Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences最新文献

Objectives: To evaluate the early clinical efficacy and safety of trans-catheter aortic valve replacement (TAVR) for patients with severe pure native aortic regurgitation (PNAR) who are not suitable for conventional surgical aortic valve replace-ment.

Methods: A retrospective analysis was conducted on 48 patients with PNAR who underwent TAVR at the Department of Cardiac Surgery, the First Affiliated Hospital of Sun Yat-sen University between March 2019 and February 2025. These included 25 cases with transfemoral approach (TF-TAVR group) and 23 cases with transapical approach (TA-TAVR group). Efficacy and safety were assessed by analyzing baseline characteristics, all-cause mortality, and procedure-related complications.

Results: Compared with the TA-TAVR group, the TF-TAVR group exhibited significantly smaller aortic annulus circumference and diameter, left ventricular outflow tract circumference and diameter, diameters of the left, right, and non-coronary sinuses, and sinotubular junction (STJ) diameter, along with a shorter distance from the STJ to the aortic annular plane ring plane, a smaller annulus angle (all P<0.05). Additionally, the TF-TAVR group showed a deeper prosthesis implantation depth relative to the aortic annular plane (P<0.01). The overall technical success rate was 91.67%, and the device success rate was 83.33%. Post-TAVR, both groups demonstrated significant improvement in left ventricular end-diastolic diameter (both P<0.05), while only the TA-TAVR group showed significant reduction in left ventricular end-systolic diameter (P<0.05). For primary outcomes, in-hospital mortality occurred in 2 patients (4.17%). No additional deaths were reported at 60 or 90 d after surgery. During 90-180 d after surgery, one patient in the TF-TAVR group died of sudden cardiac death, and one in the TA-TAVR group died of gastroin-testinal bleeding. During 180 d-1 year after surgery, one patient in the TF-TAVR group died of low cardiac output syndrome. No statistically significant differences were observed in 1-year Kaplan-Meier survival curves between the two groups (P>0.05). No conduction block events occurred in TA-TAVR group during hospitalization or 1-year follow-up, while high-grade atrioventricular block, left bundle branch block, permanent pacemaker implantation occurred in TF-TAVR group during hospitalization (12.00%, 4.00%, and 12.00%, respectively).

Conclusions: TAVR demonstrates high feasibility and acceptable safety for severe PNAR patients who are not suitable for conventional SAVR. Both TF-TAVR and TA-TAVR show comparable early postoperative efficacy and safety profiles.

Objectives: To investigate the targets and mechanisms of 7-hydroxyethyl chrysin (7-HEC) in prevention and treatment of high-altitude cerebral edema (HACE) in rats.

Methods: Fifty-four male Wistar rats were randomly divided into normal control group, HACE model group, and 7-HEC-treated group (18 rats in each group). Except for the normal control group, rats in the two other groups were exposed to a hypobaric hypoxic chamber simulating a 7000 m altitude for 72 h to establish the HACE model. The 7-HEC-treated group was intraperitoneally injected with 7-HEC (150 mg·kg^－¹·d^－¹) for 3 consecutive days before modeling, while the model group received equivalent isotonic sodium chloride solution. Tandem Mass Tag (TMT) proteomics technology was used to detect differentially expressed proteins (DEPs) with screening criteria set at a fold change >1.2 and P<0.05. Western blotting was used to verify the expression levels of target proteins. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed.

Results: Compared with the normal control group, 256 DEPs were identified in the HACE model group. Compared with the HACE model group, 87 DEPs were identified in the 7-HEC-treated group. Among them, 19 DEPs that were dysregulated in the HACE model group were restored after 7-HEC intervention, of which seven (HSPA4, Arhgap20, SERT, HACL1, CCDC43, POLR3A, and PCBD1) were confirmed by Western blotting. GO enrichment analysis of the DEPs between the HACE model and 7-HEC-treated groups revealed their involvement in 13 biological processes, five cellular components, and two molecular functions. KEGG pathway analysis indicated associations with the mRNA surveillance pathway, Th17 cell differentiation, serotonergic synapse, RNA polymerase, protein processing in the endoplasmic reticulum, peroxisome, neuroactive ligand-receptor interaction, folate biosynthesis. PPI network analysis demonstrated that HSPA4, POLR3A, and HACL1, which were validated by Western blotting, interacted with multiple signaling pathways and ranked among the top 20 hub proteins by degree value, suggesting their potential role as core regulatory factors. Arhgap20, SERT and PCBD1 also exhibited interactions with several proteins, suggesting their potential as key regulatory proteins, whereas no interactions for CCDC43 were identified.

Conclusions: This study applied TMT proteomics to identify seven potential therapeutic targets of 7-HEC for the prevention and treatment of HACE. These targets may be involved in the pathogenesis of HACE through multiple pathways, including maintaining cellular homeostasis, ameliorating oxidative stress, regulating energy metabolism, and reducing vascular permeability.

A 32-year-old woman presented with a progressively enlarging left breast mass for about one year. Breast magnetic resonance imaging (MRI) revealed a mass at the 9 o'clock position in the left breast, classified as BI-RADS category 6. The patient underwent endoscopic left breast-conserving surgery and sentinel lymph node biopsy. Histological examination (HE staining) revealed a tumor composed of sheets of epithelioid cells and fascicles of spindle cells, with areas of transition between the two components. Epithelioid cells were small, round to short-spindled, with scant cytoplasm, crowded arrangement, and coarse chromatin. Spindle cells were loosely arranged with indistinct borders, mildly eosinophilic cytoplasm, inconspicuous nucleoli, and intervening pale pink matrix. Immunohistochemistry demonstrated: epithelioid cells were diffusely positive for CK8/18, CAM5.2 and E-cadherin; partially positive for pan-CK and CK7; focally positive for CK5/6, CK14, high molecular weight cytokeratin and P63; and negative for vimentin. Spindle cells were positive for synaptophysin, CD56 and vimentin, and for glial fibrillary acidic protein, but negative for epithelial markers (pan-CK, CK7, CK8/18, CAM5.2, E-cadherin). The diagnosis was metaplastic carcinoma with heterologous mesenchymal (neuroectodermal) differentiation. Postoperatively, the patient received 8 cycles of EC-T systemic chemotherapy. Follow-up with breast MRI and chest CT every 3 months for 23 months showed no evidence of tumor recurrence or metastasis.

Myocardial infarction is a cardiovascular disease with high morbidity and mortality rates. Hydrogel biomaterials mimicking the extracellular matrix have recently been shown to demonstrate excellent biocompatibility, low immunogenicity, favorable biodegradability, and multifunctionality, showcasing significant potential for treatment of myocardial infarction. Hydrogels can provide mechanical support to the damaged myo-cardium, alleviating pathological remodeling. Moreover, their porous structure makes them ideal carriers for localized and sustained drug delivery. Hydrogels derived from various matrices-including polysaccharides, polypeptides, proteins, decellularized extracellular matrix, and synthetic polymers-exhibit distinct properties in terms of biocompatibility, mechanical performance, and drug delivery capacity. These hydrogels support tissue regeneration and enable targeted release of diverse therapeutics, meeting the various therapeutic demands for myocardial repair. In the infarcted myocardial microenvironment, endogenous signals such as low pH, specific enzyme expression, and elevated levels of reactive oxygen species can trigger responsive drug release from hydrogels, while external physical stimuli-such as ultrasound, light, and magnetic fields-can also be employed to precisely control the release process, thereby enhancing therapeutic efficacy and reducing systemic side effects. This review summarizes recent advances in hydrogel-based drug delivery systems for treatment of myocardial infarction, focusing particularly on the characteristics and advantages of different hydrogel materials for myocardial repair. Furthermore, the responsive drug release behavior of hydrogels is analyzed in the context of the cardiac injury microenvironment, providing a reference for future research.

The tumor microenvironment (TME) is a critical determinant of tumor initiation, progression, and therapeutic response, and serves as the basis for designing precise delivery strategies. Its marked heterogeneity underscores the need for a more comprehensive understanding of its composition and function. In addition to the extensively studied classical TME, emerging evidence highlights the significant roles of the tumor mechanical microenvironment and the tumor microbial microenvironment in modulating treatment efficacy. These non-classical dimensions not only independently influence tumor behavior but also interact dynamically with classical TME components. Mechanical cues within the TME, including matrix stiffness and solid stress, significantly affect drug distribution and treatment efficacy, suggesting that mechanical remodeling represents a potential strategy to enhance therapeutic outcomes. Concurrently, tumor-associated microbiota and their metabolites participate in immune regulation and metabolic reprogramming, contributing to tumor development and offering novel therapeutic targets. Moreover, recent advances have broadened our understanding on the multilayered regulatory landscape of the TME through the investigation of previously underappreciated factors such as neural regulation, metabolic niche dynamics, spatiotemporal heterogeneity, and epigenetic modulation. This review systematically summarizes the characteristics of these diverse TME dimensions and highlights recent progress in targeted delivery strategies, to facilitate the development of more personalized and effective anticancer therapies.

Objectives: To fabricate an injectable composite microsphere hydrogel reinforced with silk fibroin/hyaluronic acid microspheres, achieving synergistic enhance-ment of mechanical robustness and biofunctionality.

Methods: Methacrylated hyaluronic acid (HAMA) and thiolated silk fibroin (TSF) were synthesized. Monodisperse microspheres generated via microfluidics were UV-cured (420 nm) through thiol-ene click reaction. These microspheres were embedded in a TSF/HAMA matrix to form photo-cured composites. The grafting rate of TSF and HAMA was characterized by H1-NMR; particle size distribution of microsphere hydrogels in soybean oil was observed by optical microscopy; gel point of composite microsphere hydrogels was determined by advanced extensional rheometer; microscopic morphology of microsphere hydrogels was observed by scanning electron microscopy; elemental distribution of microsphere hydrogels was detected by X-ray energy dispersive spectroscopy; tunability of composite microsphere hydrogels was observed by inverted confocal microscopy; mechanical properties of composite microsphere hydrogels were tested by compression testing; swelling ratio, degradation rate and water retention rate of composite microsphere hydrogels were measured by gravimetric method. Cytotoxicity of the composite microsphere hydrogels was determined by Calcein-AM/propidium iodide dual staining and CCK-8 assay; cell migration capability was observed by scratch assay.

Results: The grafting rates of HAMA and TSF was 48.03% and 17.99%, respectively. Microsphere hydrogels with particle sizes of (43.3±1.2), (78.1±3.0), and (130.8±1.9) μm were prepared. The gel time of the composite microsphere hydrogels was 48-115s. The laser confocal imaging confirmed dynamic regulation characteristics of the composite microsphere hydrogels. The compressive strength of the composite microsphere hydrogels reached 22.7 kPa and maintained structural integrity at 40% strain after 20 compression cycles. The composite microsphere hydrogels exhibited differential deswelling behaviors in simulated physiological environments, and reducing microsphere particle size could significantly enhance its stability under moist conditions. The degradation rate of the composite microsphere hydrogels was (49.1±0.9)% after 200 h, and water retention rate was maintained at 40%-60% after 96 h. Biocompatibility assays confirmed >95% cell viability and unimpaired cell migration abilities.

Conclusions: The TSF/HAMA composite microsphere hydrogel developed in this study has characteristics of rapid fabrication, adjustable mechanical properties, enhanced environmental stability and excellent biocom-patibility, thus providing a new material solution for tissue repair and regenerative medicine.

Adoptive cell transfer (ACT) shows significant efficacy against hema-tological malignancies but is limited in solid tumors due to poor homing, immunosuppre-ssion, and potential toxicity. Biomaterials spanning from nano- to macroscales-including nanoparticles, microspheres/micropatches, and hydrogels-offer unique advantages for ex vivo cell engineering, in vivo delivery, and modulation of the tumor microenvironment. Specifically, nanoparticles enable gene delivery, artificial antigen-presenting cell engi-neering, and immune microenvironment remodeling. Microspheres/micropatches improve immune cell expansion, targeted activation, and localized retention. Hydrogels enhance ACT via in situ genetic engineering, 3D culture support, and cytokine co-delivery. This review summarizes advances in biomaterial-enhanced ACT, highlighting their potential to improve delivery efficiency, amplify antitumor responses, and reduce toxicity. These insights may accelerate the clinical translation of ACT for solid tumors.

Neutrophils, as the most abundant immune cells in the human body, possess the inherent ability to rapidly migrate to sites of inflammation and infection. Novel drug delivery systems leveraging neutrophils capitalize on their natural targeting and phagocytic capabilities to achieve precise drug delivery. Efficient drug loading into neutrophils within neutrophil-based delivery systems can be achieved through physical adsorption, chemical conjugation, and phagocytosis. Design strategies emphasize carrier selection and targeting ligand design to enhance delivery precision. Compared to traditional drug delivery systems, neutrophil-based systems offer significant advantages, including excellent biocompatibility and strong tissue penetration. These properties can significantly improve drug bioavailability and reduce adverse reactions associated with non-target tissue accumulation. However, these systems also face several challenges that require resolution, such as difficulties in cell collection and preservation, the need for stability optimization, challenges in large-scale production, and a lengthy clinical translation cycle. In disease treatment applications, neutrophil-based drug delivery systems enable precise delivery of anti-cancer drugs to tumor sites, potentially disrupting immunosuppression of the tumor microenvironment and enhancing therapeutic efficacy. For brain diseases, their unique ability to cross the blood-brain barrier facilitates effective drug delivery. In chronic inflammatory diseases, neutrophil-based systems can precisely deliver anti-inflammatory agents to mitigate inflammation. Performance enhancements for neutrophil-based systems can be achieved by the development of novel nanomaterials and optimization of targeting ligand affinity, thereby improving the accuracy and efficiency of drug delivery. This review comprehensively explores the design strategies, advantages, challenges, and future directions of neutrophil-based drug delivery systems. It summarizes research progress in disease treatment applica-tions, aiming to offer key insights for the development of novel drug delivery systems and advance precision medicine and targeted therapy.

Nano-drug delivery systems offer significant benefits, including high specific surface area, structural and functional diversity, and surface modifiability. When formulated as inhalable nano-formulation, these can not only enable precise pulmonary drug delivery but also improve pulmonary bioavailability and enhance thera-peutic efficacy. Currently, there are four types of inhalable nano-formulations for the treatment of respiratory diseases. Inhalable liquid preparations exhibit facile manufactur-ability and broad applicability yet demonstrate compromised stability during aerosolization. Through structure optimization, surface modification, dispersion medium optimization and device improvement, the atomization stability of nano-drug has been enhanced. Pressurized metered-dose inhalers loaded with nano-drugs face technical challenges: conventional propellants may dissolve nano-carriers, whereas co-solvents like ethanol compromise delivery efficiency. Thus, it is necessary to develop novel propellants that provide thermodynamic stability and optimal delivery performance. Nano-drug formulations in dry powder inhalers exhibit relatively favorable physical stability, however, pulmonary delivery efficiency and nanoparticles integrity during processing remain problematic. Pulmonary delivery efficiency can be improved by employing strategies such as blending excipients to promote the re-dispersibility of nanoparticle agglomerates, optimizing the design of microcarrier, and innovating preparation processes. In contrast, soft mist inhalers are an ideal option for pulmonary delivery of nano-drugs owing to their gentle and efficient atomization properties to maintain nano-drug integrity. This review summarizes the inhalable nano-formulations and focuses on challenges and proposed strategies encoun-tered in integrating nano-drug delivery systems and inhalation drug delivery systems. It aims to provide references for the future development of inhalable nano-formulations.