ObjectiveThis study aimed to establish a monocrotaline （MCT）-induced pulmonary arterial hypertension （PAH） rat model to systematically evaluate the protective effect of Xiao Qinglongtang （XQLT） on right cardiac function in model rats and further elucidate the underlying regulatory mechanism. MethodsSixty male SD rats were randomly assigned to the normal group， model group， XQLT low-， medium-， and high-dose groups （XQLT-L/M/H）， and the beraprost sodium tablet group （BST）. Except for the normal group， rats in all other groups were given a single subcutaneous injection of MCT （60 mg·kg^-1） to induce PAH. Three weeks after injection， rats in the XQLT-L/M/H groups were administered XQLT intragastrically at 3.07， 6.14， 12.28 g·kg^-1·d^-1， respectively. Rats in the BST group received beraprost sodium at 12.6 μg·kg^-1·d^-1， and rats in the model group received an equal volume of saline. All treatments lasted for 3 weeks. Right ventricular systolic pressure （RVSP） was measured by right ventricular catheterization. Cardiac function was assessed by echocardiography. The right ventricle was weighed to calculate the right ventricular hypertrophy index （RVHI）. Hematoxylin-eosin （HE） staining， Masson staining， and transmission electron microscopy were used to observe myocardial morphology. Serum metabolomic changes were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）. Data-independent acquisition （DIA） proteomics was used to detect differentially expressed （DE） proteins in the right ventricle， and Western blot was used to measure the expression of uncoupling protein 3 （UCP3）， phosphatidylinositol 3-kinase catalytic subunit p110α （PIK3CA）， L1 cell adhesion molecule （L1CAM）， and quinone oxidoreductase （CRYZ）. UPLC-MS/MS was used to analyze the chemical components of XQLT. ResultsCompared with the normal group， the model group showed significantly increased RVSP and RVHI （P<0.05）， along with pathological changes in myocardial morphology. Compared with the model group， all XQLT-treated groups exhibited reductions in RVSP and RVHI as well as significant improvements in cardiac function and myocardial morphology. Among the XQLT groups， XQLT-M showed the most pronounced effects （P<0.05）， comparable to the BST group. Serum metabolomics revealed 105 differential metabolites in the XQLT groups versus the model group ［variable importance in projection （VIP） >1， P<0.05］， including 58 upregulated and 47 downregulated metabolites. KEGG enrichment analysis indicated that XQLT intervention downregulated phenylalanine metabolism （P<0.01） and upregulated unsaturated fatty acid biosynthesis （P<0.05）. Proteomics analysis showed that 982 DE proteins were identified in the MCT groups versus the normal group， including 455 upregulated and 527 downregulated proteins （|fold change （FC）| >1.3， P<0.05）. Compared with the model group， 237 DE proteins were identified in the XQLT groups， including 124 upregulated and 113 downregulated proteins （|FC| >1.3， P<0.05）， with 57 overlapping DE proteins. KEGG enrichment suggested that XQLT mainly modulated pathways related to mineral absorption， ribosomal biogenesis， peroxisomes， glycolysis/gluconeogenesis， spliceosomes， and thyroid hormone signaling. Western blot analysis showed that， compared with the model group， XQLT increased the expression of UCP3， PIK3CA， and L1CAM， while decreasing the expression of CRYZ （P<0.05）. ConclusionXQLT exerts a protective effect on right heart function in MCT-induced PAH rats， and its mechanism is associated with maintaining myocardial homeostasis and alleviating right ventricular remodeling.

To evaluate the application value of the Peyton four-step teaching method in the standardized training of intestinal ultrasound and compare it with traditional teaching methods, so as to provide an optimized approach for clinical ultrasound training.

Background/Aims: Lenvatinib resistance remains a critical barrier in advanced hepatocellular carcinoma (HCC) therapy. However, the underlying mechanisms and strategies for reversing resistance remain incompletely understood. Methods: Integrated transcriptomics of lenvatinib-resistant patient tumors and an acquired-resistance murine model identified a novel macrophage subpopulation. Functional validation employed CRISPR-SAM screening, conditioned medium (CM) assays, subcutaneous/orthotopic xenografts, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs). Mechanistic studies included ChIP-qPCR, co-immunoprecipitation, and pharmacologic targeting. Clinical relevance was assessed in a retrospective cohort. Results: Resistant HCC exhibited significant enrichment of a COLEC12high TAM subset , which correlated with poor survival and treatment response. These TAMs secreted neuregulin-1 (NRG1) , activating HER2/HER3-AKT signaling in tumor cells to drive cancer stemness and lenvatinib resistance. Mechanistically, in TAMs COLEC12 sequestered STAT1 in the cytoplasm, preventing its phosphorylation, and thereby derepressing STAT3-mediated NRG1 transcription. Depletion of NRG1 reversed the stemness phenotypes and resensitized tumors to lenvatinib both in vitro and in vivo. Clinically, high NRG1 expression predicted an inferior lenvatinib response and shorter survival. Crucially, the bispecific anti-HER2/HER3 antibody zenocutuzumab restored lenvatinib efficacy in PDOs, PDXs, and murine models. Conclusions Our work establishes the COLEC12high TAM/NRG1 axis as a master regulator of therapeutic resistance and identifies NRG1 as a predictive biomarker, providing a clinically actionable strategy to overcome lenvatinib resistance in HCC.

ObjectiveTo investigate the physical fitness status and associated factors among preschool children aged 3 to 6 years in Tongzhou District of Beijing, and to provide evidence for promoting physical development in this population. MethodsBased on the 2020 National Physical Fitness Surveillance data for Tongzhou District of Beijing, a total of 416 children were included for standardized physical tests, including morphological, physiological, and fitness indicators, and questionnaire surveys. Independent sample t-tests and ANOVA were used to compare differences in physical indicators across groups, while multivariate linear regression models were applied to analyze influencing factors. ResultsThe comprehensive fitness score of children aged 3 to 6 years old in Tongzhou District of Beijing was (79.98±6.97) points, with an overall physical fitness pass rate of 99.52%. The proportions of excellent, good, and pass grades were 37.50%, 39.90%, and 22.12%, respectively. The average heights for the 3-years-old, 4-years-old, 5-years-old, and 6-years-old groups in Tongzhou District were (102.13±4.24) cm, (107.92±4.66) cm, (115.43±4.70) cm, and (119.16±4.33) cm, respectively. The corresponding average body weights were (16.63±2.46) kg, (18.66±2.54) kg, (21.60±4.02) kg, and (23.46±4.64) kg, respectively. Among children aged 3 to 6 years, the average BMI was (15.95±1.79) kg‧m^-2, body fat percentage was (21.92±4.77)%, resting pulse rate was (95.24±9.70) beats per minute, grip strength was (5.74±2.07) kg, standing long jump distance was (78.12±19.95) cm, sit-and-reach flexibility was (12.25±4.65) cm, continuous two-foot jump time was (6.29±2.55) seconds, 15-meter obstacle shuttle run time was (7.94±1.30) seconds, and balance beam walking time was (5.11±2.25) seconds. Multiple linear regression analyses showed that higher composite fitness scores were significantly positively associated with female gender (b=1.72, 95%CI: 0.42-3.01), aged 4 years old and above (b=2.97, 95%CI: 1.35-4.59), mixed feeding (b=4.16, 95%CI: 1.60-6.72) or breastfeeding (b=3.23, 95%CI: 0.36-6.10) during infancy, taller paternal (b=0.16, 95%CI: 0.02-0.30) and maternal (b=0.25, 95%CI: 0.11-0.39) height (all P<0.05). ConclusionThe physical fitness of children aged 3 to 6 years in Tongzhou District of Beijing is generally favorable, with gender, age, feeding patterns, and genetic factors identified as key correlating factors. Comprehensive strategies are recommended to improve early childhood physical health.

To investigate the effectiveness of a teaching model combining real-case bedside instruction with mixed-level group teaching in intestinal ultrasound training, and to provide reference forestablishing an efficient and practical training system for intestinal ultrasound.

ObjectiveTo establish a semi-automated workflow for hyoid motion tracking based on submental ultrasound videos, evaluate the reliability of manual measurements and the validity of semi-automated tracking, and compare the analytical efficiency. MethodsA total of 46 healthy adults were recruited at Xiamen Fifth Hospital from October, 2024 to August, 2025, and performed dry swallows and swallows of 5 mL and 10 mL moderately-thick liquid boluses. A total of 414 sagittal-plane submental ultrasound videos were acquired. After video quality screening and tracking quality-control procedures, 286 videos were included for paired analysis. A semi-automated tracking pipeline was constructed combining the channel-and-spatial-reliability tracker and You Only Look Once version 8 small (YOLO v8s). Intra-class correlation coefficients [ICC(A,1)] based on the absolute-agreement single-measurement model were calculated for test-retest and inter-rater manual measurements. Using the manual repeated-measurement results as the reference standard, Pearson correlation coefficient (r), ICC(A,1) and concordance correlation coefficient (CCC) were computed for the semi-automated measurements. A total of 5 000 subject-clustered bootstrap resamples were performed to calculate 95% confidence intervals. Cumulative analysis time of manual and semi-automated workflows was compared. ResultsFor the independent test set of YOLOv8s, precision and recall reached 0.940 and 0.956. The mean average precision was 0.974 at an intersection-over-union threshold of 0.5, and 0.609 averaged across thresholds ranging from 0.5 to 0.95. For manual measurements of maximum horizontal and vertical hyoid displacement, the test-retest ICC(A,1) values were 0.925 and 0.912, respectively; the inter-rater ICC(A,1) values were 0.815 and 0.775. For semi-automated versus manual reference measurements, r = 0.865，ICC(A,1) = 0.843，CCC = 0.843 in maximum horizontal displacement; and r = 0.754，ICC(A,1) = 0.746，CCC = 0.745 in maximum vertical displacement. Mean biases were -0.772 mm and -0.229 mm, with 95% limits of agreement of -4.567 to 3.023 mm and -2.918 to 2.460 mm for horizontal and vertical directions. Cumulative manual analysis time was 526 minutes for rater A and 713 minutes for rater B. The semi-automated workflow consumed 155 minutes, in which 40 minutes for computational processing and 115 minutes for manual review. ConclusionManual measurement of maximum hyoid displacement is reliable using qualified submental ultrasound videos. Semi-automated tracking achieves acceptable agreement with manual reference and greatly reduces analysis workload.

Background: Diabetic macrovascular and microvascular complications often coexist and may share similar risk factors and pathological pathways. We aimed to investigate whether 10-year atherosclerotic cardiovascular disease (ASCVD) risk, which is commonly assessed in diabetes management, can predict incident diabetic nephropathy (DN) and retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: This prospective cohort study enrolled 2,891 patients with clinically diagnosed T2DM who were free of ASCVD, nephropathy, or retinopathy at baseline in the Guangzhou (2017–2022) and Shaoguan (2019–2021) Diabetic Eye Study in southern China. The 10-year ASCVD risk was calculated by the Prediction for ASCVD Risk in China (China-PAR) equations. Multivariable- adjusted Cox proportional hazard models were developed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive capability. Results: During follow-up, a total of 171 cases of DN and 532 cases of DR were documented. Each 1% increment in 10-year ASCVD risk was associated with increased risk of DN (pooled HR, 1.122; 95% CI, 1.094 to 1.150) but not DR (pooled HR, 0.996; 95% CI, 0.979 to 1.013). The model demonstrated acceptable performance in predicting new-onset DN (pooled AUC, 0.670; 95% CI, 0.628 to 0.715). These results were consistent across cohorts and subgroups, with the association appearing to be more pronounced in women. Conclusion Ten-year ASCVD risk predicts incident DN but not DR in our study population with T2DM. Regular monitoring of ASCVD risk in routine diabetes practice may add to the ability to enhance population-based prevention for both macrovascular and microvascular diseases, particularly among women.

Probiotics have shown excellent application prospects in preventing and treating many diseases. However, their sensitivity to the harsh environment in vivo always leads to a massive loss of viability and insufficient therapeutic effect. Fortunately, modified probiotics have emerged and provide multiple possibilities for their use in various diseases. Modification not only endows probiotics with extra capacity to resist severe environments but also gives them exogenous characteristics, such as prolonged retention time and improved therapeutic effects. Modified probiotics could combine with other therapies, which has opened up new avenues to enhance the efficacy of probiotic-based therapy. In this review, we have summarized the current physicochemical and biological modification strategies of probiotics. In addition, the progress of research on probiotic-based combination therapy has also been extensively reviewed, which contributes to the enhanced delivery of probiotics or other active constituents and provides new ideas for disease treatment, bioimaging, and diagnosis.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

This study investigated the role of the nuclear factor of activated T cells c3 (NFATc3) in vascular smooth muscle cells (VSMCs) during aortic aneurysm and dissection (AAD) progression and the underlying molecular mechanisms. Cytoplasmic and nuclear NFATc3 levels were elevated in human and mouse AAD. VSMC-NFATc3 deletion reduced thoracic AAD (TAAD) and abdominal aortic aneurysm (AAA) progression in mice, contrary to VSMC-NFATc3 overexpression. VSMC-NFATc3 deletion reduced extracellular matrix (ECM) degradation and maintained the VSMC contractile phenotype. Nuclear NFATc3 targeted and transcriptionally upregulated matrix metalloproteinase 9 (MMP9) and MMP2, promoting ECM degradation and AAD development. NFATc3 promoted VSMC phenotypic switching by binding to eukaryotic elongation factor 2 (eEF2) and inhibiting its phosphorylation in the VSMC cytoplasm. Restoring eEF2 reversed the beneficial effects in VSMC-specific NFATc3-knockout mice. Cabamiquine-targets eEF2 and inhibits protein synthesis-inhibited AAD development and progression in VSMC-NFATc3-overexpressing mice. VSMC-NFATc3 promoted VSMC switch and ECM degradation while exacerbating AAD development, making it a novel potential therapeutic target for preventing and treating AAD.