First Hospital of Shanxi Medical University

Coronary microvascular dysfunction (CMD) is a major contributor to cardiovascular complications in diabetes. Although noninvasive techniques such as arterial spin labeling cardiac MRI (ASL-MRI) and transthoracic echocardiography (TTE) are available, their comparative performance for CMD remains unclear. To compare ASL-MRI and TTE for CMD assessment in type 1 and type 2 (T1DM, T2DM) mouse models and relate functional indices to histological microvascular and myocardial remodeling, including early-stage T2DM (8w-T2DM). Prospective. Forty 8-week-old male C57BL/6J mice allocated to five groups: control, T1DM, and T2DM (n = 10 per group, imaged 16 weeks postinduction), and early-stage T2DM (8w-T2DM) and age-matched controls (n = 5 per group, imaged 8 weeks post-induction). Segmented FLASH cine, steady-pulsed labeling ASL, and inversion-recovery segmented FLASH (T1 mapping) sequences at 9.4 T. Rest/stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) were derived from ASL data using a model-based approach incorporating native T1 (from segmented FLASH data). Coronary flow velocity (CFV) and reserve (CFVR) were measured by TTE at rest (1.5% isoflurane) and stress (2.5% isoflurane). Histology included assessment of hematoxylin-eosin (myocyte area), Masson (collagen), and IB4 (capillary density). Group comparisons used t-tests, Mann-Whitney U tests, and one-/two-way ANOVA with Bonferroni correction; correlations were assessed with Pearson or Spearman coefficients (r). p < 0.05 was considered significant. 38 animals completed MR and TTE imaging. At 16 weeks, stress diastolic MBF was significantly lower in T1DM (14.67 ± 1.62 mL/g/min) and T2DM (13.42 ± 2.44 mL/g/min) vs. controls (22.19 ± 0.25 mL/g/min), with significantly reduced MPR in T2DM (1.53 ± 0.17 vs. 2.27 ± 0.15). TTE showed significantly reduced CFVR only in T2DM (2.16 ± 0.24 vs. 2.75 ± 0.24). In 8w-T2DM, ASL-MRI detected significantly reduced MPR (1.87 ± 0.16 vs. 2.26 ± 0.13), whereas TTE showed no significant CFVR change (p = 0.900). Capillary density significantly decreased in 16-week and 8-week T2DM. IB4-positive area correlated with CFVR (r = 0.673) and more strongly with MPR (r = 0.810). ASL-MRI detected CMD in diabetic mice, outperforming TTE in early-stage disease and showing a strong association with microvascular injury. 1. Stage 2.

Cardiometabolic multimorbidity (CMM) is a prevalent syndrome among middle-aged and older adults, significantly impairing quality of life and imposing substantial health and economic burdens on China's aging healthcare system. The development of timely predictive models is crucial for enabling early intervention. This study aimed to integrate multidimensional data from the China Health and Retirement Longitudinal Study (CHARLS) to develop an effective predictive model for assessing the five-year risk of CMM onset, thereby facilitating early intervention and management for individuals at risk in China. We analyzed data from the 2015 to 2020 CHARLS surveys, involving 5,388 middle-aged and older adults initially free of CMM. The dataset was randomly split into a training set (70%) and a validation set (30%). Key predictors were identified from 31 potential variables using LASSO regression with 10-fold cross-validation. Selected predictors underwent correlation analysis and were used to construct both Extreme Gradient Boosting (XGBoost) and Logistic Regression (LR) models. Variable contributions in the XGBoost model were interpreted using SHapley Additive exPlanations (SHAP) values, while the LR model was visualized via a nomogram. The performance of the superior model was evaluated using receiver operating characteristic curves, calibration curves, and decision curve analysis. LASSO regression screened significant variables from the initial 31 candidates. Correlation analysis ultimately identified nine key predictors: systolic blood pressure, BMI, fasting blood glucose, total cholesterol, triglycerides, uric acid, age, comorbidities, and pain. The logistic regression model demonstrated superior and more stable predictive performance on the validation set, with an area under the curve (AUC) of 0.732 (95% CI: 0.703-0.761). Calibration curves indicated reliable predictive accuracy, and decision curve analysis established the clinical net benefit across a range of risk thresholds. This study developed and validated a reliable, clinically applicable logistic regression model, supplemented by a nomogram, for assessing the five-year risk of CMM in Chinese middle-aged and older adults. The model effectively identifies high-risk individuals, supporting targeted early intervention and management strategies to alleviate the health and economic burdens associated with CMM in this population.

Germline pathogenic alleles predispose carriers to malignancies; failure to recognize the underlying cancer susceptibility and subsequent delayed diagnosis may lead to severe health impairment. It remains largely undetermined what the somatic mutation characteristics are in colorectal cancer (CRC) patients with pathogenic/likely pathogenic (P/LP) germline mutations and whether, and how, these germline mutations typically located in non-mismatch repair genes, are associated with CRC tumorigenesis. From 8,676 Chinese patients with CRC, we initially screened those who had undergone both germline and somatic mutation testing. We analyzed the relationship between germline mutations and the somatic mutational landscape in this cohort. Germline alterations were examined with a 556- or 105- gene next-generation sequencing panel, and somatic alterations were examined with a 556-gene panel. Overall, 80 CRC patients were identified as carriers of P/LP germline mutations. After excluding 6 patients lacking somatic mutation testing data, 74 patients with P/LP germline mutations and 100 patients without germline mutations were finally enrolled in this study. Twenty-one germline genes were detected in the 74 patients. Compared with patients without P/LP mutations (non-P group), those in the P/LP mutations (P group) had significantly lower age and a higher ratio of microsatellite instability. Patients harboring P/LP germline mutations in MMR genes (P-MMR) were significantly younger and more frequently exhibited high tumor mutational burden. The most frequent somatic variations were KRAS and TP53. The somatic mutational landscape revealed a significantly higher mutational frequency in the P group than in the non-P group, and in the P-MMR group than in the P-non-MMR group. The MAPK pathway was significantly enriched in the P and P-MMR groups. Our data showed lower mutation rate of MSH2 among all MMR genes than in the Western population. Population-based risk analysis indicated that the odds ratio of BRCA2 and ATM mutations exceeded 10. Our findings offer a comprehensive overview of genetic susceptibility in Chinese CRC, which may help to shape a more comprehensive understanding of genetic structure of CRC and generate accurate individualized risk management strategies for mutation carriers.

Chronic obstructive pulmonary disease (COPD) is highly prevalent in later life and is a major driver of long-term care needs among older adults. In ageing societies, care for older adults with COPD is predominantly provided by spousal caregivers, many of whom are older adults themselves. This situation reflects a context of dual ageing, in which both the care recipient and the caregiver experience age-related vulnerabilities. Despite growing global efforts to promote age-friendly health and social care environments, the unmet needs of older spousal caregivers remain poorly synthesised and are often insufficiently addressed within existing geriatric care models. This scoping review aimed to map and synthesise evidence on the unmet needs of older spousal caregivers of older adults with COPD, with a specific focus on how these needs are shaped within a context of dual ageing. Following Arksey and O’Malley’s framework, we conducted a scoping review of qualitative, quantitative, and mixed-methods studies examining unmet needs among older spousal caregivers of older adults with COPD. A comprehensive search was performed across ten English- and Chinese-language databases, last searched on 30 August 2025. Data were charted and synthesised using a narrative approach, with unmet needs mapped using the International Classification of Functioning, Disability and Health (ICF) framework. Eighteen studies were included. Older spousal caregivers reported multidimensional unmet needs, including psychological and emotional support, role balance, communication with healthcare professionals, information and caregiving skills, gender-specific concerns, and systemic and social support. These needs clustered into six categories across four ICF domains and were shaped by the combined effects of caregiving demands, ageing-related vulnerabilities, and long-term spousal interdependence. Older spousal caregivers of older adults with COPD experience multidimensional unmet needs that are shaped by the context of dual ageing and extend beyond individual caregiving burden to system-level gaps in care. These findings highlight the need for caregiver-inclusive and age-sensitive approaches within age-friendly health and social care environments. The review protocol was registered on the Open Science Framework (OSF) (https://doi.org/10.17605/OSF.IO/RYF3C).

Patients with moderate-to-severe allergic rhinitis (AR) often experience a heavy clinical burden and require more medications to alleviate nasal symptoms. The aim of this study was to evaluate the efficacy and safety of GSP301, a fixed-dose combination nasal spray containing olopatadine hydrochloride and mometasone furoate, in patients with seasonal AR (SAR). In this multicenter, randomized, double-blind, parallel-group study, moderate-to-severe SAR patients were assigned at a 1:1:1 ratio to receive intranasal GSP301, olopatadine hydrochloride (OLO), or mometasone furoate (MF) for 14 days. The primary endpoint was the change from baseline in the average A.M. and P.M. 12-hour reflective total nasal symptom score (rTNSS). Secondary endpoints included changes in the instantaneous TNSS (iTNSS), individual nasal symptoms, reflective total ocular symptom score (rTOSS), instantaneous total ocular symptom score (iTOSS), individual ocular symptoms, and rhinoconjunctivitis quality-of-life questionnaire (RQLQ). Exploratory endpoints and adverse events were also analyzed. Among the 534 subjects, the GSP301 group demonstrated statistically significant improvements in the average rTNSS compared with the OLO group [posterior least square mean difference (LSMD) = -0.56; P < 0.0001] and the MF group (posterior LSMD = -0.43; P < 0.0001). Consistent benefits were observed across secondary endpoints, including iTNSS, rTOSS, RQLQ, and individual nasal and ocular symptoms (all P < 0.05). Additionally, GSP301 reduced the levels of interleukin (IL)-5 and eosinophilic cationic protein (ECP) in nasal secretions. Treatment-emergent adverse events (TEAEs) occurred in 11.2%, 13.5%, and 11.3% of patients in the GSP301, OLO, and MF groups, respectively. Compared with OLO and MF, GSP301 demonstrated superior efficacy, safety, and potential advantages in alleviating local inflammation in patients with moderate-to-severe SAR.