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Pleomorphic adenoma (PA), the most common benign salivary gland tumor, harbors unpredictable risks of recurrence and malignant transformation into carcinoma ex pleomorphic adenoma (CXPA), posing significant clinical challenges. To better delineate the tumor transformation trajectory, we performed single-cell RNA sequencing of normal salivary gland, primary PA, recurrent PA (rPA), and CXPA. Cell trajectory reconstruction, differential expression gene identification, and key gene network analysis were integrated to characterize molecular transitions and intercellular crosstalk driving PA recurrence and malignant transformation. Immunohistochemistry was used to validate key findings. GALNT13 + myoepithelial cells were identified as CXPA-specific malignant progenitors, delineating early malignant conversion. Concurrently, MIF + myoepithelial cells exhibited enhanced tissue-destructive capabilities. Fibroblasts enforced fibrotic restraint in primary PA and drove extracellular matrix degradation in CXPA. The tumor microenvironment exhibited stage-specific adaptations, with CXPA favoring pro-inflammatory MIF-CD74/CD44 signaling and rPA adopting immunosuppressive traits. Stromal reprogramming and immune-editing dynamics collectively orchestrated microenvironmental adaptation, linking cellular heterogeneity to clinical aggressiveness. This study provides the first comprehensive molecular atlas of PA-to-CXPA transformation, revealing malignant specialization of the myoepithelial subpopulation, fibroblast-mediated stromal reprogramming, and immune-editing driven microenvironmental adaptation. These findings provide a framework for precision stratification of the malignant potential of PA, while positioning microenvironmental intervention as a cornerstone of future clinical strategies.

The clinical activity of neoadjuvant immunochemotherapy (NAIC) for treating locally advanced oral squamous cell carcinoma (LA-OSCC) remains uncertain. This single-arm, phase II trial (ChiCTR2200066119) tested 2 cycles of NAIC with camrelizumab plus nab-paclitaxel and cisplatin in LA-OSCC patients. For primary endpoint, the major pathological response (MPR) rate was 69.0% (95% confidence interval (CI): 49.2%-84.7%). The treatment was well-tolerated, with only 2 patients (6.45%) having grade 3 or 4 treatment-related adverse events during neoadjuvant treatment. For secondary endpoints, the pathological complete response rate was 41.4% (95%CI: 23.5%-61.1%) and the objective response rate was 82.8% (24/29, 95%CI: 64.2%-94.2%). The 18-month overall survival and disease-free survival probabilities were 96.77% (95%CI: 79.23%-99.54%) and 85.71% (95%CI: 53.95%-96.22%), respectively. Exploratory analysis showed that patients with MPR exhibited higher density of baseline CD4_Tfh_CXCL13 cells, and increased density of tertiary lymphoid structures after NAIC. Baseline CD4_Tfh_CXCL13 cells might be potential predictive biomarker of efficacy. The interaction between CXCL13 on CD4_Tfh_CXCL13 cells and CXCR5 on B cells may play a role in treatment response. These findings suggest the potential of NAIC as a promising treatment for LA-OSCC and offer preliminary insights into responsive biomarkers. The clinical activity of neoadjuvant immunochemotherapy for treating locally advanced oral squamous cell carcinoma (LA-OSCC) remains uncertain. In this single-arm, phase II trial, the authors show that neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin provides a favourable pathological response and manageable safety in patients with LA-OSCC while baseline CD4_Tfh_CXCL13 cells may serve as a predictive biomarker of efficacy.

Background The prevalence of dentin hypersensitivity (DH) differed significantly among previous reports, which may confuse clinicians and public health practitioners. This study aimed to identify which survey methods contributed to the difference in reported DH prevalence. Methods A systematic search was performed in Medline, Embase, ProQuest, CNKI, and ClinicalTrial.gov databases up to November 2022. Two authors extracted the basic characteristics and survey methods independently. A random-effect meta-analysis was performed to estimate the effects of survey methods on estimated DH prevalence. The Newcastle-Ottawa Scale (NOS) was employed to appraise the methodological quality of the studies included in the analysis. Results Thirty-nine studies were included. The average estimate of DH prevalence was 32% (95% CIs: 27 − 37%). The statistical heterogeneity was very high among studies ( I 2  = 99.7%, P  < 0.001), especially in the field of survey methods. Variables were observed in sampling approaches, study settings, and inclusion criteria. Besides, clinical examination protocols and reporting of inter-examiner reliability remained inconsistent. Meta-regression analysis showed that the DH prevalence might be underestimated when the clinical examinations were conducted only for participants with positive subjective symptoms ( P  = 0.001). The included studies scored 5.74 ± 1.7 on the NOS, indicating relatively low methodological quality. The lower study quality was primarily attributed to insufficient elaboration on representativeness of the exposed cohort, comparability of cohorts on the basis of the design or analysis controlled for confounders, and follow-up procedures. Conclusion The included studies demonstrated substantial heterogeneity in survey methods. Conducting clinical examinations for all participants enhanced detection rates. The reliability of our pooled prevalence estimates was substantially compromised due to the studies’ low methodological quality and high heterogeneity. It is recommended to propose the instructive detailed guideline to standardize the design and improve the quality of studies.