浙江大学医学院

Osteoarthritis (OA) is characterized by progressive glycosaminoglycan (GAG) depletion caused by insufficient matrix replenishment and excessive proteoglycan catabolism. Here, we developed a spatially coordinated strategy that integrates GAG deposition in the cartilage extracellular matrix (ECM) with intracellular regulation of GAG enrichment and degradation in chondrocytes. To achieve this strategy, we engineered a hierarchical “Nanorocket” comprising a chondroitin sulfate (CS)-cationic peptide Booster and an HDMBr/siADAMTS5 Satellite. The Nanorocket facilitated cartilage penetration and prolonged the intra-articular retention of both components. The Booster supported CS deposition within the cartilage extracellular matrix, whereas the internalized Satellite increased CHPF/CHSY2 expression and silenced ADAMTS5, thereby promoting GAG enrichment while limiting proteoglycan degradation. This coordinated regulation preserved GAG content, reduced matrix porosity, and maintained the mechanical properties of human cartilage explants. In a surgical OA mouse model, periodic treatment preserved cartilage thickness and matrix integrity, mitigated subchondral bone alterations, and improved gait performance. These findings establish the proof-of-concept feasibility of spatially coordinating GAG deposition and metabolism to preserve cartilage homeostasis during early OA progression.

Objectives There is no established standard regimen for end-stage patients suffering from multi-line refractory diffuse hepatic metastases. This case series intended to assess the antitumor activity, treatment tolerance and palliative value of whole-liver low-dose radiotherapy combined with PD-1 immunotherapy, with special attention paid to the occurrence of systemic abscopal effect. Patients and methods This retrospective case series aimed to evaluate the clinical efficacy and safety of low-dose whole-liver radiotherapy (LDRT) combined with PD-1 inhibitor immunotherapy in patients with refractory diffuse hepatic metastases from solid tumors. Six patients who developed progressive diffuse hepatic metastases after one or more lines of prior systemic therapy and subsequently received LDRT plus immunotherapy were enrolled. All patients were followed up until the predefined cutoff date of July 2026. The primary endpoints were objective response rate (ORR) and the incidence of treatment-related adverse events (TRAEs). The secondary endpoints included symptomatic improvement and changes in quality of life. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and adverse events were graded based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All enrolled patients presented with extensive diffuse intrahepatic metastasis at baseline. Results With a median follow-up of 7.5 months, tumor regression or radiological remission was observed in several patients,yielding an objective response rate (ORR) of 66.7%. Clinical symptomatic relief and improved quality of life were achieved in four patients after combination treatment. In terms of safety, No grade 3 or higher TRAEs definitively attributable to this combined regimen were observed during treatment.The combined regimen appeared to be generally tolerable for the liver. Collectively, these preliminary findings suggest a potential clinical benefit and acceptable safety of this LDRT plus immunotherapy combination in one or more lines pretreated patients with diffuse hepatic metastases. Conclusion This exploratory case-series generates the hypothesis that low-dose radiotherapy combined with immunotherapy may yield clinical benefits for selected patients with diffuse treatment-refractory hepatic metastases. Further prospective clinical trials and translational research are warranted to elucidate the underlying immunomodulatory mechanisms and define patient subsets most likely to derive clinical benefit from this approach.

Cartilage regeneration by bone marrow stromal cells (BMSCs) has become a promising therapeutic approach. However, the BMSC-engineered cartilage (BEC) is highly prone to ossification once implanted in vascularized and innervated subcutaneous microenvironments, ultimately leading to failure of cartilage regeneration. Herein, we innovatively developed a living cell-based encapsulation coating technique (designated as EC@GelMA) aimed at creating a biophysical barrier for BMSCs to maintain their stability in cartilage regeneration within an ectopic non-neurovascularized microenvironment. In vitro experimental results confirm that, both technically and theoretically, EC@GelMA could provide a hypoxic and biologically active biomimetic cartilage microenvironment for internally encapsulated BMSCs. In vivo experiments confirmed that EC@GelMA can provide BMSCs with a biomimetic cartilage microenvironment that isolates blood vessels and nerves, achieving stable cartilage regeneration of BMSCs in the ectopic microenvironment. All our results provide an effective solution for repairing cartilage defects in subcutaneous ectopic microenvironments, such as ear and nasal cartilage, using BMSCs, and facilitates its clinical translation.

Orthopaedic infections are increasingly prevalent in the aging population, posing a significant clinical and economic burden. Despite progress in antimicrobial therapies, challenges such as antibiotic resistance and superbug emergence persist. Gas therapy has emerged as a promising strategy for managing orthopaedic infections. Classical gasotransmitters—including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S)—exhibit antibacterial and immunomodulatory effects at controlled concentrations, though improper dosing may induce adverse effects. This review critically examines the dual mechanisms through which gasotransmitters combat infection while promoting orthopaedic regeneration. We also survey advanced delivery platforms—such as smart scaffolds, nano-reservoirs, and on-demand release systems—engineered for targeted gasotransmitter delivery to infected bone tissue. Finally, we discuss current limitations and future prospects, aiming to inspire novel biomaterial designs for targeted therapeutic delivery and to advance gas therapy as a viable option for orthopaedic infection treatment.

Although increasing evidence links internet addiction (IA) with depressive symptoms in adolescents, the temporal dynamics between specific symptoms, especially across developmental stages and genders, remains insufficiently understood. This study aimed to examine the dynamic longitudinal relations between IA and depression at the symptom level and to characterize how these relations evolve from mid- to late-adolescence. A total of 2,864 Chinese adolescents (49.2% males; aged 12-18 years) participated in this study. Depressive symptoms and IA were assessed using the Center for Epidemiologic Studies-Depression (CES-D) scale and the 8-item Internet Addiction Diagnostic Questionnaire (IAD-DQ-8) scale at two time points. Cross-lagged panel network (CLPN) analysis was conducted to examine longitudinal symptom-to-symptom relations between IA and depression. Across the overall network, escape use (I8), negative affect (D2), and loss of interest (D3) emerged as key bridge nodes. In mid-adolescence, risking friends or opportunities (I6) negatively predicted depressive symptoms, with unsigned In-BEI concentrated on negative affect (D2) and loss of interest (D3). In late-adolescence, concealment of use (I7) and escape use (I8) formed the most prominent pathways, with In-BEI centered on somatic (D1) and interpersonal difficulties (D4). Males showed greater sensitivity to somatic (D1), preoccupation (I1), and escape use (I8), whereas females were more sensitive to interpersonal difficulties (D4), irritability (I4), and concealment of use (I7). Symptom-level links between IA and depression differed by developmental stage and gender. Mid-adolescents showed approach-oriented use driven by reward and mood regulation, suggesting structured management of internet use with diversified offline activities. Late adolescents exhibited escape-driven, distress-regulating use, calling for interventions that address stress sources rather than impose blanket restrictions. For males, enhancing self-control and preventing overuse are key, whereas for females, strengthening real-life interpersonal ties is crucial.