Southwest Hospital

Diabetic wounds represent a significant clinical challenge owing to infection, oxidative stress, and immune dysregulation. In this study, a multifunctional photoimmunotherapy nanoplatform (I-P-T NPs) was developed through the self-assembly of the near-infrared photosensitizer IR820, the immunomodulatory agent thymopentin (TP5), and the antioxidant phloretin (Phl) via intermolecular hydrogen bonding and hydrophobic interactions. This nanoplatform integrates photothermal therapy (PTT), immune modulation, and reactive oxygen species scavenging to address the infection-oxidation-immunosuppression triad in diabetic wounds. The I-P-T NPs exhibited robust photothermal conversion under 808 nm irradiation, generating localized hyperthermia with antibacterial effects. In vitro experiments demonstrated that I-P-T NPs promoted M2 macrophage polarization, reduced oxidative stress, enhanced endothelial and keratinocyte migration, and suppressed pro-inflammatory cytokine release. Additionally, the nanoplatform displayed potent antibacterial activity against both Gram-positive and Gram-negative bacteria. In a streptozotocin-induced diabetic mouse model with infected wounds, topical application of I-P-T NPs combined with photothermal treatment accelerated wound closure, enhanced re-epithelialization and collagen deposition, and mitigated inflammation. The self-assembled design improved the solubility of Phl and enabled spatiotemporally controlled delivery of multiple therapeutic components. No significant systemic toxicity was observed, confirming the biocompatibility of I-P-T NPs. This study presents a novel nanoplatform that synergistically combines photothermal sterilization, TP5-mediated immune regulation, and Phl-driven antioxidant effects, offering a promising strategy for managing complex diabetic wounds. This modular design highlights the potential for translating multifunctional nanotherapies into clinical applications for the treatment of chronic wounds.

Despite encouraging clinical benefits have gained by anti-PD-1 and Lenvatinib combination, in-depth characterizations about the mechanisms of action remain poorly characterized. Furthermore, although the combination of systemic anti-PD-1 or Lenvatinib treatment and locoregional transcatheter arterial chemoembolization (TACE) is widely carried out to treat unresectable HCC in clinical, the efficacies of different combination regimens are uncertain due to limited researches.

We firstly generated murine HCC models to validate the enhanced anti-tumor effects of anti-PD-1 and Lenvatinib combination therapy. Then single cell mass cytometry (CyTOF) was employed to phenotypically reveal their mechanisms of action. After that, we further compared the effectiveness of TACE plus Lenvatinib (i.e., TACE-Len) dual therapy with TACE, Lenvatinib plus anti-PD-1 (i.e., TACE-Len-PD-1) triple therapy as conversion therapy for unresectable HCC.

Lenvatinib and anti-PD-1 combination could generate activated immune profiles not only by increasing systemic CD4⁺, CD8⁺T cells and B cells proportions, but also by weakening the immune-tolerance functions derived from both immunosuppressive cells (i.e., MDSCs) and co-inhibitory mediators (i.e., PD-L1 and LAG-3). Meanwhile, our study also suggested that TACE-Len-PD-1 triple therapy could achieve better clinical responses with powerful immune profiles for unresectable HCC compared to TACE-Len dual therapy.

Our study provided a delicate immune landscape of anti-PD-1and Lenvatinib combination, and we also offered scientific evidences that TACE-Len-PD-1 triple therapy could fulfill better clinical benefits than TACE-Len dual therapy, which is anticipated to provide objective and effective evidences for clinical use.

The intricate interplay between neurons and gliomas has emerged as an important area of investigation in glioma biology. Accumulating evidence underscores that structural and material alterations constitute the fundamental basis of neuron‒glioma interactions and their pathological consequences. This review comprehensively examines the mechanisms underlying these interactions, with a particular emphasis on specialized structures that facilitate neuron‒glioma communication, including synapses, cell surface ion channels, and tumor microtubules (TMs). In addition to classical neurotransmitters, we highlight the exchange of cytokines, proteins, and extracellular vesicles (EVs) between these cell types. By synthesizing current research findings, this review establishes a conceptual framework for developing innovative therapeutic strategies targeting neuron‒glioma interfaces, offering new perspectives for glioma treatment approaches.