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Study participants with rheumatoid arthritis (RA) have an elevated risk for nontuberculous mycobacterial pulmonary disease (NTM-PD), which limits the treatments for RA. Biomarkers for NTM-PD in study participants with RA are required. Patients with NTM-PD have been studied for small-molecule metabolites, although few have been performed for NTM-PD associated with RA. Therefore, we performed lipidomic profiling of NTM-PD in the urine specimens of study participants with RA to discover useful biomarkers. Urine specimens provided by 90 study participants with RA, with or without NTM-PD were subjected to lipidomic analysis. Univariate analysis found that the urinary concentrations of lysophosphatidic acid (LPA) 22:5 and phosphatidic acid (PA) 36:1 were altered in study participants with RA and NTM-PD (respective areas under the curves of receiver operating characteristic (AUROCs) were 0.977 and 0.811; P = 3.83 × 10 Show less

The bidirectional cavopulmonary connection (BCPC) is a pivotal stage in the surgical palliation of single-ventricle patients. However, there is ongoing debate regarding the benefits and drawbacks of BCPC with additional or antegrade pulmonary blood flow (AAPBF) in optimizing the subsequent stage-total cavopulmonary connection (TCPC). To determine the influence of BCPC with AAPBF on pulmonary artery growth and hemodynamic outcomes. A retrospective review was conducted of 167 single-ventricle patients who underwent BCPC at Siriraj Hospital between 2006 and 2022. Patients were categorized into two groups based on AAPBF status: group 1 (with AAPBF, Median ages at pre-BCPC assessment were 1.06 years (group 1) and 2.17 years (group 2), and at pre-TCPC assessment were 6.19 and 7.27 years, respectively. Median age at BCPC operation was similar between groups (1.58 BCPC with AAPBF effectively promotes pulmonary artery growth without adversely affecting ventricular volume loading or pulmonary artery pressure. Further investigation into the development of arteriovenous malformations is recommended. Show less

Thrombosis of ductus arteriosus aneurysm (DAA) is a well-known complication of DAA that can lead to vascular obstruction or thromboembolic events. A full-term male newborn presented with isolated right ventricular hypoplasia (IRVH). Follow-up echocardiography at 19 days of life revealed a pedunculated mass, suggesting a thrombus partially obstructing the left pulmonary artery (LPA). The patient remained clinically stable but was admitted to the neonatal intensive care unit for close monitoring. CT and MRI confirmed DAA thrombosis involving LPA. Due to a lack of resolution with conservative treatment, the patient underwent a thrombectomy and resection of the ductus arteriosus (DA). The postoperative course was uneventful, and the follow-up echocardiography showed normalisation of the right ventricular cavity and no residual thrombus. This case highlights the importance of early detection and investigation in neonates with echocardiographic findings of intrauterine ductus arteriosus closure, stenosis, or DA closure in the first 12 h of life to prevent life-threatening complications. Show less

Heart failure (HF) and atherosclerosis represent two major cardiovascular diseases that are intricately linked, both contributing significantly to global morbidity, mortality, and healthcare burden. Despite substantial progress in diagnostic methods and therapeutic strategies, the overall impact of these conditions remains considerable. This is largely due to their complex and overlapping pathophysiological mechanisms, persistent residual atherosclerotic risk, and the ongoing challenges associated with implementing guideline-directed medical therapy for HF in routine clinical practice. Recent advancements in the management of diverse HF phenotypes, lipid abnormalities, atherosclerotic cardiovascular disease (ASCVD), and obesity have facilitated the adoption of multidrug regimens. These include β-blockers, renin-angiotensin-aldosterone system inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1), which have collectively improved outcomes in HF populations. Lipid-lowering therapy, particularly statins, has demonstrated significant efficacy in reducing ASCVD events and slowing HF progression, as well as lowering the risk of HF-related hospitalizations. Elevated lipoprotein(a) [Lp(a)] has emerged as an independent risk factor for both ASCVD and HF, being associated with increased risk of incident HF, disease progression, hospitalization, and adverse outcomes. However, there remains a lack of conclusive evidence as to whether targeted reduction of Lp(a) leads to a decrease in major adverse cardiovascular events or improves HF incidence or outcomes. In parallel, contemporary therapeutic advances in coronary and peripheral artery revascularization, along with novel pharmacologic treatments for obesity such as GLP-1 receptor agonists including semaglutide and tirzepatide have shown beneficial effects in reducing cardiovascular mortality, HF progression, and body weight, irrespective of HF status. These converging therapeutic strategies underscore the close interrelationship between HF and atherosclerosis. This review aims to elucidate the shared pathophysiological mechanisms linking these conditions and to examine their clinical overlap with ischemic heart disease, cerebrovascular disease, peripheral arterial disease, dyslipidemia, and obesity. A comprehensive understanding of these interrelated cardiovascular entities may offer valuable insights to inform future research directions and optimize the clinical management of patients affected by both HF and atherosclerotic disease. Show less

Endometrial cancer (EC) is a malignant tumor arising from the endometrial epithelium and is among the most prevalent gynecological malignancies worldwide. Increasing evidence suggests that lipid profiles, hyperglycemia, and other metabolic factors play a role in EC pathogenesis. However, research on the association between lipoprotein(a) [Lp(a)] levels and EC prognosis remains limited. This retrospective cohort study analyzed Lp(a) levels in patients diagnosed with EC at Ganzhou Hospital, affiliated with Nanchang University, between January 2017 and January 2022. Lp(a) concentrations were measured post-admission, and patient prognosis was categorized as favorable or poor. Multivariate logistic regression analysis was performed to determine the adjusted odds ratio (OR) and 95% confidence interval (CI). The study included 296 EC patients, out of whom 72.3% (214/296) had a favorable prognosis, defined as no recurrence within five years post-surgery. The overall healing rate was 72.3% (214/296). When stratified by Lp(a) levels, patients in the first quantile (Q1 ≤ 122.2 g/L) had a favorable prognosis rate of 77.7% (115/148), whereas those in the second quantile (Q2 > 122.2 g/L) had a rate of 66.9% (99/148), with a statistically significant difference between groups (p < 0.05). In the multivariate regression model, the log2-transformed Lp(a) values and their corresponding ORs (95% CIs) for prognosis at two upper normal limits (ULN) were 1.7248 (1.0288 - 2.8918) and 2.0365 (1.1843 - 3.5018), respectively. Interaction analysis indicated that Lp(a) levels significantly influenced EC prognosis. Lp(a) is strongly associated with EC prognosis and holds potential clinical significance. Further studies are required to validate these findings. Show less

Intrinsic motivation is critical for dementia prevention but remains poorly understood. A total of 347 middle-aged adults completed questionnaires on intrinsic factors for dementia prevention, demographics, dementia risk, and healthy lifestyle behaviors. Latent profile analysis (LPA) grouped participants with similar intrinsic patterns. Subgroup differences in demographics, extrinsic factors, and healthy behaviors were examined. LPA identified four intrinsic profiles: Profile 1 had low motivation; Profile 2 had high motivation and self-efficacy, but poor dementia knowledge; Profile 3 had moderate motivation; and Profile 4 had low motivation and high apathy. Subsequent analyses showed that profiles further differed on extrinsic factors, demographic characteristics, and engagement in health behaviors. Specifically, Profile 1 had the lowest dementia risk, best sleep quality, and least loneliness; Profile 2 had the highest income, greater dementia risk, highest cognitive activity, and greatest loneliness; Profile 3 had more caregiving experience and moderate engagement in all healthy behaviors; and Profile 4 had lower incomes, the worst health, and lowest engagement in all healthy behaviors. Results identified groups of middle-aged adults with distinct intrinsic patterns who also differed in demographic/extrinsic factors and health behaviors. These profiles may benefit from different types of intervention strategies for dementia prevention. Show less

Recent studies have shown glycerolipid metabolism played an essential role in multiple tumors, however, its function in osteosarcoma is unclear. This study aimed to explore the role of glycerolipid metabolism in osteosarcoma. We conducted bioinformatics analysis using data from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database and single-cell RNA sequencing. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to identify the Glycerolipid metabolism-related genes associated with the clinical outcome of osteosarcoma. Tumor-associated macrophages (TAMs) and their interactions with immune cells were examined through single-cell analysis and co-culture experiments. Virtual screening was employed to identify the potential lysophosphatidic acid receptor 6 (LPAR6) inhibitors. Glycerolipid metabolism-related genes 1-acylglycerol-3-phosphate O-acyltransferase 3 ( Show less

Calcific aortic valve stenosis (CAVS) can lead to cardiac adverse outcomes; however, currently, no effective pharmacological interventions are available to prevent or delay disease progression. Emerging evidence has identified significant associations between CAVS and key biomarkers, including Lp(a) (lipoprotein [a]), low-density lipoprotein cholesterol, and PCSK9 (proprotein convertase subtilisin/kexin type 9). However, robust evidence from randomized controlled trials is still lacking to substantiate these associations. The EPISODE (Effect of PCSK9 Inhibitors on Calcific Aortic Valve Stenosis) trial is a prospective, evaluator-blinded, randomized controlled trial designed to assess the therapeutic efficacy of PCSK9 inhibitors in patients with CAVS. A total of 160 patients with mild-to-moderate or asymptomatic severe CAVS will be randomly assigned to receive either statin monotherapy or a combination of statins and PCSK9 inhibitors. Participants will undergo follow-up assessments at 3-month intervals for 24 months, including transthoracic ultrasonic cardiogram, computed tomography, and quality-of-life evaluations using the EuroQol-5 Dimension-3 Level questionnaire. The primary end point is the annualized change in peak aortic jet velocity, whereas secondary end points encompass changes in aortic valve area, calcification score, incidence of heart valve surgery, and quality of life. Safety end points include all-cause mortality and cardiovascular events. The trial aims to evaluate the efficacy of PCSK9 inhibitors in modulating disease progression, reducing adverse cardiovascular events, and improving clinical outcomes in patients with CAVS. The anticipated findings are expected to provide critical insights for developing novel therapeutic strategies for early intervention in CAVS. URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04968509. Show less

Patients suffering coronary artery disease (CAD) with calcific aortic valve disease (CAVD) are facing worse prognosis with more complex operation strategies. As the primary stage of CAVD, it is helpful to confirm the risk factors of aortic valve calcification (AVC) in advance for exploring the secondary prevention as well as early intervention strategies of CAVD for CAD patients. Lipoprotein(a) [Lp(a)] has been confirmed as the risk factor of both CAD and CAVD. But whether Lp(a) level still affects the occurrence and development of CAVD in CAD patients has not been demonstrated yet. We firstly investigate the predictive value of Lp(a) for new-onset AVC in patients with CAD. Patients who were admitted to the Department of Cardiology, Zhujiang Hospital, Southern Medical University from March 2021 to December 2022 and diagnosed with CAD by elective coronary angiography(CAG)were included when met the criteria. Baseline data were collected through the electronic medical record system. Patients were followed up to repeat echocardiography with an interval at least 6 months, which was up to September 2023. The primary endpoint was new-onset AVC, according to which patients were divided into new-onset AVC group (n = 43) and the opposite(n = 165). Analyses were conducted using SPSS 26.0 and GraphPad Prism 10.1.2. A total of 208 patients with CAD were included, with a median follow-up time of 16 (12, 20) months. Compared with AVC-free group, patients with new-onset AVC had higher body mass index (BMI) (p = 0.003), higher proportion of tree-vessel disease(p < 0.001), higher rates of diabetes (p = 0.001) and atrial fibrillation (p = 0.017), higher Lp(a) levels(p < 0.001), lower left ventricular systolic function (LVEF) (p < 0.001) and thicker left ventricular posterior wall (LVPW) (p < 0.001). Increased BMI, three-vessel disease, Lp(a) > 26.65 nmol/L, increased LVPW were found independent risk factors for new-onset AVC. Using a cutoff level of 26.65 nmol/L, Lp(a) predicted new-onset AVC with a sensitivity of 79.1% and a specificity of 59.4% (AUC: 0.740, 95% CI: 0.657-0.823, p < 0.001). When combined with BMI, there present a higher AUC value of 0.752(95%CI: 0.668-0.836, p < 0.001); however, the statistical significance remains limited (p = 0.732). High-level serum Lp(a) was independently associated with new-onset AVC in patients with CAD. Lp(a) demonstrates a significant predictive value for the onset of new AVC in CAD patients, with an established cut-off threshold of 26.65 nmol/L. Show less

Rheumatoid arthritis (RA) is a systemic autoimmune disease associated with a markedly increased risk of cardiovascular disease (CVD) that is not fully explained by traditional risk factors. Lipoprotein(a) [Lp(a)], a genetically determined lipoprotein with proatherogenic, prothrombotic, and proinflammatory properties, has emerged as a potential contributor to this excess cardiovascular burden. Growing evidence suggests that Lp(a) may represent a mechanistic link between chronic inflammation, immune dysregulation, and accelerated atherosclerosis in RA. This narrative review synthesizes evidence from observational studies, mechanistic research, genetic analyses, biomarker investigations, and emerging therapeutic trials examining Lp(a) in RA. Relevant literature was identified through comprehensive searches of major biomedical databases, with emphasis on studies addressing pathophysiology, cardiovascular outcomes, disease activity, and treatment effects on Lp(a). RA patients frequently exhibit elevated Lp(a) levels, particularly in the presence of active systemic inflammation. Lp(a) contributes to vascular injury through enhanced arterial wall retention, carriage of oxidized phospholipids, endothelial activation, and impaired fibrinolysis. Clinical studies associate elevated Lp(a) with subclinical atherosclerosis, arterial stiffness, and increased cardiovascular events in RA, independent of conventional lipid parameters. Inflammatory cytokines, particularly interleukin-6 (IL-6), appear to modulate Lp(a) metabolism, providing a biological rationale for the Lp(a)-lowering effects observed with IL-6 receptor blockade. Advances in standardized assays, genetic insights into LPA polymorphisms, and novel RNA-based therapies have revitalized interest in Lp(a) as both a biomarker and therapeutic target in RA. Lp(a) occupies a critical intersection between inflammation and atherosclerosis in RA. Incorporating Lp(a) into cardiovascular risk stratification and exploring targeted therapies may enable more precise, integrated management of cardiovascular risk in RA patients, warranting dedicated prospective studies. Show less

The Interaction of Person-Affect-Cognition-Execution (I-PACE) model offers a framework for understanding the interplay between cognitive, affective, and behavioral factors in internet addiction (IA). Our study aims to explore the heterogeneity of IA, identify bridge connectors, and compare the efficacy of cognitive behavioral therapy combined with mindfulness-based intervention (CBT+MBI) versus CBT alone in reducing IA levels among Chinese college students. In study 1, 1,030 Chinese college students completed assessments of IA, automatic thoughts, self-control, and anxiety. Latent profile analysis (LPA) was employed to identify distinct symptom profiles of IA across individuals. Network analysis (NA) identified bridge connectors for targeted intervention. In study 2, 36 participants randomly selected from the high IA and low IA groups of study 1 were randomly assigned to CBT+MBI, CBT alone, or a control group. The CBT+MBI group received an 8-week dual-modality intervention and the CBT alone received an 8-week CBT intervention, both designed to target the bridge connectors identified via NA in Study 1, while the control group only completed basic questionnaires. In study 1, LPA identified four subgroups: regular, at-risk, low IA, and high IA groups. NA pinpointed automatic thoughts and anxiety as bridge connectors. In study 2, targeted interventions significantly reduced college students' levels of IA. CBT+MBI resulted in greater and more sustained improvements compared to CBT alone, with effects maintained for six-month post-intervention. Our study not only reinforces the I-PACE model but also provides actionable strategies for designing evidence-based, multidimensional interventions to reduce addictive behaviors among college students. Show less

This study aimed to identify the latent profiles of cognitive function among community-dwelling and institutionalized older adults, and to examine their associated influencing factors, in order to inform the development of targeted interventions. A convenience sampling method was used to select 6,708 elderly people aged 60 years and older from six communities and nine long-term care institutions across China, who were assessed using a general information questionnaire, Mini-Mental State Examination (MMSE), the Frailty Scale, the Anxiety Scale, the Depression Scale, and the Pittsburgh Sleep Quality Index. Latent profile analysis (LPA) was performed based on the MMSE scores, and multiple logistic regression was used to analyse the influencing factors of cognitive function categories. A total of three cognitive function profiles were identified: High cognitive Function group (41.2%), Moderate Cognitive Function Group (48.2%) and Low cognitive Function group (10.7%). Higher Frailty [odds ratio (ORs) = 1.070-1.246], higher depressive symptom scores (OR = 1.059-1.191) and poorer sleep quality (higher PSQI; OR = 1.088) were associated with higher odds of belonging to the Moderate/Low cognitive profiles, whereas adequate social support (Yes vs. No; OR = 0.530-0.696), selected middle-income categories versus ≥¥6,000 in per-capita monthly household income (OR = 0.462-0.735) and male sex (OR = 0.556-0.876) were associated with lower odds. Cognitive function among older adults can be classified into three distinct latent profiles, each associated with different influencing factors. These findings underscore the need for stratified and personalized interventions at the community level to support stratified screening and tailored community programs; given the cross-sectional design, these associations do not establish causality or intervention effects. Show less

Death anxiety is a critical mental-health concern among young adults; however, its heterogeneity and underlying psychological mechanisms remain understudied. This study aimed to identify latent profiles of death anxiety in Chinese youth and examine the predictive roles of self-esteem, perceived social support, and security. We conducted a cross-sectional survey of 623 young adults ( Three latent death anxiety profiles emerged, High Death Anxiety (56.2%), Moderate Cognition and Low Death Anxiety (8.8%), and Low Cognition and Moderate Death Anxiety (35%). Higher self-esteem ( Death anxiety among young adults is heterogeneous, influenced by distinct psychological profiles and demographic factors. Interventions should prioritize enhancing self-esteem, social support networks, and security to mitigate death anxiety, especially in high-risk subgroups. Future research should employ longitudinal designs and cross-cultural samples to validate causal pathways and refine targeted strategies. Show less

Cognitive decline is prevalent among older adults and may be associated with their daily activity behaviours. However, no studies have examined how cognitive decline affects older adults' activity behaviours within a 24-h framework. This study investigates the relationship between cognitive function and 24-h activity behaviours in older adults, further exploring whether these associations differ by sex. This study analyses data from the eighth wave of the Survey of Health, Ageing and Retirement in Europe, conducting a cross-sectional analysis of 814 older adults. Cognitive function was assessed using the SHARE-Cog tool, encompassing 10-word immediate recall, 10-word delayed recall, verbal fluency, and self-reported memory. 24-h activity behaviours (moderate-to-vigorous physical activity [MVPA], light physical activity [LPA], sedentary behaviour [SB], and sleep) were objectively measured with thigh-worn accelerometers. Compositional multivariate linear regression models were constructed using compositional data as the response variable, with cognitive function measures as predictors. Higher MVPA was linked to better cognitive outcomes (verbal fluency, 10-word immediate recall, and 10-word delayed recall) while SB and longer sleep related to poorer performance, with these associations being stronger in women (model p ≤ 0.001). Among women, cognitive outcomes were significantly associated with all activity behaviours (p range = 0.010-0.045). Women who self-reported poor memory and scored 0 on the verbal fluency spent approximately 45% of their day in SB, whereas those reporting excellent memory and scoring 60 spent 40.06% (37.18%, 42.86%) and 36.41% (31.53%, 41.10%) of their day sedentary, respectively. In contrast, men's 24-h activity composition did not vary significantly with cognitive function (p range = 0.051-0.845). Older adults with better cognitive function tend to engage in more PA and reduce sedentary and sleep time. This relationship differed by sex, with females' activity behaviours being more sensitive to cognitive function changes. These findings suggest that interventions promoting healthy lifestyles in older adults should account for cognitive function, particularly in females. Show less

Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle composed of apolipoprotein B-100 covalently linked to apolipoprotein(a) [apo(a)] via a disulfide bond. The Lp(a) particle is enriched with oxidized phospholipids (OxPLs), which confer enhanced atherogenic and pro-inflammatory properties compared with low-density lipoprotein (LDL). Robust genetic and epidemiologic evidence demonstrates that elevated Lp(a) levels are independently associated with atherosclerotic cardiovascular disease and calcific aortic valve stenosis. However, no pharmacologic therapy has yet been approved that specifically lower Lp(a) or to demonstrate a reduction in cardiovascular events. Antisense oligonucleotides (e.g., pelacarsen), small-interfering RNAs (e.g., olpasiran, lepodisiran, and zerlasiran), and oral small-molecule Lp(a) inhibitors (e.g., muvalaplin) have demonstrated profound reductions in circulating Lp(a) concentrations, typically achieving decreases of 80-90%. In some studies, the reductions approached or achieved a near-complete suppression. Current genetic and modeling evidence suggests that an absolute reduction of at least 50 mg/dL in Lp(a) levels is required to achieve meaningful cardiovascular benefits. Large-scale outcome trials are now underway to assess the effects of these emerging therapies on cardiovascular and valvular outcomes. Early findings indicate favorable effects on oxidized phospholipids and vascular inflammation, suggesting broader anti-atherogenic potential. As these agents progress toward clinical use, routine Lp(a) measurement and risk stratification will become increasingly essential for personalized cardiovascular prevention. This review summarizes the molecular biology of Lp(a), highlights the limitations of current therapies, and discusses emerging RNA-based and small-molecule approaches with the potential to redefine the management of residual cardiovascular risk. Show less

This study aimed to identify and characterize the sedentary behavior (SED) and breaks accumulation patterns of children and adolescents and investigate the associations of these derived patterns with adiposity indicators. A total of 348 children and 562 adolescents from China participated in this study. Accelerometers were used to measure the bouts of SED and breaks. Adiposity indicators included body mass index (BMI) z-score, fat mass percentage (FM%), and fat mass index (FMI). Latent profile analysis was used to identify the SED and breaks accumulation patterns on the basis of 11 compositions of SED bouts and breaks. Mixed-effects multivariable linear regression models were used to analyze the associations of accumulation patterns with adiposity indicators. Four accumulation patterns were identified in children: "prolonged sitters" (N = 77, 22.1%), "shortened sitters" (N = 90, 25.9%), "LPA breakers" (N = 69, 19.8%), and "MVPA breakers"(N = 112, 32.2%). "MVPA breakers" had significantly lower BMI z-score, FM%, and FMI than "prolonged sitters." No significant differences in adiposity indicators were observed among the other three patterns. In adolescents, "prolonged sitters" (N = 250, 44.5%), "moderate sitters" (N = 211, 37.5%), and "breakers" (N = 101, 18.0%) were identified. "Breakers" had the lowest BMI z-score, FM%, and FMI among the three groups, followed by "moderate sitters" and "prolonged sitters." Different accumulation patterns of SED and breaks were identified for children and adolescents in China. Among them, "MVPA breakers" and "Breakers" are most beneficial to maintain a normal weight status. Health promotion efforts could consider increasing MVPA and decreasing SED time for children and restricting SED to at least 30 min for adolescents to improve their adiposity indicators. Show less

The mediation effect of 24-hour physical activities on the association between type 2 diabetes and mortality is unclear. Additionally, Little evidence was found on the isotemporal substitution effect of 24-hour physical activities components on changing Life expectancy among patients with type 2 diabetes diagnosed. To address the abovementioned research gap, the study has a two-fold aims: first, to examine the mediation effect of 24-hour physical activities in type 2 diabetes and mortality; and second, to address how reallocating time on different daily activities would affect life expectancy. Analysis was conducted on the accelerometer data of 103,359 participants in the UK Biobank, with a median age of 57 years (range 39 to 70). Compositional mediation cox model was conducted to analyze the mediating effects of 24-hour physical activities. Additionally, the cohort Life table method was utilized to estimate the changes of Life-years over the next 10 years resulting from the substitution effect of different physical activities. During a mean follow-up of 13.95 (range 2.95-16.28) years, 2,649 deaths were recorded. Diabetes was significantly associated with increased time spent engaging in sedentary behavior (SB), and reduced time spent on moderate-to-vigorous physical activity (MVPA) and light-intensive physical activity (LPA), thereby demonstrating an association with higher mortality risk. The indirect effect of physical activity (HR = 1.27, 95% CI 1.23-1.30) accounted for 41.9% of the total effect of diabetes on mortality. Furthermore, the Life expectancy gains with a maximum of 1.32 years over the next 10 years was found when reallocating SB time to MVPA. The results revealed that 24-hour physical activities might mediate the association between diabetes and mortality. Therefore, promoting participation in MVPA and reducing sedentary activities among diabetes patients was expected to have a positive effect on Life expectancy over the next 10 years. Show less

Lysophosphatidic acid (LPA) signaling has emerged as a central regulatory axis in both normal physiology and disease, orchestrating diverse cellular processes such as proliferation, survival, migration, immune modulation, and tissue remodeling. Originally identified as a bioactive lipid that regulates smooth muscle contraction and vascular tone, LPA has since emerged as a pleiotropic signaling molecule implicated in multiple physiological systems and a wide spectrum of pathological states. These include cancer, neurodegenerative disorders, cardiovascular and metabolic syndromes, inflammatory conditions, and fibrotic diseases. Elevated LPA levels, overexpression of autotaxin (ATX), and aberrant activation of LPA receptors (LPARs) contribute to disease initiation and progression, positioning the LPA axis as both a diagnostic biomarker and a promising therapeutic target. This review describes the multimodal and multinodal organization of the LPA signaling network, detailing upstream biosynthesis, receptor diversity, and downstream effectors across diverse organ systems. Therapeutic strategies targeting ATX, LPARs, and intracellular mediators are critically assessed, along with a review of ongoing and emerging clinical trials. Furthermore, we introduce a context-aware AI-based neural network model to simulate LPA signaling dynamics, providing a framework for predictive modeling and personalized therapeutic interventions. By integrating mechanistic insights with adaptive computational frameworks, this review positions the LPA axis as a powerful and versatile target for systems biology-guided precision medicine strategies in both health and disease. Show less

Elevated Lipoprotein(a) Lp(a) levels are associated with coronary atherosclerosis as detected by cardiac computed tomography angiography (CCTA). However, quantitative data including coronary plaque volumes and characteristics are scarce. The current study evaluated the sex-specific correlations between (Lp(a)) levels and the extent and composition of coronary stenosis and plaques. 1,946 patients undergoing CCTA (third-generation dual-source scanner) for suspected coronary artery disease were included whose Lp(a) levels were available. Lp(a) values ≥ 125 nmol/L were classified as high. High Lp(a) levels were observed in 336 patients, who had greater maximum degree of stenosis (49.5 ± 26.4% vs. 43.5 ± 27.6%, P = 0.002), mainly as a result of the pronounced difference in males (53.8 ± 26.0% vs. 46.2 ± 26.8%, P = 0.001). A strong correlation between higher Lp(a) values and high-risk plaque features was noted in the overall cohort (odds ratio [OR]: 1.645; 95% confidence interval [CI]: 1.011 to 2.593; P = 0.037), independent of age and LDL-cholesterol values. In males, high Lp(a) levels were associated with greater total plaque volumes (118.1 [IQR 18.3-284.4] vs. 83.2 [IQR 11.8-226.3] mm Our study identifies novel sex-specific correlations between Lp(a) levels and coronary plaque characteristics. High Lp(a) levels in men seems to be associated with increased fibrotic plaque volumes and may contribute to greater total plaque burden and high-risk plaque features. Show less

To investigate the risk factors associated with coronary heart disease (CHD) in patients with metabolic-associated fatty liver disease (MAFLD) and develop a nomogram prediction model. This study included 394 patients with MAFLD who underwent coronary angiography at The Affiliated Hospital of Qingdao University between December 2019 and December 2024. The study cohort was divided in a 7:3 ratio into training and validation sets comprising 277 and 117 cases, respectively. The training group was further divided into the MAFLD-only ( Of the 394 MAFLD cases, 313 had CHD-related complications. Of the 277 patients in the training set, 220 had CHD, and of the 117 patients in the validation set, 93 had CHD. LASSO regression analysis revealed that the following variables were associated with the risk of CHD: sex, lipoprotein(a) (Lp[a]), low-density lipoprotein cholesterol, white blood cell count (WBC), glycated triglyceride-glucose index (TyG), and atherosclerosis index (AIP). Multivariate logistic regression analysis revealed that sex, Lp(a), WBC, TyG, and AIP were independent risk factors for CHD in MAFLD cases. A nomogram was constructed and an ROC curve was plotted, based on which the optimal cutoff value was determined as 0.698. The area under the curve of the nomogram in the training and validation cohorts was 0.860 (95% CI = 0.807-0.913) and 0.843 (95% CI = 0.757-0.929), respectively. Calibration curves for CHD risk probability showed good agreement between the nomogram's predicted probabilities and the observed event rates. DCA demonstrated the net clinical benefit of the constructed nomogram. Sex, Lp(a), WBC, TyG, and AIP emerged as independent risk factors for CHD in patients with MAFLD and the nomogram prediction model constructed using these factors could effectively predict CHD occurrence. Show less

The purpose of this study is to explore the effect of physical activity on the executive function of 5-6-year-old children and to provide a theoretical and empirical basis for further research on improvements in the executive function of children caused by physical activity. A total of 170 children (5-6 years old) from several kindergartens were selected via multistage stratified sampling. All the children wore 7-day accelerometers (ActiGraph GT3X) to measure their daily physical activities. Parents completed the preschool children's executive function questionnaire (BRIEF-P) to assess their daily executive function. (1) The total duration of physical activity (TPA) was 110.84 ± 22.52 min/day, the duration of low-intensity physical activity (LPA) was 36.23 ± 7.53 min/day, and the duration of medium- and high-intensity physical activity (MVPA) was 74.55 ± 16.77 min/day. A total of 82.6% of the children reached the recommended amount of MVPA. (2) After adjusting for body mass index (BMI), parents' highest educational background and parents' total monthly income, MVPA was negatively correlated with children's total executive function score ( Physical activity can improve the executive function of children aged 5-6 years to some extent. MVPA can improve children's executive function and subdomains, and there is a correlation between boys' physical activity and executive function. Show less

This study aimed to identify heterogeneous patterns of medical coping modes (MCM) and to examine the moderating role of social support in the relationship between these patterns and social disability in young and middle-aged patients after percutaneous coronary intervention (PCI). A cross-sectional study was conducted among 129 post-PCI patients from a single center in China. Participants completed the Medical Coping Modes Questionnaire (MCMQ), the Social Support Rating Scale (SSRS), and the Social Disability Screening Schedule (SDSS). Latent profile analysis (LPA) was used to identify distinct coping patterns. The moderation effect of social support was tested using the Johnson-Neyman technique. Two distinct coping profiles were identified via LPA: "Adaptive Copers" (55.1%), characterized by higher confrontation and lower avoidance/resignation, and "Maladaptive Copers" (44.9%), showing the opposite pattern. A counterintuitive finding emerged, with the Maladaptive Copers reporting significantly lower social disability scores. Furthermore, beyond this profile differentiation, social support demonstrated a significant U-shaped moderating effect in the coping-disability relationship. Its moderating role was statistically significant only at very low (<39.884) and very high (>52.924) levels of support. This study reveals two key findings: first, post-PCI patients are heterogeneous in coping, comprising adaptive and maladaptive subgroups; second, the impact of these coping styles on social disability is non-linearly moderated by social support. Clinicians should assess both coping profiles and social support levels to tailor interventions effectively. Show less

Despite advances in therapies that target low-density lipoprotein (LDL), atherosclerotic cardiovascular disease (ASCVD) remains a major cause of morbidity and mortality. This has led to the investigation of other biomarkers, including lipoprotein(a) [Lp(a)]. Lp(a) is a variant of LDL that is genetically determined, has proatherogenic, proinflammatory, and prothrombotic effects, and has a linear correlation with ASCVD risk. Approximately 20%-30% of the global population has elevated serum Lp(a). Recommendations for increased Lp(a) testing has heightened the need for effective medications to target this biomarker. Although traditional antilipemic agents have demonstrated negligible effects on Lp(a), multiple targeted therapies are emerging, including antisense oligonucleotides, small interfering RNA agents, and small molecules. The efficacy of these novel agents observed in early clinical trials and the development of alternate treatment modalities, including gene editing and RNA-based innovations, signal a promising new era of ASCVD prevention via non-LDL pathways. SIGNIFICANCE STATEMENT: Lipoprotein(a) is a genetically determined biomarker that significantly impacts atherosclerotic risk. The development of novel therapies that lower lipoprotein(a) warrants a broad understanding to increase comfortability and optimize utilization upon market approval. Show less

Aortic valve stenosis (AS) is a progressive valvular disease characterized by fibrocalcific remodeling of the aortic valve leaflets, contributing to significant cardiovascular morbidity and mortality. While valve calcification has been extensively studied, the relationship between valve fibrosis, lipoprotein(a) [Lp(a)], systemic inflammation, sex differences, and valve morphology remains less explored. We prospectively enrolled 45 patients with severe AS undergoing preoperative echocardiography and contrast-enhanced cardiac computed tomography (CT) at Centro Cardiologico Monzino. Aortic valve calcium and fibrosis volumes were quantified using threshold-based segmentation on CT images. Lp(a) was measured by ELISA, while a multiplex Luminex assay measured a panel of 44 cytokines. Patients were stratified by Lp(a) levels (≤ 50 vs. > 50 mg/dL), sex, and valve morphology (bicuspid vs. tricuspid) to explore associations with the fibrocalcific components of stenotic aortic valves. The median Lp(a) level was 34.4 mg/dL (12.6; 93.4). No significant differences in valvular calcium load were observed between low and high Lp(a) groups. However, a modest increase in fibrotic volume was noted in patients with elevated Lp(a), particularly among men (p = 0.075). Several cytokines, including IL-1RA, IL-8, and TGF-α in men, and EGF, GM-CSF, IP-10, and IL-10 in women, were positively correlated with calcium burden. Fibrotic volume was associated with elevated eotaxin and PDGF-AA levels, with sex-specific patterns. Patients with bicuspid valve exhibited higher fibrocalcific volumes but lower circulating levels of several cytokines compared to patients with tricuspid valve morphology. In patients with severe AS, circulating cytokine profiles show sex- and valve-morphology-specific associations with the fibrocalcific composition of the valve. However, Lp(a) was not associated with valvular calcification, and any relationship with fibrosis appeared at most modest, more evident in men. These results support the relevance of inflammatory profiling in assessing AS pathophysiology. Show less

Patients experiencing premature cardiovascular events (males: <55 years; females: <65 years) represent a high-risk subgroup within the atherosclerotic cardiovascular disease (ASCVD) population. Elevated lipoprotein(a) (Lp[a]) is an independent, genetic, causal risk factor for ASCVD. Lp(a) distribution among patients with premature ASCVD is poorly characterized. This study aimed to describe Lp(a) distribution and baseline characteristics in a large real-world sample of patients with premature ASCVD. We identified 17,594 patients with premature ASCVD who had Lp(a) values from US Medicare, Medicaid, and commercial plans between January 2016-September 2022. Mean age (SD) was 50.9 (10.1) years, most patients were female (68.9%), and half (52.2%) were not prescribed lipid-lowering therapy. Lp(a) levels ≥125, ≥175, and ≥225 nmol/L occurred in 26.8%, 18.8%, and 11.5%, respectively. Black patients had higher median (Q1-Q3) Lp(a) levels (111.0 [51.1-206.0] nmol/L) than Asian (35.0 [14.4-100.0] nmol/L), Hispanic (31.0 [10.9-95.0] nmol/L), or White patients (31.0 [10.7-110] nmol/L). In one of the largest studies in the US investigating Lp(a) distribution in premature ASCVD, we found over a quarter of patients had elevated Lp(a) (≥125 nmol/L). Show less

Older adults' physical and sensory function and self-perceived health state are associated with their daily health behavior, such as moderate-to-vigorous physical activity (MVPA), light physical activity (LPA), sedentary behavior (SEB), and sleep duration (SD), though most studies examine these independently, overlooking 24-hour interactions. This study aims to investigate the relationships between physical and sensory function (vision, hearing, activity limitations), self-perceived health and the pattern of 24-hour activity behaviors via compositional data analysis. A secondary data analysis was conducted on data from the Survey of Health, Ageing and Retirement in Europe. Compositional data analysis was employed to account for the inherently interdependent nature of these behaviors. Linear regression models were implemented, designating activity behaviors as the dependent variable and sensory/physical function as the independent variable. The results indicated that vision and hearing showed weaker and nonsignificant associations with activity behaviors. Activity limitations significantly influence health behavior patterns, with no limitations associated with more time in MVPA and less time in SEB and SD. Self-perceived health is significantly positively associated with more MVPA, while inversely associated with SEB and SD. This study revealed that older adults with limitations in their daily activities showed the most sedentary daily activity pattern. Future research should develop targeted interventions to improve activity behaviors in this population. Show less

Childhood cancer can disrupt family functioning, increase caregiver psychological distress, and impair caregiver quality of life. While family resilience is crucial for adaptation, most research has focused on individual-level factors, neglecting heterogeneity and multilevel influences on family resilience. Guided by the Social Ecological Model (SEM), this cross-sectional observational study used latent profile analysis (LPA) to identify distinct profiles of family resilience among caregivers of children with cancer and to explore factors associated with these profiles. Between July 2022 and March 2024, 292 caregivers were recruited. Family resilience was measured using the Family Resilience Assessment Scale. LPA was employed to identify resilience profiles, and binary logistic regression was used to explore influencing factors. Two latent profiles were identified: the Low Resources-Low Positivity profile (86%) and the High Internal Resilience profile (14%). The Low Resource-Low Positivity profile demonstrated generally lower scores, especially in utilizing social and economic resources and maintaining a positive outlook. The High Internal Resilience profile showed higher scores across all family resilience dimensions, particularly in communication/problem solving, positive outlook, and meaning-making, while the use of external social and economic resources remained relatively lower. Univariate analysis showed significant differences between profiles in residence, number of siblings, caregiver education, individual resilience, social support, caregivers' physical and psychological well-being and child communication (caregiver-reported). Binary logistic regression identified having more than one child (OR = 3.184, 95% CI: 1.437 ~ 7.057, P = 0.004) and higher individual resilience (OR = 1.095, 95% CI: 1.028 ~ 1.165, P = 0.005) as significant predictors of High Internal Resilience profile. This study identified two distinct family resilience profiles among caregivers of children with cancer. Limited use of social and economic resources was common, while caregiver resilience and having multiple children predicted higher family resilience. Interventions should enhance caregiver coping capacity, support one-child families through peer and family programs, and improve access to social support, flexible employment, and affordable care to strengthen family resilience. Not applicable. Show less

Perimenopause is a critical turning point in women's life cycle, and the issue of sleep disturbance during perimenopause not only affects individual health, but also has profound implications for family functioning, socioeconomic status, and public health policies. Therefore, this study aims to explore different potential profiles of sleep quality in perimenopausal women in the community and analyze the influencing factors of different profiles. A cross-sectional study was conducted from July 2024 to December 2024, and a total of 281 perimenopausal women in the community were recruited from 4 communities in Bengbu by convenience sampling. The participants completed the pittsburgh sleep quality index (PSQI), and self-rating anxiety scale (SAS), self-rating depression scale (SDS) and simplified coping style questionnaire (SCSQ). Latent profile analysis(LPA) was employed to identify latent profiles of sleep quality of perimenopausal women in the community. The predictors of sleep quality in different latent profiles were assessed via multinomial logistic regression analysis. One-way ANOVA, chi-square test or Fisher exact test, and the Kruskal-Walis test were used to compare the PSQI scores of perimenopausal women in the community under different latent profile characteristics. The mean age of 281 perimenopausal women was 50.09 ± 5.08 years, and the prevalence of sleep disorders was 31.3%. The sleep quality of perimenopausal women in community could be divided into three different latent profiles: good sleep quality group (68.7%), falling sleep and maintenance difficulty group (24.2%), and poor sleep quality with sleep disorder group (7.1%). Taking the good sleep quality group as the reference group, drinking history (OR = 2.061), chronic disease history (OR = 2.154), spouse's health status (OR = 1.871) and anxiety (OR = 4.390) were the risk factors to predict the difficulty in falling asleep and maintaining sleep in community perimenopausal women (P < 0.05). Spouse's health status (OR = 2.139) and anxiety (OR = 19.029) were the risk factors for poor sleep quality and sleep disorders in community perimenopausal women (P < 0.05). There are three qualitatively different potential profile categories of sleep quality in perimenopausal women in the community, and drinking history, chronic disease, poor spouse health and anxiety have predictive effects on their profile categories. In the future, community nursing staff can take targeted interventions according to different categories of sleep quality in perimenopausal women to improve sleep quality and level of health promotion. Show less