Guangzhou First People's Hospital

Background:Aging is associated with degenerative changes in both bone and tendon tissues, leading to impaired healing at the bone-tendon interface (BTI) during rotator cuff repair. The role of fibulin-7 (FBLN7) in enhancing BTI healing in aged populations warrants an investigation because of its potential regenerative properties.Purpose:To determine whether FBLN7 can enhance tendon-bone healing and regeneration in a model of rotator cuff repair in aging mice.Study Design:Controlled laboratory study.Methods:A total of 5 young (8 weeks old) and 5 aged (18 months old) C57BL/6 mice were used for a baseline supraspinatus tendon–humerus evaluation. Another 20 aged mice underwent rotator cuff repair and were allocated to either the FBLN7 (intervention) group (n = 10), receiving a fibrin sealant with FBLN7, or a control group (n = 10), receiving a standard fibrin sealant. Mice were euthanized at 4 (n = 5 per group) and 8 (n = 5 per group) weeks after surgery. The supraspinatus tendon–humerus complexes were harvested for micro–computed tomography, histological analysis, and biomechanical testing.Results:The expression of FBLN7 was significantly lower in aged mice at the BTI compared with young mice (P < .05). Histological and biomechanical assessments revealed that the FBLN7 group exhibited improved subchondral bone morphology (P < .05) and denser cortical bone (P < .05), along with significantly higher failure loads and stiffness (P < .05), compared with the control group. Additionally, the FBLN7 group demonstrated superior fibrocartilage formation (P < .05) and the upregulated expression of osteogenic (Runx2; P < .01 at week 4 and P < .05 at week 8), chondrogenic (Sox9; P < .01 at week 4 and P < .05 at week 8), and tenogenic (SCX; P < .05 at week 4) factors.Conclusion:FBLN7 significantly enhanced healing and regeneration at the BTI in aged mice, supporting its potential as a therapeutic intervention to improve rotator cuff repair outcomes.Clinical Relevance:These findings highlight FBLN7’s potential role in clinical sports medicine, suggesting that it could be utilized to promote better recovery and healing in aged patients undergoing rotator cuff repair, addressing a critical challenge in postoperative rehabilitation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for severe aplastic anemia (SAA), with donor sources including matched sibling donors (MSDs), haploidentical donors (HIDs), and unrelated donors (URDs). However, the optimal criteria for donor selection remain undefined. We performed a multicenter retrospective study of 795 consecutive SAA patients who underwent allo-HSCT between 2012 and 2020 across 11 transplant centers in China. The overall survival (OS), failure-free survival (FFS), and GVHD-free/FFS (GFFS) rates were 85.2%, 83.6%, and 76.1%, respectively. Donor-related variables including relationship, age, sex match, blood type, and HLA mismatches were evaluated. Multivariable Cox regression identified donor age ≥50years as an independent risk factor for inferior GFFS (HR=2.13), OS (HR=2.09), and FFS (HR=2.18) (all P<0.001). To directly compare the prognostic weight of donor age versus HLA compatibility, we stratified patients into four subgroups according to donor type (HID vs. MSD) and donor age (<50 vs. ≥50years). Kaplan-Meier analysis with log-rank testing revealed that recipients of haploidentical grafts from younger donors achieved superior OS and FFS compared with those transplanted from older HLA-matched sibling donors. These findings demonstrate that donor age has a greater influence on transplant outcomes than HLA matching. With continuous improvements in haploidentical transplantation techniques, selecting younger haploidentical donors may represent a more favorable strategy than choosing older matched sibling donors.

Non-alcoholic fatty liver disease (NAFLD), a chronic metabolic disorder characterized by ectopic lipid deposition in hepatocytes, currently lacks evidence-based pharmacotherapies, rendering probiotic-based strategies-particularly those utilizing Lactobacillus rhamnosus (LR)-a promising therapeutic avenue. Bacterial extracellular vesicles from Lactobacillus rhamnosus modulate NAFLD progression, but their molecular mechanisms remain unelucidated. Lactobacillus rhamnosus (LR-BEVs) and Escherichia coli (E-BEVs) were isolated via sequential ultracentrifugation, validated for morphology/size by TEM and NTA, and their uptake into THLE-2 hepatocytes was traced with DIL fluorescent dye. Invitro, oleic acid (OA)-induced steatosis in THLE-2 cells was used to assess BEV effects via CCK-8, ALT/AST/TG, IL-1β/IL-6, ROS, and Oil Red O. Invivo, high-fat diet-induced murine NAFLD evaluated BEV therapeutic potential. Mechanistically, transcriptomics, Apelin receptor inhibition (ML221), and Western blotting explored the Apelin pathway in LR-BEV-mediated NAFLD regulation. LR-BEVs (~110 nm) were isolated and internalized by THLE-2 hepatocytes. At 100 ng/mL, LR-BEVs significantly suppressed IL-1β and IL-6 release in THLE-2 cells, contrasting with the pro-inflammatory effects of E-BEVs. Invitro, LR-BEVs ameliorated OA-induced steatosis, reversing suppressed proliferation, elevated ALT/AST levels, inflammatory cytokine secretion, ROS accumulation, and lipid droplet deposition. In a murine model of high-fat diet-induced hepatic steatosis, LR-BEV administration markedly attenuated hepatic lipid accumulation and concomitantly reduced serum levels of ALT, AST, TC, and TG, along with ameliorating hepatic inflammation and oxidative stress. Transcriptomic analysis implicated Apelin signaling as a key pathway modulated by LR-BEVs, with enrichment of target genes (APLNR, SERPINE1, EGR1, ACTA2). Functional validation demonstrated that LR-BEVs exert their anti-steatotic effects-promoting proliferation and inhibiting lipid accumulation, ALT/AST elevation, TC, and TG increase-specifically via Apelin pathway activation, as evidenced by the abrogation of these benefits by the Apelin receptor antagonist ML221. ML221 also reversed LR-BEV-induced upregulation of key Apelin pathway targets. LR-BEVs exert anti-steatotic efficacy via the Apelin signaling pathway activation invitro and invivo. These findings establish LR-BEVs as novel NAFLD therapeutics and highlight their translational potential for metabolic liver diseases.

Influenza's pandemic threat is driven by antigenic drift, which limits the efficacy of conventional vaccines. To address this challenge, we established a clinical serum-anchored computational design pipeline for a broad-spectrum multi-epitope mRNA vaccine (MEMV), bridging the gap between pure in silico design and clinical applicability. Using 36 longitudinal sera (d0/d28/d365) from 12 well-characterized human cohorts (6 vaccine recipients and 6 influenza patients) and high-density antibody-peptide microarrays, we empirically identified 12 immunodominant B-cell linear epitopes from the nucleoprotein (NP) of influenza A (H1N1/H3N2) and B viruses. These experimentally validated epitopes were combined with in silico-predicted conserved helper T-lymphocyte (HTL)/cytotoxic T-lymphocyte (CTL) epitopes (from NP/HA/NA) to construct MEMVs candidates, ensuring high antigenicity, non-toxicity, and 95.63% global HLA coverage. Molecular docking and 100 ns molecular dynamics (MD) simulations confirmed favorable conformational compatibility between MEMVs and Toll-like receptor 3 (TLR3) in silico immunization via C-ImmSim predicted robust B/T-cell responses and protective cytokine (IFN-γ/IL-10) production. Collectively, this pipeline shortens the preliminary design cycle for influenza vaccines, provides a standard epitope-combination strategy, and offers direct targets for follow-up in vitro/in vivo experiments.

BackgroundGlobally, increasing numbers of adolescents use digital devices for learning, and this educational screen exposure may alter behavioral patterns and be associated with the rising prevalence of adolescent overweight. Limited research has examined the interrelationships among educational screen exposure, adolescent overweight, physical activity, and sleep quality. This study aims to assess the impact of educational screen exposure on adolescent overweight prevalence and to identify related mediating risk behaviors.MethodsData on 41,157 adolescents from 16 cities in China were from the Database of Youth Health. Body mass and height were measured to estimate body mass index. Physical activity and sleep quality data were collected using a self-administered questionnaire. We drew data from two waves (2015 and 2017) of adolescent health surveys, which coincided with China’s online education policy since 2015. The implementation of this policy resulted in a substantial increase in adolescents’ educational screen exposure, with the intensity of the policy implementation influenced by local Internet infrastructure. We allocated adolescents into exposure and control groups based on the local Internet penetration rate. Leveraging this policy-driven natural experiment, a difference-in-differences approach was then applied to compare changes in overweight prevalence, physical activity, and sleep quality before and after the policy implementation between these two groups.ResultsThe increase in overweight prevalence of adolescents in the exposure group from 2015 to 2017 was 3.1% greater than those in the control group (Coef. 0.03, 95% CI: 0.01 to 0.05, p < 0.01). The exposure group showed significant reductions in physical activity frequency (Coef. -0.49, 95% CI: -0.52 to -0.45) and sleep quality (Coef. -0.06, 95% CI: -0.09 to -0.02). Mediation analyses suggested that reduced physical activity and sleep quality were plausible mediating variables linking educational screen exposure and overweight prevalence. Male adolescents experienced a greater increase in overweight associated with educational screen exposure compared to their peers (Coef. 0.026, 95% CI: 0.01 to 0.04).ConclusionsEducational screen exposure may contribute to increased overweight in adolescents by reducing physical exercise and impairing sleep quality. Educators, guardians, and policymakers should consider effective measures to minimize the adverse impacts of educational screen exposure by promoting physical activities among adolescents.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12889-026-26600-4.

The applicability and safety of hepatectomy in hepatocellular carcinoma (HCC) patients with clinically significant portal hypertension (CSPH) remain controversial. This study aimed to compare the safety and long-term outcomes of hepatectomy versus ablation in HCC patients within the Milan criteria and concomitant CSPH. Following the PRISMA 2020 guidelines, a systematic literature search was conducted across PubMed, Cochrane, and other databases from inception to 20 April 2025. AI-assisted screening was performed using AS Review. Meta-analysis was conducted using R software (v4.4.1). Fixed-effect or random-effect models were used to calculate the comprehensive effect magnitude for overall survival (OS) and recurrence-free survival (RFS). Sparse Bayesian meta-analysis was applied to postoperative complications. Individual patient data (IPD) reconstruction validated survival outcomes. Seven studies (1 RCT, 6 retrospective) involving 972 patients were included. Pooled analysis showed no significant difference in OS between ablation and hepatectomy (HR=1.10, 95% CI: 0.76-1.61, P =0.644), but hepatectomy significantly improved RFS (HR=2.05, 95% CI: 1.54-2.71, P < 0.001). Adjusted analyses revealed nonsignificant RFS differences (HR=1.63, 95% CI: 0.85-3.13, P =0.151). Subgroup analysis demonstrated superior RFS with hepatectomy versus radiofrequency ablation (HR=2.01, 95% CI: 1.18-3.42, P =0.008), though OS remained comparable. Notably, hepatectomy conferred dual benefits in hepatitis B virus (HBV)-related HCC for both OS (HR=1.45, P =0.016) and RFS (HR=1.90, P =0.006). IPD reconstruction further supported hepatectomy's RFS advantage (HR=1.81, P < 0.001). Ablation was associated with lower overall complication risks, particularly a 69% reduction in ascites (OR=0.31). This study suggests that the long-term survival rates of hepatectomy and ablation are comparable, but hepatectomy shows better recurrence control, especially in HBV-related cases.

Intrinsic optical signal imaging (IOSI) enables non-invasive monitoring of neural activity in the mouse cortex, yet quantitative analysis remains hindered by low signal intensity, complex spatiotemporal patterns, and the lack of standardized benchmarks. To tackle this challenge, we present MouseCortex-IOS, a novel open accessible video segmentation dataset specifically designed for standardizing IOS analysis in awake rodent models, comprising 5732 images from 14 experimental subjects. Meanwhile, we implement an efficient processing pipeline leveraging foundation models to ensure annotation consistency while minimizing manual intervention. The dataset supports quantitative characterization of neural activation parameters including signal propagation velocity and trajectory, serving as a critical benchmark for developing automated analysis tools. Furthermore, this resource facilitates technique development in neuroimaging studies and accelerates the integration of computational approaches in IOS-based neuroscience research.

Dysphagia may be caused by stroke, cranial trauma, head and neck tumor surgery, and neurodegeneration. The overall prevalence of dysphagia in China is 38.7%, which can lead to aspiration pneumonia and malnutrition, increasing mortality rates and prolonging hospitalization. As an independent predictor of death, post-stroke dysphagia mortality ranges from 29% to 37%. Indwelling nasogastric tube feeding is widely used for dysphagic patients, but complications include mucosal bleeding, tumefaction, pneumonia, and acid regurgitation. Intermittent nasogastric tubes are an alternative option, though rarely reported. This paper describes a stroke patient with dysphagia and tracheotomy who received intermittent oroesophageal tube feeding. Notably, epiglottis tumefaction caused by the indwelling nasogastric tube disappeared after switching to intermittent oroesophageal tube feeding, with concurrent improvements in nutritional indicators, gastrointestinal tolerance, and swallowing function. To avoid side effects of indwelling nasogastric tubes in dysphagic patients, intermittent oroesophageal tube feeding deserves clinical consideration.