Qin Zhao

Background: Despite successful reduction of bacterial load and clinical inflammation following periodontal therapy, high recurrence rates indicate that prior infections induce lasting host alterations, maintaining latent disease susceptibility Aim: This review elucidates the biological basis of periodontal recalcitrance through innate immune memory (trained immunity), examining durable functional reprogramming at both local and systemic levels. Materials and Methods: We comprehensively searched PubMed/MEDLINE and Scopus databases for peer‐reviewed literature published primarily within the last decade (up to 2026). The search strategy utilized combinations of terms including “periodontitis”, “trained immunity”, “epigenetic reprogramming”, “bone marrow axis”, and “clonal hematopoiesis”. Mechanistic, multi‐omics, and clinical data were evaluated and synthesized, focusing on local resident cell reprogramming, ectopic lymphoid organogenesis, the periodontium‐bone marrow axis, and clonal hematopoiesis. Results: Current evidence supports the existence of a multi‐level immunological imprint. Locally, gingival fibroblasts and resident immune cells acquire stable epigenetic modifications and undergo glycolytic shifts. These changes lower their activation thresholds, generating a hyper‐responsive microenvironment sustained by Tertiary Lymphoid Structures. Systemically, periodontal inflammation transmits endocrine signals (IL‐1β, type I interferons) to hematopoietic stem and progenitor cells. This central adaptation biases myeloid differentiation and establishes heritable epigenetic priming, accelerating the output of hyper‐reactive neutrophils. Additionally, age‐related Clonal Hematopoiesis of Indeterminate Potential (CHIP) amplifies this inflammatory dysregulation. Conclusions: Periodontitis recurrence is fundamentally driven by maladaptive immunological memory. This persistent state is encoded via epigenetic and metabolic reprogramming within local tissues and central hematopoietic niches, exacerbating destruction upon microbial restimulation. Clinical Relevance: Achieving true biological resolution in periodontitis requires a paradigm shift from solely controlling the biofilm to incorporating targeted host‐modulatory therapies that resolve these maladaptive epigenetic and metabolic adaptations

Targeting post‐transcriptional dysregulation of tumor suppressors represents a new frontier in cancer therapy. Here, we identify the alternative polyadenylation (APA) regulator NUDT21 as a pivotal therapeutic target in oral squamous cell carcinoma (OSCC). NUDT21 is highly upregulated, correlating strongly with poor survival and advanced clinical stage. We outline a pathogenic mechanism whereby NUDT21 drives this phenotype by forcing a network of tumor suppressor transcripts, notably PTEN, into translationally‐repressed, long‐3'UTR isoforms. To therapeutically “re‐engineer” this APA switch, we design a “Nano‐APA‐editor.” This platform features an HMSN core with an sgRNA‐NUDT21 payload and a hierarchical targeting strategy: a cancer‐educated dendritic cell (DC) membrane for biomimetic camouflage and homotypic affinity, “gated” by a TA‐aptamer for final precision. This system enables potent and selective NUDT21 silencing, driving a shift toward short‐3'UTR isoforms. Consequently, the Nano‐APA‐editor effectively reinstates PTEN and associated suppressors and inhibits multiple malignant phenotypes in vitro. In an orthotopic OSCC model, it demonstrates profound tumor regression, outperforming conventional chemotherapy (PTX) with excellent biocompatibility. In vivo analysis confirmed target engagement (NUDT21‐down) and functional restoration (PTEN‐, WEE1‐, TGF‐β‐up). This work validates a “post‐transcriptional re‐engineering” strategy, executed by a logically designed nanoplatform, as a powerful and safe modality for precision gene therapy.

The treatment of osteomyelitis, a deep‐tissue bacterial infection, remains challenging due to antibiotic resistance and impaired bone regeneration. Herein, the authors report a near‐infrared (NIR)‐photoresponsive nitric oxide (NO) nanotherapeutic platform (RSNO‐VP/Ti ₃ C ₂ ) constructed from a violet phosphorus (VP)/Ti ₃ C ₂ van der Waals heterostructure and an S‐nitrosothiol (RSNO) NO donor. This platform utilizes the photothermal effect of the heterostructure under 808 nm NIR irradiation to precisely trigger and control NO release from RSNO, enabling a synergistic mild photothermal and NO gas therapy. The RSNO‐VP/Ti ₃ C ₂ composite demonstrates potent antibacterial efficacy against both Staphylococcus aureus (99.51%) and Escherichia coli (96.11%), effectively eradicates biofilms, and exhibits enhanced environmental stability (degradation time constant τ = 19.31 days). Its biocompatible degradation products, phosphate ions and nano‐TiO ₂ , support osteogenic differentiation. In a murine osteomyelitis model, NIR‐triggered RSNO‐VP/Ti ₃ C ₂ treatment effectively clears bacteria, alleviates inflammation, and promotes significant bone repair. This work presents a promising non‐antibiotic strategy for comprehensive osteomyelitis therapy.

Effective preclinical training for complex procedures, such as oral bone augmentation, demands high-fidelity visual demonstration. The conventional “

Fu L, Yin C, Zhao Q, Guo S, Shao W, Xia T, Sun Q, Chen L, Li J, Wang M, Xia H. 2025. CD81+ senescent-like fibroblasts exaggerate inflammation and activate neutrophils via C3/C3aR1 axis in periodontitis. eLife 13:RP96908. doi: 10.7554/eLife.96908.

Harvesting autologous soft tissue from the hard palate is a standard procedure, but managing the donor site wound is critical for patient comfort and reducing complications. Traditional methods like palatal stents are often costly and uncomfortable. While commercially available mucoadhesive bandages offer a barrier, their adhesion alone is temporary and unreliable, often failing prematurely due to oral movements. A novel "palatal shield" technique using composite resin stabilized on adjacent teeth's palatal surface has been proposed to address postoperative discomfort, yet it still has limitations in adaptability. This article and accompanying video demonstrate a comprehensive protocol that overcomes this limitation by combining a collagen sponge scaffold with a mucoadhesive bandage, which is then firmly secured using stabilizing suspension sutures. The key protocol steps include: (1) placing a collagen sponge into the donor site after initial hemostasis; (2) applying the trimmed mucoadhesive bandage to cover the sponge and overlap onto the peripheral dry mucosa; and (3) firmly securing the entire dressing using crossed horizontal mattress suspension sutures. This multi-layer system creates a stable, long-lasting physical barrier that protects the underlying wound from mechanical irritation and bacterial contamination, addressing the issue of donor site morbidities such as postoperative bleeding and pain that plague both clinicians and patients. This method provides immediate hemostasis, significantly reduces postoperative pain, and promotes predictable, advanced healing. Compared to novel palatal stents made of light-curing hybrid composite resin, where some patients report speaking inconvenience, this protocol avoids such functional disruptions. Additionally, it eliminates the need for extra fabrication steps required by transparent palatal plates used in combination with artificial dermis. This protocol provides a reliable, cost-effective, and reproducible technique that enhances patient comfort and optimizes palatal donor site healing.

Harvesting autologous soft tissue from the hard palate is a standard procedure, but managing the donor site wound is critical for patient comfort and reducing complications. Traditional methods like palatal stents are often costly and uncomfortable. While commercially available mucoadhesive bandages offer a barrier, their adhesion alone is temporary and unreliable, often failing prematurely due to oral movements. A novel "palatal shield" technique using composite resin stabilized on adjacent teeth's palatal surface has been proposed to address postoperative discomfort, yet it still has limitations in adaptability. This article and accompanying video demonstrate a comprehensive protocol that overcomes this limitation by combining a collagen sponge scaffold with a mucoadhesive bandage, which is then firmly secured using stabilizing suspension sutures. The key protocol steps include: (1) placing a collagen sponge into the donor site after initial hemostasis; (2) applying the trimmed mucoadhesive bandage to cover the sponge and overlap onto the peripheral dry mucosa; and (3) firmly securing the entire dressing using crossed horizontal mattress suspension sutures. This multi-layer system creates a stable, long-lasting physical barrier that protects the underlying wound from mechanical irritation and bacterial contamination, addressing the issue of donor site morbidities such as postoperative bleeding and pain that plague both clinicians and patients. This method provides immediate hemostasis, significantly reduces postoperative pain, and promotes predictable, advanced healing. Compared to novel palatal stents made of light-curing hybrid composite resin, where some patients report speaking inconvenience, this protocol avoids such functional disruptions. Additionally, it eliminates the need for extra fabrication steps required by transparent palatal plates used in combination with artificial dermis. This protocol provides a reliable, cost-effective, and reproducible technique that enhances patient comfort and optimizes palatal donor site healing.