Background: Postoperative hypoparathyroidism (hypoPT) is a common complication following thyroid surgery. However, current research findings on the risk factors for post-thyroid surgery hypoPT are not entirely consistent, and the same risk factors may have different impacts on transient and permanent hypoPT. Therefore, there is a need for a comprehensive study to summarize and explore the risk factors for both transient and permanent hypoPT after thyroid surgery. Materials and methods: Two databases (PubMed and Embase) were searched from inception to 2024. The Newcastle–Ottawa Scale was used to rate study quality. Pooled odds ratios were used to calculate the relationship of each risk factor with transient and permanent hypoPT. Subgroup analyses were conducted for hypoPT with different definition-time (6 or 12 months). Publication bias was assessed using Begg’s test and Egger’s test. Results: A total of 19 risk factors from the 93 studies were included in the analysis. Among them, sex and parathyroid autotransplantation were the most frequently reported risk factors. Meta-analysis demonstrated that sex (female vs. male), cN stage, central neck dissection, lateral neck dissection, extent of central neck dissection (bilateral vs. unilateral), surgery [total thyroidectomy (TT) vs. lobectomy], surgery type (TT vs. sub-TT), incidental parathyroidectomy, and pathology (cancer vs. benign) were significantly associated with transient and permanent hypoPT. Preoperative calcium and parathyroid autotransplantation were only identified as risk factors for transient hypoPT, while preoperative PTH was a protective factor. Additionally, node metastasis and parathyroid in specimen were associated with permanent hypoPT. Conclusion: The highest risk of hypoPT occurs in female thyroid cancer patients with lymph node metastasis undergoing TT combined with neck dissection. The key to preventing postoperative hypoPT lies in the selection of surgical approach and intraoperative protection.

Hypoxanthine phosphoribosyl transferase 1 (HPRT1) is traditionally believed to be a housekeeping gene. However, recent reports have indicated that HPRT1 overexpression is associated with a poor prognosis in various types of cancers. Using The Cancer Genome Atlas (TCGA), HPRT1 was found to be highly expressed in various cancer types, especially in head and neck squamous cell carcinoma (HNSCC). Therefore, we measured HPRT1 expression in human cancer tissues and adjacent non-carcinoma tissues (ANT) and explored the relationship between HPRT1 expression and clinical pathological factors and prognosis in patients with oral squamous cell carcinoma (OSCC), a common type of HNSCC. We built OSCC cells with stable knockdown and overexpression of HPRT1 to observe its influence on chemoresistance and malignancy in vitro and vivo. We found that highly expressed HPRT1 was associated with a poor prognosis and could promote resistance to cisplatin (CDDP) in OSCC cells in both in vitro and in vivo. An RNA sequence assay was carried out to explore the mechanism of function of HPRT1, we found that HPRT1 could positively regulate the expression of MMP1 and the activation of the PI3K/AKT pathway, to regulate the resistance to CDDP of OSCC. In conclusion, HPRT1 can no longer be simply believed to be a housekeeping gene. HPRT1 overexpression indicates a worse prognosis and can improve CDDP resistance for patients with OSCC by promoting the MMP1/PI3K/Akt axis. HPRT1 may be a potential prognostic biomarker and therapeutic target in OSCC.

Background: The nutritional risk index (NRI) is an excellent indicator of nutritional status and a significant prognostic factor in several malignancies, but the relationship between NRI and the prognosis of head and neck soft tissue sarcoma (HNSTS) patients remains unclear. The aim of this study was to investigate the role of NRI in patients with HNSTS. Methods: We retrospectively reviewed patients with HNSTS between 1990 and 2021. In order to determine the optimal cut-off value of NRI, the Maximally selected log-rank statistic was performed. We evaluated the effect of NRI on overall survival (OS) and progression-free survival (PFS) by using the Kaplan–Meier method and Cox regression analysis. Then, OS and PFS nomograms based on NRI were constructed. Results: In total, 436 HNSTS patients were included in this study. The optimal cut-off value of NRI was 99.34. Patients with low-NRI showed significantly worse OS and PFS than patients with high-NRI, respectively (5-year OS rate of 43.0 vs. 70.8%, 5-year PFS rate of 29.0 vs. 45.0%, all p < 0.05). In the multivariate analysis, distant metastasis, deep tumor depth, tumor grade, and NRI were prognostic factors for both PFS and OS, and treatment modality was associated with OS but not PFS. The concordance indexes (C-indexes) of OS and PFS nomograms were 0.794 (95% CI, 0.759–0.829) and 0.663 (95% CI, 0.626–0.700), respectively, which also performed well in the validation set. Conclusions: NRI is an independent predictor of OS and PFS in HNSTS patients. The validated nomograms based on NRI provide useful predictions of OS and PFS for patients with HNSTS.

Background: Anaplastic thyroid carcinoma (ATC) is a rare, aggressive solid tumor with poor prognosis. Traditional treatment such as surgery, radiotherapy, and chemotherapy has limited therapeutic effects. In recent years, immunotherapy is changing the treatment pattern of them. We systematically summarize the research status and application of immunotherapy in ATC to provide clinicians and relevant researchers with a comprehensive perspective. Method: A comprehensive search of the PubMed and Embase databases identified 18 studies investigating the application of immunotherapy in ATC. These included ten cohort studies and eight case reports. The quality of the included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS) and Joanna Briggs Institute checklist (JBI). Subsequently, a single-proportion meta-analysis and meta-regression were performed to evaluate the efficacy of immunotherapy in ATC. Results: The favorable response rate to immunotherapy in ATC patients (33–100%) varies across cohorts, indicating substantial heterogeneity. The combination of immunotherapy with targeted therapy, as well as the use of neoadjuvant treatment, has led to improved outcomes for ATC. Single-proportion meta-analysis suggests that immunotherapy may provide clinical benefits for a subset of ATC patients (approximately one-third to one-half), but its effectiveness in controlling disease progression remains limited. Meta-regression further indicates that ATC patients with PD-L1 expression or BRAF ^V600E mutations tend to have better treatment responses. Among the 8 case reports, two patients achieved complete remission after immunotherapy, and four patients died of disease progression after immunotherapy. Mild adverse effects are common, but interstitial pneumonia is associated with poor prognosis in immunotherapy. Conclusion: Immunotherapy for ATC has demonstrated safety and efficacy in several studies, especially in patients with PD-L1 expression or BRAF ^V600E mutations. However, immune-related side effects should be carefully managed, particularly to prevent interstitial pneumonia.

Betel nut chewing represents a primary risk factor for oral squamous cell carcinoma (OSCC), with arecoline as its principal bioactive alkaloid. Yet, the mechanisms underlying arecoline-driven malignant progression remain incompletely understood. Here, we show that arecoline activates a ROS-driven NRF2-MT2A axis to suppress cuproptosis in OSCC. Transcriptomic analyses revealed that betel nut–associated OSCC exhibited enhanced oxidative stress signatures, reduced cuproptosis scores, and elevated MT2A expression, which correlated with poorer overall and progression-free survival. Arecoline increased intracellular ROS, activated NRF2 signaling, and upregulated MT2A in OSCC cells, while suppressing cuproptosis and promoting copper toxicity resistance. Pharmacologic ROS scavenging or genetic silencing of NRF2 blunted arecoline‑induced MT2A expression, restored cuproptosis, and attenuated cell viability, clonogenicity, migration and invasion in vitro. CUT&Tag profiling demonstrated direct NRF2 occupancy on the MT2A promoter, and MT2A overexpression partially rescued the loss of pro‑survival and anti‑cuproptotic effects caused by NRF2 knockdown. In xenograft models, knockdown of NRF2 or MT2A significantly inhibited tumor growth, while enforced MT2A expression reversed the effect of NRF2 depletion. Moreover, copper chelation with TTM rescued the tumor suppressive effect of MT2A knockdown, further confirming the role of MT2A in protecting OSCC against cuproptosis in vivo. Collectively, these data define a ROS‑NRF2‑MT2A signaling axis that protects OSCC cells from cuproptosis and promotes malignant progression in the context of betel nut exposure, highlighting redox and copper‑dependent cell death pathways as potential therapeutic vulnerabilities in arecoline‑related OSCC.

Background Locally advanced head and neck squamous cell carcinoma (LA HNSCC) remains a disease with a challenging prognosis. Concurrent chemoradiotherapy has long been the standard of care, yet efforts to enhance outcomes through the addition of induction or adjuvant therapies have largely failed. Recently, immune checkpoint inhibitors, particularly PD-1 inhibitors, have demonstrated efficacy in managing HNSCC, becoming a first-line treatment for recurrent/metastatic cases. This study aims to evaluate whether adding PD-1 inhibitors to induction chemotherapy can improve long-term outcomes in newly diagnosed LA HNSCC patients. Patients and methods This retrospective analysis included 204 newly diagnosed LA HNSCC patients treated between February 2012 and February 2023. Patients were divided into two cohorts: TPI group (n=115), who received induction chemotherapy including PD-1 inhibitors, and TP group (n=89), who received induction chemotherapy alone. The primary outcome was overall survival (OS), while secondary outcomes included progression-free survival (PFS) and objective response rate (ORR). Baseline characteristics were balanced using overlap propensity score weighting. Survival analyses were conducted using the Kaplan-Meier method, and subgroup analyses employed Cox proportional hazards models. Results With a median follow-up of 29.23 months, baseline characteristics were balanced after weighting. The addition of PD-1 inhibitors significantly improved OS (HR: 0.11, 95% CI: 0.03–0.37, p<0.001) and PFS (HR: 0.43, 95% CI: 0.20–0.89, p=0.024). Furthermore, the TPI group showed a significant improvement in the best radiological responses (p=0.02). Subgroup analyses identified specific factors associated with enhanced PFS and OS. Conclusions The addition of PD-1 inhibitors to induction chemotherapy significantly improves overall survival in patients with LA HNSCC, underscoring the potential for further clinical trials to refine and optimize treatment strategies.