Thyroid eye disease (TED) is a vision-threatening and quality-of-life-impairing manifestation of autoimmune thyroid disease, driven by orbital fibroblast activation, inflammation, and tissue remodeling. This review synthesizes current evidence on TED epidemiology and pathogenesis, with a particular focus on the pathogenic synergy between the thyrotropin receptor (TSHR) and the insulin-like growth factor-1 receptor (IGF-1R). We discuss how this receptor complex propagates intracellular signaling that leads to disease hallmarks: fibroblast proliferation, glycosaminoglycan secretion, and adipogenesis. While we outline the established paradigm of management—encompassing glucocorticoids, orbital radiotherapy, and surgery—a key emphasis is placed on the recent therapeutic revolution ushered in by targeted biological agents, most notably IGF-1R inhibition. As well as research on new targets for immunotherapy such as Tregs and other aspects such as IL-6 or TNF-α. Finally, we explore the nascent role of artificial intelligence in refining diagnosis and prognostic assessment. This overview aims to equip clinicians and researchers with a forward-looking perspective on the evolving landscape of TED management.

BACKGROUND:Currently, there is no clear guidance on the appropriate population or timing for adaptive radiotherapy (ART) in high-grade glioma (HGG) patients. This study aims to provide individualized ART for HGG patients. METHODS:Participants received standard "radiotherapy combined with temozolomide" and underwent MRI before radiotherapy (FX0), after fraction 10 (FX10), and after fraction 20 (FX20). The primary endpoint was anatomical and dosimetric changes in targets and organs at risk (OARs). RESULTS:Among the 73 eligible patients, significant anatomical changes occurred during chemoradiotherapy, particularly at FX10. ART significantly improved target dose coverage and reduced OAR doses compared with projection plans. Univariable and multivariable logistic regression analysis identified Relative volume change (Vrel)_CTV ≥ 7% as an independent risk factor for dosimetric changes, with IDH wild-type and tumor diameters < 5 cm as independent risk factors. Median follow-up was 12 months; median progression-free survival (PFS) was 18 months. D_migration_max_CTV ≥ 8.5 mm was associated with worse PFS. CONCLUSIONS:Implementing ART after FX10 is recommended. HGG patients with wild-type IDH and tumor diameters < 5 cm should be prioritized for ART. Patients with D_migration_max_CTV ≥ 8.5 mm require more intensive treatment. TRIAL REGISTRATION:The trial was prospectively registered (ClinicalTrials.gov, NCT06201351).

H3K27M-mutant diffuse midline gliomas (DMGs) are highly aggressive, immunosuppressive tumors that are resistant to conventional therapies. Median overall survival is typically 8–11 months after diagnosis; fewer than 10

Ferroptosis is an iron-dependent regulated cell death modality driven by lipid peroxidation and is mechanistically distinct from apoptosis, necroptosis, and pyroptosis. Morphologically, ferroptosis is associated with mitochondrial alterations, including increased membrane density and condensed mitochondria. Targeting ferroptosis may provide therapeutic opportunities to address tumor heterogeneity and circumvent apoptosis resistance. Glioblastoma is a highly malignant, treatment-refractory brain tumor with a distinct metabolic state and oxidative-stress landscape, which may render it particularly susceptible to ferroptosis-based interventions. Standard-of-care therapy for glioblastoma comprises maximal safe resection followed by radiotherapy and temozolomide; however, durable efficacy is frequently limited by resistance to therapy-induced cell death. Therefore, identifying targets that reverse chemo- and radioresistance, together with developing delivery strategies that overcome the blood–brain barrier, is critical for improving therapeutic outcomes. Emerging evidence suggests that ferroptosis influences chemoresistance and radioresistance and may be leveraged to enhance targeted drug delivery. This review synthesizes recent advances in ferroptosis research in glioblastoma, with an emphasis on pathway regulation, autophagy-dependent ferroptosis mechanisms, approaches to overcome chemoradiation resistance, emerging therapeutics, and nanomedicine-based, blood–brain barrier-penetrant delivery strategies. We also discuss current challenges, knowledge gaps, and future directions for ferroptosis-based glioblastoma therapy.

Gliomas are the most common primary malignant brain tumors, characterized by aggressive invasion, limited therapeutic options, and poor prognosis. Despite advances in surgery, radiotherapy, and chemotherapy, the median survival of glioma patients remains disappointingly low. Therefore, identifying glioma-associated therapeutic targets and biomarkers is of significant clinical importance. Circular RNAs (circRNAs) are a class of naturally occurring long non-coding RNAs (lncRNAs), notable for their stability and evolutionary conservation. Increasing evidence indicates that circRNA expression is dysregulated in gliomas compared to adjacent non-tumor tissues and contributes to the regulation of glioma-related biological processes. Furthermore, numerous circRNAs function as oncogenes or tumor suppressors, mediating glioma initiation, progression, and resistance to temozolomide (TMZ). Mechanistically, circRNAs regulate glioma biology through diverse pathways, including acting as miRNA sponges, binding RNA-binding proteins (RBPs), modulating transcription, and even encoding functional peptides. These features highlight the potential of circRNAs as diagnostic and prognostic biomarkers, as well as therapeutic targets for glioma. This review summarizes the dysregulation and functions of circRNAs in glioma and explores key mechanisms through which they mediate tumor progression, including DNA damage repair, programmed cell death (PCD), angiogenesis, and metabolic reprogramming. Our aim is to provide a comprehensive perspective on the multifaceted roles of circRNAs in glioma and to highlight their potential for translational application in targeted therapy.

Lysophosphatidic acid receptor 1 (LPAR1) mediates various biological behaviors in physiological and pathological processes. This study aims to comprehensively evaluate the prognostic value of LPAR1 expression and methylation in LGG, and explore their functional effects on tumor progression and immune regulation. The GEO database was used to analyze LPAR1 expression in tumors and normal tissues. The TCGA-LGG and CGGA datasets were used to analyze the expression, methylation, immunity and prognostic significance of LGG. Immune cells and immune pathways were detected by flow cytometry, ELISA and western blot analysis. The role of LPAR1 in LGG was validated by RT-PCR, TUNEL assay, CCK-8 assay, flow cytometry, wound healing assay and transwell assay. We included 627 patients who contained complete information required for analysis in the TCGA-LGG and CGGA datasets. Methylation of the LPAR1 promoter suppresses its expression. High methylation levels were associated with better overall survival (OS) and progression-free survival (PFS) (P < 0.05) in LGG. Decreased LPAR1 expression and increased methylation levels were significantly associated with age, histological types and isocitrate dehydrogenase (IDH) mutation status (P < 0.05). Multivariate analysis showed that LPAR1 was an independent prognostic factor for LGG (P = 0.002). Meta-analysis showed that high LPAR1 expression was indeed a poor prognosis for patients’ OS in LGG (HR, 1.06; 95

INTRODUCTION:Medulloblastoma is the predominant malignant neuroepithelial tumor in the central nervous system among children and is recognized as one of the most aggressive tumor types. Despite advances in multimodal therapy, prognosis for certain subgroups remains poor, and survivors often face severe long-term sequelae. Artificial intelligence (AI), a field focused on enabling computers to replicate human-like intelligent behavior, is increasingly being applied to the management of challenging diseases. AREAS COVERED:In this review, the authors provide a comprehensive overview of AI applications across the entire clinical spectrum of medulloblastoma. Using articles retrieved through literature searches from PubMed and Google Scholar, through to early 2025, the authors cover AI's roles in radiological segmentation and diagnosis, noninvasive molecular subtyping, pathological analysis, tumor microenvironment characterization and prognosis prediction. The review critically appraises the current evidence level for these technologies, from proof-of-concept to clinical validation. EXPERT OPINION:AI holds immense promise for personalizing medulloblastoma care, but its clinical integration faces significant hurdles. Key challenges include the need for large, diverse datasets, robust multi-center validation, improved model interpretability, and addressing pediatric-specific ethical concerns. Future success will depend on interdisciplinary collaboration to translate these powerful tools into safe, effective, and equitable clinical practice, ultimately improving outcomes for children worldwide.

Glioblastoma (GBM) is the most common primary malignant brain tumor, characterized by its aggressive behavior, limited treatment options, and poor prognosis. Despite advances in surgery, radiotherapy, and chemotherapy, the median survival of GBM patients remains disappointingly short. Recent studies have underscored the critical role of histone modifications in GBM malignant progression and therapy resistance. Histones, protein components of chromatin, undergo various modifications, including acetylation and methylation. These modifications significantly affect gene expression, thereby promoting tumorigenesis and resistance to therapy. Targeting histone modifications has emerged as a promising therapeutic approach. Numerous pre-clinical studies have evaluated histone modification agents in GBM, including histone deacetylase inhibitors and histone methyltransferase inhibitors. These studies demonstrate that modulating histone modifications can alter gene expression patterns, inhibit tumor growth, induce apoptosis, and sensitize tumor cells to conventional treatments. Some agents have advanced to clinical trials, aiming to translate preclinical efficacy into clinical benefit. However, clinical outcomes remain suboptimal, as many agents fail to significantly improve GBM patient prognosis. These challenges are attributed to the complexity of histone modification networks and the adaptive responses of the tumor microenvironment. This review provides a comprehensive overview of epigenetic regulation mechanisms involving histone modifications in GBM, covering their roles in tumor development, tumor microenvironment remodeling, and therapeutic resistance. Additionally, the review discusses current clinical trials targeting histone modifications in GBM, highlighting successes, limitations, and future perspectives.

AbstractBackground and ObjectiveHigh‐grade glioma (HGG) is known to be characterized by a high degree of malignancy and a worse prognosis. The classical treatment is safe resection supplemented by radiotherapy and chemotherapy. Tumor treating fields (TTFields), an emerging physiotherapeutic modality that targets malignant solid tumors using medium‐frequency, low‐intensity, alternating electric fields to interfere with cell division, have been used for the treatment of new diagnosis of glioblastoma, however, their administration in HGG requires further clinical evidence. The efficacy and safety of TTFields in Chinese patients with HGG were retrospectively evaluated by us in a single center.MethodsWe enrolled and analyzed 52 patients with newly diagnosed HGG undergoing surgery and standard chemoradiotherapy regimens from December 2019 to June 2022, and followed them until June 2023. Based on whether they used TTFields, they were divided into a TTFields group and a non‐TTFields group. Progression‐free survival (PFS) and overall survival (OS) were compared between the two groups.ResultsThere were 26 cases in the TTFields group and 26 cases in the non‐TTFields group. In the TTFields group, the median PFS was 14.2 months (95% CI: 9.50–18.90), the median OS was 19.7 months (95% CI: 14.95–24.25) , the median interval from surgery to the start of treatment with TTFields was 2.47 months (95% CI: 1.47–4.13), and the median duration of treatment with TTFields was 10.6 months (95% CI: 9.57–11.63). 15 (57.69%) patients experienced an adverse event and no serious adverse event was reported. In the non‐TTFields group, the median PFS was 9.57 months (95% CI: 6.23–12.91) and the median OS was 16.07 months (95% CI: 12.90–19.24). There was a statistically significant difference in PFS (p = 0.005) and OS (p = 0.007) between the two groups.ConclusionsIn this retrospective analysis, TTFields were observed to improve newly diagnosed HGG patients' median PFS and OS. Compliance was much higher than reported in clinical trials and safety remained good.

BACKGROUND AND OBJECTIVE:Radiofrequency ablation (RFA) is an emerging treatment of lung cancer, yet it is accompanied by certain safety concerns and operational limitations. This first multi-centre, large-scale clinical trial aimed to investigate the technical performance, efficacy and safety of an innovative transbronchial RFA system for lung tumours. METHODS:The study enrolled patients with malignant lung tumours who underwent transbronchial RFA using an automatic saline microperfusion system between January 2021 and December 2021 across 16 medical centres. The primary endpoint was the complete ablation rate. The performance and safety of the technique, along with the 1-year survival rates, were evaluated. RESULTS:This study included 126 patients (age range: 23-85 years) with 130 lung tumours (mean size: 18.77 × 14.15 mm) who had undergone 153 transbronchial RFA sessions, with a technique success rate of 99.35% and an average ablation zone size of 32.47 mm. At the 12-month follow-up, the complete ablation rate and intrapulmonary progression-free survival rates were 90.48% and 88.89%, respectively. The results of patients with ground-glass nodules (GGNs) were superior to those of the patients with solid nodules (12-month complete ablation rates: solid vs. pure GGN vs. mixed GGN: 82.14% vs. 100% vs. 96.08%, p = 0.007). No device defects were reported. Complications such as pneumothorax, haemoptysis, pleural effusion, pulmonary infection and pleural pain were observed in 3.97%, 6.35%, 8.73%, 11.11% and 10.32% of patients, respectively. Two subjects died during the follow-up period. CONCLUSION:Transbronchial RFA utilizing an automatic saline microperfusion system is a viable, safe and efficacious approach for the treatment for lung tumours, particularly for patients with GGNs.

BackgroundHistiocytic sarcoma originates in various tissues, including the skin, lymph nodes, gastrointestinal tract, lungs, bone marrow, and central nervous system. Primary central nervous system histiocytic sarcoma (PCNSHS) is exceptionally rare, known for its aggressive behavior and poor prognosis. This report describes a case of PCNSHS in the cerebellum treated with surgery and radiotherapy.Case presentationA 30-year-old woman presented with progressive dizziness and headache. Magnetic resonance imaging scans showed right cerebellar neoplastic lesions approximately 3.6 cm*3.0 cm with cerebral edema and fourth ventricle and brainstem compression. The patient underwent surgical debulking, and the pathological diagnosis was PCNSHS. Two months after the surgery, the patient underwent adjuvant radiotherapy at a dose of 60 Gy. No tumor progression has been observed during the one-year follow-up period.ConclusionsThis case report provides an example of effective central nervous system control using resection and radiation therapy. A review of the literature confirms that surgery alone or combined concurrent or sequential treatment of radiotherapy and chemotherapy is often used; however, the best treatment plan remains unclear. Moreover, the prognosis is poor, with a median survival of six months. Thus, ongoing research aims to better understand the biology of histiocytic sarcomas and find more effective strategies.

Background: A significant part of blast injury is accompanied by hemorrhagic shock (BS), while research on its fluid resuscitation strategies have not been reported. Although blood products are usually recommended in most resuscitation cases, they are less available in certain conditions. To this end, here, we focused on a widely used and more accessible fluid type- crystalloid fluid, in BS treatment. Methods: We conducted studies in rats comparing the therapeutic effects of 3 different crystalloid solutions at different time points after BS, and explored the underlying mechanisms. Generally, the survival rates gradually dropped along with the time when fluid resuscitation was given. Results: Among different types of solution, the hypertonic saline (HS) group showed the highest survival rates. The lactated Ringer’s solution (LR) only displayed lifesaving effect at 0.5 h resuscitation time point. Moreover, it is worth noting that the survival rates of the normal saline (NS) group at all the time points were lower than the non-treatment control. Mechanism study in rats indicated that the therapeutic differences may be caused by varied degrees of pulmonary edema and inflammatory responses under different crystalloid fluid resuscitation. Conclusion: In conclusion, we assessed the effects and investigated the mechanisms of different crystalloid fluid resuscitation strategies for BS for the first time, which potentially contributes to the establishment of guidance for crystalloid fluid resuscitation of BS patients.

Paclitaxel (PTX) is an anti-microtubule agent, used for the treatment of various types of cancers; however, it produces painful neuropathy which limits its use. Many neuroprotective agents have been introduced to mitigate PTX-induced neuropathic pain (PINP), but they pose many adverse effects. The purpose of this study was to evaluate the pharmacological characteristics of soy isoflavone, and daidzein (DZ) in attenuating PINP. At the beginning of the investigation, the effect of DZ was confirmed through behavioral analysis, as it reduced pain hypersensitivity. Moreover, changes in the histological parameters were reversed by DZ administration along with vascular permeability. PTX administration upregulated transient receptor potential vanilloid 1 (TRPV1) channels and purinergic receptors (P2Y), contributing to hyperalgesia; but administration of DZ downregulated the TRPV1 and P2Y, thus reducing hyperalgesia. DZ increased nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1), playing a pivotal role in the activation of the antioxidant pathway. DZ also decreased neuronal apoptosis by decreasing caspase-3 and Bcl2-associated X-protein (Bax), while simultaneously, increasing Bcl-2. PTX administration produced severe DNA damage, which was mitigated by DZ. Similarly, DZ administration resulted in inhibition of neuroinflammation by increasing antioxidant enzymes and reducing oxidative stress markers. PTX caused increased in production of pro-inflammatory mediators such as the cytokines production, while DZ inhibited the pro-inflammatory mediators. Additionally, in silico pharmacokinetic and toxicodynamic study of DZ was also conducted. In summary, DZ demonstrated significant neuroprotective activity against PTX induced neuropathic pain.

High-grade gliomas (grades III and IV) are highly malignant and aggressive brain tumors that present significant treatment challenges. Despite advances in surgery, chemotherapy, and radiation therapy, the prognosis for patients with glioma remains poor, with a median overall survival (mOS) range of 9–12 months. Therefore, exploring new and effective therapeutic strategies to improve glioma prognosis is of utmost importance and ozone therapy is a viable option. Ozone therapy has been used in various cancers, such as colon, breast, and lung, yielding significant results in preclinical studies and clinical trials. Only a few studies have been conducted on gliomas. Furthermore, since the metabolism of brain cells involves aerobic glycolysis, ozone therapy may improve the oxygen condition and enhance glioma radiation treatment. However, understanding the correct ozone dosage and optimal time of administration remains challenging. Herein, we hypothesize that ozone therapy should be more effective in gliomas compared with other tumors. This study provides an overview of the use of ozone therapy in high-grade glioma, including mechanisms of action, preclinical data, and clinical evidence.

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s12906-022-03629-7.

Understanding the clinical features and accurately predicting the prognosis of patients with locally advanced hypopharyngeal squamous cell carcinoma (LA-HPSCC) is important for patient centered decision-making. This study aimed to create a multi-factor nomogram predictive model and a web-based calculator to predict post-therapy survival for patients with LA-HPSCC. A retrospective cohort study analyzing Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2015 for patients diagnosed with LA-HPSCC was conducted and randomly divided into a training and a validation group (7:3 ratio). The external validation cohort included 276 patients from Sichuan Cancer Hospital, China. The Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression analysis was used to identify independent factors associated with overall survival (OS) and cancer-specific survival (CSS), and nomogram models and web-based survival calculators were constructed. Propensity score matching (PSM) was used to compare survival with different treatment options. A total of 2526 patients were included in the prognostic model. The median OS and CSS for the entire cohort were 20 (18.6-21.3) months and 24 (21.7-26.2) months, respectively. Nomogram models integrating the seven factors demonstrated high predictive accuracy for 3-year and 5-year survival. PSM found that patients who received surgery-based curative therapy had better OS and CSS than those who received radiotherapy-based treatment (median survival times: 33 months vs 18 months and 40 months vs 22 months, respectively). The nomogram model accurately predicted patient survival from LA-HPSCC. Surgery with adjuvant therapy yielded significantly better survival than definitive radiotherapy. and should be prioritized over definitive radiotherapy.

Background:To comprehensively investigate the behaviors of oncologists with different working experiences and institute group styles in deep learning-based organs-at-risk (OAR) contouring. Methods:A deep learning-based contouring system (DLCS) was modeled from 188 CT datasets of patients with nasopharyngeal carcinoma (NPC) in institute A. Three institute oncology groups, A, B, and C, were included; each contained a beginner and an expert. For each of the 28 OARs, two trials were performed with manual contouring first and post-DLCS edition later, for ten test cases. Contouring performance and group consistency were quantified by volumetric and surface Dice coefficients. A volume-based and a surface-based oncologist satisfaction rate (VOSR and SOSR) were defined to evaluate the oncologists' acceptance of DLCS. Results:Based on DLCS, experience inconsistency was eliminated. Intra-institute consistency was eliminated for group C but still existed for group A and group B. Group C benefits most from DLCS with the highest number of improved OARs (8 for volumetric Dice and 10 for surface Dice), followed by group B. Beginners obtained more numbers of improved OARs than experts (7 v.s. 4 in volumetric Dice and 5 v.s. 4 in surface Dice). VOSR and SOSR varied for institute groups, but the rates of beginners were all significantly higher than those of experts for OARs with experience group significance. A remarkable positive linear relationship was found between VOSR and post-DLCS edition volumetric Dice with a coefficient of 0.78. Conclusions:The DLCS was effective for various institutes and the beginners benefited more than the experts.