Acral melanoma (AM), the predominant melanoma subtype in Asia, responds poorly to immune checkpoint inhibitors, representing a critical unmet medical need. The efficacy of tumor-infiltrating lymphocyte (TIL) therapy in this population is unknown. An Investigator-Initiated Trial evaluates autologous TIL therapy (LM-103) in four Chinese patients with advanced AM, achieving a 75% disease control rate (DCR) and a 25% objective response rate (ORR), including one durable complete response. To define the determinants of response, we performed integrated single-cell RNA and T-cell receptor sequencing on infused TIL products, tumors, and longitudinal peripheral blood. Responders' infused products were significantly enriched for T follicular helper (Tfh) and intermediate exhausted (TEX_int) CD8⁺ T cells, which mediated robust cell-cell signaling networks (e.g., CD40, FASLG). In contrast, the non-responder's product was dominated by terminally exhausted (TEX_term) cells. Clonal tracking revealed that these Tfh and TEX_int subsets possessed higher clonality, and in the complete responder, a dominant clone originating from the TEX_int population persisted systemically by differentiating into a progenitor-like (TEX_prog) state. These findings demonstrate that TIL therapy is clinically active in AM and that durable response is mechanistically linked to the infusion and persistence of Tfh and TEX_int subsets, defining a key cellular and clonal architecture for therapeutic success.

BACKGROUND:This study aimed to compare the real-world efficacy and safety of rituximab and inebilizumab in patients with aquaporin-4 immunoglobulin G (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (NMOSD). METHODS:This retrospective study included patients treated with rituximab or inebilizumab at two tertiary hospitals in China between January 2015 and June 2025. Propensity score matching was conducted to reduce between-group imbalance. The primary endpoint was time to first confirmed relapse. Secondary outcomes included changes in annualized relapse frequency, EDSS scores, and serum IgG and AQP4-IgG levels. Safety profiles were also assessed. RESULTS:A total of 276 patients were analyzed (rituximab: 211; inebilizumab: 65), yielding 61 well-balanced pairs after propensity score matching. In terms of efficacy, clinical outcomes and AQP4-IgG dynamics were comparable between groups in pre- and post-matching analyses, although inebilizumab exhibited a significantly greater reduction in serum IgG levels at 6 months. Safety profiles differed. Rituximab was associated with a higher incidence of overall adverse events, driven primarily by infusion-related reactions, whereas other adverse events remained comparable. CONCLUSIONS:In our real-world study of 276 patients, rituximab and inebilizumab demonstrated comparable efficacy in the medium term but differed in their safety profiles, with a significantly higher incidence of infusion-related reactions observed in the rituximab group.

Abstract Acral melanoma (AM), the predominant melanoma subtype in Asia, shows poor response to immune checkpoint inhibitors, underscoring the need for alternative immunotherapies. An investigator-initiated trial evaluates autologous tumor-infiltrating lymphocyte (TIL) therapy (LM-103) in four Chinese patients with advanced AM, achieving a 75% disease control rate and one durable complete response. To define determinants of therapeutic outcome, integrated single-cell RNA sequencing (scRNA-seq) and T-cell receptor sequencing (TCR-seq) are performed on infused TIL products, tumors, and longitudinal peripheral blood. Single-cell profiling reveals marked heterogeneity within the infused products, including naïve, regulatory, follicular helper (Tfh), cytotoxic, and multiple exhausted T-cell states. Responders demonstrate striking enrichment of Tfh and intermediate exhausted (TEX_int) CD8+ T cells, whereas the non-responder product is dominated by terminally exhausted subsets. Pseudotime analysis supports a conserved exhaustion continuum in which TEX_int cells occupy a plastic, functionally competent intermediate state.Cell-cell communication modeling shows that responder products contain a densely connected signaling ecosystem driven by Tfh- and TEX_int-mediated costimulatory pathways, such as CD40, CD70, and FASLG. In contrast, non-responder products exhibit sparse, immunosuppressive networks dominated by TGFβ and MIF signaling. TCR integration demonstrates higher clonality within Tfh and TEX_int subsets in responders.Longitudinal tracking reveals that the complete responder maintains stable high clonality after infusion. Notably, a dominant clonotype enriched in the TEX_int population of the infused product persists in peripheral blood and later adopts a progenitor-like exhausted (TEX_prog) state. This finding provides direct in vivo evidence that intermediate exhausted T cells can differentiate into a progenitor-like state after adoptive transfer, establishing a durable, self-renewing reservoir capable of sustaining long-term anti-tumor immunity.These results define the cellular and clonal architecture underlying successful TIL therapy in AM. Durable benefit is determined not by the size of the infused product but by the presence and persistence of coordinated Tfh-TEX_int ecosystems that seed long-lived progenitor-like immunity. These insights offer mechanistic biomarkers and provide a foundation for optimizing TIL manufacturing for melanoma subtypes refractory to current immunotherapies. Citation Format: Chao Zhang, Jilong Yang, Xiangchun Li, Kexin Chen, Hongru Shen. The cellular architecture of the infused T cell predicts efficacy of autologous tumor-infiltrating lymphocyte therapy (LM-103) in acral melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4007.

Introduction. Cell morphology has been a crucial area of study since the invention of the microscope, evolving significantly with the advancement of ultramicroscopic techniques. This study analyzes the top 100 most cited publications on cell morphology to uncover key research trends and influential works from the past three decades. Materials and Methods. A bibliometric analysis was conducted using the Web of Science Core Collection database, covering articles published from January 1985 to April 2023. From an initial pool of 1,251,024 articles, the top 100 most cited publications were identified. Data on publication year, citation counts, journals, authors, geographical distribution, institutions, and keywords were extracted. VOSviewer and Bibliometrix were used for statistical analysis. Results. The top 100 articles were published in 43 journals, including high-impact publications such as Nature, Science, and Cell. The most cited article, "Matrix Elasticity Directs Stem Cell Lineage Specification," had 9,832 citations. The United States contributed 70 articles. Key research themes identified included the mechanical microenvironment, stem cell research, and advanced imaging techniques. Conclusion. This study highlights the importance of the extracellular matrix and signaling pathways in determining cell morphology. It underscores the predominant role of high-impact journals and emphasizes the need for multidisciplinary approaches in future research on cell morphology.

ObjectiveThe management of generalized myasthenia gravis (gMG) poses a therapeutic challenge. Efgartigimod, a neonatal Fc receptor (FcRn) inhibitor, has significant efficacy in patients with positive acetylcholine receptor (AChR) antibodies. However, approximately 30% of patients exhibit a poor early response. This study aimed to explore whether the complement C5 inhibitor, eculizumab, can bring clinical benefits to patients who have a poor early response to efgartigimod, thereby investigating potential sequential treatment strategies.MethodsWe first conducted a prospective study to rigorously evaluate and longitudinally follow up 103 patients with gMG who received one treatment cycle of efgartigimod, ultimately enrolling 18 patients who demonstrated an inadequate response to the therapy. Then, these patients received eculizumab induction (900 mg weekly for four weeks) followed by maintenance dosing (1200 mg every two weeks or extended to once every three weeks). Clinical outcomes were assessed using MG-specific activities of daily living (MG-ADL) and quantitative myasthenia gravis (QMG) scores. Safety was evaluated through adverse event reporting.ResultsSignificant clinical improvements were observed during the induction phase, with mean MG-ADL scores demonstrating a reduction from 7.9 ± 3.9 before eculizumab to 2.6 ± 1.7 [-5.3 (95% CI: -7.6 to -3.0); P < 0.001], while QMG scores dropped from 14.1 ± 6.6 to 6.5 ± 3.2 [-7.4 (95% CI: -10.2 to -4.7); P < 0.001]. All patients achieved clinically meaningful improvement (≥2-point MG-ADL reduction), with four patients reaching minimal symptom expression (MSE, defined as an MG-ADL score ≤1-point) by week 4. Among the 12 patients who completed the 16-week follow-up, seven patients (58.3%) achieved minimal symptom expression. Glucocorticoid doses were successfully reduced to ≤5mg per day in seven patients. Two mild adverse events (urinary tract infection and limb edema) were reported.ConclusionEculizumab exhibited rapid and significant efficacy in patients with gMG who were poor early response to efgartigimod, and exhibited a favorable safety profile. These findings suggest that complement inhibition may serve as a potential sequential therapy when FcRn antagonist modulation failure.

IntroductionB001 is a recombinant humanized anti-CD20 monoclonal antibody targeting CD20+ B cells, that has demonstrated superior B cell depletion and anti-proliferative and cytotoxic effects compared to rituximab in a pre-clinical study. The present phase 1b trial assessed the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy of B001 in aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (NMOSD).MethodsThis phase 1b randomized, double-blind, placebo-controlled trial screened 25 NMOSD patients (April 2022–June 2024). Twenty-two patients received intravenous B001 (350, 700 or 1,000 mg) or placebo via a 3 + 3 dose escalation design, randomized 3:1 to active drug or placebo on days 1 and 15. The primary endpoints were the occurrence of dose-limiting toxicity (DLT) and to recommend the dosage for the phase 2 trial.ResultsAmong 22 randomized patients (350 mg: n = 3; 700 mg: n = 8; 1,000 mg: n = 6; placebo: n = 5), 20 (90.9%) completed the study. No DLT occurred in evaluable patients. Treatment-related adverse events (TRAEs) occurred in 7/21 (33.3%) patients, including urinary tract infection (14.3%), infusion-related reactions (9.5%), abnormal blood routine tests (9.5%) and hyperlipidemia (4.8%). No TRAEs led to discontinuation, dose reduction or death. Pharmacokinetic analysis revealed that supra-proportional exposure increased at 1,000 mg vs. 700 mg. Pharmacodynamics showed sustained B cell depletion (nearly 0/μL) for 24 weeks. No NMOSD relapses occurred during the 24-week study.ConclusionB001 demonstrated favorable safety and tolerability, with 700 mg selected as the recommended phase 2 dose.Clinical Trial Registrationhttps://clinicaltrials.gov/study/NCT05145361, identifier NCT05145361.

Tumor-infiltrating lymphocytes (TIL) therapy has demonstrated clinical potential in malignancies. However, limited understanding of why only a subset of patients respond to TIL therapy, coupled with the lack of simple and efficient methods to genetically engineer fragile TIL, has hindered efforts to enhance TIL efficacy through genetic modification. A T-Editor platform enabling rapid and efficient CRISPR-mediated gene editing in TIL was developed and optimized. To minimize the risk of chromosomal translocations associated with Cas9-induced double-strand breaks (DSBs), single-guide RNAs (sgRNAs) were designed for cytosine base editing (CBE). The expansion capacity, phenotypic profile, cytokine production, and in vitro cytolytic activity of base-edited TIL were compared with those of Cas9-KO TIL. In vivo efficacy was assessed using patient-derived xenograft (PDX) mouse models. The T-Editor platform was optimized for TIL gene editing by refining stimulation conditions, electroporation parameters, and CRISPR/Cas9 reagent dosing. FAM84B emerged as the top candidate, with its knockout resulting in the most pronounced enhancement of TIL cytolytic activity. CBE-mediated C·G-to-T·A conversion in the FAM84B exon achieved high editing efficiency with minimal insertion-deletion (indel) events. Base-edited TIL exhibited comparable expansion, phenotype, cytokine production, and in vitro cytolytic activity relative to Cas9-KO TIL. Compared with non-engineered control TIL, FAM84B-edited TIL displayed an increased CD62L+ memory subset, enhanced effector function and cytolytic activity, and improved in vivo antitumor efficacy. In conclusion, the T-Editor platform enables rapid and efficient CRISPR-mediated gene editing for engineering TIL to enhance its therapeutic potency. FAM84B may represent a novel potential target for improving TIL-mediated antitumor activity.

OBJECTIVE:The objective of this study was to compare clinical features and prognosis of late-onset neuromyelitis optica spectrum disorder (LO-NMOSD, onset age ≥60 years) with adult-onset NMOSD (AO-NMOSD, onset age 18-59 years), and to provide insights for individualized management in elderly patients. METHODS:Data from 748 patients with NMOSD (diagnosed according to the 2015 International Panel for NMO Diagnosis criteria) in the China National Registry of Neuro-Inflammatory Diseases (CNRID) were analyzed. Patients were stratified into AO-NMOSD (18-59 years, n = 617) and LO-NMOSD (≥ 60 years, n = 131). Demographics, clinical manifestations, imaging, treatments, and outcomes were compared using appropriate statistical methods including Kaplan-Meier survival curves and Cox proportional hazards regression. RESULTS:LO-NMOSD showed distinct traits: a lower female predominance (76.34% vs 86.55%), higher transverse myelitis (TM) incidence at onset (57.36% vs 40.17%), elevated annualized relapse rate (ARR; 0.52 ± 0.03 vs 0.38 ± 0.01), and accelerated disability (median Expanded Disability Status Scale [EDSS] 4.75 vs 3.0). TM-predominant relapses (39 of 45, 86.67% in LO vs 96 of 148, 64.86% in AO) contributed significantly to disability. Kaplan-Meier analysis showed LO-NMOSD had a higher risk of relapse (hazard ratio [HR] = 1.932, 95% confidence interval [CI] = 1.427-2.615), disability (HR = 3.192, 95% CI = 1.932-5.274) and reaching visual acuity (VA) ≤20 of 30 (HR = 3.523, 95% CI = 1.585-7.828). Cox regression confirmed that onset age ≥60 years was an independent risk factor for relapse (HR = 2.05, 95% CI = 1.60-2.59), disability (HR = 3.16, 95% CI = 2.14-4.62), and reaching VA ≤20 of 30 (HR 3.26, 95% CI = 1.83-5.48). INTERPRETATION:LO-NMOSD is characterized by myelitis-predominance with recurrent spinal cord involvement, high risk of relapses, and severe disability. It thus underscores the need for heightened clinical attention, with rigorous monitoring that balance safety and efficacy for elderly patients with NMOSD. ANN NEUROL 2026;99:1139-1151.

Abstract Giant cell tumor of bone (GCTB) is a locally aggressive osteolytic neoplasm characterized by neoplastic stromal cells and abundant osteoclast-like giant cells, yet the microenvironmental architecture and regulatory networks that sustain tumor progression remain incompletely understood. Here, we performed integrated single-cell RNA sequencing and spatial transcriptomics on six treatment-naïve primary GCTB specimens to generate a high-resolution atlas of stromal, immune, myeloid, osteoclastic and vascular compartments. We identify a structured mesenchymal hierarchy linking pericytes, osteoblast precursors and tumor stromal cells through a continuous transcriptional trajectory, providing evidence that the neoplastic stromal population arises from, or co-evolves with, osteogenic and perivascular lineages. Tumor cells display marked inter- and intra-patient heterogeneity, characterized by discrete EMT-, coagulation-, myogenesis- and androgen-responsive subclusters, indicating diverse functional specializations within the stromal tumor compartment.Despite substantial cytotoxic T-cell infiltration across all patients, ligand-receptor inference revealed that effector immune signals—including CCL and PARs pathways—are preferentially directed toward osteoclast-like giant cells rather than tumor cells, suggesting an “immune diversion” or “immune sink” mechanism that may blunt anti-tumor immunity despite preserved T-cell functional states. Beyond confirming the canonical tumor-derived RANKL engagement of giant cells, we uncover two additional regulatory circuits: (i) a tumor-specific CHAD-ITGA2 signaling axis, with ITGA2 expression uniquely restricted to giant cells, implicating a selective osteoclastogenic mechanism with therapeutic potential; and (ii) a multisource CSF1/IL34-CSF1R network arising from tumor cells, osteoblast precursors and pericytes, cooperatively shaping myeloid recruitment and giant-cell formation, further supporting a shared stromal origin among these lineages.Finally, we identify a tumor-exclusive APELA-APLNR (APJ) angiogenic axis linking ligand production strictly in tumor cells to receptor expression exclusively in endothelial cells. Spatial transcriptomics confirmed that APELA is enriched within RANKL-high tumor niches, revealing a spatially confined angiogenic microdomain functionally distinct from the broadly distributed VEGF pathway.Together, this atlas defines the cellular logic and intercellular circuitry underlying GCTB progression and identifies multiple stromal, immune, osteoclastogenic and vascular vulnerabilities—including the CHAD-ITGA2 and APELA-APLNR axes—that may guide therapeutic strategies beyond RANKL inhibition. Citation Format: Chao Zhang, Jilong Yang, Xiangchun Li, Kexin Chen, Hongru Shen, Zhichao Liao. Microenvironmental rewiring in giant cell tumor of bone: Stromal lineage hierarchy, immune diversion, and novel osteoclastogenic and angiogenic circuits [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2263.

INTRODUCTION:Osteosarcoma is a highly aggressive cancer with a notably low five-year survival rate. Although aspirin has demonstrated potential in inhibiting the malignant progression of osteosarcoma, the underlying mechanisms remain unclear. METHODS:In this study, RNA sequencing (RNA-seq) was employed to identify the downstream targets of aspirin in osteosarcoma cells. Then, we examined the expression and clinical significance of PDE4D using osteosarcoma patient samples, tissue microarrays, and data from the TARGET and GTEx databases. The effects of PDE4D on cell growth and mobility were assessed by CCK-8, colony formation, transwell, and wound-healing assays. To explore how aspirin influenced the NF-κB/p65/PDE4D axis, we performed qRT-PCR, Western blotting, luciferase reporter assays, etc. Additionally, mouse models with subcutaneous tumors were used to confirm the roles of aspirin and PDE4D. RESULTS:Our results showed that aspirin significantly impeded the proliferation, migration, and invasion of osteosarcoma cells by various functional assays. RNA-seq identified PDE4D as a key target modulated by aspirin treatment in osteosarcoma. Clinically, PDE4D was highly expressed in osteosarcoma cells and tissues, and higher levels of PDE4D were linked to poorer patient outcomes. Functionally, PDE4D served as an oncogene that promoted the malignant traits of osteosarcoma both in vitro and in vivo. Mechanistically, our findings revealed that NF-κB/p65 directly interacted with the core region of the PDE4D promoter, increasing its expression. DISCUSSION:The findings of this study reveal a novel mechanism whereby aspirin exerts its anti-tumor effects by inhibiting the NF-κB/p65/PDE4D axis, providing a mechanistic basis for its therapeutic potential. Further validation in different animal models of osteosarcoma is warranted. CONCLUSION:Aspirin suppressed the malignant progression of osteosarcoma by targeting the NF-κB/p65/PDE4D axis, positioning PDE4D as a potential therapeutic target for aspirin- based treatment strategies.

Abstract Background: The human microbiome shapes cancer risk, progression and response to immunotherapy, but most existing microbiome models are task-specific and fail to generalize across cohorts and sequencing platforms. We developed MiFM (Microbiome Foundation Model), a self-supervised Transformer trained on ∼2 million human, animal and environmental microbiome profiles. MiFM encodes communities as multi-level tokens (species, genus and functional pathways) and uses masked reconstruction plus contrastive learning to obtain transferable embeddings that capture taxonomic and functional structure. Here, we evaluated whether MiFM embeddings can support continuous, clinically interpretable readouts of cancer trajectories and immunotherapy response. Methods: From MiFM embeddings we derived two continuous metrics: (1) a disease pseudotime placing each patient along a microbiome-encoded cancer progression trajectory; and (2) a microbiome cancer risk clock estimating microbiome-derived cancer risk and immunotherapy non-response at the individual level. We applied this framework to colorectal cancer (CRC) cohorts spanning normal mucosa, adenoma and carcinoma, and to 12 independent pan-cancer immune checkpoint blockade cohorts (n =1237). We additionally defined a microbiome-based aging acceleration signature and evaluated its association with disease pseudotime, the risk clock and overall survival. Results: In CRC, disease pseudotime recapitulated the adenoma-carcinoma sequence, with median values of 0.15 (normal), 0.38 (adenoma) and 0.72 (carcinoma; p < 0.001), and separated disease states more clearly than conventional stage. The risk clock identified high-risk individuals within histologically normal mucosa whose microbiome embeddings resembled adenomas (AUC = 0.85) or carcinomas (AUC = 0.92), indicating a preclinical window for intervention. Across 15 CRC cohorts (n = 3739), baseline gut microbiome embeddings identified non-responders to immune checkpoint blockade with a median cross-cohort AUC of 0.84 and an AUC of 0.95 in a non-small cell lung cancer cohort. The aging acceleration signature correlated with both disease pseudotime and the risk clock and independently predicted overall survival (HR = 2.52, p < 0.001). Conclusions: To our knowledge, MiFM is the first large-scale microbiome foundation model applied to oncology, yielding continuous microbiome-derived readouts of cancer progression and immunotherapy response. The disease pseudotime and microbiome cancer risk clock capture cancer trajectories beyond conventional staging, enable ultra-early identification of high-risk lesions in normal-appearing mucosa and support robust prediction of immunotherapy resistance across cohorts. This framework delivers concrete microbiome biomarkers and a scalable platform for microbiome-guided precision oncology. Citation Format: Hongru Shen, Yajing Bi, Yan Zong, Zhangyan Lyu, Chao Zhang, Kexin Chen, Xiangchun Li, . Microbiome foundation modeling of cancer: MiFM-derived continuous trajectories and risk clocks for pan-cancer immunotherapy response prediction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2765.

This study aims to investigate the incidence of and factors associated with bone metastasis (BM) in patients with lung cancer and provide guidance for the screening of BM in patients with lung cancer. Lung cancer patients who were treated at the Tianjin Medical University Cancer Institute and Hospital between 2009 and 2018 were retrospectively reviewed. Patients with synchronous BM were obtained to investigate the risk factors for BM development. Both demographic and clinical characteristics were included. Univariate and multivariate logistic regression analyses were performed to identify risk factors. A further scoring system was established to classify patients into 3 different risk groups. Five significant risk factors were identified, namely, male sex, Karnofsky score of 50 to 70, multiple primary lesions, lymph node metastasis, and adenocarcinoma. The total score was generated by the integration of the score based on each individual factor. The incidence of BM among patients with lung cancer with a total score >= 7 was 46.73%, the incidence among patients with a total score <= 4 was 16.59%, and the incidence of BM in patients with total scores between 5 and 6 was 34.23%. This scoring system can predict the risk of BM in patients with lung cancer and can guide the performance of BM screening.

Meningeal lymphatic vessels (mLVs) are critical for central nervous system waste clearance and immunomodulation， implicated in multiple sclerosis pathogenesis. Although ofatumumab is effective in treating relapsing-remitting MS (RRMS), its effects on mLVs function remain unclear. This study aimed to investigate its impact on mLVs drainage in RRMS patients. Fifteen RRMS patients were enrolled in this prospective cohort study with ofatumumab, and nine healthy controls were recruited. Drainage function of mLVs was quantified via dynamic contrast-enhanced magnetic resonance imaging at baseline, month 6 and month 12. Correlations between changes in drainage function and immune cell subsets were analyzed. Following ofatumumab treatment, significant reductions were observed in mean time-to-peak (0.75 to 0.52, p = 0.007) and area under the curve (AUC, 30.70 to 12.67, p = 0.001) within mLVs. Baseline mLVs parameters did not differ between RRMS patients and healthy controls. Change of AUC (ΔAUC) was positively associated with regulatory T cell frequency (ΔTreg, r = 0.539, p = 0.038) and negatively associated with central memory CD4+ T cells (ΔTCM, r = -0.535, p = 0.040). Symbol Digit Modalities Test scores were negatively associated with TTP at baseline (r = -0.535, p = 0.040), whereas no correlations were observed between changes in mLVs parameters and clinical outcomes (all p > 0.05). Ofatumumab improved mLVs drainage in RRMS and was associated with a shift toward regulatory T cell phenotype. These findings suggest that modulation of meningeal lymphatics may contribute to the immunomodulatory effects of anti-CD20 therapy.

Depression after a stroke is the most frequent and burdensome neuropsychiatric post-stroke complication. This study aimed to determine the relationship between post-stroke depression (PSD) and the levels of homocysteine (HCY) in patients with spontaneous intracerebral hemorrhage (SICH). We collected data from patients with hemorrhagic stroke (HS) admitted to the hospital and recorded their demographic and clinical characteristics. We also searched for information regarding HAM-D17 (Hamilton Depression) scores and HCY levels at 3 m, the use of antidepressant medications and folic acid during the follow-up period in the group of patients diagnosed with PSD and hyperhomocysteinemia (HHcy) in the acute phase. A total of 1,852 patients were included. 642 (34.7

Abstract Background The role of extrachromosomal DNA (ecDNA)-related genes in osteosarcoma remains largely unexplored. The aim of this study is to investigate the association between ecDNA-related genes and prognosis and tumor microenvironment (TME) in osteosarcoma. Methods Differential gene expression analysis of GEO datasets was conducted to identify ecDNA-related genes in osteosarcoma. Based on bulk RNA-seq data, a novel ecDNA-related Gene Prognostic Score Model (EGPSM) was developed using an integrated framework of 101 machine learning algorithms, which was validated in training, testing, and external cohorts. The associations between risk scores, prognosis, and TME characteristics were comprehensively evaluated. Single-cell RNA sequencing (scRNA-seq) data were further analyzed to elucidate the relationship between EGPSM, pro-tumor behaviors, and immune modulation in osteosarcoma, as well as to identify key prognostic genes involved in tumor progression. Lastly, we conducted in vitro and in vivo assays to characterize the biological roles of MTDH and to elucidate its regulatory effects on CD8⁺ T cell function. Results A robust EGPSM was constructed, demonstrating superior predictive accuracy with a maximum C-index of 0.803. High-risk patients exhibited poorer survival, higher metastatic potential, and an "immune-cold" TME characterized by diminished CD8⁺ T/NK cell infiltration and impaired effector functions. Single-cell analysis confirmed the enrichment of malignant cells and depletion of T/NK populations with lower effector scores in the high-risk group. MTDH was identified as a key driver; functional assays showed it promotes proliferation and invasion while inhibiting apoptosis. Notably, MTDH knockdown potentiated CD8⁺ T-cell cytotoxicity by increasing the levels of granzyme B, IFN-γ, and perforin. Conclusion The newly developed EGPSM represents an effective tool for prognostic assessment and therapeutic stratification in osteosarcoma. MTDH may serve as a promising prognostic biomarker and therapeutic target.

IntroductionSoft tissue sarcomas (STS) are rare mesenchymal malignancies with limited treatment options in advanced stages. Anthracycline-based chemotherapy remains the standard of care but yields modest outcomes with significant toxicity, underscoring the need for more effective strategies.MethodsWe retrospectively analyzed 56 patients with advanced STS who received PD-1 inhibitor-based therapy at Tianjin Medical University Cancer Institute and Hospital between January 2021 and January 2026. Treatment regimens included immunotherapy alone or in combination with chemotherapy or targeted therapy. The observed primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). Survival outcomes were analyzed by Kaplan–Meier analysis; factors associated with prognosis were identified by a Cox proportional hazards regression model. Outcomes were compared with a historical cohort of 53 patients treated with chemotherapy alone.ResultsA total of 56 patients were included, and the median follow-up time in the immunotherapy cohort was 19.2 months (range, 1.32–52.8 months). Patients with UPS had a longer median PFS than those with non-UPS histology (P = 0.045). Patients receiving immunotherapy combined with chemotherapy had longer median PFS (P = 0.047) and median OS (P = 0.046) compared with those receiving immunotherapy without chemotherapy. Multivariable Cox regression identified UPS histology (P = 0.023) and immunotherapy combined with chemotherapy (P = 0.047) as factors associated with PFS in advanced STS. Compared with 53 patients who received chemotherapy alone, the immunotherapy-based comprehensive treatment group had longer median PFS in the overall population (P = 0.023); the pure chemoimmunotherapy group (n = 22) also showed longer PFS (P = 0.014). This association was also observed in the UPS subgroup (P = 0.006). Treatment-related adverse events were predominantly grade 1–2; no grade 4–5 severe adverse events or treatment-related deaths occurred.DiscussionImmunotherapy-based regimens, particularly chemoimmunotherapy, showed a suggested PFS benefit over conventional chemotherapy in advanced STS, with UPS showing a suggested association with disease control. The safety profile was acceptable. Nevertheless, the limitations inherent to the retrospective design, historical controls, modest sample size, and immature overall survival data warrant cautious interpretation.

Stochastic cortical self-reconstruction (SCSR) enables personalized mapping of gray matter atrophy, a hallmark of neurodegenerative disorders such as Alzheimer's disease (AD), onto high-resolution cortical surfaces. Unlike conventional normative modeling approaches, which typically operate at a coarse regional level and remain inherently constrained by the covariates included during training, SCSR estimates an individualized healthy reference directly from the observed cortical thickness at the vertex level. This allows the detection of subtle, subject-specific deviations from healthy cortical shape. In this work, we investigate the generalization and transferability of SCSR, originally trained on UK Biobank (UKB) data, to an independent Chinese population dataset. Specifically, we evaluate the ability of SCSR-derived Z-scores to discriminate between healthy scans, individuals with mild cognitive impairment (MCI), and patients with AD, while also assessing model robustness across the lifespan. We compare four training strategies: direct application of the UKB-trained model, fine-tuning on Chinese data, training from scratch, and joint training on UKB and Chinese cohorts. As reconstruction backbones, we consider both a multilayer perceptron (MLP) and a Spherical UNet (SUNet). Our results demonstrate that SCSR provides robust detection of cortical atrophy in the Chinese population across all evaluated models. The highest discriminative performance was achieved by the fine-tuned SUNet model (average pairwise AUC = 0.848), followed closely by the UKB-trained SUNet. Moreover, reconstruction errors remained low across the lifespan, even when the training population exhibited a substantially narrower age distribution, indicating strong cross-population transferability.

Purpose Unilateral biportal endoscopic (UBE) technique is increasingly utilized in spine surgery, offering minimally invasive solutions with promising outcomes. This study conducts a comprehensive bibliometric analysis of global research trends and key influences in UBE application. Methods A systematic search in the Web of Science Core Collection was performed on June 9, 2024, focusing on English publications related to UBE and spine surgery. Bibliographic data were analyzed using R and VOSviewer to visualize trends, collaborations, and citation networks. Results A total of 231 articles from 59 sources were identified, with World Neurosurgery being the most prolific journal. Publications peaked in 2023, with South Korea and China leading the field through significant collaborations. HEO DH emerged as the most productive and cited author. Key research focuses included "decompression," "surgery," and "discectomy." Conclusion The analysis highlights increasing research interest in UBE, with key contributors and collaborations shaping advancements. It provides insights into research trends, main areas of focus, and emerging topics, guiding future UBE research and applications.