CircRNAs are a new class of noncoding RNA and play regulatory roles in a variety of human diseases. However, the clinical significance of circRNAs in early-onset acute myocardial infarction (AMI) remains unknown. Therefore, we sought to explore the expression profile of circRNAs in early-onset AMI. CircRNA microarray was used to screen differentially expressed circRNAs between early-onset AMI patients and matched healthy controls. The highest fold-changed circRNAs were validated by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in independent samples. Biological processes and potential signaling pathways of differentially expressed circRNA were predicted by the circRNA–miRNA–mRNA network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. One hundred differentially expressed circRNAs, including 64 upregulated and 36 downregulated, were detected between 5 early-onset AMI patients and 5 healthy controls. Among the 8 circRNAs with the highest fold-change magnitude, only circSEC31A was validated by qRT-PCR in an independent cohort (12 early-onset AMI patients vs. 12 healthy controls), showing significant upregulation in AMI patients (fold change = 2.27, P = 0.030). CircRNA–miRNA–mRNA network, GO and KEGG analysis indicated that circSEC31A was associated with apolipoprotein and cholesterol metabolism. CircSEC31A is differentially expressed in plasma of patients with early-onset AMI and may represent a candidate molecule for further investigation into the mechanisms of this condition. Bioinformatics analysis suggests potential links to apolipoprotein and cholesterol metabolism.

BackgroundElderly patients with coexisting coronary artery disease (CAD) and atrial fibrillation (AF) are at significantly increased risk of mortality. Accurate risk stratification is crucial for improving clinical management, yet a dedicated predictive tool for this specific population is lacking. The widely used CHA2DS2-VASc score demonstrates limited performance in predicting all-cause mortality in this complex comorbid group.MethodsA cohort of elderly inpatients (≥65 years) diagnosed with CAD and AF were retrospectively enrolled from the Department of Cardiology at the Chinese PLA General Hospital between January 2010 and December 2017. Baseline clinical data during hospitalization were collected, and all patients were followed up for all-cause mortality. Patients were randomly divided into a training set (70%) and a validation set (30%). Variable selection was performed using LASSO-Cox regression. Predictive models were established through a Cox proportional hazards model (via LASSO-Cox) to predict all-cause mortality risk. To assess model robustness and address potential overfitting, we performed 10-fold cross-validation and bootstrap resampling (500 replicates) with optimism-corrected C-statistics. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA), and compared against the CHA2DS2-VASc score.ResultsA total of 1678 elderly patients with CAD and AF were randomly divided into a training set (n = 1174) and a validation set (n = 504). Through LASSO-Cox regression, 17 variables were identified as predictors associated with all-cause mortality. Two distinct models were developed: LASSO-Cox Model A included factors such as age, left ventricular ejection fraction, blood glucose, plasma fibrinogen, D-dimer, prothrombin time, NT-proBNP, hemoglobin, and hematocrit; LASSO-Cox Model B incorporated all variables from Model A plus acute myocardial infarction, history of myocardial infarction, renal insufficiency, heart failure, diabetes, stroke, chronic obstructive pulmonary disease, and malignant tumor.The analysis of Cox proportional hazards regression models showed that in the training sets, the Area Under Curves (AUC) of model A, model B and CHA2DS2-VASc scores for predicting 1-year all-cause death were 0.83, 0.85 and 0.66, respectively; the AUC for 5-year all-cause death were 0.74, 0.76 and 0.62, respectively. In the validation sets, the AUC of model A, model B and the CHA2DS2-VASc score for predicting 1-year all-cause mortality were 0.79, 0.78 and 0.57, respectively; the AUC for 5-year all-cause death were 0.74, 0.75 and 0.57, respectively. The 10-fold cross-validation yielded a mean AUC of 0.83 (SD: 0.04) for 1-year mortality, and bootstrap resampling produced an optimism-corrected C-statistic of 0.679 (95% CI: 0.651–0.708), confirming that the model maintains clinically meaningful discriminative ability after accounting for optimism. Model B demonstrated better calibration and provided greater net clinical benefit in DCA.ConclusionThe LASSO-Cox machine learning model demonstrates superior predictive performance for all cause mortality relative to the traditional CHA2DS2-VASc score in elderly patients with CAD and AF.

AIMS:The increasing frequency of heat events driven by climate change poses a serious challenge to cardiovascular health. This study aimed to investigate the relationship between high temperature and acute cardiovascular disease (CVD) incidence in China and to quantify the heat-related burden of CVD. METHODS AND RESULTS:A total of 856 357 incident acute CVD cases were used from CVD surveillance in China in 2023. A distributed lag non-linear model was applied to evaluate the dose-response relationship between temperature and CVD incidence, as well as the best linear unbiased prediction of the minimum incidence temperature (MIT). The heat-related burden was quantified using attributable fraction and attributable number for two temperature ranges: all heat and extreme heat. Higher temperatures were associated with an increased risk of acute CVD incidence. Extreme heat exposure resulted in a cumulative relative risk (RR) of 1.17 [95% confidence interval (CI) 1.05-1.30], with the highest cumulative risk observed on the fourth day following exposure. All heat exposure accounted for 3.19% of CVD cases, while extreme heat contributed to 0.08%. The burden was particularly pronounced among individuals aged ≥65 years (RR = 1.20, 95% CI 1.05-1.37), rural populations (RR = 1.18, 95% CI 1.01-1.37), and those living in temperate monsoon and temperate continental climates (RR = 1.25, 95% CI 1.05-1.49). Minimum incidence temperature varied geographically, ranging from 16.0°C in northern regions to 26.2°C in southern regions, with the highest MITs concentrated in tropical areas. CONCLUSION:These findings emphasize the urgent need for region-specific public health strategies that integrate climate change adaptation and CVD prevention to mitigate the growing health risks associated with rising temperatures.

To determine whether postoperative delirium (POD) accelerates perioperative frailty worsening in older surgical patients and how their combined effect influences long-term survival. POD was independently associated with a higher risk of perioperative frailty worsening. Both POD and frailty worsening predicted increased 1-year mortality, and their coexistence conferred the greatest mortality risk. Early identification and management of POD may help slow frailty progression and improve survival in older surgical patients. Postoperative delirium (POD) is a frequent complication in older surgical patients and is associated with adverse outcomes, while frailty is also highly prevalent during the perioperative period. This study aimed to determine whether POD accelerates perioperative frailty worsening and to assess the effect of their coexistence on 1-year mortality. We analyzed prospectively collected data from a multicenter cohort of patients aged ≥65 years undergoing non-cardiac, non-neurosurgical surgery. Frailty was assessed using the FRAIL scale before surgery and at 1 month postoperatively. Perioperative frailty worsening was defined as an increase in the postoperative score compared with the preoperative score. POD was diagnosed using the 3-Minute Diagnostic Interview for Confusion Assessment Method. Logistic regression was employed to examine the associations between POD and frailty worsening, as well as the combined effect of their coexistence on 1-year mortality. Subgroup analysis was performed to confirm the robustness of the findings. Of the 6196 patients included, 648 (10.5

Background:Postoperative delirium (POD) is a common and severe complication in older surgical patients. Although systemic inflammation and frailty are established risk factors, the predictive value of the lymphocyte-to-monocyte ratio (LMR) across different frailty strata remains unclear. This study aimed to evaluate the association between preoperative LMR and POD and to determine whether this relationship varies according to frailty status. Methods:We performed a retrospective analysis of prospectively collected data from a multicenter cohort of 6,475 patients aged ≥65 years undergoing elective non-cardiac, non-neurosurgical surgery in China. Preoperative LMR was calculated from preoperative blood tests. Logistic regression and restricted cubic spline (RCS) analyses were used to assess the association between preoperative LMR and POD, with further stratified analyses performed across different frailty groups. Results:Among 6,475 patients, 789 (12.2%) developed POD. After adjustment for potential confounders, higher LMR was independently associated with a lower risk of POD (per 1-unit increase: OR 0.94, 95% CI 0.90-0.98, P = 0.009). A significant inverse dose-response relationship was observed. Compared with the lowest quartile (Q1), the adjusted ORs (95% CIs) for Q2-Q4 were 0.73 (0.59-0.90), 0.69 (0.56-0.86), and 0.68 (0.54-0.85), respectively. Stratified analyses revealed distinct patterns across frailty status: a significant nonlinear association was observed only in pre-frail patients (Q4 vs. Q1: adjusted OR 0.69, 95% CI 0.50-0.95; P for nonlinearity = 0.003). In contrast, the association in frail individuals was weaker and primarily linear, while no significant association was observed in robust patients. Conclusion:Preoperative LMR is independently associated with POD in older surgical patients. Its predictive value varies across frailty strata, with the association most evident among pre-frail individuals.

PURPOSE:Frailty is common among patients with acute ischemic stroke (AIS) and is associated with adverse health outcomes. Although hyperhomocysteinemia (Hhcy) is a recognized biomarker in AIS, its association with frailty remains unclear. This study aimed to examine the relationship between Hhcy and frailty and assess whether Hhcy is independently associated with frailty in AIS patients. PATIENTS AND METHODS:We conducted a cross-sectional study involving 397 AIS patients admitted between April 2023 and April 2024. Frailty was assessed using the Tilburg Frailty Indicator (TFI). Clinical and laboratory data, including homocysteine levels, were collected at admission. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for variable selection, followed by multivariable logistic regression to examine the independent association between Hhcy and frailty in AIS. RESULTS:Of the 397 AIS patients, 154 (38.8%) were identified as frail. Hhcy was significantly associated with frailty across all adjusted models (adjusted odds ratios: 1.660-1.859, all p < 0.05), independent of sociodemographic characteristics, medical history, clinical parameters, and health indicators. Other significant factors associated with frailty included age ≥75 years, being unmarried, vitamin B12 levels, NIHSS score, and PHQ-9 score. CONCLUSION:Hhcy is independently associated with frailty in AIS patients. This finding suggests that homocysteine may serve as a potential biomarker for early frailty risk stratification in this population.

PURPOSE:The purpose of this study is to provide a decision-making basis for skin care of older hospitalized patients through a penalized statistical prevalence association model. DESIGN:We reviewed nine eligible institutions as multi-center research centers in China. SUBJECTS AND SETTING:We conducted a multicenter cross-sectional study on July 17, 2023, from which 4851 valid questionnaires were collected. METHODS:LASSO regression with 10‑fold cross‑validation was first used to select candidate variables. Variables with a selection frequency >0.8 after 1000 bootstrap resampling steps were retained as stable identify. To address rare‑events bias, Firth's penalized logistic regression was then applied. Model discrimination was assessed using the ROC curve, AUC, and C‑index with 95% CI via bootstrap. Calibration was evaluated by calibration plots, slope, intercept, and the Brier score. A leave-one-center-out generalizability assessment was performed to evaluate model applicability across centers. Clinical utility was examined using decision curve analysis (DCA). RESULTS:Seven variables (age, albumin, hemoglobin, diabetes, painkillers, antipsychotics, Braden score were identified. The model demonstrated excellent discrimination (AUC = 0.916, 95% CI [0.892,0.916]; C-index = 0.916 [0.890,0.939]; sensitivity 0.91, specificity 0.80) and good calibration (slope 1.035, intercept -0.001, Brier score 0.018). In the leave-one-center-out generalizability assessment, the model demonstrated a mean cross-center AUC of 0.905 [0.835-0.967]. Decision curve analysis confirmed clinical utility within the 0-15% threshold probability range. CONCLUSIONS:This large-sample multi-center prevalence association model based on penalization and resampling techniques provides an accurate, stable, and clinically applicable tool for individualized pressure injury risk assessment in hospitalized older patients.

Frailty is a prevalent yet reversible condition in older adults. While exercise is a cornerstone intervention, the optimal protocols tailored to varying functional levels remain underdefined. This study aimed to evaluate the feasibility and effectiveness of a Timed Up and Go (TUG)-based graded multi-component exercise (GME) program in reversing frailty among community-dwelling older adults. This study was a multi-center, parallel-group, superiority randomized controlled trial conducted in community settings in Beijing, China. Participants were aged ≥ 60 years and diagnosed with pre-frailty or frailty according to the Fried phenotype. Participants were randomly assigned (1:1) via a centralized computer-generated randomization tool (random.org) to either the GME group or the Medical Health Education (MHE) group. The GME group received a 5-month, twice-weekly exercise program (aerobic, resistance, balance, flexibility) graded by TUG performance (Levels A, B, C). The MHE comparator group received weekly health education. The primary outcome was the Fried frailty score. Data collectors and statistical analysts were blinded to group assignment, while participants and exercise instructors were not. Among 111 participants (GME: n = 66, MHE: n = 45), the GME group showed superior reduction in Fried frailty scores (P = 0.008), with 21.2

ABSTRACT Background and Aim Among the oldest‐old, the impact of body composition on survival outcomes exhibits pronounced heterogeneity. Although the obesity paradox has been widely discussed, clear evidence is still lacking regarding whether the biological effects of adipose reserves are modulated by functional status. Therefore, this study aims to investigate the association between adipose reserve indicators and long‐term all‐cause mortality risk in the oldest‐old and to elucidate the regulatory role of frailty, thereby providing an evidence‐based foundation for precision clinical health management. Methods This prospective cohort study included 529 community‐dwelling oldest‐old individuals. Participants were categorized into prefrailty and frailty groups at baseline using the Fried frailty phenotype. Bioelectrical impedance analysis was utilized to measure body composition. Stratified multivariate Cox proportional hazards regression models were employed to evaluate the relationship between adipose indicators and all‐cause mortality. Additionally, restricted cubic splines (RCS) and Kaplan–Meier curves were used to analyse survival heterogeneity. Results During a median follow‐up of 3.84 years, 88 deaths (16.6%) occurred. In the prefrail oldest‐old, adipose reserves exhibited significant protective effects on survival: The fully adjusted model showed that PBF (HR = 0.92, 95% CI: 0.87–0.98, p = 0.006), VFA (HR = 0.99, 95% CI: 0.97–0.99, p = 0.013) and WHR (HR = 0.91, 95% CI: 0.86–0.95, p < 0.001) were all inversely associated with mortality risk. In contrast, these protective effects vanished in the frail oldest‐old (all p > 0.05), suggesting that the benefits of adipose tissue are contingent upon the individual's basal functional reserve. RCS analysis revealed a linear dose–response relationship between adipose indicators and mortality risk (all p for non‐linearity > 0.05), with no significant threshold effect observed. Interaction analyses confirmed that frailty status significantly modulated the prognostic value of adipose metrics (p < 0.05), with protective effects restricted exclusively to prefrail individuals. Kaplan–Meier curves confirmed that individuals in the prefrailty stage with higher adipose reserves achieved the highest survival rates (all Log‐rank p < 0.001). Conclusion These findings suggest that the protective effect of adipose reserves is frailty‐dependent in the oldest‐old, and that weight management strategies should consider baseline functional status.

BACKGROUND:Multiple scales are available to evaluate the health status of older surgical patients; however, their relative ability to predict postoperative major adverse cardiac and cerebrovascular events (MACCE) remains unclear. OBJECTIVE:To examine the association between preoperative health status, as measured by four commonly used scales, and 30-day postoperative MACCE in older surgical patients, and to compare their predictive performance and incremental value against the Revised Cardiac Risk Index (RCRI). DESIGN:A retrospective study of a large multicentre cohort. SETTING:Nineteen tertiary hospitals across China participating in a perioperative database. PATIENTS:Patients aged ≥65 years who underwent noncardiac, non-neurosurgical surgery between April 2020 and April 2022 were included in the analysis. The Activities of Daily Living (ADL), EuroQol Five-Dimension Five-Level (EQ-5D-5L), Metabolic Equivalent of Task (MET), FRAIL, and RCRI were evaluated preoperatively. MAIN OUTCOME MEASURE:The primary outcome was the occurrence of MACCE within 30 days after surgery, defined as any of the following: stroke, myocardial infarction, angina pectoris, congestive heart failure, cardiac arrest, or all-cause mortality. RESULTS:Among the 7996 patients, 126 (1.6%) experienced MACCE. Similar to the RCRI, the four health assessments were significantly associated with MACCE risk. The RCRI alone yielded an area under the curve (AUC) of 0.610 [95% confidence interval (CI): 0.563 to 0.658]. Incorporating each scale improved the predictive performance of the RCRI. The RCRI-Plus model, comprising RCRI, age, severity of anaemia, and surgical duration, achieved an AUC of 0.692 (95% CI: 0.643 to 0.741). Further addition of the four scales to the RCRI-Plus increased discrimination, with the highest AUC observed for the RCRI-Plus model incorporating FRAIL (AUC 0.724; 95% CI: 0.679 to 0.770). However, DeLong's test showed no significant differences between this model and the RCRI-Plus models incorporating ADL, EQ-5D-5L, or MET. CONCLUSIONS:Preoperative health status assessed by four geriatric scales was significantly correlated with postoperative MACCE and provided improved risk discrimination beyond the RCRI. Adding any of these assessments to the RCRI enhanced predictive performance, with FRAIL showing the greatest incremental benefit. These findings underscore the value of multidimensional health status evaluation for preoperative cardiac and cerebrovascular risk stratification, with frailty assessment warranting particular attention. TRIAL REGISTRY:ClinicalTrials.gov, NCT04911530.

Epithelial–mesenchymal transition (EMT)-associated stemness and therapeutic resistance are major drivers of HNSCC progression; however, the upstream regulators coordinating these malignant programs remain incompletely understood. TCGA-HNSC, GEO, and single-cell RNA sequencing datasets were analyzed to evaluate CHGB expression, prognostic value, and its association with epithelial–mesenchymal transition (EMT). EMT scoring, gene set enrichment analysis, weighted gene co-expression network analysis, and Cox regression analyses were performed. Gain- and loss-of-function approaches, xenograft models, tumorsphere formation assays, cisplatin sensitivity assays, and rescue experiments were used to investigate the biological functions and molecular mechanisms of CHGB in HNSCC. CHGB was significantly upregulated in HNSCC tissues and associated with poor overall survival. Integrative analyses identified a strong association between CHGB expression and EMT-related transcriptional programs. Functionally, CHGB depletion inhibited proliferation, migration, cell-cycle progression, primary and secondary tumorsphere formation, cisplatin resistance in vitro, and tumor growth in vivo, whereas CHGB overexpression exerted opposite effects. Mechanistically, CHGB promoted EMT-associated stemness and chemoresistance by sustaining ZEB1 expression through PI3K/AKT signaling. ZEB1 restoration partially rescued the impaired self-renewal capacity and enhanced cisplatin sensitivity induced by CHGB knockdown, whereas ZEB1 silencing attenuated CHGB-driven malignant phenotypes. Single-cell transcriptomic analyses further confirmed that CHGB was enriched in malignant cells and positively associated with EMT and stemness programs. CHGB functions as a critical regulator of EMT-associated stemness and chemoresistance through the PI3K/AKT/ZEB1 axis and represents a potential prognostic biomarker and therapeutic target in HNSCC.

ABSTRACT Background Endocrine therapy with CDK4/6 inhibitor has been the main treatment for HR+/HER2− breast cancer in the adjuvant setting; however, the data on the application in the neoadjuvant setting is limited. We compared neoadjuvant efficacy and safety of sequential chemotherapy‐CDK4/6 inhibitors with chemotherapy alone in HR+/HER2− breast cancer patients. Methods Female patients with HR+/HER2− breast cancer who received neoadjuvant therapy at the Fifth Medical Center of the PLA General Hospital from November 2019 to March 2025 were enrolled. The objective response rate (ORR), pathological complete response (pCR), and event‐free survival (EFS) between the two treatment groups were analyzed. Results Among the 181 enrolled patients, 142 received chemotherapy alone (NCT cohort) and 39 received CDK4/6 inhibitors plus endocrine therapy (NCT‐ET cohort) after chemotherapy as preoperative therapy. Overall pCR was similar across cohorts (3.5% in NCT cohort vs. 2.6% in NCT‐ET cohort, p = 1.000), as was ORR (72.5% vs. 69.2%, p = 0.685). The 3‐year EFS rate was numerically higher in the NCT‐ET cohort (96.7% vs. 83.6%, p = 0.111). However, among patients who failed to achieve partial response (PR) within 4 cycles of chemotherapy, switching to endocrine therapy was associated with improved ORR (61.3% vs. 30.4%, p = 0.005). Overall pCR (3.2% vs. 0.0%, p = 0.356) and 3‐year EFS rate (95.7% vs. 78.0%, p = 0.105) were numerically higher in the NCT‐ET cohort. The total incidence of grade ≥ 3 adverse effects was higher in the NCT‐ET cohort (69.2% vs. 47.8%). However, for patient received endocrine therapy after chemotherapy, grade ≥ 3 events decreased from 66.7% during chemotherapy phase to 20.5% after switching to endocrine therapy. Conclusions Despite no statistically significant differences in observed overall pCR and 3y‐EFS between patients treated with NCT or NCT‐ET, the sequential endocrine strategy was associated with improved ORR among patients who did not achieve PR after four cycles of chemotherapy and a lower incidence of adverse events during endocrine therapy.

Background Intraplaque neovascularization is a biomarker of vulnerable plaque. However, no data are available whether the increase in neovascularization within carotid plaques is a result of ischemia or an increase in adventitial vasa vasorum (VV). Objective To evaluate the VV signal in carotid vulnerable plaques. Methods Contrast-enhanced ultrasound (CEUS) examination was performed to examine changes in VV density in 47 patients with carotid plaque, and 21 patients received CT angiography (CTA) examination to assess the VV signal. In addition, a single-channel flow tissue model was fabricated for use in vitro studies to exclude pseudo-enhancement interferences in the distal wall of arteries by CEUS. Results The intensities of adventitial VV behind carotid plaque were lower than that of adventitial VV at the same level adjacent to the plaque in both CEUS and CTA examinations (P u0026lt; 0.05). In vitro study, the intensities of far wall increased as the microbubble concentration increased (P u0026lt; 0.05). However, no significant differences of intensities of far wall were found between different thicknesses tubes at the concentration of microbubble concentrations of 0.3% and 0.5% (P u2265 0.05). Conclusion The formation of intraplaque neovascularization in carotid arteries is associated with the adventitial VV, and ischemia of VV may be a potential mechanism for intraplaque neovascularization.

Given the clear association between obstructive sleep apnea (OSA) and metabolic disorders, coupled with a limited understanding of sarcopenia in patients with OSA, this study aimed to investigate the relationship between triglyceride-glucose (TyG) index and sarcopenia and in an elderly population with OSA. Multiple hematological and sleep-breathing status were meticulously recorded in the cohorts. The SARC-F scale ≥ 4 was considered indicative of probable sarcopenia. The correlations between clinical indicators and the SARC-F score were analyzed. The area under the curve (AUC) was utilized to assess the predictive ability of TyG for sarcopenia and sarcopenic obesity. Logistic regression analysis and sensitivity stratification were employed to explore the influence of TyG. A total of 1,148 individuals were included, among whom the median age was 66 (62, 71). 46.3

To examine the correlation among body composition, sleep-breathing indicators, and Framingham risk score (FRS) to identify and amplify nontraditional factors that influence the risk of CVD in males, A total of 195 male participants underwent examinations for body composition and sleep-breathing monitoring. We compared the differences in individual factors across various FRS groups. We further conducted multiple linear regression analysis. A cutoff value of FRS ≥ 14 was utilized, and potential influencing factors were examined by logistic regression analysis. Statistical differences were observed in the levels of fasting blood glucose (FBG), CO2, serum ferritin, hemoglobin (HB), and ECT/TBW among the FRS tripartite groups. However, no significant differences were found in AHI and MSpO2. The multiple linear regression analysis revealed positive correlations between ECW/TBW and FBG with FRS (β = 0.324 and 0.324, p < 0.001), while HB and muscle/fat mass exhibited negative correlations with the score (β = -0.185 and - 0.169, p < 0.01). These five factors-ECW/TBW, FBG, HB, serum ferritin, and muscle/fat mass-collectively accounted for 28.6% of the variation in FRS. A higher ECW/TBW was significantly associated with FRS ≥ 14 (OR = 2.208, 95% CI: 1.503-3.244). Conversely, reduced levels of muscle/fat mass, HB, and basal metabolic rate (BMR) were significantly linked to moderate-to-high CVD risk (ORratio = 0.532, 95% CI: 0.284-0.996; ORHB = 0.961, 95% CI: 0.932-0.991; ORBMR = 0.997, 95% CI: 0.995-1.000). This study revealed correlations among ECW/TBW, HB, FBG, and muscle-to-fat mass ratio with the risk of CVD predicted using FRSs.