Wei Zhang

Objectives: This study aimed to evaluate the effectiveness of manikin‐head simulator‐based demonstration training in improving intraoral suturing proficiency among dental residents, and to understand the perspectives of residents in China's Standardized Residency Training (SRT) program on preclinical training. Methods: Eighteen postgraduate dental residents from the Hospital of Stomatology, Wuhan University, participated in the intraoral suturing training program. Theoretical instruction by a senior oral surgery instructor delivered lectures on four fundamental suturing techniques. Then, residents engaged in hands‐on practice using a customized silicone model integrated into a manikin head simulator. Subsequently, optimal suturing techniques were demonstrated, after which residents replicated the suturing procedure. Completion time was recorded, and suture quality was assessed using a 32‐point validated rubric evaluating seven domains. In addition, participants completed questionnaires to provide subjective feedback on the training. Paired t ‐tests compared pre‐ and post‐demonstration completion times and scores. Results: Residents' operational time significantly decreased (from 23.99 ± 2.55 to 14.54 ± 1.99 min, p  < 0.001) with improved quality scores (from 21.22 ± 5.12 to 29.67 ± 2.35, p  < 0.001). Junior participants showed greater score improvements than seniors, who maintained higher baseline scores and efficiency. Participants reported enhanced suturing speed, which was consistent with objective time metrics. Participants also noted improved instrument proficiency and reported improved perceived confidence. All participants agreed that the training effectively addressed clinical skill gaps. Conclusion: Manikin‐head‐based demonstration training effectively enhances simulated intraoral suturing performance and self‐reported confidence among dental residents in a preclinical setting. This approach bridges critical gaps between undergraduate education and clinical demands in China's SRT program by providing scalable, cost‐effective preclinical practice, which may ultimately contribute to improved patient safety and clinical outcomes.

Background: Immune checkpoint blockade targeting programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) has revolutionized cancer therapy. However, its efficacy is frequently limited by primary and acquired resistance. While inflammatory signals transiently upregulate PD-L1 transcription, post-translational regulation is crucial for its sustained expression in chronically stressed tumors. Whether and how tumor-intrinsic stress-response pathways control PD-L1 stability to promote immune evasion remains incompletely understood. Methods: Using human oral squamous cell carcinoma (OSCC) specimens, syngeneic mouse models, single-cell RNA sequencing, and genetic and pharmacological perturbations, we dissected the role of the unfolded protein response effector ATF4 in regulating PD-L1 stability and antitumor immunity. Its therapeutic potential was further evaluated in immunocompetent mice treated with anti-PD-1 therapy. Results: We identified ATF4 as a tumor-intrinsic driver of immune evasion. In malignant cells, ATF4 induced reactive oxygen species (ROS), which activated the AKT-mTOR pathway and suppressed autophagy, thereby stabilizing the PD-L1 protein independently of inflammatory cues. Genetic ablation of ATF4 or pharmacological inhibition of ROS-AKT-mTOR signaling restored autophagic flux, reduced PD-L1 levels, and enhanced CD8 ⁺ T-cell infiltration and function. When combined with PD-1 blockade, ATF4 targeting further suppressed tumor growth. Clinically, ATF4 expression was inversely correlated with CD8 ⁺ T-cell infiltration and autophagy markers, positively correlated with PD-L1 levels, and predicted a poor response to immunotherapy in patients with OSCC. Conclusions: Our findings establish ATF4 as a stress-responsive regulator of PD-L1 proteostasis, directly linking tumor-intrinsic stress adaptation to immune checkpoint stabilization and therapy resistance. Targeting the ATF4-ROS-AKT-mTOR axis may represent a promising strategy to overcome resistance to PD-1/PD-L1 blockade.

Supplementary materials and methods Figure S1 to S17 Table S1 to S7

The clinical imaging typically presents as a multicystic lesion in the jawbone, which is mostly diagnosed as ameloblastoma, myxoma, or odontogenic keratocyst. Preoperative biopsy is often challenging due to the intraosseous location of these lesions. Consequently, clinicians frequently rely on these characteristic multicystic imaging features to diagnose either ameloblastoma or odontogenic keratocyst, subsequently planning treatments ranging from marginal resection to mandibular segmental osteotomies with concurrent autogenous bone grafting. However, we encountered two cases of multicystic lesions in the jawbone with a pathological diagnosis of periapical cyst. The treatment for periapical cyst typically involves only curettage of the periapical lesion, eliminating the necessity for bone resection or grafting procedures. In most cases, tooth extraction is also unnecessary. Therefore, compared with the management of ameloblastomas and odontogenic keratocysts, periapical cyst treatment results in significantly less irreversible damage and patient discomfort. This study reports 2 rare cases of multicystic periapical cysts with detailed clinical, imaging, and pathological analyses. Through these cases, we aim to enhance clinicians’ awareness of the possibility that multicystic jaw lesions with multilocular radiographic features could represent periapical cysts. When necessary, a biopsy should be performed to determine the pathological type before formulating a treatment plan.

Purpose: Neoadjuvant anti–PD-1 immunotherapy combined with chemotherapy has shown promising pathologic responses in various cancers, including oral squamous cell carcinoma (OSCC). However, the pathologic response of lymph node (LN) metastases remains poorly understood. This study aims to systematically evaluate the pathologic response rates (pRR) of LN metastases in patients with OSCC and identify potential targets to improve therapeutic outcomes. Patients and Methods: We assessed the pRRs of LN metastases and matched primary tumors (PT) in patients with OSCC enrolled in a randomized, two-arm, phase II clinical trial (NCT04649476). Single-cell and spatial transcriptomics and multiplex IHC were performed to analyze the tumor microenvironment and identify potential therapeutic targets in LN metastases. A neoadjuvant orthotopic OSCC mouse model was established to evaluate the therapeutic potential of these targets. Results: We observed significant heterogeneity in pathologic regression of LN metastases, with lower pRRs compared with PTs. pRRs in LN metastases were correlated with overall and disease-free survival in patients with OSCC. We identified an abundance of macrophages in LN metastases exhibiting an unfolded protein response and activated protein kinase RNA-like endoplasmic reticulum kinase (PERK) signaling. These macrophages contributed to an extracellular matrix–enriched microenvironment through interactions with fibroblasts, which hindered T cell–mediated cytotoxicity. Pharmacologic inhibition of the PERK pathway significantly enhanced anti–PD-1 therapy in LN metastases and PTs in the mouse model. Conclusions: Our study confirms that the pathologic response of LN metastases in patients with OSCC undergoing neoadjuvant immunotherapy or immunochemotherapy is inferior to that of PTs. It suggests that targeting the PERK pathway in macrophages could be a potential strategy to enhance treatment outcomes.

The ESCRT (endosomal sorting complex required for transport) machinery is essential for various cellular processes, yet its role in head and neck squamous cell carcinoma (HNSCC) is poorly understood. We utilized The Cancer Genome Atlas (TCGA) datasets to analyze the expression of ESCRT genes. Bulk RNA-sequencing data and HNSCC tissue microarrays (TMAs) were used to evaluate VPS25 expression and its clinical significance. Single-cell RNA sequencing of tumor tissues and VPS25 knockdown experiments in CAL27 cells were used to investigate its biological functions. Immunohistochemistry, spatial transcriptomics, and immunotherapy datasets highlighted the involvement of VPS25 in immune suppression and its potential as a predictive biomarker. The results demonstrated significant VPS25 overexpression in HNSCC tissues, which correlated with poor clinical outcomes. It promoted tumor cell proliferation and migration while reducing immune cell infiltration in the tumor microenvironment (TME). Additionally, by upregulating PVR expression in tumor cells, VPS25 activated the immunosuppressive PVR-TIGIT signaling axis, thereby facilitating immune evasion. Furthermore, VPS25 emerged as a potential biomarker for predicting immunotherapy response. These findings highlight VPS25 as a pivotal regulator of tumor progression and immune evasion in HNSCC and a promising target for therapeutic strategies.