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Abstract Backgrounds The prognosis of the triglyceride-glucose (TyG) index, a validated surrogate marker for insulin resistance, in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) remains unknown. Methods This study consecutively enrolled patients diagnosed with severe AS who underwent TAVR in a Chinese tertiary hospital from March 2013 to September 2023. Participants were stratified based on the TyG index cut-off value. Cox proportional hazards regression models were utilized to explore the association between the TyG index and all-cause mortality, including an assessment of interactions between the TyG index and various covariates on mortality outcomes. Results Among 1045 patients (mean age 74.7 years, 58.2% male), there was 134 all-cause mortality, resulting in a crude mortality rate of 64.3 per 1000 person-years. Adjusting for age, sex, body mass index, smoking, hypertension, diabetes mellitus, bicuspid aortic valve, atrial fibrillation, Society of Thoracic Surgeons (STS) score, and left ventricular ejection fraction, a per-unit increase in the TyG index was associated with a 41% higher all-cause mortality risk (HR 1.41, 95% CI 1.03–1.93, p = 0.030). Notably, the relationship between the TyG index and all-cause mortality was significantly modified by age (pinteraction = 0.027), sex (pinteraction = 0.007), hypertension (pinteraction = 0.030), and STS score (pinteraction = 0.002). Conclusions A higher TyG index is significantly associated with an increased risk of all-cause mortality in AS patients after TAVR. These results underscore the importance of considering the TyG index in the prognostic evaluation of AS patients following TAVR.

Abstract Background Current cardiovascular prevention strategies are based on studies that seldom include valvular heart disease (VHD). The role of modifiable lifestyle factors on VHD progression and life expectancy among the elderly with different socioeconomic statuses (SES) remains unknown. Methods This cohort study included 164,775 UK Biobank participants aged 60 years and older. Lifestyle was determined using a five-factor scoring system covering smoking status, obesity, physical activity, diet, and sleep patterns. Based on this score, participants were then classified into “poor,” “moderate,” or “ideal” lifestyle groups. SES was classified as high or low based on the Townsend Deprivation Index. The association of lifestyle with major VHD progression was evaluated using a multistate mode. The life table method was employed to determine life expectancy with VHD and without VHD. Results The UK Biobank documented 5132 incident VHD cases with a mean follow-up of 12.3 years and 1418 deaths following VHD with a mean follow-up of 6.0 years. Compared to those with a poor lifestyle, women and men followed an ideal lifestyle had lower hazard ratios for incident VHD (0.66 with 95% CI, 0.59–0.73 for women and 0.77 with 95% CI, 0.71–0.83 for men) and for post-VHD mortality (0.58 for women, 95% CI 0.46–0.74 and 0.62 for men, 95% CI 0.54–0.73). When lifestyle and SES were combined, the lower risk of incident VHD and mortality were observed among participants with an ideal lifestyle and high SES compared to participants with an unhealthy lifestyle and low SES. There was no significant interaction between lifestyle and SES in their correlation with the incidence and subsequent mortality of VHD. Among low SES populations, 60-year-old women and men with VHD who followed ideal lifestyles lived 4.2 years (95% CI, 3.8–4.7) and 5.1 years (95% CI, 4.5–5.6) longer, respectively, compared to those with poor lifestyles. In contrast, the life expectancy gain for those without VHD was 4.4 years (95% CI, 4.0–4.8) for women and 5.3 years (95% CI, 4.8–5.7) for men when adhering to an ideal lifestyle versus a poor one. Conclusions Adopting a healthier lifestyle can significantly slow down the progression from free of VHD to incident VHD and further to death and increase life expectancy for both individuals with and without VHD within diverse socioeconomic elderly populations.

Abstract Background Calcific aortic valve stenosis (CAVS) is one of the most challenging heart diseases in clinical with rapidly increasing prevalence. However, study of the mechanism and treatment of CAVS is hampered by the lack of suitable, robust and efficient models that develop hemodynamically significant stenosis and typical calcium deposition. Here, we aim to establish a mouse model to mimic the development and features of CAVS. Methods The model was established via aortic valve wire injury (AVWI) combined with vitamin D subcutaneous injected in wild type C57/BL6 mice. Serial transthoracic echocardiography was applied to evaluate aortic jet peak velocity and mean gradient. Histopathological specimens were collected and examined in respect of valve thickening, calcium deposition, collagen accumulation, osteogenic differentiation and inflammation. Results Serial transthoracic echocardiography revealed that aortic jet peak velocity and mean gradient increased from 7 days post model establishment in a time dependent manner and tended to be stable at 28 days. Compared with the sham group, simple AVWI or the vitamin D group, the hybrid model group showed typical pathological features of CAVS, including hemodynamic alterations, increased aortic valve thickening, calcium deposition, collagen accumulation at 28 days. In addition, osteogenic differentiation, fibrosis and inflammation, which play critical roles in the development of CAVS, were observed in the hybrid model. Conclusions We established a novel mouse model of CAVS that could be induced efficiently, robustly and economically, and without genetic intervention. It provides a fast track to explore the underlying mechanisms of CAVS and to identify more effective pharmacological targets.

Abstract Background Diabetes mellitus (DM) and coronary microvascular dysfunction (CMD) increase the risk of adverse cardiac events in patients with non-ST-segment elevation myocardial infarction (NSTEMI). This study aimed to evaluate the combined risk estimates of DM and CMD, assessed by the angiography-derived index of microcirculatory resistance (angio-IMR), in patients with NSTEMI. Methods A total of 2212 patients with NSTEMI who underwent successful percutaneous coronary intervention (PCI) were retrospectively enrolled from three centers. The primary outcome was a composite of cardiac death or readmission for heart failure at a 2-year follow-up. Results Post-PCI angio-IMR did not significantly differ between the DM group and the non-DM group (20.13 [17.91–22.70] vs. 20.19 [18.14–22.77], P = 0.530). DM patients exhibited a notably higher risk of cardiac death or readmission for heart failure at 2 years compared to non-DM patients (9.5% vs. 5.4%, P

Abstract Repositionable self-expanding valves allow for repositioning during deployment to achieve optimal valve placement. However, the risk of brain injury associated with repositioning, as detected by diffusion-weighted magnetic resonance imaging (DW-MRI), is unknown. Consecutive patients undergoing transcatheter aortic valve replacement (TAVR) with repositionable self-expanding valves and receiving DW-MRI before and within 7 days post-TAVR procedure were included. The primary outcomes were incidence, number, total volume, and volume per lesion of the cerebral ischemic lesion in DW-MRI after TAVR. Univariate and multivariate logistic regression assessed the association between repositioning and bigger total lesion volume (> 1 cm3 or > 0.5 cm3). Negative binomial regressions were performed to explore the association between repositioning and number of lesions. A propensity score matching was performed to adjust the potential confounders. Moreover, inverse probability of treatment weighted regression model with nonstabilized weights was used as sensitivity analysis. Among 243 included patients, repositioning was performed in 116 (47.7%) patients. The incidence of overt stroke (1.7% vs. 1.6%, p = 0.927) and silent stroke (86.2% vs. 85.8%, p = 0.932) were comparable between two groups. However, the number of new lesions (5.0 [2.0–9.0] vs. 3.0 [2.0–6.0], p = 0.048), and total lesion volume (275.0 [90.0–947.5] mm3 vs. 180.0 [50.0–440.0] mm3, p = 0.022) were significantly higher in the repositioned group. Moreover, the proportion of patients with lesion size greater than 0.5 cm3 was higher in the repositioned group (37.9% vs. 22.0%, p = 0.007). The similar results were observed after propensity score matching. In both multivariate regression model and sensitivity analysis, the repositioning was the independent predictor of number of lesions and bigger total lesion volume after TAVR. The utilization of the repositioning feature may increase the number and volume of silent brain infarcts in DW-MRI in patients who underwent TAVR. (Transcatheter Aortic Valve Replacement Single Center Registry in Chinese Population [TORCH]; NCT02803294)

BackgroundCoronary obstruction (CO) is a rare but devasting complication during transcatheter aortic valve replacement (TAVR).ObjectivesWe aim to demonstrate that the predicted distance between the coronary ostia and the closest structure derived with patient-specific computer simulation is associated with CO risk during TAVR.MethodsWe retrospectively analysed 14 aortic stenosis patients who underwent TAVR through finite element simulation. The frame deformation predicted with patient-specific computer simulation was qualitatively and quantitatively compared to the post-operative device deformation. The minimum distance between each coronary ostium and the closest structure was calculated and compared in patients who developed CO, at high risk of CO, and at no risk of CO.ResultsFour patients experienced CO during TAVR, 5 patients were at high risk of CO, and the remaining 5 patients had no risk of CO. A high coefficient of determination was obtained for all measurements extracted from the simulated device and the post-operative device (≥0.95). Simulations predicted shorter distance between the coronary ostium and the closest structure in patients who experienced CO, compared to patients at high risk of CO or who did not experience this complication (right coronary: 5.9 vs. 6.8 vs. 8.8 mm, left coronary: 3.0 vs. 3.3 vs. 6.5 mm respectively).ConclusionsThe distance between the coronary ostium and the closest structure was lower in patients who experienced CO during TAVR through patient-specific computational simulation. This technology enables coronary obstruction analysis before TAVR in the future.

Abstract Objective To observe prosthetic-associated subclinical thrombotic events (PASTE) after transcatheter aortic valve implantation (TAVI) by cardiac CTA, and assess their impact on long-term patient outcomes. Materials We prospectively and consecutively enrolled 188 patients with severe aortic stenosis treated with TAVI from February 2014 to April 2017. At 5 years, 61 of 141 survived patients who had completed annual follow-up CTA (≥ 5 years) were included. We analyzed PASTE by CTA, including hypoattenuated leaflet thickening (HALT), sinus filling defect (SFD), and prosthesis filling defect (PFD). The primary outcome was a major adverse cardiovascular composite outcome (MACCO) of stroke, cardiac re-hospitalization, and bioprosthetic valve dysfunction (BVD); the secondary outcomes were bioprosthetic hemodynamics deterioration (PGmean) and cardiac dysfunction (LVEF). Results During a median follow-up time of 5.25 years, long-term incidence of HALT, SFD, and PFD were 54.1%, 37.7%, and 73.8%, respectively. In the primary outcome, SFD and early SFD were associated with the MACCO (SFD: p = 0.005; early SFD: p = 0.018), and SFD was a predictor of MACCO (HR: 2.870; 95% CI: 1.010 to 8.154, p = 0.048). In the secondary outcomes, HALT was associated with increased PGmean (p = 0.031), while persistent HALT was correlated with ΔPGmean (β = 0.38, p = 0.035). SFD was negatively correlated with ΔLVEF (β = −0.39, p = 0.041), and early SFD was negatively correlated with LVEF and ΔLVEF (LVEF: r = −0.50, p = 0.041; ΔLVEF: r = −0.53, p = 0.030). Conclusions PASTE were associated with adverse long-term outcomes, bioprosthetic hemodynamics deterioration, and cardiac dysfunction. In particular, SFD was a predictor of MACCO and may be a potential target for anticoagulation after TAVI (NCT02803294). Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02803294. Critical relevance statement PASTE, especially SFD, after TAVI based on cardiac CTA findings impacts the long-term outcomes of patients which is a predictor of long-term major adverse outcomes in patients and may be a potential target for anticoagulation after TAVI. Key Points Transcatheter aortic valve implantation is being used more often; associated subclinical thromboses have not been thoroughly evaluated. Prosthetic-associated subclinical thrombotic events were associated with adverse outcomes, bioprosthetic hemodynamics deterioration, and cardiac dysfunction. Studies should be directed at these topics to determine if they should be intervened upon. Graphical Abstract

Abstract Myocardial Infarction (MI) is a leading cause of death worldwide. Metabolic modulation is a promising therapeutic approach to prevent adverse remodeling after MI. However, whether material‐derived cues can treat MI through metabolic regulation is mainly unexplored. Herein, a Cu2+ loaded casein microgel (CuCMG) aiming to rescue the pathological intramyocardial metabolism for MI amelioration is developed. Cu2+ is an important ion factor involved in metabolic pathways, and intracardiac copper drain is observed after MI. It is thus speculated that intramyocardial supplementation of Cu2+ can rescue myocardial metabolism. Casein, a milk‐derived protein, is screened out as Cu2+ carrier through molecular‐docking based on Cu2+ loading capacity and accessibility. CuCMGs notably attenuate MI‐induced cardiac dysfunction and maladaptive remodeling, accompanied by increased angiogenesis. The results from unbiased transcriptome profiling and oxidative phosphorylation analyses support the hypothesis that CuCMG prominently rescued the metabolic homeostasis of myocardium after MI. These findings enhance the understanding of the design and application of metabolic‐modulating biomaterials for ischemic cardiomyopathy therapy.

BackgroundThere are limited data available on the development of arrhythmias in patients at risk of high-degree atrioventricular block (HAVB) or complete heart block (CHB) following transcatheter aortic valve replacement (TAVR). ObjectiveThis study aimed to explore the incidence and evolution of arrhythmias by monitoring patients at risk of HAVB or CHB after TAVR using smartwatches. MethodsWe analyzed 188 consecutive patients in the prospective SMART TAVR (smartwatch-facilitated early discharge in patients undergoing TAVR) trial. Patients were divided into 2 groups according to the risk of HAVB or CHB. Patients were required to trigger a single-lead electrocardiogram (ECG) recording and send it to the Heart Health App via their smartphone. Physicians in the central ECG core lab would then analyze the ECG. The incidence and timing of arrhythmias and pacemaker implantation within a 30-day follow-up were compared. All arrhythmic events were adjudicated in a central ECG core lab. ResultsThe mean age of the patients was 73.1 (SD 7.3) years, of whom 105 (55.9%) were men. The mean discharge day after TAVR was 2.0 (SD 1.8) days. There were no statistically significant changes in the evolution of atrial fibrillation or atrial flutter, Mobitz I, Mobitz II, and third-degree atrial ventricular block over time in the first month after TAVR. The incidence of the left bundle branch block (LBBB) increased in the first week and decreased in the subsequent 3 weeks significantly (P

Abstract There lacks real‐world study with a large sample size assessing olmesartan medoxomil‐amlodipine besylate (OM‐AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM‐AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM‐AML (20/5 mg) tablet were analyzed in the current prospective, single‐arm, multi‐center, real‐world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was ‐10.8 ± 0.4/‐6.6 ± 0.3 mmHg at W4 and ‐12.7 ± 0.5/‐7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home‐measured SeSBP and SeDBP decreased from W1 to W8 (both p

The heart requires high levels of mitochondria to sustain function, and mitochondrial stressors can be transmitted to the nucleus and reprogram metabolism. Here, the authors show that a mitochondrial ribosomal protein is important for heart development in mice by increasing nuclear Klf15 expression.

Mesenchymal stromal cell (MSC) transplantation has been a promising therapeutic strategy for repairing heart tissues post-myocardial infarction (MI). Nevertheless, its therapeutic efficacy remains low, which is mainly ascribed to the low viability of transplanted MSCs. Recently, long noncoding RNAs (lncRNAs) have been reported to participate in diverse physiological and pathological processes, but little is known about their role in MSC survival. Using unbiased transcriptome profiling of hypoxia-preconditioned MSCs (HP-MSCs) and normoxic MSCs (N-MSCs), we identified a lncRNA named lung cancer-associated transcript 1 (LUCAT1) under hypoxia. LUCAT1 knockdown reduced the survival of engrafted MSCs and decreased the MSC-based therapeutic potency, as shown by impaired cardiac function, reduced cardiomyocyte survival, and increased fibrosis post-MI. Conversely, LUCAT1 overexpression had the opposite results. Mechanistically, LUCAT1 bound with and recruited jumonji domain-containing 6 (JMJD6) to the promoter of forkhead box Q1 (FOXQ1), which demethylated FOXQ1 at H4R3me2(s) and H3R2me2(a), thus downregulating Bax expression and upregulating Bcl-2 expression to attenuate MSC apoptosis. Therefore, our findings revealed the protective effects of LUCAT1 on MSC apoptosis and demonstrated that the LUCAT1-mediated JMJD6-FOXQ1 pathway might represent a novel target to potentiate the therapeutic effect of MSC-based therapy for ischemic cardiovascular diseases.

Mental stress has been recognized as an essential risk factor for hypertension. Therefore, experts specializing in cardiology, psychiatry, and Traditional Chinese Medicine organized by the Psycho-Cardiology Group of College of Cardiovascular Physicians of Chinese Medical Doctor Association and Hypertension Group of Chinese Society of Cardiology proposed the expert consensus on the diagnosis and treatment of adult mental stress-induced hypertension in March 2021, which includes the epidemiology, etiology, diagnosis, and treatment of the mental stress-induced hypertension. This consensus will hopefully facilitate the clinical practice of this disorder. In addition, the COVID-19 pandemic has become one of the primary global sources of psychosocial stressors since the beginning of 2020, and the revision of this expert consensus in 2022 has increased the relevant content. This consensus consists of Part A and Part B. Part A includes (I) Background and epidemiological characteristics, (II) Pathogenesis, and (III) Diagnosis and Part B includes (IV) Treatment recommendations and (V) Prospects. This part presents the content of Part A.

Mental stress has been recognized as an essential risk factor for hypertension. Therefore, experts specializing in cardiology, psychiatry, and Traditional Chinese Medicine organized by the Psycho-cardiology Group, College of Cardiovascular Physicians of Chinese Medical Doctor Association, and Hypertension Group of the Chinese Society of Cardiology proposed the expert consensus on the diagnosis and treatment of adult mental stress-induced hypertension in March 2021, which includes the epidemiology, etiology, diagnosis, and treatment of the mental stress-induced hypertension. This consensus will hopefully facilitate the clinical practice of this disorder. In addition, the COVID-19 pandemic has become one of the primary global sources of psychosocial stressors since the beginning of 2020, and the revision of this expert consensus in 2022 has increased the relevant content. This consensus consists of two parts. The sections of Part A include (I) Background and epidemiological characteristics, (II) Pathogenesis, and (III) Diagnosis. The sections of Part B contain (IV) Treatment recommendations, and (V) Prospects. This article presents Part B of the consensus.

BackgroundThere are only limited reports on the trends of NT-proBNP after transcatheter aortic valve replacement (TAVR) in aortic stenosis (AS) and even fewer report on the prognostic value of the NT-proBNP trajectory following TAVR.ObjectivesThis study aims to investigate short-term NT-proBNP trajectory following TAVR and explore its association with clinical outcomes in TAVR recipients.MethodsAortic stenosis patients undergoing TAVR were included if they had NT-proBNP levels recorded at baseline, prior to discharge, and within 30 days after TAVR. We used latent class trajectory models to identify NT-proBNP trajectories based on their trends over time.ResultsThree distinct NT-proBNP trajectories were identified from 798 TAVR recipients, which were named class 1 (N = 661), class 2 (N = 102), and class 3 (N = 35). Compared to those with trajectory class 1, patients with trajectory class 2 had a more than 2.3-fold risk of 5-year all-cause death and 3.4-fold risk of cardiac death, while patients with trajectory class 3 had a more than 6.6-fold risk of all-cause death and 8.8-fold risk of cardiac death. By contrast, the groups had no differences in 5-year hospitalization rates. In multivariable analyses, the risk of 5-year all-cause mortality was significantly higher in patients with trajectory class 2 (HR 1.90, 95% CI 1.03–3.52, P = 0.04) and class 3 (HR 5.70, 95% CI 2.45–13.23, P < 0.01).ConclusionOur findings implied different short-term evolution of NT-proBNP levels in TAVR recipients and its prognostic value for AS patients following TAVR. NT-proBNP trajectory may have further prognostic value, in addition to its baseline level. This may aid clinicians with regards to patient selection and risk prediction in TAVR recipients.

Background: Decreased length of stay in the index hospitalization is a tendency in transcatheter aortic valve replacement (TAVR) era. In this study, we aim to evaluate the feasibility and safety of next-day discharge (NDD) in bicuspid aortic valve (BAV) patients following TAVR. Methods: The study analyzed patients who received TAVR in 2019 to 2022. Thirty-day mortality and readmission rate were compared between BAV and tricuspid aortic valve (TAV) patients. Results: The proportion of NDD was similar between the BAV and TAV group (45.3 % vs 41.3 %, p = 0.487). In NDD patients, the lower age (72.0 [67.0, 77.0] yrs vs 74.0 [70.0, 80.0] yrs, p = 0.011) and STS score (2.33 [1.56, 3.54] % vs 3.82 [2.38, 5.70] %, p

Abstract Background Fractional flow reserve (FFR) is a widely used gold standard to evaluate ischemia-causing lesions. A new method of non-invasive approach, termed as AccuFFRct, for calculating FFR based on coronary computed tomography angiography (CCTA) and computational fluid dynamics (CFD) has been proposed. However, its diagnostic accuracy has not been validated. Objectives This study sought to present a novel approach for non-invasive computation of FFR and evaluate its diagnostic performance in patients with coronary stenosis. Methods A total of 54 consecutive patients with 78 vessels from a single center who underwent CCTA and invasive FFR measurement were retrospectively analyzed. The CT-derived FFR values were computed using a novel CFD-based model (AccuFFRct, ArteryFlow Technology Co., Ltd., Hangzhou, China). Diagnostic performance of AccuFFRct and CCTA in detecting hemodynamically significant coronary artery disease (CAD) was evaluated using the invasive FFR as a reference standard. Results Diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for AccuFFRct in detecting FFR ≤ 0.8 on per-patient basis were 90.7, 89.5, 91.4, 85.0 and 94.1%, respectively, while those of CCTA were 38.9, 100.0, 5.71, 36.5 and 100.0%, respectively. The correlation between AccuFFRct and FFR was good (r = 0.76 and r = 0.65 on per-patient and per-vessel basis, respectively, both p

Recent advances in the field of optical tweezer technology have shown intriguing potential for applications in cardiovascular medicine, bringing this laboratory nanomechanical instrument into the spotlight of translational medicine. This article summarizes cardiovascular system findings generated using optical tweezers, including not only rigorous nanomechanical measurements but also multifunctional manipulation of biologically active molecules such as myosin and actin, of cells such as red blood cells and cardiomyocytes, of subcellular organelles, and of microvessels in vivo. The implications of these findings in the diagnosis and treatment of diseases, as well as potential perspectives that could also benefit from this tool, are also discussed.

Cardiac dysfunction is a common complication of sepsis with high mortality. The present study was designed to identify the effect of neutrophil-derived lipocalin-2 (LCN2) in septic cardiac dysfunction (SCD) and its potential mechanism. Wild-type (WT) and LCN2-knockout (LCN2 KO) mice were peritoneally injected with lipopolysaccharide (LPS) to induce SCD. The cardiac function was assessed 12 h after LPS injection by echocardiography. Cardiac tissue was harvested for the evaluation of malonaldehyde (MDA) and prostaglandin E synthase 2 (PTGS2) mRNA levels. LPS induced ferroptosis and SCD in mice. LCN2 deficiency attenuated cardiac injury post-LPS administration. In vitro, LCN2 expression in neutrophils increased in response to LPS. Ferroptosis of cardiomyocytes induced by conditioned medium (CM) from LPS-induced neutrophils of WT mice could be attenuated in CM from LPS-induced neutrophils of LCN2 KO mice. Exogenous LCN2 induced H9C2 cell ferroptosis via increasing labile iron pool (LIP). In conclusion, our results showed that LCN2 deficiency prevented heart dysfunction and ferroptosis in SCD mice and suggested that neutrophil-derived LCN2 might be a promising therapeutic target for SCD.

BackgroundCoronary occlusion is an uncommon but fatal complication of transcatheter aortic valve replacement (TAVR) with a poor prognosis.Case PresentationA patient with symptomatic severe bicuspid aortic valve stenosis was admitted to a high-volume center specializing in transfemoral TAVR with self-expanding valves. No anatomical risk factors of coronary occlusion were identified on pre-procedural computed tomography analysis. The patient was scheduled for a transfemoral TAVR with a self-expanding valve. Balloon pre-dilatation prior to prosthesis implantation was routinely used for assessing the supra-annular structure and assessing the risk of coronary occlusion. Immediately after the tubular balloon inflation, fluoroscopy revealed that the right coronary artery was not visible, and the flow in the left coronary artery was reduced. The patient would be at high-risk of coronary occlusion if a long stent self-expanding valve was implanted. Therefore, our heart team decided to suspend the ongoing procedure. A transapical TAVR with a 23 mm J-valve was performed 3 days later. The prosthesis was deployed at a proper position without blocking the coronary ostia and the final fluoroscopy showed normal flow in bilateral coronary arteries with the same filling as preoperatively.DiscussionOur successful case highlights the importance of a comprehensive assessment of coronary risk and a thorough understanding of the TAVR procedure for the heart team. A short-stent prosthesis is feasible for patients at high risk of coronary occlusion. Most importantly TAVR should be called off even if the catheter has been introduced when an extremely high risk of coronary obstruction is identified during the procedure and no solution can be found.

Cardiac fibrosis occurs in most cardiac diseases, which reduces cardiac muscle compliance, impairs both systolic and diastolic heart function and, ultimately, leads to heart failure. Long noncoding RNAs (lncRNAs) have recently emerged as important regulators of a variety of biological processes; however, little is known about the expression and function of lncRNAs in cardiac fibrosis. Using unbiased transcriptome profiling in a mouse model of myocardial infarction (MI), we identified a cardiac fibroblast-enriched lncRNA (AK048087) named cardiac fibroblast-associated transcript (Cfast), which is significantly elevated after MI. Silencing Cfast expression by small interfering RNAs (siRNAs) or lentiviral short hairpin RNAs (shRNAs) resulted in suppression of fibrosis-related gene expression and transdifferentiation of myofibroblasts into cardiac fibroblasts. Depletion of Cfast by lentiviral shRNAs in mouse hearts significantly attenuated cardiac fibrosis induced by MI or isoproterenol-infusion. Importantly, inhibition of Cfast ameliorated cardiac function following cardiac injury. RNA pull-down followed by mass spectrometry analyses identified COTL1 (coactosin-like 1) as one of the Cfast interacting proteins. Mechanistically, Cfast competitively inhibits the COTL1 interaction with TRAP1 (transforming growth factor-β receptor-associated protein 1), which enhances TGF-β signaling by augmenting SMAD2/SMAD4 complex formation. Therefore, our study identifies Cfast as a novel cardiac fibroblast-enriched lncRNA that regulates cardiac fibroblast activation in response to pathophysiological stress. Cfast could serve as a potential therapeutic target for the prevention of cardiac fibrosis and cardiac diseases.

Abstract Background Intravascular ultrasound (IVUS) is the golden standard in accessing the coronary lesions, stenosis, and atherosclerosis plaques. In this paper, a fully automatic approach by an 8-layer U-Net is developed to segment the coronary artery lumen and the area bounded by external elastic membrane (EEM), i.e., cross-sectional area (EEM-CSA). The database comprises single-vendor and single-frequency IVUS data. Particularly, the proposed data augmentation of MeshGrid combined with flip and rotation operations is implemented, improving the model performance without pre- or post-processing of the raw IVUS images. Results The mean intersection of union (MIoU) of 0.937 and 0.804 for the lumen and EEM-CSA, respectively, were achieved, which exceeded the manual labeling accuracy of the clinician. Conclusion The accuracy shown by the proposed method is sufficient for subsequent reconstruction of 3D-IVUS images, which is essential for doctors’ diagnosis in the tissue characterization of coronary artery walls and plaque compositions, qualitatively and quantitatively.

Background In the recent decades, the development of novel digital health technologies enables doctors to monitor ECG and vital signs remotely. But the data on applying the noninvasive wearable smartwatch on patients with transcatheter aortic valve replacement (TAVR) are unknown. Methods and Results We performed a prospective, observational cohort study to evaluate the feasibility of a novel, virtual, and remote health care strategy for patients with TAVR discharged to home with smart wearable devices. A total of 100 consecutive patients with severe aortic stenosis who underwent elective transfemoral TAVR were enrolled and received the Huawei smartwatch at least 1 day before TAVR. Vital signs, including heart rate, rhythm, oxygen saturation, and activity, were continuously recorded. Single‐lead ECG was recorded twice per day in the week following TAVR discharge and at least 2 days a week for the subsequent month after TAVR discharge. A designated heart team member provided remote health care with the data from the smartwatch when the patient had a need. Thirty‐eight cardiac events were reported in 34 patients after discharge, with most of the events (76.0%) detected and confirmed by the smartwatch. Six patients were advised and readmitted to the hospital for arrhythmia events detected by the smartwatch, of whom 4 patients received pacemaker implantation. The remaining 28 (82.4%) patients received telemedicine monitoring instead of face‐to‐face clinical visits, and 3 of them received new medication treatment under the online guidance of doctors. New‐onset left branch bundle block was found in 48 patients, with transient characteristics, and recovered spontaneously in 30 patients, and new‐onset atrial fibrillation was detected in 4 patients. There were no significant differences in the average weekly heart rates or the ratio of abnormal or low oxygen saturation when compared with the baseline. The average daily steps increased over time significantly (baseline, 870±1353 steps; first week, 1986±2406 steps; second week, 2707±2716 steps; third week, 3059±3036 steps; fourth week, 3678±3485 steps, P

Abstract Background Arrhythmogenic cardiomyopathy (AC) is one of the leading causes for sudden cardiac death (SCD). Recent studies have identified mutations in cardiac desmosomes as key players in the pathogenesis of AC. However, the specific etiology in individual families remains largely unknown. Methods A 4-generation family presenting with syncope, lethal ventricular arrhythmia and SCD was recruited. Targeted next generation sequencing (NGS) was performed and validated by Sanger sequencing. Plasmids containing the mutation and wild type (WT) were constructed. Real-time PCR, western-blot and immunofluorescence were performed to detect the functional change due to the mutation. Results The proband, a 56-year-old female, presented with recurrent palpitations and syncope. An ICD was implanted due to her family history of SCD/ aborted SCD. NGS revealed a novel heterozygous frame-shift variant (c.832delG) in Desmoplakin (DSP) among 5 family members. The variant led to frame-shift and premature termination, producing a truncated protein. Cardiac magnetic resonance (CMR) of the family members carrying the same variant shown myocardium thinning and fatty infiltration in the right ventricular, positive bi-ventricular late gadolinium enhancement and severe RV dysfunction, fulfilling the diagnostic criteria of AC. HEK293T cells transfected with mutant plasmids expressed truncated DSP mRNA and protein, upregulation of nuclear junction plakoglobin (JUP) and downregulation of β-catenin, when compared with WT. Conclusion We infer that the novel c.832delG variant in DSP was associated with AC in this family, likely through Wnt/β-catenin signaling pathway.

Abstract Background Extensive bioactivities of alkaloids from the genus Macleaya (Macleaya cordata (Willd.) R. Br. and Macleaya microcarpa (Maxim.) Fedde) have been widely reported, as well as more and more concerned from the scientific communities. However, systematic research on the phytochemical information of M. microcarpa is incomplete. The aim of this study was to rapidly and conveniently qualitative analyze alkaloids from M. microcarpa by ultra-performance liquid chromatography/quadrupole-time-of-fight mass spectrometry (UHPLC–Q-TOF-MS) using accurate mass weight and characteristic fragment ions, furthermore separate and identify the main alkaloids, test antitumor activity in vitro and antiangiogenic activity in vivo. Results A total of 14 alkaloids from fruits of M. microcarpa were identified by UHPLC–Q-TOF-MS, including 5 protopines, 2 benzophenanthridines, 1 dimer, 1 dihydrobenzophenanthridines and 5 unknown structure compounds. Two major alkaloids were isolated by various column chromatographic methods. Their structures were determined by NMR data and related literatures. The two major alkaloids were evaluated for intro cytotoxic activities against HL-60, MCF-7, A-549, and in vivo antiangiogenic activity using transgenic zebrafish. Conclusions Current qualitative method based on UHPLC–Q-TOF-MS technique provided a scientific basis for isolation, structural identification, and in vitro or in vivo pharmacological further study of alkaloids from M. microcarpa in the future.

A SiC trench MOSFET with an enhanced vertical RESURF effect is proposed and analyzed in this article. The device features a deep oxide trench surrounded by a P-type doping layer at the source-side. With the assistant depletion effect of the P-type layer, the concentration of the N-drift region is increased and the specific on-resistance (Ron,sp) is thus reduced. The P-type doping can significantly reduce the intensity of the electric field at the gate oxide corner, and modulate the bulk electric field for the device. The breakdown voltage (BV) is therefore improved. As a result, the proposed SiC MOSFET has a better trade-off of BV and Ron,sp. The Ron,sp decreases by 59% and the BV increases by 16% for the proposed device without a CSL layer compared with the conventional trench MOSFET with a CSL layer. Meanwhile, the device exhibits a lower gate-to-drain charge (Qgd) which is reduced by 52% and the switching loss is also reduced by 19%.

Collapsible loess is a kind of soil with special properties, and is widely distributed in China. When it is not wetted by water, its strength is generally high and its compressibility is low. However, when collapsible loess is wetted by water under a certain pressure, the soil structure will be rapidly destroyed, resulting in large additional subsidence. Therefore, when engineering constructions on collapsible loess sites are carried out, appropriate foundation treatment measures must be taken to eliminate foundation collapsibility. Because of their advantages, static pressure plain soil compaction (SP−PSC) piles are widely used for collapsible loess foundation treatments in China. However, at present, there is still a lack of accurate understanding of the distribution of compaction coefficient of soil among SP−PSC pile groups on collapsible loess foundations. The present study systematically investigated the distribution of the soil compaction coefficient among SP−PSC pile groups based on SP−PSC pile group tests and finite element analyses. The effect of different factors on soil compaction coefficient was analyzed and explored, including the pile diameter and length of SP−PSC piles, the soil moisture content, the pile spacing within the SP−PSC pile group, and the depth to ground. Finally, the simplified calculation models of the compaction coefficient of the soil at the center of pile group and at the midpoints of adjacent piles were analytically formulated. These models established a theoretical basis for the design and construction of SP−PSC pile groups on collapsible loess foundations.

Puerarin has been reported as a potential agent for neuro-inflammatory disorders. However, there have been no reports of using puerarin for the treatment of depression based on Toll-like receptor 4 (TLR4)–mediated inflammatory injury. In this study, we evaluated the protective effects of puerarin on depression-like rats induced by a high-fat diet (HFD) combined with chronic unpredictable mild stress (CUMS). The mechanism was screened by lipidomics and molecular docking and confirmed by in vivo tests. Puerarin treatment significantly improved 1% sucrose preference and ameliorated depression-like behavior in the open-field test. The antidepressive effects of puerarin were associated with decreased pro-inflammatory cytokine production, including interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), and increased anti-inflammatory cytokine levels (IL-10) in rat hippocampal tissues and plasma. Hematoxylin–eosin (H&E), immunofluorescence staining, and Western blotting results displayed that puerarin alleviated inflammatory injury by suppressing TLR4 expression and by repairing the intestine mucus barrier via enhancing the expression of claudin-1 and occludin. Non-targeted lipidomics analysis showed that the most significantly different metabolites modified by puerarin were phospholipids. Puerarin treatment–altered biomarkers were identified as PC (15:1/20:1), PE (15:1/16:1), and PI (18:2/20:1) in comparison with the HFD/CUMS group. Molecular docking modeling revealed that puerarin could bind with cytosolic phospholipase A2 (cPLA2) and cyclooxygenase-2 (COX-2), which play central roles in TLR4-mediated phospholipid metabolism. In vivo, puerarin treatment decreased the enzyme activities of cPLA2 and COX-2, resulting in lower production of prostaglandin E2 (PGE2) in hippocampal and intestinal tissues. In conclusion, puerarin treatment reverses HFD/CUMS-induced depression-like behavior by inhibiting TLR4-mediated intestine mucus barrier dysfunction and neuro-inflammatory damages via the TLR4/cPLA2/COX-2 pathway.

Background: Subclinical leaflet thrombosis (SLT) is an important sequela that compromises the durability of the bioprosthetic valve.Objectives: To better determine the effect of SLT in bicuspid aortic valve (BAV), we performed a retrospective assessment of CT-defined SLT in BAV and tricuspid aortic valve (TAV) stenotic patients.Methods: We consecutively collected patients undergoing the TAVR between August 2015 and March 2020 in our center. A total of 170 BAV and 201 TAV cases were enrolled. Multidetector computed tomography was performed within 30 days and at 1-year.Results: Twenty cases in the BAV group and 19 cases in the TAV group had hypoattenuated leaflet thickening (HALT) in 30 days (12.5 vs. 9.9%, p = 0.449), and 52 cases in BAV and 61 cases in TAV had the HALT (34.9 vs. 36.7%, p = 0.733) at 1-year follow-up. The mean aortic gradient (MAG) and effective orifice areas (EOA) values were comparable between the two groups at 30 days (HALT vs. no HALT; 10.8 ± 4.8 vs. 11.3 ± 6.0, p = 0.638; 1.6 ± 0.4 vs. 1.6 ± 0.3, p = 0.724), and still, no difference was observed in the MAG at 1-year (11.5 ± 5.6 vs. 10.6 ± 5.1, p = 0.164). However, the EOA at 1-year was statistically different between the two groups (1.5 ± 0.3 vs. 1.6 ± 0.4, p = 0.004). The multivariate logistic regression analysis demonstrated the anticoagulation and age as independent predictors both in the BAV and TAV groups at 1-year. There was no difference in clinical events between the HALT and no HALT group in relevant to BAV or TAV at 1-year follow-up.Conclusions: The presence of subclinical leaflet thrombosis defined by the CT was comparable between the BAV and TAV in the first year after the TAVR procedure. Age and anticoagulation were the independent predictors of the subclinical leaflet thrombosis at 1 year after the TAVR. There was no difference in relevant clinical events between the BAV and TAV groups at 1-year follow-up.

Background: Perturbation of energy metabolism exacerbates cardiac dysfunction, serving as a potential therapeutic target in congestive heart failure. Although circulating free fatty acids (FFAs) are linked to insulin resistance and risk of coronary heart disease, it still remains unclear whether circulating FFAs are associated with the prognosis of patients with acute heart failure (AHF).Methods: This single-center, observational cohort study enrolled 183 AHF patients (de novo heart failure or decompensated chronic heart failure) in the Second Affiliated Hospital, Zhejiang University School of Medicine. All-cause mortality and heart failure (HF) rehospitalization within 1 year after discharge were investigated. Serum FFAs were modeled as quartiles as well as a continuous variable (per SD of FFAs). The restricted cubic splines and cox proportional hazards models were applied to evaluate the association between the serum FFAs level and all-cause mortality or HF rehospitalization.Results: During a 1-year follow-up, a total of 71 (38.8%) patients had all-cause mortality or HF rehospitalization. The levels of serum FFAs positively contributed to the risk of death or HF rehospitalization, which was not associated with the status of insulin resistance. When modeled with restricted cubic splines, the serum FFAs increased linearly for the incidence of death or HF rehospitalization. In a multivariable analysis adjusting for sex, age, body-mass index, coronary artery disease, diabetes mellitus, hypertension, left ventricular ejection fraction and N-terminal pro-brain natriuretic peptid, each SD (303.07 μmol/L) higher FFAs were associated with 26% higher risk of death or HF rehospitalization (95% confidence interval, 2–55%). Each increasing quartile of FFAs was associated with differentially elevated hazard ratios for death or HF rehospitalization of 1 (reference), 1.71 (95% confidence interval, [0.81, 3.62]), 1.41 (95% confidence interval, [0.64, 3.09]), and 3.18 (95% confidence interval, [1.53, 6.63]), respectively.Conclusion: Serum FFA levels at admission among patients with AHF were associated with an increased risk of adverse outcomes. Additional studies are needed to determine the causal-effect relationship between FFAs and acute cardiac dysfunction and whether FFAs could be a potential target for AHF management.

Objective: To evaluate the predictors of new-onset conduction disturbances in bicuspid aortic valve patients using self-expanding valve and identify modifiable technical factors.Background: New-onset conduction disturbances (NOCDs), including complete left bundle branch block and high-grade atrioventricular block, remain the most common complication after transcatheter aortic valve replacement (TAVR).Methods: A total of 209 consecutive bicuspid patients who underwent self-expanding TAVR in 5 centers in China were enrolled from February 2016 to September 2020. The optimal cut-offs in this study were generated from receiver operator characteristic curve analyses. The infra-annular and coronal membranous septum (MS) length was measured in preoperative computed tomography. MSID was calculated by subtracting implantation depth measure on postoperative computed tomography from infra-annular MS or coronal MS length.Results: Forty-two (20.1%) patients developed complete left bundle branch block and 21 (10.0%) patients developed high-grade atrioventricular block after TAVR, while 61 (29.2%) patients developed NOCDs. Coronal MS 73 years (OR: 2.26, 95% CI: 1.17–4.36, p = 0.015), Δcoronal MSID 3.2% (OR: 3.42, 95% CI: 1.74–6.72, p < 0.001) showed best predictive value of NOCDs, with c-statistic = 0.768 (95% CI: 0.699–0.837, p < 0.001). The incidence of NOCDs was much lower (7.5 vs. 55.2%, p < 0.001) in patients without Δcoronal MSID 3.2% compared with patients who had these two risk factors.Conclusion: The risk of NOCDs in bicuspid aortic stenosis patients could be evaluated based on MS length and prosthesis oversizing ratio. Implantation depth guided by MS length and reducing the oversizing ratio might be a feasible strategy for heavily calcified bicuspid patients with short MS.

Background: Patient-specific computer simulation of transcatheter aortic valve replacement (TAVR) can provide unique insights in device-patient interaction.Aims: This study was to compare transcatheter aortic valve sealing behavior in patients with bicuspid aortic valves (BAV) and tricuspid aortic valves (TAV) through patient-specific computational modeling.Methods: Patient-specific computer simulation was retrospectively performed with FEops HEARTguide for TAVR patients. Simulation output was compared with postprocedural computed tomography and echocardiography to validate the accuracy. Skirt malapposition was defined by a distance larger than 1 mm based on the predicted device-patient interaction by quantifying the distance between the transcatheter heart valve (THV) skirt and the surrounding anatomical regions.Results: In total, 43 patients were included in the study. Predicted and observed THV frame deformation showed good correlation (R2 ≥ 0.90) for all analyzed measurements (maximum diameter, minimum diameter, area, and perimeter). The amount of predicted THV skirt malapposition was strongly linked with the echocardiographic grading of paravalvular leakage (PVL). More THV skirt malapposition was observed for BAV cases when compared to TAV cases (22.7 vs. 15.5%, p < 0.05). A detailed analysis of skirt malapposition showed a higher degree of malapposition in the interleaflet triangles section for BAV cases as compared to TAV patients (11.1 vs. 5.8%, p < 0.05).Conclusions: Patient-specific computer simulation of TAVR can accurately predict the behavior of the Venus A-valve. BAV patients are associated with more malapposition of the THV skirt as compared to TAV patients, and this is mainly driven by more malapposition in the interleaflet triangle region.

Background: A new method for calculating fraction flow reserve (FFR) without pressure-wire (angiography-derived FFR) based on invasive coronary angiography (ICA) images can be used to evaluate the functional problems of coronary stenosis.Objective: The aim of this study was to assess the diagnostic performance of a novel method of calculating the FFR compared to wire-based FFR using retrospectively collected data from patients with stable angina.Methods: Three hundred patients with stable angina pectoris who underwent ICA and FFR measurement were included in this study. Two ICA images with projections >25° apart at the end-diastolic frame were selected for 3D reconstruction. Then, the contrast frame count was performed in an angiographic run to calculate the flow velocity. Based on the segmented vessel, calculated velocity, and aortic pressure, AccuFFRangio distribution was calculated through the pressure drop equation.Results: Using FFR ≤ 0.8 as a reference, we evaluated AccuFFRangio performance for 300 patients with its accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Comparison of AccuFFRangio with wire-measured FFR resulted in an area under the curve (AUC) of 0.954 (per-vessel, p < 0.0001). Accuracy for AccuFFRangio was 93.7% for Pa set from measurement and 87% for Pa = 100 mmHg in this clinical study. Overall sensitivity, specificity, PPV, and NPV for per-vessel were 90, 95, 86.7, 96.3, and 57.5, 97.7, 90.2, 86.3%, respectively. Overall accuracy, sensitivity, specificity, PPV, and NPV for 2-dimensional (2D) quantitative coronary angiography (QCA) were 63.3, 42.5, 70.9, 34.7, and 77.2%, respectively. The average processing time of AccuFFRangio was 4.30 ± 1.87 min.Conclusions: AccuFFRangio computed from coronary ICA images can be an accurate and time-efficient computational tool for detecting lesion-specific ischemia of coronary artery stenosis.

Background: The three-dimensional (3D) geometry of coronary atherosclerotic plaques is associated with plaque growth and the occurrence of coronary artery disease. However, there is a lack of studies on the 3D geometric properties of coronary plaques. We aim to investigate if coronary plaques of different sizes are consistent in geometric properties.Methods: Nineteen cases with symptomatic stenosis caused by atherosclerotic plaques in the left coronary artery were included. Based on attenuation values on computed tomography angiography images, coronary atherosclerotic plaques and calcifications were identified, 3D reconstructed, and manually revised. Multidimensional geometric parameters were measured on the 3D models of plaques and calcifications. Linear and non-linear (i.e., power function) fittings were used to investigate the relationship between multidimensional geometric parameters (length, surface area, volume, etc.). Pearson correlation coefficient (r), R-squared, and p-values were used to evaluate the significance of the relationship. The analysis was performed based on cases and plaques, respectively. Significant linear relationship was defined as R-squared > 0.25 and p < 0.05.Results: In total, 49 atherosclerotic plaques and 56 calcifications were extracted. In the case-based analysis, significant linear relationships were found between number of plaques and number of calcifications (r = 0.650, p = 0.003) as well as total volume of plaques (r = 0.538, p = 0.018), between number of calcifications and total volume of plaques (r = 0.703, p = 0.001) as well as total volume of calcification (r = 0.646, p = 0.003), and between the total volumes of plaques and calcifications (r = 0.872, p < 0.001). In plaque-based analysis, the power function showed higher R-squared values than the linear function in fitting the relationships of multidimensional geometric parameters. Two presumptions of plaque geometry in different growth stages were proposed with simplified geometric models developed. In the proposed models, the exponents in the power functions of geometric parameters were in accordance with the fitted values.Conclusion: In patients with coronary artery disease, coronary plaques and calcifications are positively related in number and volume. Different coronary plaques are consistent in the relationship between geometry parameters in different dimensions.

Abstract Angiogenesis is essential for vascular development. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating angiogenesis remain under‐explored. Human embryonic stem cell‐derived mesenchymal stem cells (hES‐MSCs) are shown to exert more potent cardioprotective effects against cardiac ischemia than human bone marrow‐derived MSCs (hBM‐MSCs), associated with enhanced neovascularization. The purpose of this study is to search for angiogenic lncRNAs enriched in hES‐MSCs, and investigate their roles and mechanisms. AC103746.1 is one of the most highly expressed intergenic lncRNAs detected in hES‐MSCs versus hBM‐MSCs, and named as SCDAL (stem cell‐derived angiogenic lncRNA). SCDAL knockdown significantly reduce the angiogenic potential and reparative effects of hES‐MSCs in the infarcted hearts, while overexpression of SCDAL in either hES‐MSCs or hBM‐MSCs exhibits augmented angiogenesis and cardiac function recovery. Mechanistically, SCDAL induces growth differentiation factor 6 (GDF6) expression via direct interaction with SNF5 at GDF6 promoter. Secreted GDF6 promotes endothelial angiogenesis via non‐canonical vascular endothelial growth factor receptor 2 activation. Furthermore, SCDAL‐GDF6 is expressed in human endothelial cells, and directly enhances endothelial angiogenesis in vitro and in vivo. Thus, these findings uncover a previously unknown lncRNA‐dependent regulatory circuit for angiogenesis. Targeted intervention of the SCDAL‐GDF6 pathway has potential as a therapy for ischemic heart diseases.

The miR-17-92 cluster has been shown to regulate cardiomyocyte proliferation in vitro and in genetic mutation and overexpression models. Here the authors show that the cluster member miR-19a/19b regulates cardiomyocyte proliferation in vivo, and that delivery of miR-19a/19b to the heart leads to both short-term and long-term protective responses to myocardial infarction.

The theoretical analysis of breakdown model for a deep trench superjunction (DT-SJ) SiC VDMOS is presented in this paper. The vertical electric field distribution is derived by the electric field decomposition. Then, a fitting dependence of the critical electric field on the doping concentration for the device is obtained, based on which, the model of breakdown voltage is given for the DT-SJ SiC VDMOS. Analytical results are compared with simulative results with the same thicknesses of drift region from 8 μm to 16 μm and the doping concentrations from 4 × 1016 cm-3 to 8 × 1016 cm-3. It is numerically demonstrated that the errors between model and simulation are less than 3% when N pillar and P pillar have the same width of 1μm.

Abstract Stem cell‐based therapy has great potential in regenerative medicine. However, the survival and engraftment rates of transplanted stem cells in disease regions are poor and limit the effectiveness of cell therapy due to the fragility of stem cells. Here, an approach involving a single‐cell coating of surface‐anchored nanogel to regulate stem cell fate with anti‐apoptosis capacity in the hypoxic and ischemic environment of infarcted hearts is developed for the first time. A polysialic acid‐based system is used to anchor microbial transglutaminase to the external surface of the cell membrane, where it catalyzes the crosslinking of gelatin. The single‐cell coating with surface‐anchored nanogel endows mesenchymal stem cells (MSCs) with stress resistance by blocking the activity of apoptotic cytokines including the binding of tumor necrosis factor α (TNFα) to tumor necrosis factor receptor, which in turn maintains mitochondrial integrity, function and protects MSCs from TNFα‐induces apoptosis. The administration of surface engineered MSCs to hearts results in significant improvements in engraftment, cardiac function, infarct size, and vascularity compared with using uncoated MSCs in treating myocardial infarction. The surface‐anchored, biocompatible cell surface engineering with nanogel armor provides a new way to produce robust therapeutic stem cells and may explore immense potentials in cell‐based therapy.

Background: Atherosclerotic plaques are the major cause of coronary artery disease (CAD). Currently, computed tomography (CT) is the most commonly applied imaging technique in the diagnosis of CAD. However, the accurate extraction of coronary plaque geometry from CT images is still challenging.Summary of Review: In this review, we focused on the methods in recent studies on the CT-based coronary plaque extraction. According to the dimension of plaque extraction method, the studies were categorized into two-dimensional (2D) and three-dimensional (3D) ones. In each category, the studies were analyzed in terms of data, methods, and evaluation. We summarized the merits and limitations of current methods, as well as the future directions for efficient and accurate extraction of coronary plaques using CT imaging.Conclusion: The methodological innovations are important for more accurate CT-based assessment of coronary plaques in clinical applications. The large-scale studies, de-blooming algorithms, more standardized datasets, and more detailed classification of non-calcified plaques could improve the accuracy of coronary plaque extraction from CT images. More multidimensional geometric parameters can be derived from the 3D geometry of coronary plaques. Additionally, machine learning and automatic 3D reconstruction could improve the efficiency of coronary plaque extraction in future studies.

Objectives Transcatheter aortic valve replacement (TAVR) is increasingly performed. Physically small Asians have smaller aortic root and peripheral vessel anatomy. The influence of gender of Asian patients undergoing TAVR is unknown and may affect outcomes. The aim of this study was to assess sex differences in Asian patients undergoing TAVR.Methods Patients undergoing TAVR from eight countries were enrolled. In this retrospective analysis, we examined differences in characteristics, 30-day clinical outcomes and 1-year survival between female and male Asian patients.Results Eight hundred and seventy-three patients (54.4% women) were included. Women were older, smaller and had less coronary artery and lung disease but tended to have higher logistic EuroSCOREs. Smaller prostheses were used more often in women. Major vascular complications occurred more frequently in women (5.5% vs 1.8%, p

By analyzing the relation between time and speed, the relation between time and gravitational field, the gravitational redshift of photon and the black-body radiation theorem, the conclusion that time on an object is proportional to the fourth power of the absolute temperature of the object is obtained. Applying the above conclusion about the nature of time, the author analyzes the Mpemba effect and the inverse Mpemba effect, and reaches the following conclusion: the Mpemba effect is the time effect produced when heat flows from objects into space, and the “inverse” Mpemba effect is the time effect produced when heat flows from space into objects.

Double silicon drift layers are used to reduce the specific on-resistance (Ron,sp) for a trench-gate-integrated lateral double-diffused MOSFET (DDL TG LDMOS) based on SOI technology in this paper. A trench-gate is incorporated into the oxide trench, a n-type drift layer with a high doping concentration is introduced on the topside of the original drift layer around the oxide trench, and a p-type pillar layer with a high doping concentration is inserted between the dual drift layers. First, the incorporated trench-gate constitutes dual current conduction channels, which decreases the Ron,sp. Second, the whole electric fields on the device surface and around the oxide trench are modulated on the basis of RESURF condition, leading to a higher breakdown voltage (BV) at off-state. Finally, the doping concentration of the drift layers is increased by an assistant depletion effect from the p-pillar, which not only improves the BV but also reduces the Ron,sp. Consequently, compared with those of the conventional trench SOI LDMOS on the same drift region of 18 μm and top silicon layer of 25 μm, a higher BV of 477 V and a lower Ron,sp of 32.1 mΩ∙cm2 are obtained for the DDL TG SOI LDMOS, while BV is improved by 33.5% and Ron,sp is reduced by 92.9%, respectively.

Mesenchymal stem cell (MSC) transplantation has demonstrated its potential in repairing infarct heart tissue and recovering heart function after myocardial infarction (MI). However, its therapeutic effect is still limited due to poor MSC engraftment at the injury site whose tissue stiffness and local inflammation both dynamically and rapidly change after MI. Whether and how inflammatory cytokines could couple with stiffness change to affect MSC engraftment in the infarct zone still remain unclear. In this study, we characterized dynamic stiffness changes of and inflammatory cytokine expression in the infarct region of rat heart within a month after MI. We found that the tissue stiffness of the heart tissue gradually increased and peaked 21 days after MI along with the rapid upregulation of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in the first 3 days, followed by a sharp decline. We further demonstrated in vitro that immobilized inflammatory cytokine IL-6 performed better than the soluble form in enhancing MSC adhesion to stiffened substrate through IL-6/src homology 2 (SH2) domain-containing tyrosine phosphatase-2 (SHP2)/integrin signaling axis. We also confirmed such mechano-immune coupling of tissue stiffness and inflammatory cytokines in modulating MSC engraftment in the rat heart after MI in vivo. Our study provides new mechanistic insights of mechanical–inflammation coupling to improve MSC mechanosensing and adhesion, potentially benefiting MSC engraftment and its clinical therapy for MI.

BackgroundPoor cell survival after transplantation restricts the therapeutic potential of mesenchymal stem cell (MSC) transplantation into infarcted hearts, particularly in older individuals. TPP1, a component of the shelterin complex that is involved in telomere protection, is highly expressed in young MSCs but declines in aged ones. Here, we explore whether TPP1 overexpression in aged mouse MSCs improves cell viability in vivo and in vitro.MethodsAged mouse MSCs overexpressing TPP1 were injected into the peri-infarct area of the mouse heart after left anterior descending coronary artery ligation. In parallel, to evaluate cellular-level effects, H2O2 was applied to MSCs in vitro to mimic the microenvironment of myocardial injury.ResultsIn vivo, the transplantation of aged MSCs overexpressing TPP1 resulted in improved cell survival, enhanced cardiac function, and reduced fibrosis compared to unmodified aged MSCs. In vitro, TPP1 overexpression protected aged MSCs from H2O2-induced apoptosis and enhanced DNA double-strand break (DSB) repair. In addition, the phosphorylation of AKT and the key DSB repair protein MRE11 were both significantly upregulated in aged MSCs that overexpressed TPP1.ConclusionsOur results reveal that TPP1 can enhance DNA repair through the AKT/MRE11 pathway, thereby improving the therapeutic effects of aged MSC transplantation and offering significant potential for the clinical application of autologous transplantation in aged patients.

To reduce specific on-resistance (Ron,sp) of power devices, a novel SOI (silicon-on-insulator) trench gate LDMOS with heavily doping L-shaped P/N pillars and vertical dual-trench-gates is proposed in this paper, and its physical mechanism and electrical performance are investigated by numerical simulation. The L-shaped P-pillar raises the optimal doping impurity concentration of the drift region (Nd) remarkably from 1.7 × 1015 cm−3 to 1.25 × 1016 cm−3 by causing assistant depletion effect for drift region, hence a lower specific on-resistance (Ron,sp) with a 3.6 mΩ·cm2 is achieved. Meanwhile, the voltage capacity of the new structure is improved resulting from two new electric-field peaks produced by L-shaped P/N pillars. Consequently, a much lower Ron,sp and a higher breakdown voltage (BV) are achieved by the proposed structure. Simulated results show that the Ron,sp, BV, and Baliga’s figure of merit (FOM, FOM = BV2/Ron,sp) for the new structure are improved by 84.3%, 31.4%, and 991%, respectively, in comparison with the conventional trench LDMOS.

Angiogenesis is the nature and pathological process of blood vessel growth from pre-existing vascular buds. It plays an important role in cancer and cardiovascular disease. The aorta ring assay is an approach to study angiogenesis. In this experiment, we used the aorta of rat as the study material, cleaned the surrounding tissue of aorta and cut it into 1 mm long rings. Next, the rings were cultured in growth factor-reduced matrigel polymerized at 37 °C. Angiogenesis was assessed at 7 days by using an inverted microscope platform.

Mesenchymal stromal cells (MSCs) are promising candidates for regenerative medicine because of their multipotency, immune-privilege, and paracrine properties including the potential to promote angiogenesis. Accumulating evidence suggests that the inherent properties of cytoprotection and tissue repair by native MSCs can be enhanced by various preconditioning stimuli implemented prior to cell transplantation. Growth hormone-releasing hormone (GHRH), a stimulator in extrahypothalamus systems including tumors, has attracted great attentions in recent years because GHRH and its agonists could promote angiogenesis in various tissues. GHRH and its agonists are proangiogenic in responsive tissues including tumors, and GHRH antagonists have been tested as antitumor agents through their ability to suppress angiogenesis and cell growth. GHRH-R is expressed by MSCs and evolving work from our laboratory indicates that treatment of MSCs with GHRH agonists prior to cell transplantation markedly enhanced the angiogenic potential and tissue reparative properties of MSCs through a STAT3 signaling pathway. In this review we summarized the possible effects of GHRH analogues on cell growth and development, as well as on the proangiogenic properties of MSCs. We also discussed the relationship between GHRH analogues and MSC-mediated angiogenesis. The analyses provide new insights into molecular pathways of MSCs-based therapies and their augmentation by GHRH analogues.