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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.

The stem cell niche plays a pivotal non–cell-autonomous role in maintaining stem cell function, yet it can be disrupted by tissue injury or cancer therapy. Here, we propose that dying cells induced by external insults actively construct a novel, enhanced stem cell niche that facilitates stem cell survival under harsh conditions. This phenomenon is evolutionarily conserved across diverse species and evolutionary hierarchies, contributing critically to both tissue regeneration and tumor recurrence. In the context of tissue regeneration, dying differentiated daughter cells reinforce stemness by secreting ligands and protective factors that support self-renewal. Additionally, damaged environmental cells, including stromal and inflammatory cells, contribute to niche reconstruction through paracrine signaling. The clearance of dying cells further modulates the niche to better support stem cell for regeneration or tumor regrowth. Among cell death modalities, apoptosis, particularly caspase-3–mediated apoptosis, plays a central role by orchestrating microenvironmental remodeling and activating pro-stemness signaling pathways. These mechanisms are also hijacked by cancer cells to reinforce therapy resistance, which are often overlooked. Unraveling how dying cells dynamically reshape the stem cell niche provides novel insights into regenerative biology and may inform therapeutic strategies to overcome tumor therapy resistance.

In the terahertz band, how integrating multiple functions into a device with a tiny unit structure is a challenge. In this paper, an optically-controlled multifunctional linear polarization conversion metasurface working in the terahertz band is proposed. The reflection and transmission polarization conversion functions can be realized by irradiating the metasurface with pump light with different wavelengths. The metasurface is designed with a multilayer structure, and a photosensitive semiconductor alone is used to control multiple functions, which makes the manipulation of multifunctional devices easy. When the photosensitive semiconductor germanium (Ge) and silicon (Si) are in different states, the metasurface can realize broadband reflection and transmission polarization conversion functions, the corresponding relative bandwidth are 102.4% and 98.9%, respectively, and the work efficiency can be regulated by pump light with different intensity and wavelength. In addition, the working principle of the metasurface is analyzed by eigenmode theory and surface current distributions. The stability of the metasurface to structural parameters and incident angles are discussed.

The polymorphic microbiome has been proposed as a new hallmark of cancer. Intratumor microbiome has been revealed to play vital roles in regulating tumor initiation and progression, but the regulatory mechanisms have not been fully uncovered. In this review, we illustrated that similar to other components in the tumor microenvironment, the reside and composition of intratumor microbiome are regulated by tumor cells and the surrounding microenvironment. The intratumor hypoxic, immune suppressive, and highly permeable microenvironment may select certain microbiomes, and tumor cells may directly interact with microbiome via molecular binding or secretions. Conversely, the intratumor microbiomes plays vital roles in regulating tumor initiation and progression via regulating the mutational landscape, the function of genes in tumor cells and modulating the tumor microenvironment, including immunity, inflammation, angiogenesis, stem cell niche, etc. Moreover, intratumor microbiome is regulated by anti‐cancer therapies and actively influences therapy response, which could be a therapeutic target or engineered to be a therapy weapon in the clinic. This review highlights the intratumor microbiome as a vital component in the tumor microenvironment, uncovers potential mutual regulatory mechanisms between the tumor microenvironment and intratumor microbiome, and points out the ongoing research directions and drawbacks of the research area, which should broaden our view of microbiome and enlighten further investigation directions.

Introduction: Low molecular weight heparin (LMWH), a natural sulfated glycosaminoglycan with an affinity for proangiogenic factors, is produced by chemical or enzymatic depolymerization of unfractionated heparin (UFH). Known for its anticoagulant effects, LMWH has recently been reported to have a strong anti-inflammatory effect on colitis, myocarditis, and airway inflammation. However, as a newly-developed drug, its anti-inflammatory mechanism in upper respiratory tract inflammation has not been well-studied. Methods: SD rats were randomly divided into control and experimental groups. The experimental group was established by building an acute nasal sinusitis model with expansion sponges mixed with Streptococcus pneumoniae . Then the experimental group rats were subcutaneously injected with different concentrations of LMWH. After seven consecutive days of injection, some rats were sacrificed, and blood and nasal mucosa samples were taken to determine their inflammation status. The remaining acute sinusitis rats were randomly selected for a week of nasal irrigation with normal saline or saline mixed with different concentrations of LMWH. One week later, rats were sacrificed, and samples of blood and nasal mucosa were taken to determine the inflammation status. Results: Rat nasal mucosa in the model group had obvious inflammation. The degree of nasal mucosa inflammation damage in the experimental group was lower than in the experimental control group, proving that LMWH has a protective effect on the nasal mucosa and that the effect correlates with dosage. Irrigation of the nose with saline mixed with LMWH can improve the anti-inflammatory effect. Protein related to the TLR4-MyD88-NF-κB signaling pathway was activated in the acute sinusitis rat model, and LMWH can significantly inhibit its expression. Conclusion: This is the first report of the anti-inflammatory effect of LMWH in acute upper respiratory tract inflammation, together with an explanation of its anti-inflammatory mechanism. The findings contribute a theoretical basis for its potential anti-tumor effect.

Anaplastic thyroid carcinoma (ATC) is one of the most lethal human malignancies, often evolving from differentiated thyroid carcinoma (DTC) through a poorly understood dedifferentiation process. To elucidate this transition, spatial transcriptomic sequencing (spRNAseq) is performed on seven samples containing coexisting regions of ATC, poorly differentiated thyroid carcinoma, and DTC. SpRNAseq revealed that ATC regions were characterized by upregulated genes involved in immune suppression, angiogenesis, and extracellular matrix remodeling. Whole‐exome sequencing and inferCNV analysis confirmed that adjacent DTC regions harbored mutational burdens comparable to those of ATC regions, suggesting early genomic priming for dedifferentiation. Trajectory analysis delineated a stepwise reprogramming process and identified four gene modules associated with the loss of thyroid differentiation, among which PDCD4 and TYMP emerged as key regulators. Notably, TYMP⁺ tumor‐associated macrophages (TAMs) were highly enriched in ATC regions and contribute to an immunosuppressive microenvironment. Mechanistic experiments demonstrated that loss of PDCD4 led to eIF4A‐dependent overexpression of immunosuppressive effectors, promoting the high infiltration of TYMP⁺TAMs in ATC. These findings support that coexisting DTC regions with ATC‐like genomic alterations undergo sequential transcriptomic reprogramming and immune microenvironment remodeling to evolve into a full ATC pathological phenotype, in which PDCD4 loss–induced TAMs formation plays a critical role. Spatial transcriptomic analysis of Anaplastic thyroid carcinoma (ATC)‐differentiated thyroid carcinoma (DTC) coexisting tumors reveals that coexisting DTC regions with ATC‐like genomic alterations undergo sequential transcriptomic reprogramming and immune microenvironment remodeling, ultimately evolving into a full ATC pathological phenotype. Notably, PDCD4 loss drives eIF4A‐dependent upregulation of immunosuppressive effectors, promoting TYMP⁺ tumor‐associated macrophages enrichment, which represents a key mechanism in establishing the immunosuppressive microenvironment of ATC.

Forkhead box D1 (FOXD1) belongs to the FOX protein family, which has been found to function as a oncogene in multiple cancer types, but its role in head and neck squamous cell carcinoma (HNSCC) requires further investigation. Our research aimed to investigate the function of FOXD1 in HNSCC. Bioinformatics analysis indicated that mRNA level of FOXD1 was highly expressed in HNSCC tissues, and over-expressed FOXD1 was related to poor prognosis. Moreover, FOXD1 knockdown increased the ratio of senescent cells but decreased the proliferation ability, while FOXD1 overexpression obtained the opposite results. In vitro experiments revealed that FOXD1 bound to the p21 promoter and inhibited its transcription, which blocked the cyclin dependent kinase 2 (CDK2)/retinoblastoma (Rb) signaling pathway, thus preventing senescence and accelerating proliferation of tumor cells. CDK2 inhibitor could reverse the process to some extent. Further research has shown that miR-3oe-5p serves as a tumor suppressant by repressing the translation of FOXD1 through combining with the 3’-untranslated region (UTR). Thus, FOXD1 resists cellular senescence and facilitates HNSCC cell proliferation by affecting the expression of p21/CDK2/Rb signaling, suggesting that FOXD1 may be a potential curative target for HNSCC.

PurposeSeveral studies have reported different findings on the prognosis of differentiated thyroid carcinoma combined with Graves’ disease. To assess the effect of Graves’ disease on differentiated thyroid carcinoma, a meta-analysis was undertaken.MethodsPubMed, OVID and the Cochrane Library were systematically searched for trials published prior to Oct. 2018. Studies containing data on the outcomes of Graves’ disease with differentiated thyroid carcinoma were included. Summary estimates of the prevalence of recurrence/disease progression/persistence and mortality as well as odds ratios and weighted mean differences were calculated with a random-effects model.ResultsOf the 916 related articles found, 13 fulfilled the inclusion criteria. The recurrence/disease progression/persistent rate was not significantly different between the Graves’ disease group and the non-Graves’ disease group (P = 0.86). However, the analysis of three studies with K–M curves or HRs showed that there was a significant difference between the two groups (P = 0.04). Subgroup analysis showed that the contradictory results could be due to the location/race assessed in the studies. Graves’ disease almost acted as a risk factor (OR = 1.77, 95%C.I. = 0.99–3.16) for differentiated thyroid carcinoma in European studies. When heterogeneous studies were excluded, the analyses show that GD was a risk factor for recurrence/disease progression/persistence (P = 0.03, OR = 1.75, 95%C.I. = 1.04–2.95). The overall mortality rate was significantly higher in the Graves’ disease group than in the non-Graves’ disease group (P = 0.02, OR = 2.93, 95%C.I. = 1.17–7.37).ConclusionsGraves’ disease acts as a risk factor for the prognosis of differentiated thyroid carcinoma. The recurrence/disease progression/persistent rate may be affected by TSAbs in a specific location/race and with a genetic immunization background. However, the histotypes and subtypes may play an important role in mortality rate.

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 prognostic value of nutritional status in anaplastic thyroid carcinoma (ATC) remains unclear. The Prognostic Nutritional Index (PNI) is a reliable indicator of overall nutritional and immune status, and it has emerged as a significant prognostic factor in various malignancies. This study aimed to explore the utility of PNI in ATC. Methods We systematically reviewed ATC patients in our institute from January 2000 to June 2023 and categorized them into high and low PNI groups based on the median PNI value. Kaplan–Meier analysis and Cox regression were employed to assess the impact of PNI on overall survival, while ROC curve analysis evaluated the predictive value of PNI. Mimics software was used for three-dimensional reconstruction of pre- and post-immunotherapy tumor volumes, enabling the assessment of treatment response. Results A total of 77 ATC patients were included in this study. Low baseline PNI was associated with significantly shorter overall survival (1-year survival rate: 5.26% vs 30.77%; median survival time: 5.30 months vs 8.87 months). The 1-year, 2-year, and 3-year AUC values for PNI were 0.82, 0.79, and 0.77, respectively. In the multivariate analysis, both PNI and tumor size emerged as independent prognostic factors for patient overall survival. Among ATC patients receiving 2–3 cycles of immunotherapy, an increase in post-treatment PNI levels was positively correlated with a reduction in tumor volume. Conclusion PNI is an independent predictor of overall survival and holds the potential to serve as a valuable indicator for assessing and predicting immunotherapy efficacy in ATC patients.