Machine learning-based analysis of risk factors for chronic total occlusion in an Asian population.

OBJECTIVES: Chronic total occlusion (CTO) is a form of coronary artery disease (CAD) requiring percutaneous coronary intervention. There has been minimal research regarding CTO-specific risk factors and predictive models. We developed machine learning predictive models based on clinical characteristics to identify patients with CTO before coronary angiography. METHODS: Data from 1473 patients with CAD, including 317 patients with and 1156 patients without CTO, were retrospectively analyzed. Partial least squares discriminant analysis (PLS-DA), random forest (RF), and support vector machine (SVM) models were used to identify CTO-specific risk factors and predict CTO development. Receiver operating characteristic (ROC) curve analysis was performed for model validation. RESULTS: For CTO prediction, the PLS-DA model included 10 variables; the ROC value was 0.706. The RF model included 42 variables; the ROC value was 0.702. The SVM model included 20 variables; the ROC value was 0.696. DeLong's test showed no difference among the three models. Four variables were present in all models: sex, neutrophil percentage, creatinine, and brain natriuretic peptide (BNP). CONCLUSIONS: Validation of machine learning prediction models for CTO revealed that the PLS-DA model had the best prediction performance. Sex, neutrophil percentage, creatinine, and BNP may be important risk factors for CTO development.

A LASSO-derived developing and validating risk model for chronic total occlusion in Asian population before coronary angiography.

Background: Despite several previous studies that have explored the predictors of high morbidity in coronary artery disease (CAD) and developed nomograms for CAD patients prior to coronary angiography (CAG), there is a lack of models available to predict chronic total occlusion (CTO). The aim of this study is to develop a risk model and a nomogram for predicting the probability of CTO prior to CAG. Methods: The study included 1,105 patients with CAG-diagnosed CTO in the derivation cohort and 368 patients in the validation cohort. Clinical demographics, echocardiography results, and laboratory indexes were analyzed using statistical difference tests. Independent risk factors affecting the CTO indication were selected using least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression analysis. A nomogram was built and validated based on these independent indicators. The performance of the nomogram was evaluated using area under the curve (AUC), calibration curve, and decision curve analysis (DCA). Results: LASSO and multivariate logistic regression analysis revealed that 6 variables, including sex (male), lymphocyte percentage (LYM%), ejection fraction (EF), myoglobin (Mb), non-high-density lipoprotein cholesterol (non-HDL), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), were independent predictors of CTO. The nomogram constructed based on these variables showed good discrimination (C index of 0.744) and external validation (C index of 0.729). The calibration curves and DCA demonstrated high reliability and precision for this clinical prediction model. Conclusions: The nomogram based on sex (male), LYM%, EF, Mb, non-HDL, and NT-proBNP could be used to predict CTO in CAD patients, enhancing the ability to predict their prognosis in clinical practice. Further research is needed to validate the efficacy of the nomogram in other populations.

Cathepsin S inhibition in dendritic cells prevents Th17 cell differentiation in perivascular adipose tissues following vascular injury in diabetic rats.

In the context of diabetes mellitus (DM), the circulating cathepsin S (CTSS) level is significantly higher in the cardiovascular disease group. Therefore, this study was designed to investigate the role of CTSS in restenosis following carotid injury in diabetic rats. To induce DM, 60 mg/kg of streptozotocin (STZ) in citrate buffer was injected intraperitoneally into Sprague-Dawley rats. After successful modeling of DM, wire injury of the rat carotid artery was performed, followed by adenovirus transduction. Levels of blood glucose and Th17 cell surface antigens including ROR-γt, IL-17A, IL-17F, IL-22, and IL-23 in perivascular adipose tissues (PVAT) were evaluated. For in vitro analysis, human dendritic cells (DCs) were treated with 5.6-25 mM glucose for 24 h. The morphology of DCs was observed using an optical microscope. CD4+ T cells derived from human peripheral blood mononuclear cells were cocultured with DCs for 5 days. Levels of IL-6, CTSS, ROR-γt, IL-17A, IL-17F, IL-22 and IL-23 were measured. Flow cytometry was conducted to detect DC surface biomarkers (CD1a, CD83, and CD86) and Th17 cell differentiation. The collected DCs presented a treelike shape and were positive for CD1a, CD83, and CD86. Glucose impaired DC viability at the dose of 35 mM. Glucose treatment led to an increase in CTSS and IL-6 expression in DCs. Glucose-treated DCs promoted the differentiation of Th17 cells. CTSS depletion downregulated IL-6 expression and inhibited Th17 cell differentiation in vitro and in vivo. CTSS inhibition in DCs inhibits Th17 cell differentiation in PVAT tissues from diabetic rats following vascular injury.

Sex differences involved in persistent atrial fibrillation recurrence after radiofrequency ablation.

BACKGROUND: In recent years, the difference in outcomes of radiofrequency catheter ablation (RFCA) in persistent atrial fibrillation patients has risen. In particular, biological sex seems involved in a different response to the AF ablation procedure. In our study, we analyzed the AF recurrences after RFCA assessing the other association between male/female patients with the outcomes. METHODS: We enrolled 106 patients (74.5% men) with persistent atrial fibrillation with scheduled follow-up. The baseline clinical characteristics and AF recurrence after RFCA were compared between men and women. Cox regression analyses were performed to determine the risk predictors of AF recurrence. RESULTS: The proportion of RFCA in women was lower than that in men. Men with persistent AF were younger than women (58.6 ± 10.4 years vs. 65.1 ± 8.7 years, respectively; p = 0.003). The left atrium (LA) diameter was higher in males (43.7 ± 4.6 mm vs. 41.3 ± 5.5 mm; p = 0.028), and the level of left heart ejection fraction (LVEF) was higher in females (59.4 ± 6.9% vs. 64.1 ± 5.5%; p = 0.001). Sex differences in AF recurrence after RFCA were significant during the median 24.4-month (interquartile range: 15.2-30.6 months) follow-up period, and the recurrence rate of AF in women was significantly higher than that in men (p = 0.005). Univariable Cox regression analysis showed that female sex was a risk factor for persistent AF recurrence after RFCA [HR: 2.099 (1.087-4.053)]. Univariate Cox regression analysis revealed that non-PV ablation not associated with AF recurrence [HR: 1.003 (0.516-1.947)]. CONCLUSION: In a monocentric cohort of persistent AF patients, the female biological sex was associated with a higher risk of AF recurrence after RFCA.

Effect of high-sensitivity C-reactive protein on the relationship between haemoglobin A1c and cardiovascular events in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a cohort study.

Background: There are different opinions on haemoglobin A1c (HbA1c) in predicting cardiovascular events after percutaneous coronary intervention (PCI). Some factors may affect the ability of HbA1c to predict cardiovascular events, resulting in this inconsistency. Inflammation is a direct and whole-process participant in atherosclerosis. However, no one has studied the effect of inflammation on the correlation between HbA1c and cardiovascular events. Therefore, we aimed to test the hypothesis that high-sensitivity C-reactive protein (hsCRP) modulates HbA1c-related cardiovascular events in patients with the acute coronary syndrome (ACS) undergoing PCI. Methods: This was a retrospective cohort study. We enrolled patients with ACS who were hospitalized for PCI and followed up for 24 months. The primary outcome was the composite of major adverse cardiovascular and cerebrovascular events (MACCEs), including all-cause death, nonfatal myocardial infarction, nonfatal stroke, and unplanned repeat revascularization. We stratified the overall population by HbA1c tertiles and hsCRP median. The relationship between HbA1c, hsCRP, and cardiovascular events was analysed by the Cox proportional hazard regression model. Results: A total of 2,023 patients were enrolled in this study (age: 59.7±10.03 years old, 78.1% male patients). After the 24-month follow-up, 152 (7.51%) events occurred. Patients with hsCRP >1.21 mg/L had an increased cardiovascular risk compared with patients with hsCRP ≤1.21 mg/L [hazard ratio (HR) 1.58, 95% confidence interval (CI): 1.12-2.24, P=0.010]. We did not observe a significant correlation between HbA1c and cardiovascular events. Furthermore, we stratified patients by hsCRP ≤1.21 or >1.21 mg/L and found that the correlation between HbA1c and cardiovascular events was only significant in patients with hsCRP ≤1.21 mg/L (tertile 2 vs. tertile 1: HR 1.76, 95% CI: 0.79-3.90, P=0.165, tertile 3 vs. tertile 1: HR 3.03, 95% CI: 1.50-6.12, P=0.002; P=0.008 for trend) but not in patients with hsCRP >1.21 mg/L. Conclusions: This study showed that hsCRP may affect the relationship between HbA1c and the risk of cardiovascular events in patients with ACS after PCI. This finding suggests that the risk of cardiovascular events may be underestimated when only HbA1c is used as a predictor of cardiovascular risk. HbA1c has a better predictive value in the absence or low levels of inflammation states represented by hsCRP as a predictor of cardiovascular events.

Prognostic Significance of Percutaneous Coronary Intervention for First Acute Myocardial Infarction with Heart Failure: Five-Year Follow-Up Results.

Objective: The study aimed to investigate the incidence and influencing factors of heart failure after 5 years of percutaneous coronary intervention (PCI) for first acute myocardial infarction. Methods: A total of 1235 patients, diagnosed as acute myocardial infarction and treated with PCI in Beijing Anzhen Hospital, Capital Medical University, from January 1, 2014, to December 31, 2014, were enrolled. Based on the exclusion criteria, 671 patients were followed up to obtain echocardiographic results 5 years after the onset of myocardial infarction (from January 1, 2019, to December 31, 2019). Of 671 patients, 62 were lost to follow-up. Finally, 609 patients were recruited in this study. According to the results of the echocardiographic examination, patients were divided into a heart failure group (n = 97) (LVEF < 50%) and a nonheart failure group (n = 512) (LVEF ≥ 50%). The clinical characteristics were compared between the two groups, and the influencing factors of heart failure after 5 years of PCI in patients with acute myocardial infarction were analyzed using logistic regression and receiver-operating characteristic (ROC) analyses. Results: Of 609 patients, 97 had heart failure within 5 years after PCI for first myocardial infarction, with an incidence of 15.9%. Multivariate regression analysis finally examined the predictors related to the occurrence of heart failure, including age (aOR, 1.008; 95% confidence interval (CI), 1.054-1.123; P ≤ 0.001), peak troponin I level (aOR, 1.020; 95% CI, 1.006-1.034; P = 0.004), left ventricular ejection fraction (LVEF) (during admission) (aOR, 0.908; 95% CI, 0.862-0.956; P ≤ 0.001), and left ventricular end-diastolic dimension (LVEDD) (at admission) (aOR, 1.136; 95% CI, 1.016-1.271; P = 0.025). Conclusion: In this study, the incidence of heart failure (LVEF < 50%) in patients with acute myocardial infarction who underwent PCI was 15.9% at a five-year follow up. Age, peak troponin I level, and LVEDD (at admission) were risk factors for heart failure, while LVEF (at admission) of patients during hospitalization was a protective factor for heart failure.

The predictive value of the triglyceride-glucose index for cardiovascular events in patients with coronary chronic total occlusion.

BACKGROUND: Chronic total occlusion (CTO) of the coronary artery is a difficult problem in clinical practice. The triglyceride-glucose (TyG) index is an effective risk predictor of cardiovascular risk. However, the relationship between the TyG index and the prognosis of CTO patients remains unstudied. Thus, the present study aimed to investigate the relationship between the TyG index and cardiovascular risk in CTO patients. METHODS: This was a single-centre, retrospective cohort study. We retrospectively enrolled 652 patients with CTO lesions diagnosed by angiography and who underwent revascularization through PCI. Patients were routinely followed up for 24 months unless meeting the endpoint. The primary endpoint was the composite of all-cause death, nonfatal myocardial infarction, unplanned revascularization, and nonfatal ischaemic stroke. To test the association of the TyG index with cardiovascular risk, the categorized TyG index and Cox proportional hazards regression models were utilized. RESULTS: A total of 652 patients were enrolled in the final analysis (male: 83.7%, age: 58.2 ± 10.49 years). The average TyG index was 8.8 ± 0.57. CTO PCIs were procedurally successfully completed in 503 (77.15%) patients. During the follow-up period of 22.8 ± 3.84 months, 73 (11.19%) major adverse cardiovascular and cerebral events (MACCEs) occurred. When fully adjusted, there was a 2.09-fold risk for MACCEs among patients with the highest TyG index compared with those with the lowest TyG index [T2 vs. T1: hazard ratio (HR) 1.24, 95% confidence interval (CI) 0.65-2.38, P = 0.057; T3 vs. T1: HR 2.09, 95% CI 1.14-3.86, P = 0.018; P for trend = 0.036]. The restricted cubic spline (RCS) analysis showed that the HR for MACCEs increased as the TyG index increased over 8.71 [HR per standard deviation (SD) 1.740, 95% CI 1.23-2.46, P = 0.002]. The risk of MACCEs increased with increasing tertiles of TyG index in successful CTO PCI patients and nondiabetes mellitus (DM) patients (P < 0.05) but not in patients with failed CTO PCI and DM patients. CONCLUSION: The study revealed that the TyG index had significant relevance to cardiovascular risk in CTO patients and suggests that the TyG index is feasible for predicting cardiovascular risk in CTO patients.

Increased cytochrome C threonine 50 phosphorylation in aging heart as a novel defensive signaling against hypoxia/reoxygenation induced apoptosis.

Previous studies have shown that aging promotes myocardial apoptosis. However, the detailed mechanisms remain unclear. Our recent studies revealed that aging not only activates apoptosis, but also activates some anti-apoptotic factors. By quantitative phosphoproteomics, here we demonstrated that aging increases cytochrome c (Cytc) phosphorylation at threonine 50 (T50), a post-translational modification with unknown functional impact. With point mutation and lentivirus transfection, cardiomyocytes were divided into four groups: empty vector group, WT (wild type), T50E (as a phosphomimic variant), and T50A (non-phosphorylatable). TUNEL staining and flow cytometry were used to determine the apoptosis ratio in different groups after hypoxic/reoxygenated (H/R) treatment. The results showed that T50-phosphorylated Cytc suppressed myocardial apoptosis induced by H/R. Furthermore, Western Blot and ELISA measurements revealed that Cytc T50 phosphorylation inhibited caspase-9 and caspase-3 activity without altering caspase-8, BCL-2, BCL-XL, and Bax expression. In our study, we demonstrated that aging increases phosphorylation Cytc at T50 and this aging-increasing phosphorylation site can suppress H/R-induced apoptosis.

High responsivity of hybrid MoTe2/perovskite heterojunction photodetectors.

Two-dimensional (2D) van der Waals heterojunction offers alternative facile platforms for many optoelectronic devices due to no-dangling bonds and steep interface carrier gradient. Here, we demonstrate a 2D heterojunction device, which combines the benefits of high carrier mobility of 2D MoTe2and strong light absorption of perovskite, to achieve excellent responsivity. This device architecture is constructed based on the charge carriers separation and transfer with the high-gain photogating effect at the interface of the heterojunction. The device exhibits high responsivity of 334.6 A W-1, impressive detectivity of 6.2 × 1010Jones. All the results provide the insight into the benefits of interfacial carriers transfer for designing hybrid perovskite-2D materials based optoelectronic devices.

lncRNA NONHSAT069381 and NONHSAT140844 Increase in Aging Human Blood, Regulating Cardiomyocyte Apoptosis.

Aging augments postischemic apoptosis via incomplete mechanisms. Our previous animal study suggests that in addition to proapoptotic effects, lncRNAs also exert antiapoptotic effects in cardiomyocytes. However, whether this unexpected phenomenon exists in humans is unknown. In the present study, we investigated the relationship between aging and apoptosis regulation in human blood samples and confirmed their role by utilizing the cardiomyocyte lines (AC16 cells). Human blood samples were collected from 20 pairs of older adult and young volunteers. Age-different apoptotic regulatory lncRNAs and miRNAs were identified by microarray and bioinformatics analysis. The results indicated that lncRNA (NONHSAT069381 and NONHSAT140844) and miRNA (hsa-miR-124-5p and hsa-miR-6507-5p) were increased in aging human blood, confirmed by both bioinformatics analysis and polymerase chain reaction (PCR). Overexpression of NONHSAT069381 in AC16 cells increased caspase-3 levels and increased cardiomyocyte apoptotic cell death (determined by TUNEL staining and caspase activity assays) after hypoxia/reoxygenation (H/R), while overexpression of NONHSAT140844 increased X-chromosome-linked inhibitor of apoptosis protein (XIAP) content and decreased the myocardial apoptotic cell death. Furthermore, luciferase reporter assay revealed that hsa-miR-124-5p might be a mediator between NONHSAT069381 and mCASP3 and hsa-miR-6507-5p might be a mediator between NONHSAT140844 and mXIAP. Overexpression of hsa-miR-124-5p decreased caspase-3 levels and overexpression of hsa-miR-6507-5p decreased XIAP content in AC16 cells. We have found evidence that lncRNAs are important regulatory molecules in aging-mediated effects upon apoptosis. More interestingly, besides apoptosis-promoting effects, aging also inhibits myocardial apoptosis after H/R. This phenomenon also exists in the human cardiomyocyte line.

Limb Remote Ischemic Conditioning Ameliorates Cognitive Impairment in Rats with Chronic Cerebral Hypoperfusion by Regulating Glucose Transport.

Cognitive impairment is closely associated with the slowing of glucose metabolism in the brain. Glucose transport, a rate-limiting step of glucose metabolism, plays a key role in this phenomenon. Previous studies have reported that limb remote ischemic conditioning (LRIC) improves cognitive performance in rats with chronic cerebral hypoperfusion (CCH). Here, we determined whether LRIC could ameliorate cognitive impairment in rats with CCH by regulating glucose transport. A total of 170 male Sprague-Dawley rats were used. Animals subjected to permanent double carotid artery occlusion (2VO) were assigned to the control or LRIC treatment group. LRIC was applied beginning 3 days after the 2VO surgery. We found that LRIC can improve learning and memory; decrease the ratio of ADP/ATP; increase glucose content; upregulate the expression of pAMPKα, GLUT1 and GLUT3; and increase the number of GLUT1 and GLUT3 transporters in cerebral cortical neurons. The expression of GLUT1 and GLUT3 in the cortex displayed a strong correlation with learning and memory. Pearson correlation analysis showed that the levels of GLUT1 and GLUT3 are correlated with neurological function scores. All of these beneficial effects of LRIC were ablated by application of the AMPK inhibitor, dorsomorphin. In summary, LRIC ameliorated cognitive impairment in rats with CCH by regulating glucose transport via the AMPK/GLUT signaling pathway. We conclude that AMPK-mediated glucose transport plays a key role in LRIC. These data also suggest that supplemental activation of glucose transport after CCH may provide a clinically applicable intervention for improving cognitive impairment.

Toward Unusual-High Hole Mobility of p-Channel Field-Effect-Transistors.

The relative low hole mobility of p-channel building block device challenges the continued miniaturization of modern electronic chips. Metal-semiconductor junction is always an efficient strategy to control the carrier concentration of channel semiconductor, benefiting the carrier mobility regulation of building block device. In this work, complementary metal oxide semiconductor (CMOS)-compatible metals are selected to deposit on the surface of the important p-channel building block of GaSb nanowire field-effect-transistors (NWFETs), demonstrating the efficient strategy of hole mobility enhancement by metal-semiconductor junction. When deposited with lower work function metal of Al, the peak hole mobility of GaSb NWFET can be enhanced to as high as ≈3372 cm2 V-1 s-1 , showing three times than the un-deposited one. The as-studied metal-semiconductor junction is also efficient for the hole mobility enhancement of other p-channel devices, such as GaAs NWFET, GaAs film FET, and WSe2 FET. With the enhanced mobility, the as-constructed CMOS inverter shows good invert characteristics, showing a relatively high gain of ≈18.1. All results may be regarded as important advances to the next-generation electronics.

Hypoxia post-conditioning promoted glycolysis in mice cerebral ischemic model.

Ischemic stroke initiated by transient or permanent cerebral blood flow decline remains the leading cause of permanent disability in industrialized nations. Therapeutic strategies to improve patient recovery are remain limited. Hypoxia post-conditioning (HPostC) has been known to be neuroprotective against ischemic injuries in vivo and in vitro. Understanding its mechanism of action may promote its clinical translation. In this study, we devised a method of HPostC treatment to provide protection from a focal cerebral ischemic induced injury and to explore the underling mechanism. We found that our HPostC method improved energy supply by elevating the level of glucose, pyruvate and ATP/ADP ratio within the cerebral hemisphere in mice. In the distal middle cerebral artery occlusion (dMCAO) mice, this HPostC treatment reduced infarct size, and was associated with increased levels of pyruvate, pyruvate/lactate ratio and ATP/ADP ratio. Western blot analysis indicated that the HPostC treatment up-regulated AMPK signaling activities in the cerebral hemisphere. Our results suggest that this HPostC treatment exerts its neuroprotective effect by promoting glycolysis to elevate the ATP/ADP level, and the AMPK/PFKFB3 signaling pathway. These findings may provide biomarkers for clinical use of HPostC methods.

Evaluating the Intention and Behaviour of Private Sector Participation in Healthcare Service Delivery via Public-Private Partnership: Evidence from China.

Private sector participation in the healthcare market via public-private partnership (PPP) could be considered an available approach to narrow down the medical resource gap and improve the operational efficiency of healthcare facilities. Accordingly, this study aims to examine the influence and relative importance among critical factors for the intention and behaviour of the private sector towards participation in Chinese healthcare market (CHM) via PPP. We defined five hypotheses from previous literature and built a theoretical model based on modified theory of planned behaviour. Then, covariance-based structural equation modelling was applied to analyse the questionnaires provided by 248 respondents from construction companies, real estate developers, pharmaceutical companies, private hospitals, asset management companies, and medical industry property investment companies in China. Results indicated that attitude towards behaviour (ß = 0.466, P < 0.001), subjective norm (ß = 0.167, P < 0.05), perceived behavioural control (ß = 0.231, P < 0.01), and facilitating conditions (ß = 0.305, P < 0.001) are positively significant to behavioural intention; behavioural intention also shows a strong linkage with behaviour (ß = 0.931, P < 0.001). Findings provide reference for governments and public authorities to exert additional efforts in implementing appropriate measures that will stimulate the private sector's motivation to participate in CHM via PPP.