Glioblastoma multiforme (GBM) is a highly aggressive and invasive type of primary brain tumor. Despite maximal safe surgical resection followed by concurrent adjuvant chemotherapy and radiotherapy, the clinical prognosis is grim, with only marginal prolongation of survival and poor quality of life. Median survival time is 15 months. This review will discuss the pathogenesis of GBM, diagnostic challenges, clinical evaluation, imaging, genomics and current therapeutic options. The intrinsic immunosuppressive properties of GBM and additional adverse changes in immune surveillance and the systemic immune environment brought about by chemoradiotherapy will be addressed. GBM stem cell properties and their role in local recurrence and preclusion of cure will be covered. We will discuss the limited penetration of the blood-brain barrier by therapeutics as a major obstacle in treatment. Advances in novel therapeutic strategies using personalized approaches, cell-based therapies, tumor vaccines and targeted drug delivery will be considered.

Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells, leading to organ damage and symptoms summarized by the acronym CRAB (calcium elevation, renal insufficiency, anemia, and bone lesions). The disease can also present with extramedullary involvement, which signifies a more aggressive course and may affect various organs such as the skin, liver, kidneys, and central nervous system. MM progresses from precursor stages like monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM), which differ in their risk of progression to active disease. Genetic alterations—including chromosomal translocations, deletions, amplifications, and point mutations—are central to pathogenesis and may influence prognosis and therapeutic response in MM. This review explores the genetic changes that drive MM progression, their prognostic implications, and the role of advanced diagnostic technologies in improving risk stratification and guiding personalized treatment. In particular, we examine key genetic alterations such as t(4;14), del(17p), and cellular myelocytomatosis oncogene (c-MYC) amplification, and their influence on treatment outcomes. The review also highlights recent advancements in diagnostic techniques, including next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR), which are transforming MM management through more precise and targeted therapeutic strategies. The integration of these diagnostic tools promises to enhance personalized treatment approaches, leading to improved outcomes and survival by tailoring therapies to each patient's genetic profile.

Rheumatic immune diseases (RIDs) comprise a heterogeneous group of autoimmune disorders with intricate etiologies, diverse clinical presentations, and challenging diagnostic processes, necessitating additional diagnostic modalities. In recent years, musculoskeletal ultrasonography (MSUS) has been increasingly applied for the evaluation of RIDs and has gradually evolved into a routine auxiliary diagnostic technique. This review highlights recent reports on the utilization of MSUS in the diagnosis and management of patients with RIDs, with particular emphasis on rheumatoid arthritis, gouty arthritis, and osteoarthritis. Special attention was given to its clinical value in improving diagnostic accuracy, guiding therapeutic interventions, and predicting disease progression. The overarching aim was to standardize practices and facilitate the broader adoption of MSUS in routine rheumatology care.

Immunotherapy using chimeric antigen receptor (CAR)-engineered T-cells has proven transformative in the management of selected haematological malignancies. However, it remains much less effective against solid tumours. In part, this is due to heterogeneity of antigen expression and the profoundly immunosuppressive nature of the tumour microenvironment. Epitope spreading entails the diversification of the immune response, allowing primed T-cells to target additional epitopes within the same antigen (intra-molecular) or a distinct antigen (inter-molecular; also known as antigen spreading). The occurrence of epitope spreading has been described in some immune competent mouse models and clinical studies of CAR T-cell immunotherapy. Interferon γ and granulocyte macrophage colony-stimulating factor have been implicated in this process through the recruitment and activation of antigen-presenting cells and T-cells. However, epitope spreading is not universally observed following CAR T-cell immunotherapy, prompting efforts to boost this. Accordingly, CAR T-cells have been engineered to produce a range of immunostimulatory factors. Moreover, alternative host cells including natural killer (NK) T-cells and macrophages have been proposed to more efficiently support epitope spreading. Additionally, a range of combination treatment strategies have been evaluated. Thus, CAR T-cells have been co-administered with vaccines, radiotherapy, stimulator of interferon genes (STING) agonists, tumour-tropic bacteria, oncolytic viruses and lipid nanoparticles. Effective harnessing of epitope spreading offers the potential to overcome key limitations of CAR T-cell therapy for solid tumours, nullifying the impact of tumour antigen loss and heterogeneity. However, it may trigger clinically significant autoimmunity in some patients.

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder characterized by exocrine gland dysfunction. Vitamin D3 (VD3), known for its immunomodulatory properties, has been implicated in modulating severity and immune responses in pSS, although the precise mechanisms are yet to be thoroughly investigated. This narrative review consolidates current research regarding the role of VD3 in pSS, with emphasis on its relationship with disease activity and immune function. Studies consistently reveal that VD3 levels are lower in pSS patients, with a negative correlation between VD3 levels and the severity of glandular damage, particularly in the salivary and lacrimal glands. Additionally, VD3 levels have been significantly associated with immune function markers, including T cell subset distribution and immunoglobulin levels. Despite the evidence, further investigation is needed to elucidate the causal relationships and mechanistic pathways involved. Overall, the existing data underscore the potential role of VD3 in the immunopathogenesis of pSS and suggest it may serve as a potential biomarker and adjunctive therapeutic target in future disease management approaches.

Inflammatory bowel disease (IBD) is a condition that is subject to genetic and environmental factors, characterized by multifaceted proinflammatory responses, which consequently can affect both hematological and non-hematological structures in the intestines. Gut microbiota dysbiosis is an environmental trigger posited to dysregulate the local immune system, initiating a complex interplay with a genetic predisposition to maintain the condition. Medicinal cannabis investigations on their anti-inflammatory characteristics have not been consistent with reports from laboratory studies with murine models. Although oral administration of medicinal cannabis, single molecules, or as mixed extracts from the flowering plant has been deemed safe, human clinical studies have not provided objective anti-inflammatory efficacy for conditions such as IBD. Anti-inflammatory efficacy was not observed for either ulcerative colitis (UC) or Crohn's disease (CD) with either Δ9-Tetrahydrocannabinol + Cannabidiol (Δ9-THC + CBD) or CBD alone, while improving the quality of life (QoL) of patients diagnosed with IBD. Mechanistically, what the current research shows is that the endocannabinoid system (ECS) tone in the gut is subject to intestinal microbiota homeostasis. Intestinal dysbiosis, as described for IBD, is posited to disturb the tone of the ECS, thereby disrupting the effects that medicinal cannabis may have in the treatment of gut inflammation. Conditions of IBD are linked with gut and vermiform appendix microbiota dysbiosis, characteristics in the colon that may destabilize the tone of the ECS and lead to medicinal cannabis failures to achieve clinically objective anti-inflammatory effects. The aim of this review is to investigate the link between the intestinal microbiota, the ECS and IBD. The quick, natural fix that medicinal cannabis appears to provide to manage the underlying IBD disease may not be suitable for all patients diagnosed with UC or CD.

Background: The Transmembrane Protease Serine 2/ERG (TMPRSS2/ERG) gene fusion results in the overexpression of ERG and dysregulation of pathways critical for prostate cancer (PC) tumor progression, invasion, and metastasis. This study aims to target the TMPRSS2/ERG fusion in the Scavenger Receptor Cysteine-Rich (SRCR) domain presents a promising and novel therapeutic strategy to control the aggression of PC malignancy. The study aims to identify targeted novel small molecules against the TMPRSS2 protein for lead identification and validation.

Methods: High-throughput virtual screening (HTVS) against the ChemBridge library was followed by protein-ligand interaction profilers, GROMACS, and GMX_Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) techniques were used for the lead identification. VCaP, LNCaP, human umbilical vein endothelial cells (HUVEC), and RWPE-1 cells were involved in the in vitro validations.

Results: HTVS identified TES7832 with favorable binding affinities of –8.0 kcal/mol to the SRCR domain of TMPRSS2. Molecular dynamic simulations demonstrated stable binding interactions with Root Mean Square Deviation values around 0.15 nm. The ΔG binding calculation was –36.76 kcal/mol (mean ± 5.63 standard deviation). Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) supported favorable small-molecule characteristics. TES7832 inhibited TMPRSS2 activity dose-dependently with a half-maximal inhibitory concentration (IC₅₀ value) of 484.1 ± 21.88 nM. The compound was selective to control the proliferation of VCaP cells expressing the TMPRSS2/ERG gene fusion with a 50% growth inhibition concentration (GI₅₀) value of 392 ± 39.15 nM. TES7832 reduced ERG and androgen receptor (AR) positive populations of VCaP cells while sparing the LNCaP or HUVEC cells that do not possess TMPRSS2/ERG fusion. The compound favored apoptosis and G₂/M cell cycle arrest in VCaP cells and inhibited hepatocyte growth factor (HGF)-induced transmigration of these cells.

Conclusion: TES7832 targeted the SRCR domain of the TMPRSS2/ERG fusion to downregulate ERG and AR activity in PC cells to control proliferation and induce apoptosis. This selectivity of TES7832 warrants further preclinical developments of the molecule against the TMPRSS2/ERG fusion-driven PC malignancy.

Background: Growing evidence suggests that arrestin domain-containing protein 3 (ARRDC3) plays a pivotal role in enhancing preeclampsia (PE) progression, and activating transcription factor 2 (ATF2) serves as a key regulator of trophoblast cell functions. Therefore, this study aims to investigate the role of the ATF2/ARRDC3 axis in mediating trophoblast cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT), providing mechanistic insights into PE pathogenesis.

Methods: The expression of ARRDC3, ATF2, EMT-related markers, both at mRNA and protein levels, was assessed using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot analyses. Trophoblast cell viability, apoptosis rate, invasion, and migration were evaluated using the Cell counting kit-8 (CCK-8) assay, flow cytometry, Transwell assay, and wound healing assay. Additionally, a correlation between ATF2 and the ARRDC3 promoter region was determined using the dual-luciferase reporter and ChIP assays.

Results: ARRDC3 overexpression inhibited trophoblast cell viability, invasion, migration, and EMT, while promoting apoptosis (p < 0.05). ATF2 promoted ARRDC3 expression by binding to its promoter region (p < 0.05). Upregulated ATF2 suppressed trophoblast cell viability, invasion, migration, and EMT; however, these effects were reversed by ARRDC3 knockdown (p < 0.05).

Conclusion: ATF2 binds to the ARRDC3 promoter region, upregulating its expression, thereby inhibiting trophoblast cell functions which in turn accelerate PE progression.

Background: Neuropathic pain (NP) following spinal cord injury (SCI) remains a major clinical challenge with limited therapeutic options. This study investigated the mechanism by which repetitive transcranial magnetic stimulation (rTMS) alleviates SCI-induced neuropathic pain (SCI-NP) via the GATA-binding protein 3 (GATA3)-Perforin 1 (PRF1) signaling axis.

Methods: Public transcriptomic datasets (GSE126611, GSE226238, GSE230149) were analyzed to identify candidate rTMS-responsive targets using protein-protein interaction (PPI) and functional enrichment analyses. In vivo, a contusive SCI model was induced in male Sprague–Dawley (SD) rats, followed by rTMS treatment (15 Hz, 6 weeks). Pain behaviors were assessed by Hargreaves and von Frey tests. Cytokine expression was quantified by enzyme-linked immunosorbent assay (ELISA), and GATA3/PRF1 expression was measured by Quantitative real-time polymerase chain reaction (qPCR) and Western blot. In vitro, binding of GATA3 to the PRF1 promoter was validated in rat spinal neurons using luciferase reporter assays and chromatin immunoprecipitation (ChIP). Functional rescue experiments were performed by intrathecal overexpression of GATA3.

Results: Bioinformatic analyses identified a regulatory interaction between GATA3 and PRF1. rTMS treatment significantly reduced mechanical allodynia and thermal hyperalgesia (p < 0.05), downregulated pro-inflammatory cytokines (interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α); p < 0.001), upregulated IL-10 (p < 0.001), and suppressed expression of GATA3 and PRF1 (p < 0.001). Mechanistically, GATA3 directly bound the PRF1 promoter. GATA3 overexpression abolished rTMS-mediated analgesic and anti-inflammatory effects (p < 0.05).

Conclusion: These findings suggest that rTMS alleviates SCI-NP by inhibiting GATA3-mediated transcriptional activation of PRF1, thereby reducing neuroinflammation.

Background: Orthodontic tooth movement can be caused by the remodeling of periodontal tissues, which is initiated by mechanical forces. Understanding the response of periodontal ligament stem cells (PDLSCs) is crucial for enhancing orthodontic treatment methods. Autophagy serves as an intrinsic defense mechanism that protects cells from mechanical stress caused by environmental changes. This study aims to explore the autophagic mechanism of PDLSCs under orthodontic compression force.

Methods: In this study, static compression force was applied to stimulate PDLSCs. Cell viability and apoptosis were assessed through Cell Counting Kit-8 assay and flow cytometry. Alkaline phosphatase staining and Alizarin red staining assays were used to examine osteogenic differentiation. Autophagy and osteogenic differentiation-related proteins were measured by means of Western blotting.

Results: Progranulin (PGRN) was expressed at high levels in PDLSCs exposed to compression force (p < 0.001). Autophagy and osteogenic differentiation of PDLSCs could be induced by compression force (p < 0.01). Moreover, the autophagy and osteogenic differentiation of compression force-stimulated PDLSCs was further enhanced upon PGRN overexpression (p < 0.01), while silencing of PGRN contributed to diametrically opposite results (p < 0.05). Mechanistically, high levels of PGRN exerted an inhibitory impact on the expression of phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (PI3K/AKT/mTOR) pathway-related proteins (p < 0.01). Furthermore, treatment with insulin-like growth factor-1 (IGF-1), a specific agonist, reversed the facilitating impacts of PGRN overexpression on autophagy and osteogenic differentiation (p < 0.05).

Conclusions: Our findings shed light on a novel autophagic mechanism of PDLSCs under orthodontic compression force and demonstrate that the inhibitory role of PGRN on the PI3K/AKT/mTOR pathway, thereby mediating the autophagy and osteogenic differentiation of compression force-stimulated PDLSCs. This may offer a new insight for periodontal remodeling during orthodontic treatment.

Background: Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, characterized by cardiac hypertrophy, fibrosis, and impaired function. Despite advances in therapeutic strategies, novel molecular targets are urgently needed to improve clinical outcomes. Trefoil factor 3 (Tff3) is reported to be upregulated in patients with heart failure. However, its functional role and underlying mechanisms in disease progression remain unclear. This study aimed to investigate the role of Tff3 in heart failure progression in vivo and to elucidate its molecular mechanisms.

Methods: A mouse model of heart failure was established via thoracic aortic coarctation (TAC). Tff3 expression in cardiac tissue was evaluated using immunoblotting and immunohistochemistry. Cardiac hypertrophy and fibrosis were assessed by immunoblotting, Masson's trichrome staining, and wheat germ agglutinin (WGA) staining. Autophagy levels were determined through immunoblotting and immunostaining. The involvement of the C-X-C Chemokine Receptor Type 4 (CXCR4)/Janus Kinase (JAK)/Signal Transducer and Activator of Transcription (STAT) signaling pathway was examined by immunoblot analysis.

Results: Tff3 expression was significantly upregulated in heart failure models (p < 0.05). Knockdown of Tff3 alleviated TAC-induced cardiac hypertrophy and fibrosis (p < 0.05). Furthermore, Tff3 depletion enhanced autophagy in heart failure models (p < 0.05). Mechanistically, Tff3 knockdown suppressed activation of the CXCR4/JAK/STAT signaling axis in heart failure mice (p < 0.05). These findings suggest that Tff3 depletion mitigates heart failure progression through the CXCR4/JAK/STAT axis (p < 0.05).

Conclusion: Tff3 knockdown promotes autophagy and attenuates cardiac hypertrophy and fibrosis by regulating the CXCR4/JAK/STAT signaling pathway. Tff3 may serve as a promising therapeutic target for heart failure.

Background: Polypyrimidine tract binding protein 1 (PTBP1) plays a crucial role in the stemness of various cancer types. Therefore, this study aimed to unveil the potential role of PTBP1 in the metastatic progression of pancreatic cancer (PC).

Methods: PTBP1 expression was confirmed in PC using bioinformatics analysis and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) data. After correlation analysis, RNA immunoprecipitation assay was employed to assess the interaction between PTBP1 and homeobox A9 (HOXA9). Based on the gain- or loss-of-function of the gene, the impact of PTBP1 in PC cells and its underlying regulatory mechanism in malignant behavior were investigated using a cell counting kit-8 (CCK-8) assay, flow cytometry, a Transwell assay and Western blot analysis.

Results: PTBP1 was found to be upregulated in PC. PTBP1 silencing enhanced cell apoptosis and dysregulated cell viability, migration, and invasion. PTBP1 silencing repressed epithelial-mesenchymal transition (EMT) by upregulating epithelial cadherin (E-cadherin) and downregulating neural cadherin (N-cadherin), Vimentin, and Snail. However, these effects were reversed by the overexpression of HOXA9. PTBP1–HOXA9 interaction upregulated HOXA9 expression. Furthermore, HOXA9 overexpression reduced apoptosis and enhanced viability, migration, invasion, and EMT in PC cells. However, these effects were counteracted by the knockdown of PTBP1.

Conclusions: PTBP1 drives EMT and promotes PC cell survival, migration, and invasion through interacting and upregulating HOXA9 expression.

Background: Immunogenic cell death (ICD) has emerged as a key factor in cancer prognosis; however, its application in prognostic modeling for acute myeloid leukemia (AML) remains unexplored. Therefore, this study aimed to develop a prognostic model for AML based on ICD-related genes.

Methods: ICD-related genes exhibiting differential expression in AML were identified from The Cancer Genome Atlas (TCGA) database. Initially, candidate genes were filtered using univariate cox proportional hazards model (Cox) and least absolute shrinkage and selection operator (LASSO) Cox regression analyses before being incorporated into a prognostic model. An ICD-related gene signature was then established via the survival package. Furthermore, immune cell infiltration was evaluated using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE), immunedeconv, and ggstatsplot.

Results: Of the total 34 ICD-related genes, 27 demonstrated differential expression, with five genes correlating with AML prognosis. By LASSO regression, we identified four ICD-related genes, including cluster of differentiation 4 (CD4), interleukin-10 (IL10), caspase-1 (CASP1), and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). Increased risk scores in our model were indicative of a poorer prognosis in AML patients (p < 0.001). Time-dependent Receiver Operating Characteristic (ROC) analysis demonstrated strong predictive capability, with overall survival rates of 0.709, 0.650, and 0.768 at 1, 3, and 5 years, respectively. Nomogram calibration curves confirmed its predictive accuracy. Furthermore, risk scores were substantially correlated with immune cell infiltration (p < 0.05). Moreover, suppression of CASP1 expression significantly diminished AML cell proliferation and increased their sensitivity to chemotherapeutic agents in vitro (p < 0.01).

Conclusion: This study developed a prognostic model for AML using four ICD-related genes (CD4, IL10, CASP1, and PIK3CA). This model demonstrates good predictive accuracy and shows close association with immune infiltration, consistent with functional verification results in vitro, underscoring its potential utility in prognosis assessment and therapeutic decision-making.

Background: Immunoglobulin G4-related disease (IgG4-RD) is a multisystem immune disorder characterized by fibroinflammatory lesions involving multiple organs. B cells play a pivotal role in IgG4-RD pathogenesis, and autophagy substantially influences their functional capacity. This study aimed to evaluate the role of B-cell autophagy in IgG4-RD.

Methods: Single-cell sequencing data were analyzed. Autophagy was assessed by flow cytometry with CYTO-ID® Autophagy Detection Kit 2.0 (CytoID) and by measuring autophagy-related proteins in peripheral blood mononuclear cell (PBMC) B cells from IgG4-RD patients and healthy controls (HCs) via polymerase chain reaction (PCR) and western blotting. Autophagy in B cells from IgG4-RD patients and HCs was inhibited, and B-cell activity was evaluated using Enzyme-linked immunoassay (ELISA) and flow cytometry.

Results: Altered autophagy levels and extracellular signal-regulated kinase (ERK) pathway activity were observed in total B cells, as well as in naïve B cells and plasmablasts. Autophagy in B cells was enhanced, as indicated by greater autophagosome formation and higher levels of autophagy-related proteins (p < 0.05). ERK phosphorylation was markedly reduced in IgG4-RD compared to HCs (p < 0.05). Following autophagy inhibition, B-cell metabolism, proliferation, antibody production, and cytokine secretion were significantly decreased in IgG4-RD (p < 0.05). Cell differentiation was similarly affected, with reduced memory B-cell and plasma cell proportions but elevated regulatory B-cell proportions (p < 0.05), whereas the reduction of memory B cells in HCs was not significant.

Conclusion: IgG4-RD patients exhibited defective B-cell autophagy and elevated autophagy levels associated with multiple serological and hematological markers, alongside impaired autophagy flux. Significantly reduced ERK1/2 phosphorylation was uniquely observed among signaling pathways, suggesting potential autophagy-apoptosis interactions. Upon autophagy inhibition, B cells exhibited a broad functional decline and anti-inflammatory features, highlighting an autophagy-B-cell activity relationship that may be valuable for disease monitoring.

Background: Intestinal ischemia-reperfusion injury (IRI) is a severe complication of major surgeries and shock, leading to intestinal barrier dysfunction and systemic inflammation. Treatment options remain limited due to poorly defined mechanisms. Galectin-3, a β-galactoside-binding lectin that regulates inflammatory processes, has emerged as a potential modulator of tissue injury. This study aimed to investigate the role of Galectin-3 in IRI, focusing on janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) regulation to identify potential therapeutic targets.

Methods: After establishing a murine intestinal IRI model, mice were treated with varying doses of G3-C12, a Galectin-3 inhibitor. Intestinal injury, inflammation, tight junction protein (TJP) expression, apoptosis, and JAK2/STAT3 pathway activation were assessed using hematoxylin-eosin (H&E) staining, quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, and caspase activity assays. Additionally, the Caco-2 oxygen-glucose deprivation/reoxygenation (OGD/R) model was employed to validate the mechanism of Galectin-3, with pathway dependency evaluated using the JAK2 agonist C-A1.

Results: IRI induced significant intestinal structural disruption, increased pro-inflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α], p < 0.001), reduced anti-inflammatory interleukin-10 (IL-10) (p < 0.001), downregulated TJPs (p < 0.001), and elevated apoptosis (p < 0.001) in mice. These alterations coincided with upregulation of Galectin-3, phosphorylated JAK2 (p-JAK2), and phosphorylated STAT3 (p-STAT3) (p < 0.001). G3-C12 treatment markedly alleviated histopathological injury, reduced inflammation and apoptosis, dose-dependently restored TJP expression, and suppressed JAK2/STAT3 pathway activation (p < 0.01 or p < 0.001). In vitro OGD/R assays further demonstrated that G3-C12 improved cell viability, reduced lactate dehydrogenase (LDH) release, attenuated inflammation and apoptosis, and restored TJP levels, effects that were partially reversed by JAK2 activation with C-A1.

Conclusion: Galectin-3 is upregulated during IRI and promotes JAK2/STAT3 pathway activation, exacerbating inflammation and intestinal barrier dysfunction. Inhibition of Galectin-3 suppresses this aberrant signaling, mitigates intestinal injury, reduces apoptosis and inflammation, and restores TJPs expression and mucosal barrier integrity. These findings suggest Galectin-3 as a promising therapeutic target for IRI.

Background: Fracture healing involves complex cellular and molecular interactions. While osteoprotegerin (OPG) facilitates bone repair by inhibiting osteoclast activity, its role in chondrocyte differentiation and cartilage formation remains unclear. This study examined the effects of OPG on bone and cartilage during fracture repair.

Methods: A murine femoral fracture model was established and treated with subcutaneous injections of OPG recombinant protein or OPG-neutralizing antibodies. Bone healing was assessed by micro-computed tomography (Micro-CT) and Safranin O staining to evaluate callus size and cartilage formation. Immunohistochemistry detected Ace-tubulin, γ-tubulin, Ki-67, and Collagen II expression. qRT-PCR assessed chondrogenic markers, including SRY-box transcription factor 9 (Sox9), Collagen II, Aggrecan, and Collagen X. OPG shRNA was transfected into chondrocytes to evaluate cell viability (CCK-8 assay), Ace-tubulin and γ-tubulin expression (immunofluorescence), and acidic mucopolysaccharides (Alcian blue staining). Western blot was performed to examine the effect of OPG on the Transforming Growth Factor-β (TGF-β) pathway.

Results: OPG expression was significantly elevated during fracture healing (p < 0.05). Administration of recombinant OPG increased fracture callus size and improved bone parameters, including bone volume/total volume (BV/TV) ratio, trabecular number (Tb.N), and trabecular thickness (Tb.Th), while reducing trabecular separation (Tb.Sp) (p < 0.05). Conversely, OPG blockade produced opposite effects (p < 0.05). OPG treatment also upregulated Ace-tubulin, γ-tubulin, Ki-67, Sox9, Collagen II, Aggrecan, and Collagen X (p < 0.05), whereas anti-OPG reduced their expression (p < 0.05). In vitro, OPG knockdown reduced chondrocyte viability, diminished Ace-tubulin and γ-tubulin expression, reduced acidic mucopolysaccharide accumulation, and downregulated chondrogenic markers (p < 0.05). Furthermore, OPG silencing suppressed TGF-β signaling by lowering TGF-β1, TGF-βRI, and Smad2/3 phosphorylation (p < 0.05).

Conclusions: OPG promotes chondrocyte differentiation and bone formation by regulating TGF-β signaling, highlighting its potential as a therapeutic target for enhancing fracture healing.

Background: Thyroid eye disease (TED) is a common autoimmune inflammatory disease that significantly impairs quality of life. Mitochondrial metabolism is a key driver for the pathogenesis of inflammatory diseases, yet its role in TED remains poorly understood. Our study aimed to investigate the mechanisms by which mitochondrial metabolism contributes to TED and identify potential treatment targets using a multi-methodological approach.

Methods: We performed a series of bioinformatics analyses, including the identification of differentially expressed genes (DEGs), Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis, immune infiltration assessments, genome-wide association studies (GWAS), and machine learning.

Results: By integrating the datasets GSE58331, GSE105149, and GSE185952, we ultimately screened 14 mitochondria-related (DEGs) from TED samples and applied machine learning to select diagnostic markers. 3 disease-associated diagnostic biomarkers (Ifi27, Cyba, and Cmpk2) were identified. Immune cell infiltration analysis revealed 4 immune cell types significantly associated with TED: follicular helper T (Tfh) cells, monocytes, M1 macrophages, and neutrophils. Multiple specific correlations were observed between these immune cells and the diagnostic biomarkers.

Conclusion: We identified a unique mitochondrial-related genetic signature essential for TED progression, which provides valuable insights into immune infiltration. These findings may advance molecular research on TED and offer novel strategies and therapeutic approaches for this condition.

Background: Circular stapling is the most commonly used anastomosis method after esophagectomy. However, it is unclear to what extent the diameter of the stapler affects the occurrence of postoperative anastomotic leakage, given the elasticity of gastrointestinal tissues that can adapt to a range of stapler sizes. This study aimed to observe and evaluate the possible effects of various diameters of circular staplers on anastomotic efficacy in gastroesophageal anastomoses of the same diameter.

Methods: Four circular staplers with different diameters from the same series were used to investigate the anastomotic effect on eight groups of fresh porcine esophagogastric tissues, with 32 anastomoses being tested. Anastomotic seepage was inspected using normal saline diluted with methylene blue.

Results: No stapling failure was observed in any of the 32 anastomoses; however, two anastomoses in the 21 mm stapler group showed deviation in staple line approximation and mild fluid leakage. This issue was corrected by intensive tissue trimming at the root of the stapler's base.

Conclusion: A smaller circular stapler may cause poor anastomotic alignment and seepage of the digestive juices due to the thicker esophageal tissue remaining at the base of the stapler. It is recommended that the internal diameter of the esophagus be tested in clinical practice using a valve-size tester, similar to that used in valve surgery, to select a larger circular stapler whenever possible.

Background: Intracerebral hemorrhage (ICH) is a subtype of stroke causing severe neuronal injury and functional deficits. This study aims to investigate the impact of bromodomain-containing protein 4 (BRD4) on ICH progression and the therapeutic efficacy of the bromodomain and extraterminal (BET) inhibitor JQ1.

Methods: An ICH rat model was established by injecting autologous blood into the basal ganglia. During treatment, the rats received either JQ1 (50 mg/kg) or vehicle. Neurological and motor outcomes were measured via the foot-fault test, modified neurological severity score, and rotarod performance test. Cognitive function of the experimental rats was tested with the Morris water maze. Brain edema of the animals was evaluated using the wet–dry weight method, coupled with some histopathologic assessments by hematoxylin–eosin (H&E) staining, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assays were employed to analyze neuronal apoptosis. Expression of proteins related to apoptosis, autophagy, and the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) pathway were evaluated using Western blotting.

Results: BRD4 expression was notably increased in the cerebral tissue of ICH rats (p < 0.01), while the administration of JQ1 decreased the levels of BRD4 in rats with ICH (p < 0.01). The administration of JQ1 resulted in a reduction in the modified neurological severity score of ICH, a decrease in the misstep frequency of the left forelimb, and a longer time to slip (p < 0.01). Furthermore, relative to the ICH group, rats in the ICH + JQ1 group exhibited a reduction in escape latency, as well as increased platform crossings and longer durations in the target area (p < 0.05). Also, JQ1 reduced the water content, tissue damage, and apoptosis levels in the cerebral tissue affected by ICH (p < 0.01). The JQ1-induced reduction in BRD4 expression inhibited apoptosis-linked protein expression and promoted autophagy-associated protein expression (p < 0.01). Furthermore, JQ1 treatment elevated the p-AMPK/AMPK ratio and suppressed p-mTOR/mTOR levels (p < 0.01).

Conclusion: JQ1 holds the promise in alleviating ICH-induced brain injury by inhibiting BRD4 and modulating the AMPK/mTOR pathway.

Background: Cytoskeleton-associated protein 2-like (CKAP2L) has been implicated in various malignancies, including ovarian cancer. However, its role in modulating the immune microenvironment of ovarian cancer remains poorly understood. This study aimed to investigate the role of CKAP2L in regulating ovarian cancer cell proliferation, migration, and apoptosis.

Methods: The impact of CKAP2L knockdown on ovarian cancer cells and the immune microenvironment was examined. CKAP2L was silenced in ovarian cancer cell lines, and subsequent effects on proliferation, migration, and apoptosis were assessed. Macrophage polarization differentiated from peripheral blood mononuclear cells (PBMCs) co-cultured with ovarian cancer cells was evaluated. Expression of the adenosine A2A receptor (ADORA2A) in macrophages, and interleukin-1β (IL-1β), interleukin-10 (IL-10) and vascular endothelial growth factor (VEGF) levels in ovarian cancer cells, were analyzed using western blotting and cytokine antibody arrays.

Results: CKAP2L knockdown significantly reduced proliferation and migration of ovarian cancer cell, while promoting apoptosis (p < 0.01). Flow cytometry revealed that CKAP2L knockdown inhibited M2-type and promoted M1-type polarization of PBMC-derived macrophages induced by ovarian cancer cells (p < 0.001). Furthermore, CKAP2L knockdown reduced ADORA2A expression in macrophages, increased IL-1β secretion, and reduced IL-10, VEGF secretion by ovarian cancer cells (p < 0.01).

Conclusions: CKAP2L promotes ovarian cancer progression by enhancing proliferation and migration while suppressing apoptosis. It also regulates the immune microenvironment by influencing macrophage polarization and cytokine secretion. These findings highlight the pivotal role of CKAP2L in the pathogenesis of ovarian cancer and support its potential as a therapeutic target for regulating tumor growth and immune responses.

Background: Diffuse large B-cell lymphoma (DLBCL) is a type of highly heterogeneous malignancy. Histone deacetylase 1 (HDAC1) plays a key role in various malignancies, but its function remains elusive in DLBCL. This study aims to explore the pivotal role and the mechanism of HDAC1 in DLBCL.

Methods: HDAC1 expression was detected in DLBCL tissues and cells. The glycolytic activity was assessed using pyruvate, lactic acid and glucose consumption assay kits. Cell apoptosis and proliferative capacity were measured by flow cytometry, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and 5-Ethynyl-2′-deoxyuridine (EdU) assays. Western blotting was used to detect the expression of HDAC1, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and glycolysis-related proteins. The effects of HDAC1 on tumor growth in vivo were explored by establishing a xenotransplantation model. Expressions of HDAC1, Ki-67, and c-myc in mouse tumors were detected by means of immunohistochemistry.

Results: High levels of HDAC1 were found in DLBCL tissues and cells (p < 0.05). HDAC1 knockdown repressed cell proliferation, glycolysis, and PI3K/AKT/mTOR pathway in DLBCL cells (p < 0.05). Moreover, 740Y-P (PI3K/AKT/mTOR pathway activator) partly reversed the inhibition of HDAC1 knockdown on cell proliferation and glycolysis (p < 0.05). Importantly, tumor xenotransplantation models showed that HDAC1 knockdown inhibited tumor growth in vivo (p < 0.05).

Conclusions: HDAC1 facilitates the proliferation and glycolysis of DLBCL by mediating the PI3K/AKT/mTOR pathway, offering a therapeutic target for DLBCL.

Background: Ischemia-reperfusion (I/R) injury involves oxidative stress, inflammation, and mitochondrial dysfunction. Galectin-3 (Gal-3) plays a key regulatory role in these processes; however, its association with the Mitochondrial Transcription Factor A/Peroxisome Proliferator-Activated Receptor Beta (TFAM/PPARβ) signaling pathway remains unclear. Therefore, this study aims to investigate the role of Gal-3 in I/R injury, focusing on its impact on oxidative stress, inflammatory responses, and the TFAM/PPARβ signaling pathway. Furthermore, it explores the role of TFAM in Gal-3-mediated I/R injury.

Methods: A mouse I/R model was established, and recombinant Gal-3 protein or anti-Gal-3 antibody was injected to modulate Gal-3 expression. mRNA and protein levels of Gal-3 in mouse serum, as well as relevant oxidative stress and inflammation markers, were evaluated using quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR), Western blotting, and histological analysis. The human myocardial AC16 cell line was used to establish an in vitro I/R model, and Sh-Gal-3 or Gal-3 overexpression plasmids were transfected to regulate Gal-3 expression, further assessing the effects of Gal-3 on oxidative stress and inflammatory response. Additionally, Sh-Gal-3 and Sh-TFAM were co-transfected into the I/R in vitro cell model to explore the role of TFAM in Gal-3-mediated effects.

Results: In the in vivo I/R model, compared to the Sham group, Gal-3 mRNA and protein levels were significantly increased in the serum of I/R mice (p < 0.05). Recombinant Gal-3 protein treatment aggravated myocardial injury, as evidenced by increased levels of Creatine Kinase-MB (CK-MB), Creatine Kinase (CK), Left Ventricular End-Diastolic Diameter (LVEDD), and Left Ventricular End-Systolic Diameter (LVESD), with a substantial increase in cardiac pathological damage. In contrast, anti-Gal-3 antibody treatment significantly alleviated these adverse effects. Masson staining revealed a significant increase in myocardial fibrosis in the I/R group, and Gal-3 further exacerbated fibrosis, which was counteracted by anti-Gal-3 treatment. Furthermore, the levels of pro-inflammatory cytokines and oxidative stress markers were significantly elevated in the I/R group, with administration of Gal-3 recombinant protein further enhancing these changes, while anti-Gal-3 treatment reduced them. In the in vitro model, Gal-3 overexpression significantly increased the levels of inflammatory factors and reactive oxygen species (ROS), whereas Gal-3 knockdown reduced these levels. After co-transfection of Sh-Gal-3 and Sh-TFAM, compared to the Sh-Gal-3 group, there was a significant increase in ROS fluorescence intensity, Malondialdehyde (MDA) levels, and 5,5′,6,6′-Tetrachloro-1,1′,3,3′-tetraethyl-imidacarbocyanine iodide (JC-1) disaggregation levels, while Superoxide Dismutase (SOD) levels were significantly reduced (p < 0.05). Additionally, the levels of Interleukin-6 (IL-6), Interferon-gamma (IFN-γ), and Tumor Necrosis Factor-alpha (TNF-α) in the Sh-Gal-3+Sh-TFAM group were significantly higher than those in the Sh-Gal-3 group.

Conclusions: This study demonstrates that Gal-3 plays a crucial role in I/R injury, promoting oxidative stress, inflammation, and myocardial damage, by modulating the TFAM/PPARβ signaling pathway. Furthermore, TFAM plays a critical regulatory role in Gal-3-mediated oxidative stress and inflammation. These findings provide new insights into treating I/R injury, and targeting Gal-3 and TFAM may offer a potential therapeutic strategy for I/R-induced injury.

Background: Myocardial injury induced by ischemia-reperfusion (I/R) remains a major barrier to improved clinical outcomes and continues to compromise human health. Adenosine diphosphate-ribosylation factor GTPase-activating protein (ArfGAP) with homology 3 (SH3) domain, ankyrin repeat, and pleckstrin homology (PH) domain-containing protein 3 (ASAP3) is a key regulator involved in cytoskeletal remodeling, membrane dynamics, and signal transduction. Its potential role in the pathogenesis of myocardial I/R injury, however, remains unclear. This study aims to elucidate the function of ASAP3 in myocardial I/R injury.

Methods: A hypoxia-reperfusion (H/R) injury model was established in H9c2 cells. The expression of ASAP3 and ras-related C3 botulinum toxin substrate 1 (RAC1) was modulated by transfection. Cell viability and apoptosis were subsequently assessed. Additionally, intracellular Ca²⁺ accumulation, mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential, and adenosine triphosphate (ATP) levels were evaluated. Endoplasmic reticulum (ER) stress and mitochondria-ER crosstalk were also investigated. Co-immunoprecipitation (Co-IP) experiments were conducted to verify the ASAP3-RAC1 interaction.

Results: ASAP3 expression was significantly downregulated following H/R injury (p < 0.01), concomitant with reduced cell viability and increased apoptosis in H9c2 cells (p < 0.01). Overexpression of ASAP3 significantly improved cell viability and decreased apoptosis under H/R conditions (p < 0.01). Furthermore, ASAP3 overexpression reduced intracellular Ca²⁺ accumulation (p < 0.01), preserved mitochondrial and ER function as evidenced by increased JC-1 and ATP levels, and reduced ROS production and ER stress markers (p < 0.01). Co-IP experiments confirmed a physical interaction between ASAP3 and RAC1, suggesting a possible direct regulatory mechanism. Notably, RAC1 overexpression abolished the protective effects of ASAP3 (p < 0.01), highlighting an antagonistic interplay between these proteins.

Conclusions: Overexpression of ASAP3 in cells subjected to H/R injury inhibits RAC1 activation and facilitates mitochondria-endoplasmic reticulum crosstalk, thereby alleviating cardiomyocyte injury.

Background: Sanguinarine, a benzophenanthridine alkaloid, is extracted from the rhizomes of Sanguinaria canadensis and other poppy species (Fumaria). Although its antitumor activity is not fully understood, sanguinarine has demonstrated various biological effects, including antioxidant, antimicrobial, and anti-inflammatory properties. This work hypothesizes that sanguinarine's novel anti-angiogenic mechanism may enhance the efficacy of anticancer therapy.

Methods: The Cell Counting Kit-8 (CCK-8) assay and colony formation assay were conducted to evaluate the effect of sanguinarine on angiogenesis. Preliminary mechanisms of sanguinarine were investigated through cell cycle and apoptosis assays. A tube formation assay was performed to examine the impact of sanguinarine on angiogenesis in vitro. RT-qPCR and western blot analyses were primarily used to elucidate the underlying mechanisms, which were further validated through a vascular endothelial growth factor (VEGF) recovery experiment. Additionally, an animal xenograft model was employed to assess the effect of sanguinarine on tumor growth and to analyze potential toxicity.

Results: Sanguinarine significantly inhibited the proliferation of rat smooth muscle cells (A7r5) and human microvascular endothelial cells (HMVECs) and increased the cell population in the G2/M phase (p < 0.05). Sanguinarine also reduced cell migration capacity and angiogenesis (p < 0.05). These effects were mediated by inhibiting the VEGF signaling pathway, as sanguinarine downregulated VEGF expression at both mRNA and protein levels, with partial recovery observed upon VEGF supplementation in the medium (p < 0.05). Additionally, sanguinarine exposure inhibited phosphorylation activity across multiple kinases downstream of VEGF (p < 0.05). In animal experiments, sanguinarine suppressed tumor growth without significant toxicity (p < 0.05).

Conclusion: Sanguinarine exerts an inhibitory effect on blood vessel cell proliferation, presenting a valuable therapeutic approach in cancer treatment.

Background: Investigations into identifying novel immunohistochemical indicators are on the rise, aiming to elucidate tumor characteristics better. Therefore, this study examined the expression and distribution characteristics of nestin within the pleomorphic adenoma (PA) stromal component, and explored the potential mechanism underlying its formation, providing a comprehensive understanding of nestin's role as an immunohistochemical indicator.

Methods: This retrospective study included 51 patients diagnosed with PA of the parotid glands. The expression levels in the stromal component were assessed in patients' tissue specimens using immunostaining. Combined with computed tomography (CT) image analysis, the chi-square test, paired-sample t-test, Pearson's correlation coefficient, and principal component analysis (PCA) were used to explore the potential relationship between nestin expression characteristics and tumor parameters.

Results: Nestin was diffusely expressed in PA sections. The cellular arrangement in stromal components resulting from pseudopod-like protrusions appeared in “loose” and “reticular” patterns. These patterns were visualized through immunohistochemical staining, and the images were semi-quantitatively analyzed using ImageJ software. The two cellular arrangements showed statistical differences in the histomorphology of the stromal component, particularly between the “mucus-rich” and “cell-rich” (p < 0.05). CT imaging combined with Principal Component Analysis (PCA) revealed that the key factors affecting these two histomorphology types of stromal components were tumor area and CT value.

Conclusions: The formation of stromal components in PA is associated with changes in pseudopod-like cellular protrusions under different microenvironments. The tumor microenvironment and adjacent host tissue likely play a role in the development of PA. Furthermore, the “mucus-rich” structure tends to be more frequent in larger tumors. Nestin expression may contribute to maintaining the benign nature of PA, despite the stromal component being invasive. These results highlight the potential of nestin as an immunohistochemical marker, strongly associated with the formation and structural organization of stromal components.

Background: Sepsis-associated acute kidney injury (SA-AKI) is a critical clinical complication with high mortality, involving ferroptosis and mitochondrial dysfunction, although the regulatory mechanisms remain incompletely defined. E3 ubiquitin ligases play key roles in post-translational regulation of cell death pathways, but their specific involvement in SA-AKI-associated ferroptosis is poorly understood. This study aimed to investigate the role and mechanism of the E3 ubiquitin ligase mind bomb 2 (MIB2) in SA-AKI, focusing on its regulation of ferroptosis and mitochondrial function via glutathione peroxidase 4 (GPX4).

Methods and Materials: An SA-AKI model was established by treating HK-2 cells with different concentrations of lipopolysaccharide (LPS). Cell viability was detected using the cell counting kit-8 (CCK-8) assay. The mRNA and protein expression levels of MIB2 and GPX4 were detected using reverse-transcription polymerase chain reaction (RT-qPCR) and Western blotting (WB). The interaction between MIB2 and GPX4 was verified by co-immunoprecipitation (Co-IP). An MIB2 knockdown model was constructed by means of sh-MIB2 transfection. The MIB2 knockdown model treated with ras-selective lethal small molecule 3 (RSL3), a GPX4 inhibitor, was subjected to the detection of reactive oxygen species (ROS), glutathione (GSH), Fe²⁺, and malondialdehyde (MDA) by means of flow cytometry and assay kits. To evaluate mitochondrial function, the mitochondrial morphology, membrane potential, and adenosine triphosphate (ATP) content were analyzed via transmission electron microscopy, JC-1 staining, and chemiluminescence.

Results: LPS reduced the viability of HK-2 cells in a manner dependent on both concentration and time, significantly increased the mRNA and protein levels of MIB2 (p < 0.001), and simultaneously decreased the mRNA and protein levels of GPX4 (p < 0.001). Co-IP confirmed a direct interaction between MIB2 and GPX4. Knocking down MIB2 could significantly reverse the down-regulation of GPX4 induced by LPS (p < 0.001), and reduced the levels of intracellular reactive oxygen species (ROS), Fe²⁺ and MDA, accompanied by glutathione (GSH) depletion and lipid ROS accumulation. MIB2 knockdown also improved mitochondrial morphological aberrations (increased proportion and length of intact cristae), increased mitochondrial membrane potential and ATP content, and enhanced cell viability (p < 0.001). Treatment with RSL3 could reverse the up-regulation effect of MIB2 knockdown on GPX4 and the protective effects on ferroptosis and mitochondrial function.

Conclusions: The E3 ubiquitin ligase MIB2 induces ferroptosis and mitochondrial dysfunction in HK-2 cells by binding to GPX4 and promoting its degradation, thus exacerbating SA-AKI. MIB2 knockdown can alleviate these pathological processes by stabilizing GPX4.

Background: Olfactory dysfunction (OD) is commonly associated with chronic rhinosinusitis (CRS), with T-helper 2 (Th2) cell polarization implicated in its pathogenesis. This study aimed to elucidate the role and underlying mechanism of the Th2-derived cytokine interleukin (IL)-4, acting via the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, in mediating olfactory epithelial injury during CRS-related OD.

Methods: The mechanism of Th2 cell dominance in CRS-associated OD through the IL-4/PI3K signaling pathway was investigated. A CRS model was established in age-matched senescence accelerated mouse resistant 1 (SAMR1) mice, with sneezing and scratching frequencies recorded. Flow cytometry quantified Th cell proportions and apoptosis, while quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blotting (WB) assessed IL-4/interleukin-4 receptor (IL-4R), IL-4/PI3K pathway components, inflammatory/apoptotic markers, and olfactory-associated proteins. Following transfection of IL-4R short hairpin RNA (shRNA) into olfactory epithelial cells (efficiency confirmed by RT-qPCR and WB), a Th2 cell-olfactory epithelial cell co-culture system was established.

Results: CRS mice exhibited decreased olfactory marker protein (OMP) expression, upregulated phosphorylated- nuclearfactor-kappaB p65 (p-p65), enhanced IL-4/PI3K pathway activity, and elevated inflammatory/apoptotic markers. Th2 co-culture reduced olfactory epithelial cell viability, increased apoptosis, activated IL-4/PI3K signaling and inflammatory/apoptotic responses, and suppressed OMP expression. Notably, IL-4R knockdown reversed these alterations.

Conclusions: CRS modeling and Th2 co-culture reduces OMP expression, activates the p-p65/IL-4/PI3K pathway, and exacerbates inflammation and apoptosis, whereas IL-4R knockdown effectively counteracts these alterations.

Background: Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionised the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL). Still, it can lead to severe immunosuppression and late-onset complications. We report a rare case of mucormycosis-related cavernous sinus orbital apex syndrome (CSOAS) in a patient with r/r DLBCL who developed prolonged pancytopenia after receiving anti-CD19 CAR-T therapy.

Case Presentation: A patient with r/r DLBCL received anti-CD19 CAR-T therapy and subsequently developed prolonged pancytopenia. The patient was initially treated with a combination of amphotericin B and isavuconazole, but amphotericin B was discontinued due to nephrotoxicity before reaching the target dose (30 mg/day). Surgical removal of the lesions and drainage of the sinuses was performed, and the patient continued on isavuconazole. Supportive treatments, including granulocyte colony-stimulating factor and eltrombopag, were administered.

Results: After surgery, the patient's fever and facial oedema resolved, and their vision improved. Blood cell counts normalised (white blood cell 4–11 × 10⁹/L) 1 week later.

Conclusion: This case represents one of the first reports of mucormycosis-associated CSOAS following CAR-T therapy successfully managed despite challenges with antifungal treatment. It underscores the importance of dynamic infection surveillance and multidisciplinary intervention in managing rare and life-threatening post-CAR-T complications.