Comparative efficacy of interventional therapies and devices for coronary in-stent restenosis: A systematic review and network meta-analysis of randomized controlled trials.

Background: In-stent restenosis (ISR) has become a significant obstacle to interventional therapy for atherosclerotic cardiovascular disease. The optimal percutaneous coronary intervention (PCI) strategy for patients with coronary ISR remains controversial. This network meta-analysis (NMA) was aimed to compare and estimate the effectiveness of different PCI strategies and commercial devices for the treatment of patients with coronary ISR. Methods: In present study, we systematically searched PubMed, Embase, Web of Science, and Cochrane Library from database inception to October 20, 2022, to identify randomized controlled trials. We included studies comparing various PCI strategies for the treatment of any type of coronary ISR. The study was registered with PROSPERO, CRD 42022364308. Results: We included 44 eligible trials including 8479 patients, 39 trials comparing the treatment effects of 10 PCIs, and 5 trials comparing the efficacy between different types of drug-eluting stent (DES) or drug-coated balloon (DCB) devices. Among the PCIs, everolimus-eluting stent was the optimal strategy considering target lesion revascularization (TLR), percent diameter stenosis (%DS), and binary restenosis (BR), and sirolimus-coated balloon was the optimal strategy considering late lumen loss (LLL). In the comparison of commercial devices, the combination strategy excimer laser coronary angioplasty plus SeQuent Please paclitaxel-coated balloon showed promising therapeutic prospects. Conclusions: DCB and DES remain the preferred treatment strategies for coronary ISR, considering both the primary clinical outcome (TLR) and the angiographic outcomes (LLL, BR, %DS). Personalized combination interventions including DCB or DES hold promise as a novel potential treatment pattern for coronary ISR.

Radiomics from dual-energy CT-derived iodine maps predict lymph node metastasis in head and neck squamous cell carcinoma.

OBJECTIVE: To develop and validate an iodine maps-based radiomics nomogram for preoperatively predicting cervical lymph node metastasis (LNM) in head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: A total of 278 patients who pathologically confirmed as HNSCC were retrospectively recruited from two medical centers between June 2012 and July 2022. The training set (n = 152) and internal set (n = 67) were randomly selected from medical center A, and the patients from medical center B were enrolled as the external set (n = 69). The minority group in the training set was balanced by the adaptive synthetic sampling (ADASYN) approach. Radiomics features were extracted from dual-energy CT-derived iodine maps at arterial phase (AP) and venous phase (VP), respectively. Three radiomics signatures were constructed to predict the LNM by using a random forest algorithm. The independent clinical predictors for LNM were identified by multivariate analysis and combined with radiomics signatures to establish a radiomic-clinical nomogram. The performance of radiomic-clinical nomogram was evaluated with respect to its discrimination and clinical usefulness. RESULTS: The AP-VP-incorporated radiomics model exhibited a great predictive performance for LNM prediction with an area under curve (AUC) of 0.885 (95% CI, 0.836-0.933) in ADASYN-training set and confirmed in all validation sets. The nomogram that incorporated AP-VP radiomics signatures, CT-reported LN status, and histological grades yielded AUCs of 0.920 (95% CI, 0.881-0.959) in ADASYN-training set, 0.858 (95% CI, 0.771-0.944) in internal validation, and 0.849 (95% CI, 0.752-0.946) in external validation, with good calibration in all cohorts (p > 0.05). Decision curve analyses indicated the nomogram was clinically useful. In addition, the predictive performance of clinical-radiomics nomogram was also validation in combing cohorts. Stratified analysis confirmed the stability of nomogram, particularly in group negative for CT-reported LNM. CONCLUSION: Clinical-radiomics nomogram based on iodine maps exhibited promising performance in predicting LNM and providing valuable information for making individualized therapy decisions.

Clinical value of dual-energy CT for predicting occult metastasis in central neck lymph nodes of papillary thyroid carcinoma.

OBJECTIVES: To predict the probability of occult lymph node metastasis (OLNM) in the central cervical by analyzing the dual-energy computed tomography (DECT) parameters derived from papillary thyroid carcinoma (PTC). METHODS: Data were retrospectively collected from patients with pathologically confirmed PTC who underwent arterial and venous phases of enhanced DECT with concurrent central neck lymph node dissection (CLND). Three clinical features, three shape-related features, and twenty-six DECT-derived parameters were measured. The univariate and multivariate analyses were applied to select the relevant parameters and develop the nomogram. RESULTS: A total 140 cases with negative diagnosis of cervical central lymph node metastases by preoperative evaluation were included, among which 88 patients with metastasis (OLNM +) and 52 patients without metastasis (OLNM -) were finally confirmed by pathology. (1) Anteroposterior/transverse diameter ratio (A/T) derived from the PTC focus had significant difference between the OLNM + and OLNM - groups (p < 0.05). (2) In the arterial phase, iodine concentration (ICarterial), normalized iodine concentration (NICarterial), effective atomic number (Zeff-arterial), electron density (EDarterial), and slope of energy curve (karterial) from PTC focus showed significant difference (all p < 0.05) between the two groups. In the venous phase, only the CT value under the 40 keV (HU40keVvenous) had differences (p < 0.05). (3) The nomogram was produced to predict the probability of OLNM, and the AUC, sensitivity, and specificity in the training and test cohort were 0.830, 75.0%, 76.9%, and 0.829, 65.9%, 84.6%, respectively. CONCLUSIONS: DECT parameters combined with shape-related feature derived from PTC might be used as predictors of OLNM in the central neck. CLINICAL RELEVANCE STATEMENT: Preoperative imaging evaluation combining shape-related features and dual-energy CT parameters could serve as a reference to discern occult lymph node metastasis in central neck during the surgically planning of papillary thyroid carcinoma. KEY POINTS: • Papillary thyroid carcinoma (PTC) patients may have occult lymph node metastasis (OLNM) in the central neck, which is extremely difficult to find by preoperative imaging examination. • Dual-energy CT quantitative evaluation has higher accuracy than conventional CT and can predicting OLNM in the central neck of PTC. • Dual-energy CT quantitative parameters and morphology of PTC can serve as a useful tool in predicting OLNM in the central neck, and as a guide for personalized treatment.

Construction and application of highly efficient waste cooking oil degrading bacteria consortium in oily wastewater.

The treatment of cooking oil wastewater is an urgent issue need to be solved. We aimed to screen for efficient oil-degrading bacteria and develop a new microbial agent for degrading waste cooking oil in oily wastewater. Three extremely effective oil-degrading bacteria, known as YZQ-1, YZQ-3, and YZQ-4, were found by the enrichment and acclimation of samples from various sources and separation using oil degradation plates. The 16S rRNA sequencing analysis and phylogenetic tree construction showed that the three strains were Bacillus tropicus, Pseudomonas multiresinivorans, and Raoultella terrigena. Under optimal degradation conditions, the maximal degradation rates were 67.30 ± 3.69%, 89.65 ± 1.08%, and 79.60 ± 5.30%, respectively, for YZQ-1, YZQ-3, and YZQ-4. Lipase activity was highest for YZQ-3, reaching 94.82 ± 12.89 U/L. The best bacterial alliance was obtained by adding equal numbers of microbial cells from the three strains. Moreover, when this bacterial alliance was applied to oily wastewater, the degradation rate of waste cooking oil was 61.13 ± 7.30% (3.67% ± 2.13% in the control group), and COD removal was 62.4% ± 5.65% (55.60% ± 0.71% in the control group) in 72 h. Microbial community analysis results showed YZQ-1 and YZQ-3 were adaptable to wastewater and could coexist with local bacteria, whereas YZQ-4 could not survive in wastewater. Therefore, the combination of YZQ-1 and YZQ-3 can efficiently degrade oil and shows great potential for oily wastewater treatment.

Global disease burden and its attributable risk factors of peripheral arterial disease.

Peripheral arterial disease (PAD) is a prevalent subtype of atherosclerotic cardiovascular diseases. It is crucial to assess the PAD-related burden and its attributable risk factors. We use the Global Burden of Disease study 2019 database to calculate the incidence, prevalence, mortality, disability-adjusted life years (DALY), attributable risk factors and estimated annual percentage change. The disease burden of PAD grows significantly with age accompanied by prominent heterogeneity between male and female. Despite the increase in the absolute numbers of disease burden from 1990 to 2019, the global PAD-related age-standardized death rate (ASDR) and age-standardized disability-adjusted life years rate (ASDALYR) have a mild downward trend from 1990 to 2019, which negatively correlated with sociodemographic index (SDI). Smoking and high systolic blood pressure (SBP) were the primary attributable risk factors for males (ASDR: 33.4%; ASDALYR: 43.4%) and females (ASDR: 25.3%; ASDALYR: 27.6%), respectively. High fasting plasma glucose (FPG) had become the second risk factor for ASDR (males: 28.5%; females: 25.2%) and ASDALYR (males: 29.3%; females: 26.3%) with an upward tendency. Low-middle SDI regions were predicted to have the most remarkable upward trend of PAD-related burden caused by high FPG. Smoking caused more disease burden in males before 85-90 years old and females before 65-70 years old, while high FPG and high SBP caused more burden after that. The patterns of PAD-related burden and its attributable risk factors are heterogeneous across ages, genders, and SDI regions. To reduce disease burden, tailored strategies should be implemented.

Application of oil-degrading agents consisted of thermophilic Bacillus subtilis and Bacillus glycinifermentans in food waste.

This work aims to investigate the effective removal of oil in food waste (FW). Two bacteria, Bacillus subtilis and Bacillus glycinifermentans, were obtained under high temperature conditions and named YZQ-2 and YZQ-5, respectively. The oil degradation rate of two bacteria was explored under different pH value, temperature, and NaCl concentration. In addition, the lipase and emulsifying activity were evaluated. The maximum oil degradation rate was 83.41 ± 0.86% and the maximum lipase activity reached 89.73 ± 20.89 U L-1 with YZQ-2. The fermentation broth of YZQ-2 displayed exceptional emulsification activity. Subsequently, YZQ-2 and YZQ-5 were added to aerobic FW composting. The moisture content of the compost treated with inoculated strains decreased at a faster rate during the first three days of composting. The microbial quantity increased rapidly in the first three days, and the oil degradation rate reached 39.96% after five days. Due to the excellent adaptability to high temperature and ability to degrade oil, strains YZQ-2 and YZQ-5 exhibit superior potential for various applications.

Epicardial fat in patients with metabolic syndrome: A systematic review and meta-analysis.

PURPOSE: Abnormally increased epicardial fat appears to be associated with an additional risk of major adverse cardiovascular events (MACEs) in the context of metabolic syndrome (MetS). However, evidence on the relationship between epicardial fat volumes (EFVs), epicardial fat thickness (EFT) and MetS remains inconsistent. METHODS: Specific searches of electronic databases from 1 January 2000 to 31 October 2022 were independently performed by two researchers. In this study, two quantification measures of epicardial fat were included: comparison of total computed tomography-based EFVs and EFT between two groups (individuals with and without MetS), estimating standardized mean difference (SMD) with corresponding 95 % confidence intervals (CIs) through a random-effects model analysis. The heterogeneity in the included studies was explored by meta-regression and subgroup analyses. RESULTS: The EFVs were significantly increased in MetS subjects compared with non-MetS subjects (SMD: 1.07, 95 % CI: 0.69-1.45, p < 0.001), and the EFT was also significantly larger in MetS patients than in the Non-MetS (SMD: 1.12, 95 % CI: 0.84-1.41, p < 0.001). We compared the Caucasian and American subgroups with the Asian and African subgroups, and the EFT was greater in the former subgroups (SMD: 1.32, 95 % CI: 0.44-2.20, p < 0.001). When comparing the EFT among the age subgroups, there was a significant SMD between adolescents and adults or elderly individuals (SMD: 1.21, 95 % CI: 0.84-1.52, p < 0.001). CONCLUSIONS: MetS patients tend to present greater EFT near the right ventricular free wall and greater total EFVs. Increased epicardial fat, an imaging biomarker, independently affects the onset of MetS.

A dual bacterial alliance removed erythromycin residues by immobilizing on activated carbon.

Removing erythromycin from the environment is a major challenge. In this study, a dual microbial consortium (Delftia acidovorans ERY-6A and Chryseobacterium indologenes ERY-6B) capable of degrading erythromycin was isolated, and the erythromycin biodegradation products were studied. Coconut shell activated carbon was modified and its adsorption characteristics and erythromycin removal efficiency of the immobilized cells were studied. It was indicated that alkali-modified and water-modified coconut shell activated carbon and the dual bacterial system had excellent erythromycin removal ability. The dual bacterial system follows a new biodegradation pathway to degrade erythromycin. The immobilized cells removed 95% of erythromycin at a concentration of 100 mg L-1 within 24 h through pore adsorption, surface complexation, hydrogen bonding, and biodegradation. This study provides a new erythromycin removal agent and for the first time describes the genomic information of erythromycin-degrading bacteria, providing new clues regarding bacterial cooperation and efficient erythromycin removal.

Effect of Traditional Chinese Exercises on Patients with Chronic Heart Failure (TCE-HF): A Systematic Review and Meta-Analysis.

Exercise-based cardiac rehabilitation is safe and effective for chronic heart failure (CHF) patients. The present study aimed to investigate the effects of traditional Chinese exercise (TCE) on patients with CHF and the impact of exercise types and duration. Evaluation of randomized controlled trials (RCTs) of TCE in patients with CHF published since 1997 from PubMed, Embase, Web of Science, the Cochrane Library, Chongqing VIP, Wanfang Databases, and the China National Knowledge was performed. A total of 41 RCTs, including 3209 patients with CHF, were included. It showed that TCE significantly increased 6-min walk distance (6MWD) [mean difference (MD) = 72.82 m, p < 0.001] and left ventricular ejection fraction (MD = 5.09%, p < 0.001), whereas reduced B-type natriuretic peptide (BNP) (MD = -56.80 pg/mL, p < 0.001), N-terminal pro-BNP (MD = -174.94 pg/mL, p < 0.05), and Minnesota Living with Heart Failure Questionnaire scores (MD = -11.31, p < 0.001). However, no significant difference was found in the effects of TCE on peak oxygen consumption. The increase in TCE weekly duration and program duration significantly improved 6MWD (MD = 71.91 m, p < 0.001; MD = 74.11 m, p < 0.001). The combination of TCE and conventional aerobic exercise significantly improved 6MWD (MD = 19.86 m, p < 0.005). TCE improves exercise capacity, cardiac function, and quality of life in patients with CHF, which might be an optimal and available pattern of exercise-based cardiac rehabilitation.

Ectopic expression of two CAULIFLOWER genes from mango caused early flowering in Arabidopsis.

APETALA1 (AP1), CAULIFLOWER (CAL) and FRUITFULL (FUL) were homologous genes with redundant functions in the process of flower transformation and floral development in Arabidopsis. Two CALs genes, MiCAL1 and MiCAL2, were cloned from mango (Mangifera indica L.). Their full-length sequences contained 717 bp and 714 bp, encoding 239 and 238 amino acids, respectively. Both the MiCAL1 and MiCAL2 proteins contained typical MADS-box and K-box domains and therefore belonged to the CAL-like protein family. MiCAL1 and MiCAL2 were expressed in all tissues at the inflorescence elongation stage and flowering stage, with the highest expression in the leaves at the flowering stage. They had similar expression patterns during flower development, with the highest expression levels in leaves during flower differentiation and the lowest expression levels during fruit development. Overexpression of MiCAL1 and MiCAL2 resulted in significantly earlier flowering in Arabidopsis. Overexpression of MiCAL1 resulted in terminal flowers with normal flower organs, while overexpression of MiCAL2 induced partially variation in floral organs but had no effect on inflorescences. Yeast two-hybrid (Y2H) experiments showed that MiCAL1 and MiCAL2 can interact with several flower-related proteins as well as stress response proteins, such as SEP1, SVP1, SVP2, SOC1G and Di19-4. These results suggest that these two MiCALs genes may have an important influence on mango flowering.

Global burden of calcific aortic valve disease and attributable risk factors from 1990 to 2019.

Background: Calcific aortic valve disease (CAVD) was highly prevalent among developed countries and caused numerous deaths. Based on the Global Burden of Disease 2019, this study was designed to present comprehensive epidemiological information, attributable risks, and relevant factors. Methods: All data were available online via the Global Health Data Exchange (GHDx). In this study, we analyzed the global incidence, prevalence, deaths, and disability-adjusted life years (DALYs) of CAVD across different regions from 1990 to 2019. We applied the estimated annual percentage changes (EAPCs) to evaluate the change trends and their attributable risks. In addition, we explored several relevant factors. Results: From 1990 to 2019, the incidence cases, prevalence cases, CAVD-related deaths, and DALYs of CAVD gradually increased globally. However, the age-standardized death rate (ASDR) was relatively stable, and the age-standardized DALYs rate gradually declined during the past 30 years. Males and elderly individuals were more likely to suffer from CAVD. High systolic blood pressure (SBP) was the predominant attributable risk of disease burden that presented a global downward trend (death: EAPC = -0.68, 95% CI -0.77~-0.59, P < 0.001; DALYs: EAPC = -0.99, 95% CI -1.09 to -0.89, P < 0.001). Alcohol consumption (R = 0.79, P < 0.001), smoking prevalence (R = 0.75, P < 0.001), and calcium (R = 0.72, P < 0.001) showed a positive correlation with the age-standardized incidence rate (ASIR), whereas classic monsoon region (R = -0.68, P < 0.001) and mean temperature (R = -0.7, P < 0.001) showed a negative correlation with age-standardized incidence rate (ASIR). Besides, medical and healthcare resources presented a positive correlation with ASIR. Meanwhile, similar relationships were found in age-standardized prevalence rate (ASPR), ASDR, and age-standardized DALY rate (ASDALYR). Conclusion: CAVD displays widely varied spatial distribution around the world, of which high SDI regions have the highest burdens. Age is a powerful factor and hypertension a predominant attributable risk factor. Moreover, controlling blood pressure, avoiding smoking, reducing alcohol consumption, and so on, could effectively reduce the burden of CAVD.

Resveratrol inhibiting TGF/ERK signaling pathway can improve atherosclerosis: backgrounds, mechanisms and effects.

Atherosclerosis (AS) is a pathological basis of cardiovascular and cerebrovascular diseases. A severe global public health problem contributes to the growing burden of cardiovascular disease due to its high risk and limited therapeutic measures. AS treatment is challenging, and requires the doctors to integrate clinical manifestations such as the multiplicity of risk factors, the complexity of lesions, and individual variability. Signal transduction is involved in the formation and progression of AS. The transforming growth factor/extracellular regulated protein kinases (TGF/ERK) signaling pathway is involved in the pathophysiological regulation such as vascular smooth muscle cell proliferation and inflammatory response, which are central links related to the development of AS. Resveratrol can exert beneficial effects at various stages of AS development by regulating lipid metabolism, inhibiting inflammatory development, and alleviating oxidative stress. We hypothesize that its anti-AS effects mainly through modulating the TGF/ERK signaling pathways. This review summarizes the current research progress of resveratrol in the treatment of AS via inhibiting the TGF/ERK signaling pathway and presents the prospects.

Genetically predicted phosphate and cardiovascular disease: A Mendelian randomization study.

Background: Extensive epidemiological studies have highlighted the correlation between serum phosphate and cardiovascular diseases. The present study aims to determine whether genetically predicted serum phosphate is causally associated with the distinct subtypes of cardiovascular events through the use of Mendelian randomization (MR) analysis. Methods: Independent and strongly correlated single-nucleotide polymorphisms (SNPs) for serum phosphate were extracted from publicly available genome-wide association studies. Summary statistics of cardiovascular diseases were derived from large-scale consortiums, including HERMES and FinnGen biobank. MR-Egger, weighted median, inverse variance weighted, pleiotropy residual sum and outlier (MR-PRESSO) methods and MR using robust adjusted profile score (MR-RAPS) were employed to analyze causality. The sensitivity analyses comprised heterogeneity, horizontal pleiotropy, and leave-one-out approaches; these were used to ensure the stability of the results. Results: Our study demonstrated that increased genetically predicted serum phosphate is causally associated with a higher risk of valvular heart disease (VHD) [For VHD including rheumatic fever: odds ratio (OR) = 2.45; 95% confidence interval (CI), 1.52-3.94; p = 0.0002; for non-rheumatic VHD: OR = 6.58; 95% CI, 2.50-17.32; p = 0.0001]. However, no causal association was detected between serum phosphate and other common cardiovascular diseases (including coronary heart disease, heart failure, atrial fibrillation, and essential hypertension). Conclusions: The results indicate strong causality between serum phosphate and valvular heart disease. Serum phosphate-lowering therapy within the physiological range may represent a novel therapeutic method for valvular heart disease.

Joint application of hybrid iterative reconstruction and adaptive filters on neck-and-shoulder CT imaging: A clinical evaluation.

PURPOSE: To assess whether the joint application of hybrid iterative reconstruction (HIR) and an adaptive filter (AF) could reduce streak artifacts and improve image quality of neck-and-shoulder computed tomography (CT). METHODS: This study included 96 patients with suspicious neck lesions who underwent a routine nonenhanced scan on a 64-slice CT scanner. The raw data were reconstructed using four different settings: filtered back projection (FBP), HIR, FBP + AF, and HIR + AF. Regions of interest were manually drawn in erector spine, axillary fat, latissimus dorsi, and dorsal cervical fat. Mean and standard deviation (SD) of the CT number, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were obtained and compared using Wilcoxon signed-rank tests. The qualitative assessments of five factors were compared by two independent investigators. RESULTS: Compared to the other three settings, HIR + AF reduced noise in the area where the streak artifact of the lower neck were most serious (SD; all p ≤ 0.001). The SNR and CNR were improved significantly (all p ≤ 0.001). Compared to the other three settings, HIR + AF showed a significant improvement in CT image quality regarding the visibility of suspicious lesions, the extent of streaking artifacts, noise, soft-tissue contrast, and visualization of small structures (all p ≤ 0.02). CONCLUSIONS: The combination of HIR and AF can significantly reduce streaking artifacts and improve image quality in neck-and-shoulder CT imaging.

Genetic liability to sedentary behavior in relation to myocardial infarction and heart failure: A mendelian randomization study.

BACKGROUND AND AIMS: Observational studies have indicated that sedentary behavior is associated with myocardial infarction (MI), heart failure (HF), and atrial fibrillation (AF). Nevertheless, whether these associations are causal remain controversial, due to confounding factors (e.g., physical activity) and reverse causality. METHODS AND RESULTS: Instrumental variables were obtained from the largest genome-wide association studies of sedentary behavior (408,815 individuals) to date. We obtained summary statistics of MI from the CARDIoGRAMplusC4D consortium (171,875 individuals), HF from the HERMES Consortium (977,323 individuals), and AF from the Atrial Fibrillation Consortium (588,190 individuals). The inverse-variance weighted method was applied to obtain Mendelian randomization (MR) estimates, and other statistical methods were conducted in the sensitivity analyses. The main analyses were repeated using data from the FinnGen study. Multivariable MR analysis and mediation analysis were performed to evaluate the role of physical activity and other confounders. Genetically determined television watching was associated with MI (odds ratio [OR], 1.38; 95% CI, 1.19-1.59; p = 1.9 × 10-5) and HF (OR, 1.23; 95%CI, 1.09-1.38; p = 7.0 × 10-4) but not AF. The main results kept robust in most sensitivity analyses. The effect of sedentary behavior on MI and HF was partly mediated by body mass index (BMI). No consistent evidence was found for the causal effect of computer use and driving on MI, HF, or AF. CONCLUSIONS: Genetic liability to prolonged television watching is associated with higher risks of MI and HF. Interventions for reducing television watching time, such as public education and awareness campaigns, should be further investigated.

Lipocalin-2 in neutrophils induces ferroptosis in septic cardiac dysfunction via increasing labile iron pool of cardiomyocytes.

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.

Sustained-Release Ivabradine Hemisulfate in Patients With Systolic Heart Failure.

BACKGROUND: Ivabradine has potent actions in reducing heart rate and improving clinical outcomes of chronic heart failure with reduced ejection fraction (HFrEF). At present, only the short-acting formulation of ivabradine is available that needs to be administered twice daily. OBJECTIVES: This study sought to evaluate the role of ivabradine hemisulfate sustained release (SR), a novel long-acting formulation of ivabradine dosed once daily, in stable patients with HFrEF. METHODS: Patients with stabilized HFrEF in New York Heart Association functional class II-IV were enrolled and randomized to receive placebo or ivabradine SR in addition to standard medications. The primary endpoint was the change of left ventricular (LV) end-systolic volume index from baseline to week 32. RESULTS: We randomly assigned 181 patients to placebo and 179 patients to ivabradine SR. After 32 weeks, a significant improvement of LV end-systolic volume index from baseline was observed in both arms with a greater effect in the ivabradine SR arm. Ivabradine SR therapy also exhibited superiority in improving LV end-diastolic volume index, LV ejection fraction, resting heart rate, the Kansas City Cardiomyopathy Questionnaire score, and hospital admission for heart failure worsening and cardiovascular disease in comparison to placebo. Overall adverse events showed no difference between the treatment arms. There were fewer occurrences of worsening heart failure in the ivabradine SR arm. CONCLUSIONS: The present study demonstrates that ivabradine SR once daily in addition to optimum standard therapy improved heart function in patients with HFrEF. (Clinical Trial of Systolic Heart Failure Treatment of IvabRadine Hemisulfate Sustained-release Tablets [FIRST]; NCT02188082).

PBL teaching in ultrasonography resident standardization training in the COVID-19 pandemic.

OBJECTIVE: To study the effect of the problem-based learning (PBL) method in ultrasonography (US) resident standardization training during the COVID-19 pandemic. METHODS: Fifty residents were divided into two groups to participate in a 30-day US training program. The residents in the observation group underwent PBL combined with the lecture-based learning (LBL) method, while the residents in the control group experienced the LBL method alone, with 25 residents in each group. A basic theoretical test, practical examination, and questionnaire were used to evaluate the teaching effect of the PBL + LBL method and the LBL method alone. RESULTS: The basic theoretical pretest score of the observation group was not significantly different from that of the control group. However, the posttest theoretical score and practical score were significantly higher in the observation group than in the control group (P < 0.01). The results of the questionnaire showed that the resident satisfaction level in the observation group with PBL combined with the LBL method was 96%, which was significantly higher than that of the control group with the LBL method alone (80%) (P < 0.05). CONCLUSION: The combination of PBL with the LBL method has obvious advantages over the LBL method alone in regard to the training of US residents during the COVID-19 pandemic.

Burden of Aortic Aneurysm and Its Attributable Risk Factors from 1990 to 2019: An Analysis of the Global Burden of Disease Study 2019.

Background: Global and national estimates on the epidemiology of aortic aneurysms are prerequisites for disease management and policymaking. Based on the Global Burden of Disease (GBD) 2019, this study aimed to discern the global aortic aneurysm burden by systematically analyzing demographic data on mortality and exploring the attributable risks and relevant factors. Methods: The data analyzed in this study were available in the Global Health Data Exchange (GHDx) online query tool. The population in our study comprised individuals from 204 countries and territories from 1990 to 2019. The estimated annual percentage changes (EAPCs) were performed to assess the temporal trends of aortic aneurysms and their attributable risks. Spearman correlation analysis was performed to explore the relationship between the burden of aortic aneurysm and covariates. Results: Although aortic aneurysm-related deaths (82.1%) and disability-adjusted life years (DALYs) (67%) increased from 1990 to 2019, the global trend of age-standardized rate of death (ASRD) (EAPC: -1.34, 95% CI = -1.46 to -1.22, P < 0.001) and age-standardized rate of DALY (ASDALYR) (EAPC: -1.06, 95% CI = -1.17 to -0.95, P < 0.001) decreased, both of which presented age dependence and gender differences. Smoking and high systolic blood pressure (SBP) were the main attributable risks of disease burden and tend to decease globally (EAPC: -1.89, 95% CI = -2.03 to -1.89, P < 0.001; -1.31 95% CI = -1.43 to -1.19, P < 0.001, respectively). Alcohol abstinence (male: R = -0.71, P < 0.001; female: R = -0.73, P < 0.001), smoking age of initiation (male: R = -0.32, P < 0.001; female: R = -0.50, P < 0.001), physical activity (male: R = -0.50, P < 0.001; female: R = -0.55, P < 0.001), and mean temperature (R = -0.62, P < 0.001) had negative correlation with ASRD. However, cholesterol level (male: R = 0.62, P < 0.001; female: R = 0.39, P < 0.001), body mass index (BMI) (male: R = 0.30, P < 0.001; female R = -0.01, P > 0.05), and alcohol consumption (male: R = 0.46, P < 0.001; female: R = 0.42, P < 0.001) had a positive correlation with ASRM. Besides, standard of living and medical resources positively related to burden of aortic aneurysm. Conclusion: In this study, a decreasing trend of aortic aneurysm burden was found globally, especially in advanced regions. Aged men who smoke and women who have hypertension should pay close attention to, particularly in deprived economic groups, and many approaches can be performed to reduce the burden of aortic aneurysms.

CXCR4 blockade in macrophage promotes angiogenesis in ischemic hindlimb by modulating autophagy.

Chemokine receptor CXCR4 plays a crucial role in leukocyte recruitment and inflammation regulation to influence tissue repair in ischemic diseases. Here we assessed the effect of CXCR4 expression in macrophages on angiogenesis in the ischemic hindlimb of a mouse. Inflammatory cells were increased in the ischemic muscles of hindlimb, and CXCR4 was highly expressed in the infiltrated macrophages but not in neutrophils. Myeloid-specific CXCR4 knockout attenuated macrophage infiltration and subsequent reduced inflammatory response in the ischemic hindlimb, accompanied with better blood reperfusion and higher capillary density as compared with that in LysM Cre+/- (Cre) mice. Similar outcomes were also observed in CRE mice whose bone marrow cells were replaced with those from CXCR4-deficient mice. Gene ontology cluster analysis reviewed that Decorin, a negative regulator of angiogenesis, was reduced in CXCR4-deficient macrophages. CXCR4-deficient macrophages were less inducible into M1 phase by lipopolysaccharide and more favorable for M2 polarization under oxygen/glucose deprivation condition. Enhanced autophagy was detected in CXCR4-deficient macrophages, which was associated with less expression of both Decorin and the inflammatory cytokines. In summary, myeloid-specific CXCR4 deficiency reduced monocyte infiltration and the secretion of inflammatory cytokines and Decorin from macrophages, thus blunting inflammation response and promoting angiogenesis in the ischemic hindlimb.