Sheng Jing Hospital

Abstract Immune checkpoint blockade (ICB) therapy has achieved remarkable breakthroughs in clinical cancer treatment; however, its efficacy is often limited by the immunosuppressive characteristics of the tumor microenvironment (TME) and the insufficient infiltration of cytotoxic T lymphocytes. Inducing immunogenic cell death (ICD) to convert “cold tumors” into “hot tumors” is an effective strategy to overcome this barrier. Herein, we propose a new ion-interference immunotherapy strategy based on the synergistic action of “ferroptosis–calcium overload” and construct a multi-responsive nanoreactor (CaO₂@MPN-HA) with a layer-by-layer (LbL) self-assembled architecture. To address the intrinsic electrostatic repulsion between the negatively charged metal–polyphenol network (MPN) and the targeting ligand hyaluronic acid (HA), we innovatively introduce the cationic polymer polyethyleneimine (PEI) as an “electrostatic bridge,” enabling surface charge reversal through electrostatic attraction. This strategy successfully constructs a robust core–shell structure and endows the material with lysosomal escape capability. Upon entering tumor cells, the nano-reactor undergoes responsive disassembly in the acidic and glutathione (GSH)-rich TME, releasing tannic acid to facilitate the reduction of Fe³⁺ to highly active Fe²⁺ and catalyze the efficient Fenton reaction fueled by self-supplied H₂O₂ from the CaO₂ core. Meanwhile, the burst release of Ca²⁺ induces mitochondrial dysfunction and synergistically amplifies oxidative stress. This cascade assault potently triggers ferroptosis-dominated ICD, promoting dendritic cell maturation and effector T-cell infiltration. In a TtT/GF thyroid tumor-bearing mouse model, the combination of CaO 2 @MPN-HA with anti-PD-1 therapy significantly suppressed primary tumor growth and effectively prevented abscopal effect by activating systemic antitumor immune memory. This work not only provides an efficient “ in situ vaccine” strategy for refractory thyroid cancer but also offers a generalizable materials-science solution to overcome electrostatic repulsion in the interfacial assembly of nanomedicines.

IntroductionRubinstein-Taybi syndrome type 2 (RSTS2; OMIM #613684) is a rare autosomal dominant disorder caused by loss-of-function variants in the EP300 gene (OMIM #602700), characterized by intellectual disability, distinctive craniofacial features, and skeletal anomalies.MethodsWhole-exome sequencing (WES) was performed on five pediatric patients presenting with neurodevelopmental delay. Candidate variants were filtered using the TGex platform and validated by Sanger sequencing for familial segregation analysis. The functional impact of variants was assessed using diverse bioinformatic tools, and pathogenicity classifications were assigned according to ACMG/AMP guidelines.ResultsFive novel EP300 variants were identified in this study: c.4774A>G (p.Lys1592Glu), c.4452 + 5G>C, c.3764A>G (p.His1255Arg), c.3591–2A>G, and c.6439C>T (p.Gln2147*). These alterations impair gene function through mechanisms including amino acid substitution, disruption of mRNA splicing, or premature protein truncation. All variants were classified as pathogenic or likely pathogenic per ACMG/AMP criteria. Literature analysis reveals that the predominant clinical manifestations in the Chinese patients encompassed neurodevelopmental impairment, accompanied by motor delay, growth retardation, and microcephaly. Strikingly, archetypal craniofacial dysmorphisms, such as arched eyebrows, long eyelashes, downslanting palpebral fissures, beaked nose, as well as significant skeletal abnormalities were absent, suggesting EP300 variants may present with a broader and more variable phenotypic spectrum than previously recognized.ConclusionThis study reports five novel pathogenic EP300 variants, expanding the variant repertoire of RSTS2 and providing an important basis for clinical diagnosis and genetic counseling.

Conventional thermoplastic polyurethane (TPU) films are commonly used in the field of waterproof and moisture-permeable textiles because of their excellent mechanical properties and flexibility. However, the high water absorption of TPU films limits their application in sophisticated waterproof and moisture-permeable products, particularly in extremely humid environments, where it may compromise the waterproof performance of textiles and negatively affect the wearing comfort. Therefore, to enhance the durability of these films, TPU was hydrophobically modified with end-hydroxy polydimethylsiloxane (PDMS). Because of its unique low-surface-energy properties and excellent hydrophobicity, PDMS substantially reduces the surface energy of the films and provides them with excellent water repellency, effectively addressing the excessive water absorption issue of TPU films. On this basis, a microporous film featuring waterproof and moisture-permeable properties is produced using phase conversion technology. Compared with that of the unmodified sample, the surface energy of silicone-modified TPU (Si-TPU) decreased by 10.56 mJ/m2. Furthermore, the water contact angle increased from 83° to 105°, whereas the water absorption rate considerably reduced after the modification. Moreover, Si-TPU was employed for the fabrication of a microporous membrane, which displayed exceptional moisture permeability (8651.34 g/(m2⸱24 h)).

Postoperative pulmonary complications (PPCs) commonly ensue after thoracic surgery and can impair patients' recovery. This study aimed to evaluate the effectiveness of preoperative respiratory training (PRT) in various perioperative outcomes in patients undergoing thoracic surgery, including pulmonary function, exercise capacity, incidence of postoperative complications, and length of hospital stay. Randomized controlled trials (RCTs) comparing PRT with routine care, that were published in the period of 1 January 2000 to 30 June 2025, were identified through PubMed, Embase, Web of Science, and Cochrane Library. Pooled analyses were performed using RevMan 5.4.1 to calculate odds ratio (OR) or mean difference (MD) with 95% CI. Nine studies were included in the meta-analysis. The results revealed that PRT significantly reduces PPCs (OR = 0.31, 95% CI: 0.21 to 0.46) and improved the change in six-minute walking distance (6MWD) (MD = 20.50, 95% CI: 11.72 to 29.28). No significant effects were observed on absolute 6MWD, forced expiratory volume in one second (FEV1), peak expiratory flow, or length of hospital stay. Sensitivity analysis confirmed result stability, and no substantial publication bias was found. PRT reduces PPCs and improves postoperative functional recovery in patients undergoing thoracic surgery. Its impact on spirometry-based pulmonary function and length of hospital stay remains uncertain. Further large-scale trials are needed to investigate the effect of integrating perioperative care into routine healthcare, especially for high-risk patients.