clinical applicability evaluation indicators. This model could assist cardiology medical staff in screening older menopausal women with CHD who are at a high risk of severe CAD to implement targeted interventions.

The burden and management competency of cardiomyopathies in China: a nationwide survey study.

Background: The public health burden of cardiomyopathies and competency in their management by health agencies in China are not well understood. Methods: This study adopted a multi-stage sampling method for hospital selection. In the first stage, nationwide tertiary hospital recruitment was performed. As a result, 88 hospitals with the consent of the director of cardiology and access to an established electronic medical records system, were recruited. In the second stage, we sampled 66 hospitals within each geographic-economic stratification through a random sampling process. Data on (1) the outpatient and inpatient visits for cardiomyopathies between 2017 and 2021 and (2) the competency in the management of patients with cardiomyopathies, were collected. The competency of a hospital to provide cardiomyopathy care was evaluated using a specifically devised scale. Findings: The outpatient and inpatient visits for cardiomyopathies increased between 2017 and 2021 by 38.6% and 33.0%, respectively. Most hospitals had basic facilities for cardiomyopathy assessment. However, access to more complex procedures was limited, and the integrated management pathway needs improvement. Only 4 (6.1%) of the 66 participating hospitals met the criteria for being designated as a comprehensive cardiomyopathy center, and only 29 (43.9%) could be classified as a primary cardiomyopathy center. There were significant variations in competency between hospitals with different administrative and economic levels. Interpretation: The health burden of cardiomyopathies has increased significantly between 2017 and 2021 in China. Although most tertiary hospitals in China can offer basic cardiomyopathy care, more advanced facilities are not yet universally available. Moreover, inconsistencies in the management of cardiomyopathies across hospitals due to differing administrative and economic levels warrants a review of the nation allocation of medical resources. Funding: This work was supported by the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (2023-I2M-1-001) and the National High Level Hospital Clinical Research Funding (2022-GSP-GG-17).

Factors associated with the delay in informed consent procedures of patients with ST-segment elevation myocardial infarction and its influence on door-to-balloon time: a nationwide retrospective cohort study.

Background and Objectives: ST-segment elevation myocardial infarction (STEMI) is the deadliest and most time-sensitive acute cardiac event. However, failure to achieve timely informed consent is an important contributor to in-hospital delay in STEMI care in China. We investigated the factors associated with informed consent delay in patients with STEMI undergoing percutaneous coronary intervention (PCI) and the association between the delay and door-to-balloon time. Methods: We conducted a nationally representative retrospective cohort study using patient data reported by hospital-based chest pain centers from 1 January 2016 to 31 December 2020. We applied generalized linear mixed models and negative binomial regression to estimate factors independently predicting informed consent delay time. Logistic regressions were fitted to investigate the association of the informed consent delay time and door-to-balloon time, adjusting for patient characteristics. Results: In total, 257, 510 patients were enrolled in the analysis. Mean informed consent delay time was 22.4 min (SD = 24.0), accounting for 39.3% in door-to-balloon time. Older age (≥65 years) was significantly correlated with informed consent delay time (RR: 1.034, P = 0.001). Compared with ethnic Han patients, the minority (RR: 1.146, P < 0.001) had more likelihood to extend consent giving; compared with patients who were single, longer informed consent time was found in married patients (RR: 1.054, P = 0.006). Patients with intermittent chest pain (RR: 1.034, P = 0.011), and chest pain relief (RR: 1.085, P = 0.005) were more likely to delay informed consent. As for transfer modes, EMS (RR: 1.063, P < 0.001), transfer-in (RR: 1.820, P < 0.001), and in-hospital onset (RR: 1.099, P = 0.002) all had positive correlations with informed consent delay time compared to walk-in. Informed consent delay was significantly associated with prolonged door-to-balloon time (OR: 1.002, P < 0.001). Conclusion: Informed consent delay is significantly associated with the door-to-balloon time which plays a crucial role in achieving better outcomes for patients with STEMI. It is essential to shorten the delay time by identifying and intervening modifiable factors that are associated with shortening the informed consent procedure in China and other countries.

Chinese Society of Cardiology guidelines on the diagnosis and treatment of adult fulminant myocarditis.

Fulminant myocarditis is an acute diffuse inflammatory disease of myocardium. It is characterized by acute onset, rapid progress and high risk of death. Its pathogenesis involves excessive immune activation of the innate immune system and formation of inflammatory storm. According to China's practical experience, the adoption of the "life support-based comprehensive treatment regimen" (with mechanical circulation support and immunomodulation therapy as the core) can significantly improve the survival rate and long-term prognosis. Special emphasis is placed on very early identification,very early diagnosis,very early prediction and very early treatment.

Single-cell RNA sequencing reveals S100a9hi macrophages promote the transition from acute inflammation to fibrotic remodeling after myocardial ischemia‒reperfusion.

Rationale: The transition from acute inflammation to fibrosis following myocardial ischemia‒reperfusion (MIR) significantly affects prognosis. Macrophages play a pivotal role in inflammatory damage and repair after MIR. However, the heterogeneity and transformation mechanisms of macrophages during this transition are not well understood. Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) and mass cytometry to examine murine monocyte-derived macrophages after MIR to investigate macrophage subtypes and their roles in the MIR process. S100a9-/- mice were used to establish MIR model to clarify the mechanism of alleviating inflammation and fibrosis after MIR. Reinfusion of bone marrow-derived macrophages (BMDMs) after macrophage depletion (MD) in mice subjected to MIR were performed to further examine the role of S100a9hi macrophages in MIR. Results: We identified a unique subtype of S100a9hi macrophages that originate from monocytes and are involved in acute inflammation and fibrosis. These S100a9hi macrophages infiltrate the heart as early as 2 h post-reperfusion and activate the Myd88/NFκB/NLRP3 signaling pathway, amplifying inflammatory responses. As the tissue environment shifts from proinflammatory to reparative, S100a9 activates transforming growth factor-ß (Tgf-ß)/p-smad3 signaling. This activation not only induces the transformation of myocardial fibroblasts to myofibroblasts but also promotes fibrosis via the macrophage-to-myofibroblast transition (MMT). Targeting S100a9 with a specific inhibitor could effectively mitigate acute inflammatory damage and halt the progression of fibrosis, including MMT. Conclusion: S100a9hi macrophages are a promising therapeutic target for managing the transition from inflammation to fibrosis after MIR.

Exosome-derived lncRNA A1BG-AS1 attenuates the progression of prostate cancer depending on ZC3H13-mediated m6A modification.

BACKGROUND: Exosome-derived long non-coding RNAs (lncRNAs) and N6-methyladenosine (m6A) modifications of lncRNAs have been shown crucial functions in prostate cancer (PCa). Herein, we aim to investigate the detailed mechanism of exosome-derived lncRNA A1BG-AS1 in PCa process. METHODS: PCa cell exosomes were extracted, exosomal marker proteins (CD63, CD9) were detected utilizing western blotting, and exosomes with overexpressing A1BG-AS1 were co-cultured with targeted PCa cells. qRT-PCR was used to detect A1BG-AS1 expression and m6A methyltransferase ZC3H13 in PCa. Transwell, colony formation and CCK-8 assays were utilized to assess the invasion, migration, and proliferation ability of PCa cells. Then, we performed actinomycin D and MeRIP assays to analyze the regulatory effect of ZC3H13 on A1BG-AS1 mRNA stability and m6A modification level. RESULTS: We observed that A1BG-AS1 and ZC3H13 expression was restricted in PCa tumors. The invasion, proliferation and migratory capacities of PCa cells could be inhibited by up-regulating A1BG-AS1 or by co-culturing with exosomes that up-regulate A1BG-AS1. Additionally, ZC3H13 promoted stable A1BG-AS1 expression by regulating the m6A level of A1BG-AS1. CONCLUSION: Exosomal A1BG-AS1 was m6A-modified by the m6A methyltransferase ZC3H13 to stabilize expression and thus prevent PCa cell malignancy. These findings offer a possible target for clinical therapy of PCa.

Macrophages promote the transition from myocardial ischemia reperfusion injury to cardiac fibrosis in mice through GMCSF/CCL2/CCR2 and phenotype switching.

Following acute myocardial ischemia reperfusion (MIR), macrophages infiltrate damaged cardiac tissue and alter their polarization phenotype to respond to acute inflammation and chronic fibrotic remodeling. In this study we investigated the role of macrophages in post-ischemic myocardial fibrosis and explored therapeutic targets for myocardial fibrosis. Male mice were subjected to ligation of the left coronary artery for 30 min. We first detected the levels of chemokines in heart tissue that recruited immune cells infiltrating into the heart, and found that granulocyte-macrophage colony-stimulating factor (GMCSF) released by mouse cardiac microvascular endothelial cells (MCMECs) peaked at 6 h after reperfusion, and c-c motif chemokine ligand 2 (CCL2) released by GMCSF-induced macrophages peaked at 24 h after reperfusion. In co-culture of BMDMs with MCMECs, we demonstrated that GMCSF derived from MCMECs stimulated the release of CCL2 by BMDMs and effectively promoted the migration of BMDMs. We also confirmed that GMCSF promoted M1 polarization of macrophages in vitro, while GMCSF neutralizing antibodies (NTABs) blocked CCL2/CCR2 signaling. In MIR mouse heart, we showed that GMCSF activated CCL2/CCR2 signaling to promote NLRP3/caspase-1/IL-1ß-mediated and amplified inflammatory damage. Knockdown of CC chemokine receptor 2 gene (CCR2-/-), or administration of specific CCR2 inhibitor RS102895 (5 mg/kg per 12 h, i.p., one day before MIR and continuously until the end of the experiment) effectively reduced the area of myocardial infarction, and down-regulated inflammatory mediators and NLRP3/Caspase-1/IL-1ß signaling. Mass cytometry confirmed that M2 macrophages played an important role during fibrosis, while macrophage-depleted mice exhibited significantly reduced transforming growth factor-ß (Tgf-ß) levels in heart tissue after MIR. In co-culture of macrophages with fibroblasts, treatment with recombinant mouse CCL2 stimulated macrophages to release a large amount of Tgf-ß, and promoted the release of Col1α1 by fibroblasts. This effect was diminished in BMDMs from CCR2-/- mice. After knocking out or inhibiting CCR2-gene, the levels of Tgf-ß were significantly reduced, as was the level of myocardial fibrosis, and cardiac function was protected. This study confirms that the acute injury to chronic fibrosis transition after MIR in mice is mediated by GMCSF/CCL2/CCR2 signaling in macrophages through NLRP3 inflammatory cascade and the phenotype switching.

Triglyceride-glucose body mass index predicts prognosis in patients with ST-elevation myocardial infarction.

Triglyceride glycemic-body mass index (TyG-BMI) is a simple and reliable surrogate for insulin resistance (IR). However, it is still unclear if TyG-BMI has any predictive value in patients having percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). The purpose of this study was to examine the TyG-BMI index's prognostic significance and predictive power in patients with STEMI. The study comprised a total of 2648 consecutive STEMI patients who underwent PCI. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE), defined as the combination of all-cause death, nonfatal myocardial infarction, nonfatal stroke, and coronary revascularization. The TyG-BMI index was formulated as ln [fasting triglycerides (mg/dL) × fasting plasma glucose (mg/dL)/2] × BMI. 193 patients in all experienced MACE over a median follow-up of 14.7 months. There was a statistically significant difference between the Kaplan-Meier survival curves for the TyG-BMI index tertiles (log-rank test, p = 0.019) for the cumulative incidence of MACE. The adjusted HRs for the incidence of MACE in the middle and highest quartiles of the TyG-BMI index compared with the lowest quartile were 1.37 (95% CI 0.92, 2.03) and 1.53 (95% CI 1.02, 2.29), respectively, in the fully adjusted Cox regression model. At six months, one year, and three years, the TyG-BMI area under the curve (AUC) for predicting MACE was 0.691, 0.666, and 0.637, respectively. Additionally, adding the TyG-BMI index to the risk prediction model enhanced outcome prediction. In STEMI patients undergoing PCI, TyG-BMI was independently linked to MACE. TyG-BMI could be a simple and solid way to assess MACE risk and prognosis.

The Incidence of Complication in the Perioperative Period of Rotational Atherectomy in Patients With Acute Coronary Syndrome: A Retrospective Study of Low Speed Versus High Speed.

The safety and efficacy of rotational atherectomy (RA) in patients with acute coronary syndrome (ACS) treated with different rotational speeds remain unclear. This was an observational retrospective registry study. Between February 2017 and January 2022, a total of 283 patients with ACS were treated with RA. The patients were divided into 2 groups: the low-speed group (130,000 to 150,000 rotations/min [rpm],182 cases) and the high-speed group (160,000 to 220,000 rpm, 101 cases) according to the maximum RA speed. The outcomes analyzed were procedural complications; incidence of heart failure, stent thrombosis, and cardiac death during hospitalization; and 30-day major cardiovascular and cerebrovascular events. Patients in the low-speed RA group had a higher incidence of vasospasm during RA (15.4% vs 6.9%, p = 0.040), whereas the incidence of slow blood flow was higher in the high-speed RA group (16.5% vs 27.7%, p = 0.031). There was no significant difference in other complications or in 30-day major cardiovascular and cerebrovascular events between the 2 groups. Moreover, logistic regression analysis identified rotational speed (160,000 to 220,000 rpm) as a predictor of slow flow during RA (odds ratio 1.900, 95% confidence interval 1.006 to 3.588, p = 0.048). For every 10,000-rpm increase in rotational speed, the risk of slow flow increased by 27% (odds ratio 1.273, 95% confidence interval 1.047 to 1.547, p = 0.015). In conclusion, patients with ACS treated with a lower RA speed (130,000 to 150,000 rpm) had a higher risk of vasospasm, whereas those treated with higher speeds (160,000 to 220,000 rpm) had a higher incidence of slow flow. High rotational speed (160,000 to 220,000 rpm) is an independent risk factor for slow flow during RA in patients with ACS.

Identification of circulating T-cell immunoglobulin and mucin domain 4 as a potential biomarker for coronary heart disease.

Efferocytosis, the process of engulfing and removing apoptotic cells, is attenuated in vulnerable plaques of advanced atherosclerosis. T-cell immunoglobulin and mucin domain 4 (TIMD4) is a recognition receptor protein for efferocytosis that has been implicated in atherosclerosis mouse models. However, the role of serum-soluble TIMD4 (sTIMD4) in coronary heart disease (CHD) remains unknown. In this study, we analyzed serum samples collected from two groups: Group 1 (36 healthy controls and 70 CHD patients) and Group 2 (44 chronic coronary syndrome [CCS]) and 81 acute coronary syndrome [ACS] patients). We found that sTIMD4 levels in patients with CHD were significantly higher than those in healthy controls and were also higher in ACS than in CCS patients. The area under the receiver operating characteristic curve was 0.787. Furthermore, our in vitro results showed that low-density lipoprotein/lipopolysaccharide activated p38 mitogen-activated protein kinase, which in turn enhanced a disintegrin and metalloproteinase 17, resulting in increased secretion of sTIMD4. This impairment of macrophage efferocytosis promoted inflammation. Thus, this study is not only the first identification of a potential novel biomarker of CHD, sTIMD4, but also demonstrated its pathogenesis mechanism, providing a new direction for the diagnosis and treatment of CHD.

The contribution of genotype-guided selection of P2Y12 inhibitor on prognosis in ACS /CCS patients undergoing percutaneous coronary intervention: a retrospective cohort study.

PURPOSE: We aimed to explore the contribution of genotype-guided selection of P2Y12 inhibitors on prognosis in Chinese patients with acute coronary syndromes (ACS) or chronic coronary syndromes (CCS) undergoing percutaneous coronary intervention (PCI). METHODS: Totally, 2063 patients were included. They were divided into empiric treatment group (n = 1025) and individualized treatment group (n = 1038) depending on whether taken CYP2C19 genetic testing. The incidences of clinical endpoint events were compared in two groups at 1-year follow-up. The effective endpoint events were major adverse cardiovascular events (MACEs), including all-cause mortality, in-stent restenosis, nonfatal myocardial infarction, nonfatal stroke and severe recurrent ischemia. Meanwhile, the safe endpoint was bleeding events defined by the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: Finally, 66.83% patients were diagnosed with ACS and 33.17% patients were diagnosed with CCS in empiric group. 68.11% patients were diagnosed with ACS and 31.89% patients were diagnosed with CCS in individualized group. At 1-year follow-up, individualized group showed lower MACEs rate than empiric group (19.61% vs. 10.69%, HR: 1.915; 95% CI: 1.534 to 2.392; P < 0.0001, log-rank test; adjusted HR: 1.983; 95% CI: 1.573 to 2.501; P = 0.000, cox proportional hazards regression models), while bleeding events were significantly less common in empiric group than in individualized group (7.32% vs. 10.40%, HR: 0.693; 95% CI: 0.519 to 0.926; P = 0.0132, log-rank test; adjusted HR: 0.695; 95% CI: 0.518 to 0.933; P = 0.016, cox proportional hazards regression models). It was mainly manifested in BARC class 1 bleeding, which did not warrant the interruption of antiplatelet therapy (ITA). Further, subgroup analyses illustrated that no significant difference existed in cumulative MACEs-free survival rate between all treatment arms of individualized group (P = 0.6579 by log-rank test), and CYP2C19 intermediate metabolizer (IM) genetype appeared to be significantly associated with bleeding events for patients treated with ticagrelor (clopidogrel vs. ticagrelor: 6.80% vs. 14.88%; adjusted HR:0.440; 95% CI: 0.246 to 0.787; adjusted P = 0.006). CONCLUSIONS: Genotype-guided selection of P2Y12 inhibitor made a very positive contribution on the prognosis in Chinese ACS/CCS patients undergoing PCI. Instead of intensifying antiplatelet strategies, conventional-dose clopidogrel could be recommended as P2Y12 inhibitor after weighing MACEs and bleeding events in CYP2C19 IM patients.

T1 Mapping for Identifying the Substrate in Patients With Apparently Idiopathic Premature Ventricular Complexes.

BACKGROUND: Myocardial fibrosis is implicated as a potential substrate responsible for arrhythmias. OBJECTIVES: This study aimed to investigate myocardial fibrosis assessed by T1 mapping in patients with apparently idiopathic premature ventricular complexes (PVCs), and to determine the relationship between this tissue biomarker and PVC features. METHODS: Patients with frequent PVC (>1,000/24 h) who underwent cardiac magnetic resonance imaging (MRI) between 2020 and 2021 were retrospectively evaluated. Patients were included if they had no indicator of known heart diseases on MRI. Sex- and age-matched healthy subjects underwent noncontrast MRI with native T1 mapping. High PVC burden was defined as the percentage of PVC >20%/24 h. RESULTS: A total of 70 patients and 70 healthy controls were included. Global T1 value was significantly higher in patients than in controls (P < 0.001). Extracellular volume was 26.03% ± 2.16% in the patients. Moreover, global T1 value showed a stepwise increase in PVC tertiles (P = 0.03) but not for extracellular volume (P = 0.85). Patients with a non-left bundle branch block (LBBB) inferior axis morphology showed higher global native T1 values than LBBB inferior axis pattern (P = 0.005). In addition, global T1 values correlated significantly with PVC burden (r = 0.28, P = 0.02). In the multivariate analysis, global T1 value independently correlated with high PVC burden (odds ratio: 1.22 per 10-ms increase, P = 0.02). CONCLUSIONS: Increased global T1, a marker of interstitial fibrosis, was detected in patients with apparently idiopathic PVC and was significantly associated with non-LBBB inferior axis morphology and high PVC burden.

Inter-Domain Repulsion of Dumbbell-Shaped Calmodulin during Electrospray Ionization Revealed by Molecular Dynamics Simulations.

The mechanisms whereby protein ions are released from nanodroplets at the liquid-gas interface have continued to be controversial since electrospray ionization (ESI) mass spectrometry was widely applied in biomolecular structure analysis in solution. Several viable pathways have been proposed and verified for single-domain proteins. However, the ESI mechanism of multi-domain proteins with more complicated and flexible structures remains unclear. Herein, dumbbell-shaped calmodulin was chosen as a multi-domain protein model to perform molecular dynamics simulations to investigate the structural evolution during the ESI process. For [Ca4CAM], the protein followed the classical charge residue model. As the inter-domain electrostatic repulsion increased, the droplet was found to split into two sub-droplets, while stronger-repulsive apo-calmodulin unfolded during the early evaporation stage. We designated this novel ESI mechanism as the domain repulsion model, which provides new mechanistic insights into further exploration of proteins containing more domains. Our results suggest that greater attention should be paid to the effect of domain-domain interactions on structure retention during liquid-gas interface transfer when mass spectrometry is used as the developing technique in gas phase structural biology.

Prediction of adverse outcomes in nonischemic dilated cardiomyopathy: A CMR-based nomogram.

OBJECTIVES: To develop and validate a novel nomogram score to predict outcomes in patients with nonischemic dilated cardiomyopathy (NIDCM) over a long follow-up period. METHODS: A total of 335 consecutive NIDCM patients who underwent cardiac magnetic resonance (CMR) imaging were retrospectively enrolled. Comprehensive clinical evaluation and imaging investigation were obtained, including measurements of late gadolinium enhancement (LGE) and feature tracking (FT) images. All patients were followed up for a composite endpoint of major adverse cardiac events (MACE) including all-cause mortality and heart transplantation. These patients were randomly divided into development and validation cohorts (7:3). RESULTS: MACE occurred in 87 (37.2%) out of 234 patients in the development cohort, and in 31 (30.7%) out of 101 patients in the validation cohort. Five variables including NYHA class III-IV, NT-proBNP, beta-blocker medication, LGE presence, and LV global longitudinal strain (GLS) were found to be significantly associated with MACE and were used for constructing the nomogram. The nomogram achieved good discrimination with C-indexes in development and validation cohorts respectively. The calibration curve for 1-, 3-, and 5-year survival probability also showed high coherence between the predicted and actual probability of MACE. Decision curve analysis identified the model was significantly better net benefit in predicting MACE. CONCLUSION: A novel nomogram score of a predictive model that incorporates clinical factors and imaging features was constructed, which could be conveniently used to facilitate risk evaluation in patients with NIDCM.

Zero-Dimensional Ignition Model of Boron Agglomerates.

Boron primarily exists in the form of agglomerates in ramjet combustion chambers. However, the model used to predict the ignition time of boron agglomerates is usually based on the single-particle assumption, resulting in inaccurate predictions. This study aims to develop a numerical model that can accurately describe the ignition of boron agglomerates. The model is based on the ignition model of a single particle boron proposed by the group of Kuo. Thiele modulus and effectiveness factor are introduced to represent the diffusion resistance of reaction gases in the pores of boron agglomerates. The model includes the necessary physical processes to accurately predict the ignition time. The rates of evaporation and heterogeneous reactions involved in the oxide layer removal process are corrected based on the fact that the diffusion rate of (BO)n in the liquid oxide layer equals to its consumption rate at the oxide-air interface. To evaluate the accuracy of the model, the obtained results for ignition time are compared with experimental data, showing reasonable consistency between them. The model is then applied to investigate the ignition characteristics of boron agglomerates. Parameters, such as initial average pore diameter, oxide layer thicknesses, initial particle diameter, O2 concentration, H2O concentration, and environmental pressure, are studied for their effects on the ignition time. In summary, the boron ignition model established in this study is a powerful tool to investigate the ignition mechanisms and characteristics of boron agglomerates. It can be further coupled with flow analysis for the detailed simulation of turbulent combustion in ramjet combustors.

Impact of Bivalirudin on Patients with Acute Coronary Syndrome Undergoing Rotational Atherectomy in Real-Life Setting: A Retrospective Cohort Study.

BACKGROUND: No evidence exists on the impact of bivalirudin in patients with the acute coronary syndrome undergoing rotational atherectomy. This study aimed to evaluate the impact of bivalirudin on patients with acute coronary syndrome undergoing rotational atherectomy. METHODS: This was a retrospective cohort study conducted in our hospital between January 2017 and December 2019. The study included patients with acute coronary syndrome undergoing rotational atherectomy. Furthermore, 2 cohorts were included in this study (bivalirudin cohort and control cohort unfractionated heparin). The primary end-point was in-hospital net adverse clinical events. The secondary endpoint was all-cause mortality at 23 months. RESULTS: The study included 157 patients with 33 (21.0%) in the bivalirudin cohort and 124 (79.0%) in the control cohort. Net adverse clinical events during hospitalization in the bivalirudin cohort were higher than that in the control cohort [9 (27.3%) vs. 14 (11.3%), P = .021]. However, there was no significant difference in all-cause mortality at 23 months between the 2 cohorts [25 (20.2%) vs. 10 (30.3%), P =.214]. After adjusting for potential confounders, the usage of bivalirudin was not associated with net adverse clinical event (odds ratio = 0.90; 95% CI: 0.18-4.45; P =.890), and the hazard ratio for all-cause mortality at 23 months was 1.01 (95% CI: 0.33-3.15; P =.983). CONCLUSION: Bivalirudin appears to exhibit a similar impact as unfractionated heparin on patients with acute coronary syndrome undergoing rotational atherectomy in real-life setting.

Pharmacological Inhibition of P-Rex1/Rac1 Axis Blocked Angiotensin II-Induced Cardiac Fibrosis.

PURPOSE: Phosphatidylinositol-3,4,5-trisphosphate-dependent Rac exchange factor-1 (P-Rex1), as one of the members of Rac-GEFs, has been proven to play a critical role in cancer progression and metastasis. Nonetheless, its role in cardiac fibrosis remains elusive. In the present study, we aimed to investigate whether and how the P-Rex1 mediates AngII-induced cardiac fibrosis. METHOD: A cardiac fibrosis mouse model was established by chronic AngII perfusion. The heart structure, function, pathological changes of myocardial tissues, oxidative stress, and cardiac fibrotic protein expression were determined in an AngII induced mouse model. To provide a molecular mechanism for P-Rex1 involvement in cardiac fibrosis, a specific inhibitor or siRNA was used to block P-Rex1, and target the relationship between Rac1-GTPase and its downstream effector. RESULTS: Blocking P-Rex1 showed down-regulation of its downstream effectors such as the profibrotic transcriptional regulator Paks, ERK1/2, and ROS generation. Intervention treatment with P-Rex1 inhibitor 1A-116 ameliorated AngII-induced abnormalities in heart structure and function. Moreover, pharmacological inhibition of the P-Rex1/Rac1 axis showed a protective effect in AngII-induced cardiac fibrosis through the down-regulation of collagen1, CTGF, and α-SMA expression. CONCLUSION: Our findings demonstrated for the first time that P-Rex1 was an essential signaling mediator in CFs activation and subsequent cardiac fibrosis, and 1A-116 could be a potential pharmacological development drug.

Overexpression of NgBR inhibits high-fat diet-induced atherosclerosis in ApoE-deficiency mice.

BACKGROUND: Hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia) is a risk factor for atherosclerosis. Nogo-B receptor (NgBR) plays important roles in hepatic steatosis and cholesterol transport. However, the effect of NgBR overexpression on atherosclerosis remains unknown. MATERIALS AND METHODS: Apolipoprotein E deficient (ApoE-/-) mice infected with adeno-associated virus (AAV)-NgBR expression vector were fed a high-fat diet for 12 weeks, followed by determination of atherosclerosis and the involved mechanisms. RESULTS: We determined that high expression of NgBR by AAV injection mainly occurs in the liver and it can substantially inhibit en face and aortic root sinus lesions. NgBR overexpression also reduced levels of inflammatory factors in the aortic root and serum, and levels of cholesterol, triglyceride, and free fatty acids in the liver and serum. Mechanistically, NgBR overexpression increased the expression of scavenger receptor type BI and the genes for bile acid synthesis, and decreased the expression of cholesterol synthesis genes by reducing sterol regulatory element-binding protein 2 maturation in the liver, thereby reducing hypercholesterolemia. In addition, NgBR overexpression activated AMP-activated protein kinase α via the Ca2+ signaling pathway, which inhibited fat synthesis and improved hypertriglyceridemia. CONCLUSIONS: Taken together, our study demonstrates that overexpression of NgBR enhanced cholesterol metabolism and inhibited cholesterol/fatty acid synthesis to reduce hyperlipidemia, and reduced vascular inflammation, thereby inhibiting atherosclerosis in ApoE-/- mice. Our study indicates that NgBR might be a potential target for atherosclerosis treatment.

Metabolite profiling and identification in living cells by coupling stable isotope tracing and induced electrospray mass spectrometry.

Direct observation of metabolites in living cells by mass spectrometry offers a bright future for biological studies but also suffers a severe challenge to untargeted peak assignment to tentative metabolite candidates. In this study, we developed a method combining stable isotope tracing and induced electrospray mass spectrometry for living-cells metabolite measurement and identification. By using 13C6-glucose and ammonium chloride-15N as the sole carbon and nitrogen sources for cell culture, Escherichia coli synthesized metabolites with 15N and 13C elements. Tracing the number of carbon and nitrogen atoms could offer a complementary dimension for candidate peak searching. As a result, the identification confidence of metabolites achieved a universal improvement based on carbon/nitrogen labelling and filtration.

Silk fibroin/chitosan coating with tunable catalytic nitric oxide generation for surface functionalization of cardiovascular stents.

Developing a functional coating for vascular stents with sustainable and tunable NO release remains challenging. In this work, we report a silk fibroin/chitosan-based biopolymer coating incorporating copper ions as a catalyst for NO generation and demonstrate its potential for the surface functionalization of cardiovascular stents. Based on the differences in silk fibroin and chitosan coordinating with copper ions, the loading, bonding, and release of copper ions could be precisely regulated over a wide range by controlling the ratio of silk fibroin and chitosan. This system shows good cytocompatibility for endothelial cells and tunable catalytic activity to decompose S-nitroso-N-acetyl-D-penicillamine (SNAP) for NO generation. Consequently, a functionalized coating with sustainable and tunable NO catalysis generation was developed on the metallic stent. Based on good biocompatibility, tunable NO release, and simple processing, the coating is expected to have great promise in the field of intervention therapy of cardiovascular disease.