BACKGROUND: Platinum-based chemotherapy remains a cornerstone in the treatment of advanced non-small cell lung cancer (NSCLC), yet its efficacy is frequently limited by drug resistance. JMJD5 (Jumonji Domain-Containing Protein 5) is a multifunctional protein implicated in tumor progression with enzymatic and non-enzymatic activities. While it has been reported to enhance the sensitivity of NSCLC cells to EGFR tyrosine kinase inhibitors (TKIs), its function in modulating response to conventional platinum chemotherapy is unknown. METHODS: The clinical relevance of JMJD5 was assessed via bioinformatics analysis of patient cohorts. In vitro functional assays in A549 and H1299 cells included overexpression modeling, cytotoxicity and colony formation, apoptosis analysis, and DNA damage assessment. An enzymatically inactive JMJD5 mutant was employed to dissect mechanism. The synergistic anti-tumor effect was validated in nude mouse xenograft models. RESULTS: Low JMJD5 expression correlated with poorer overall survival in chemotherapy-treated NSCLC patients and was downregulated in tumor tissues post-chemotherapy. Cisplatin treatment reduced JMJD5 levels in vitro. Restoring JMJD5 expression significantly sensitized cells to cisplatin, enhancing its anti-proliferative and pro-apoptotic effects. This was associated with augmented DNA damage, evidenced by elevated γH2A.X. Crucially, the chemosensitizing function was independent of JMJD5's enzymatic activity. Mechanistically, JMJD5 overexpression suppressed cisplatin-induced Chk1/Chk2 phosphorylation, indicating impaired checkpoint activation. In vivo, JMJD5 overexpression combined with cisplatin markedly suppressed tumor growth, reducing both tumor volume and weight compared to cisplatin alone. CONCLUSIONS: Our results demonstrate that JMJD5 enhances cisplatin sensitivity in NSCLC by amplifying DNA damage and apoptosis through a non-catalytic mechanism. JMJD5 thus represents a novel potential target for overcoming platinum resistance, offering a rationale for therapeutic strategies aimed at restoring or stabilizing its expression in combination with conventional chemotherapy.

Malignant melanoma is one of the most aggressive and lethal forms of skin cancer, posing a significant global health challenge. Despite therapeutic advances, current treatment strategies remain limited in efficacy, highlighting the need for alternative approaches. Photodynamic therapy (PDT) is a minimally invasive treatment that uses a photosensitizer activated by specific light wavelengths to generate reactive oxygen species (ROS), leading to targeted destruction of cancer cells. Curcumin, a natural phenolic compound derived from Curcuma longa, possesses diverse pharmacological properties, including anticancer activity, and has emerged as a potential photosensitizer. This study aimed to evaluate the in vitro efficacy of curcumin-mediated PDT in inducing cytotoxic effects in metastatic melanoma (A375) cells. A375 cells were treated with curcumin followed by irradiation using a 405 nm laser at fluence levels of 5 and 15 J/cm². Post-irradiation incubation was conducted for 24 and 48 h. Cellular responses were assessed via ROS detection assays, nuclear damage evaluation (using nuclear staining), apoptosis assays, morphological observation, and cell viability tests. Curcumin-PDT treatment induced a fluence- and time-dependent increase in intracellular ROS levels. Treated cells exhibited marked nuclear fragmentation, reduced viability, morphological alterations, and significant apoptosis compared to control groups. The extent of these effects correlated with both laser fluence and incubation time. These findings confirm that curcumin, upon photoactivation, induces oxidative stress and apoptosis in melanoma cells, thereby reducing cell survival. These results support the potential of curcumin as a natural photosensitizer in PDT and suggest its promising application in nanobioconjugate delivery systems for melanoma therapy.

Compound hybridization has received attention due to its potential to address several diseases, including neurological disorders, cancer, infectious diseases, and others. Melatonin is a hormone with antioxidant, anti-inflammatory, and neuroprotective effects. Some drug design research has focused on synthesizing hybrid molecules in which melatonin is hybridized with other pharmacologically active compounds to increase therapeutic efficacy and reduce toxicity. These hybrids demonstrate improved binding affinity, selectivity, and pharmacokinetic characteristics compared to their separate components. This review shows the pharmacological assessment and therapeutic potential of diverse melatonin-based hybrids. These hybrids have exhibited significant efficacy in the treatment of complex diseases such as Alzheimer's disease, cancer, and inflammatory disorders. Hybridization leads to the synthesis of a new generation of structures that represent a promising therapeutic approach for disease treatment.

Cystic lesions of the ovaries are common in adolescent girls. Follow-up is recommended to monitor any changes in size. In more than 90% of cases, these cysts are benign. Our aim is to draw attention to the fact, that even extremely large lesions can develop during puberty and in every case our goal is to perform accurate imaging and organ-preserving surgical management. Between 2023 and 2025, four adolescent girls underwent surgery for giant cystic ovarian lesions at the Department of Pediatric Surgery of the Győr-Moson-Sopron County Petz Aladár University Teaching Hospital. We performed a detailed retrospective analysis of the patients' medical histories and a review of the relevant literature. In all four cases, pediatric surgical and gynecological examinations, tumor marker level assessments, abdominal ultrasound, and abdominopelvic magnetic resonance imaging were performed within a short period of time. Based on the findings, surgery was carried out within a few days. Laparoscopic surgery was performed in two patients, open surgery in the other two. In every case, a large cystic lesion was identified, and no clear evidence of malignancy arose during the operations. Organ-preserving surgery was successfully performed in two patients; in the remaining cases, removal of the affected ovary and fallopian tube was necessary. The histopathological findings differed in all four cases. In the first patient, a mucinous cystadenoma was confirmed, which recurred, and needed reoperation. In the second patient, histology revealed mucinous adenocarcinoma, which is a particularly rare malignancy in this age group. In the third case, fluid accumulation caused by torsion was identified as the underlying condition. In the fourth patient, the histopathological diagnosis was a mature cystic teratoma. Although cystic ovarian lesions are common during adolescence, they rarely grow to an extreme size. Accurate imaging and analysis of tumor marker levels are essential for surgical planning. Minimally invasive procedures and organ-preserving surgery should always be preferred if possible. Histopathological findings greatly influence the need for further follow-up or additional treatment. Orv Hetil. 2026; 167(29): 1164-1171.

BACKGROUND: The modified Glasgow Prognostic Score (mGPS) and systemic immune-inflammation index (SII) are useful prognostic markers for various malignancies. This study aimed to evaluate their prognostic significance in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel (CBZ). METHODS: We retrospectively reviewed the data of 344 patients with mCRPC who initiated CBZ treatment at Kobe University Hospital and affiliated institutions. The optimal SII cutoff value for predicting overall survival (OS) was determined using the maximally selected rank statistics (Maxstat) method. The prognostic significance of the mGPS and SII was assessed using Cox proportional hazards models. RESULTS: The median OS of the entire cohort was 15.9 months. The optimal SII cutoff value determined using the Maxstat method was 850.6. A multivariate analysis demonstrated that an mGPS ≥ 1 and an SII ≥ 850.6 were independent predictors of poorer OS, with hazard ratios of 2.10 (95% confidence interval [CI], 1.55-2.85; p < 0.001) and 1.58 (95% CI, 1.13-2.21; p = 0.008), respectively. Notably, among patients with an mGPS of 0, further stratification using the SII cutoff (mGPS 0/SII-low vs. mGPS 0/SII-high) significantly discriminated OS rates. CONCLUSION: mGPS and SII are significant prognostic biomarkers in patients with mCRPC treated with CBZ. Their combined assessment may provide improved risk stratification and support clinical decision-making in this population group.

Metabolic reprogramming is a pivotal hallmark of the malignant progression of lung adenocarcinoma (LUAD), yet its core regulatory genes and underlying molecular mechanisms remain largely elusive. In this study, we systematically deciphered the core regulatory network of LUAD metabolic reprogramming by integrating multi-omics analysis with the SHAP (SHapley Additive exPlanations) algorithm. Initially, LUAD transcriptomic and clinical data were acquired from the TCGA and GEO databases. Combined with 703 metabolic reprogramming-related genes retrieved from the Genecards database, 40 differentially expressed genes were identified via differential analysis, and key genes significantly impacting patient survival were subsequently isolated through prognostic analysis. Utilizing SHAP analysis to quantify the specific prognostic contributions of these genes, GPI, PFKP, and LDHB were recognized as the core regulatory genes. Single-cell sequencing analysis revealed that these three genes are highly expressed in the epithelial cells of LUAD tumor tissues and are closely associated with immune cell infiltration. In vitro cellular functional assays confirmed that silencing GPI, PFKP, or LDHB significantly restrained the proliferation and invasion capabilities of A549 cells, whilst regulating glucose metabolism and lactate production. Virtual knockout experiments further unraveled the downstream signaling pathway networks orchestrated by these three genes. Through combined multi-omics and SHAP analysis, this study elucidates, for the first time, the central roles of GPI, PFKP, and LDHB in the metabolic reprogramming of LUAD, providing a novel theoretical foundation for the development of diagnostic biomarkers and targeted therapeutics.

Acute myeloid leukemia (AML) remains a highly lethal hematologic malignancy characterized by metabolic reprogramming, therapeutic resistance, and poor survival, particularly in older patients. Nicotinamide adenine dinucleotide (NAD⁺) metabolism has emerged as a central driver of AML progression, and recent studies have identified solute carrier family 25 member 51 (SLC25A51) as the primary mitochondrial NAD⁺ transporter in mammalian cells. SLC25A51 regulates mitochondrial redox balance, oxidative phosphorylation, and tricarboxylic acid (TCA) cycle activity, thereby sustaining leukemic proliferation and survival. Structural studies have elucidated its six-transmembrane helix architecture, salt-bridge-mediated transport mechanism, and stabilization by cardiolipin binding. Functional investigations demonstrate that SLC25A51 overexpression correlates with poor prognosis, while its depletion disrupts mitochondrial metabolism, induces apoptosis, and suppresses AML progression in vivo. Therapeutically, pharmacologic inhibition of SLC25A51 with fludarabine, or its combination with hypomethylating agents, such as 5-azacytidine, enhances antileukemic efficacy by perturbing metabolic and epigenetic regulation. Moreover, SLC25A51 expression may serve as a predictive biomarker for mitochondrial-targeted therapies, such as complex I inhibitors. Future translational research should focus on developing selective inhibitors, optimizing combination strategies with demethylating agents and BCL-2 inhibitors, and validating its prognostic significance in clinical cohorts. Collectively, SLC25A51 represents a promising metabolic target with potential to overcome therapeutic resistance and improve patient outcomes in AML. Furthermore, this review discusses its potential implications across distinct genetic subtypes of AML (e.g., mutations in TP53, NPM1, and RAS), thereby highlighting key directions for future translational research.

PURPOSE: Recent clinical advances highlight Lu-PSMA-617 radioligand therapy as a promising option for treating prostate tumors. However, drug transport mechanisms and optimization of delivery strategies remain major challenges. In this study, we developed a multiscale computational model to analyze radioligand dynamics in prostate tumors and provide insights for improving therapeutic efficacy. METHODS: A spatiotemporal computational model was constructed using image-based tumor vasculature. The model employed the convection-diffusion-reaction framework to describe transport phenomena in both vascular and interstitial domains. Physiological parameters including vascular permeability, lymphatic drainage, receptor density, ligand-receptor binding affinity, and internalization kinetics were incorporated. Parametric studies were performed to investigate the effects of injected dose, labeling efficiency, ligand affinity, receptor density, blood flow, and tumor size on radioligand uptake and time-integrated activity (TIA). RESULTS: Simulations revealed pronounced spatial heterogeneity in intravascular and interstitial pressure and velocity fields. Tumor uptake and TIA exhibited nonlinear dependence on injected dose, peaking at 500 nmol, beyond which receptor saturation limited binding. Increasing the proportion of labeled ligand (2-8%) linearly enhanced TIA. Lower dissociation constants and higher internalization rates improved retention, while elevated receptor density increased uptake up to saturation. Blood flow reduction prolonged intratumoral retention, and tumor volume showed a linear relationship with accumulated activity for 10-50 mm. CONCLUSION: The results highlight the critical role of vascular architecture and tumor-specific parameters in governing radiopharmaceutical distribution. The developed model provides mechanistic insights for optimizing Lu-PSMA therapy and guiding personalized treatment strategies in radiopharmaceutical therapies.

BACKGROUND: Cytoreductive nephrectomy (CN) combined with thrombectomy remains controversial for metastatic renal cell carcinoma with venous tumor thrombus (mRCC-VTT), and optimal patient selection remains undefined. METHODS: We retrospectively analyzed 238 patients with RCC-VTT treated at a single center between February 2006 and December 2023. Patients were stratified as non-metastatic surgical (nmRCC-VTT-S, n = 135), metastatic surgical (mRCC-VTT-S, n = 53), or metastatic non-surgical (mRCC-VTT-NS, n = 50). Inverse probability of treatment weighting (IPTW) was used to reduce measured confounding. Perioperative outcomes, OS, PFS, subgroup heterogeneity, and 3-month landmark sensitivity analyses were evaluated. RESULTS: After IPTW adjustment, perioperative outcomes were comparable between metastatic and non-metastatic surgical cohorts (all P > 0.05). In the metastatic cohort, surgery was associated with longer OS than non-surgical management (P = 0.027), and this association remained significant in the 3-month landmark analysis after re-estimating IPTW (P = 0.018). PFS showed no significant difference after primary IPTW adjustment (P = 0.517) and showed only a non-significant favorable trend after landmark IPTW adjustment (P = 0.064). Mayo level modified the association between surgery and OS (P for interaction < 0.001) and PFS (P for interaction = 0.034). For OS, surgery was associated with longer survival in Mayo 0-II thrombi (HR 0.56, P = 0.045), whereas patients with Mayo III-IV thrombi had worse outcomes after surgery (HR 6.22, P = 0.016). CONCLUSIONS: CN combined with thrombectomy appeared feasible and was associated with improved OS in selected patients with mRCC-VTT, particularly those with low-level thrombi. Mayo level should inform surgical decision-making, and systemic therapy-first strategies should be considered for high-level thrombi.

Rare breast cancers represent a clinically important but underrepresented group of malignancies. In this Perspective, rare breast cancers are considered within the broader rare cancer definition of an annual incidence below 6 cases per 100,000 persons, while also recognizing breast-specific rarity based on uncommon histology, molecular hallmarks, clinical presentation or sex-specific occurrence. These conditions are characterized by limited case numbers, biological heterogeneity, reduced clinical trial inclusion and fragmented evidence. These constraints challenge artificial intelligence (AI) development because many systems depend on large, balanced and externally validated datasets. AI may support diagnosis, histopathology, molecular interpretation, prognostic stratification and precision oncology decision support, but its use in rare breast cancers requires evidence standards adapted to small cohorts. This Perspective proposes an evidence-informed clinical governance framework organized around five domains: intended clinical use, small-cohort validation, synthetic data governance, human oversight and lifecycle monitoring. Its distinctive contribution is to translate general AI reporting and governance principles into rare breast cancer-specific safeguards, including objective data-quality checks, leakage prevention, uncertainty-aware validation, synthetic data plausibility scoring, pan-rare model reporting, patient involvement and post-deployment surveillance. Synthetic data may support development and simulation, but should not replace validation on real clinical cases. By linking small-cohort methodology with clinical oversight, regulatory alignment and lifecycle monitoring, the framework offers a practical roadmap for safe AI-enabled rare breast cancer precision oncology.

PURPOSE: Soft-tissue reconstruction following oncologic resection of spinal tumors often leaves extensive dead space vulnerable to infection, cerebrospinal fluid leak, and impaired function. En bloc resection with wide margins remains standard for disease control, but closure of these complex defects is challenging. Plastic and reconstructive surgeons (PRS) are often consulted for soft-tissue closure, yet their role in spinal sarcoma care has not been comprehensively reviewed. We aimed to (1) describe indications and timing of PRS consultation, (2) summarize reconstructive options by anatomic site, and (3) report outcome differences where comparative data were available. METHODS: Following PRISMA-ScR guidelines, we performed a scoping review of Scopus, PubMed, Embase, Web of Science, and CINAHL databases (January 2000-April 2025). Eligible studies reported spinal sarcoma or mixed oncologic spine cohorts with extractable sarcoma data undergoing flap-based or microvascular reconstruction with postoperative outcome data. RESULTS: We included 21 primary studies encompassing 10,854 patients and four secondary sources; two additional narrative reviews published after the original search period were incorporated as contextual sources. PRS teams primarily employed flap-based closure in higher-risk patients, including those with prior irradiation, infection, large posterior defects, or multilevel instrumentation. In comparative observational cohorts, immediate flap-based closure was associated with lower wound complication rates and fewer hardware-related complications. Sacral and chest wall tumors were most anatomically complex, frequently requiring PRS consultation. CONCLUSION: PRS involvement is preferentially utilized in higher-risk settings and is associated with comparable or lower wound morbidity, supporting early PRS consultation when high-risk features are present. These findings support standardized multidisciplinary consultation pathways and future validation of risk stratification tools in this patient population.

Lung cancer is the leading cause of cancer-related mortality worldwide, with LUAD being characterized by high incidence and mortality rates. Despite the use of various treatments, including surgery, chemotherapy, immunotherapy, and molecular targeted therapy, the prognosis in LUAD patients remains unfavorable. As a result, the diagnosis and management of LUAD still present major challenges. There is an urgent need to identify novel therapeutic targets. In this study, we analyzed to explore single-cell transcriptomic data (GSE253013 dataset) to investigate epithelial cells heterogeneity in LUAD. Tumor-specific epithelial subpopulations were identified, and the signature genes were evaluated for prognostic, diagnostic potential across several GEO datasets. Functional assays were conducted to validate the role of CRABP2 in lung cancer cells. Xenograft mouse models, rescue experiments and mechanistic analyzes involving ATRA-RAR signaling were further performed to elucidate the molecular mechanism. CRABP2 expression was positively correlated with MDK in LUAD. Functional assays demonstrated that CRABP2 promoted cell proliferation, migration, invasion, and vasculogenic mimicry through activation of the MDK/VEGF/MMP2/9/AKT signaling axis. In vivo xenograft experiments further confirmed that CRABP2 knockdown suppressed tumor growth and angiogenesis. Rescue experiments identified MDK as a critical downstream effector of CRABP2. Mechanistically, CRABP2 enhanced MDK transcription via activation of the ATRA-RAR signaling pathway and increased RARA occupancy at the MDK promoter. Clinically, elevated CRABP2 expression was associated with poor prognosis and showed strong diagnostic performance in LUAD. Collectively, our findings identify CRABP2-ATRA-RAR-MDK signaling axis that drives LUAD progression and angiogenesis. CRABP2 promotes MDK transcription through activation of RAR signaling, thereby enhancing malignant phenotypes and vasculogenic mimicry. These results establish CRABP2 as a promising diagnostic and prognostic biomarker and suggest that targeting the CRABP2-MDK axis may represent a potential therapeutic strategy for LUAD.

Aflatoxins, toxic metabolites produced by Aspergillus species, are frequently reported contaminants of dairy cattle feed worldwide, particularly in tropical and subtropical regions where climatic conditions favor fungal growth, and they can be transferred into milk and dairy products. Their presence poses major public health risks, including liver cancer and growth impairment, among others. Understanding the extent of carryover from feed to milk is critical for food safety and regulatory control. A systematic review was conducted to synthesize evidence on aflatoxin carryover in dairy systems over the past two decades. Literature searches were performed in PubMed, Scopus, Web of Science, and Embase. Studies investigating aflatoxin levels in dairy feed and milk, as well as carryover rates, were included. Data extraction focused on contamination levels, feed treatment efficiency and carryover rates of aflatoxins as well as mitigation measures. Twenty-seven eligible studies were identified. Aflatoxin B concentrations in dairy feed ranged from undetectable to 598 µg/kg. In milk, AFM levels reached up to 22.2 µg/kg, with reported carryover rates as high as 15%. The findings highlight variability in contamination across regions and production systems. This review underscores the continuing risk of aflatoxin in dairy products, identifies knowledge gaps and emerging threats, and emphasizes the need for improved interventions to safeguard food safety and public health.

We report a DNA-compatible linchpin strategy for the construction and late-stage diversification of macrocyclic peptide DNA-encoded libraries (MPDELs). Treatment of DNA-conjugated linear peptides with 1,5-dichloropentane-2,4-dione (DPD) enabled highly efficient macrocyclization while introducing a versatile 1,3-diketone linchpin. Subsequent DNA-compatible late-stage diversification afforded four classes of heterocycle-embedded DNA-conjugated macrocycles, including pyrazoles, azolopyrimidines, 2-aminonicotinamides, and 2-hydroxynicotinonitriles, with a broad substrate scope and high conversion. A scale-up test, cross-substrate scope study, and enzymatic ligation demonstrated excellent compatibility with DNA-encoded library synthesis, providing a versatile platform for expanding the chemical space of macrocyclic peptide DNA-encoded libraries.

Total neoadjuvant therapy (TNT) has become an important treatment strategy for locally advanced rectal cancer (LARC), increasing the need for pretreatment biomarkers that may predict major tumor response and support organ-preserving approaches. This study aimed to evaluate whether pretreatment stromal CD4⁺ and CD8⁺ T-cell densities, together with stromal tumor-infiltrating lymphocytes (TILs), are associated with response to TNT in patients with LARC. In this retrospective study, 45 patients with LARC who completed TNT were analyzed; pretreatment colonoscopic biopsy specimens were available for all patients, and paired post-treatment resection specimens were available for 40 surgically treated patients. CD4⁺ and CD8⁺ T-cell densities were assessed immunohistochemically in stromal hotspot areas and expressed as cells/mm², while stromal TILs were evaluated on hematoxylin-eosin sections. A favorable response was defined as tumor regression grade (TRG) 0-1 in surgically treated patients or clinical complete response in patients managed with a watch-and-wait strategy. Median pretreatment CD4⁺ T-cell density, CD8⁺ T-cell density, and stromal TIL percentage were 320 cells/mm², 64 cells/mm², and 30%, respectively. Receiver operating characteristic (ROC) analysis identified a pretreatment stromal CD4⁺ T-cell density cutoff of 410 cells/mm² for favorable response, with an area under the curve (AUC) of 0.68 (p=0.041). CD4⁺ T-cell density >410 cells/mm² was significantly associated with favorable response and remained independently associated with response in multivariable logistic regression analysis (odds ratio [OR]=5.05, 95% confidence interval [CI]: 1.21-20.83, p=0.026). In contrast, pretreatment CD8⁺ T-cell density and stromal TIL percentage were not significantly associated with response. In paired specimens, CD8⁺ T-cell density increased significantly after treatment (p<0.001), whereas CD4⁺ T-cell density and stromal TIL percentage did not change significantly. Lymphovascular invasion (LVI) and perineural invasion (PNI) were associated with non-favorable response. High pretreatment stromal CD4⁺ T-cell density may represent a candidate biomarker of favorable response to TNT in LARC, while the post-treatment increase in CD8⁺ T-cell density suggests a potential immunomodulatory effect of TNT; however, prospective validation in larger cohorts is required.

BACKGROUND: Cervical cancer remains a major global health burden. Preoperative conization has been proposed to reduce tumor burden and potential intraoperative tumor dissemination, but its survival benefit in patients with stage IB cervical cancer remains uncertain. This study aimed to evaluate the association between preoperative conization and survival outcomes after radical surgery in patients with FIGO 2018 stage IB cervical cancer. METHODS: This retrospective study included 1,614 patients with FIGO 2018 stage IB1-IB3 cervical cancer who underwent radical surgery between 2007 and 2016 at a single center. Patients were classified into four groups based on surgical approach and conization status. Progression-free survival (PFS) and overall survival (OS) were analyzed. Inverse probability of treatment weighting (IPTW) based on propensity scores was used to balance baseline characteristics. Survival outcomes were compared using weighted Kaplan-Meier analysis. RESULTS: After IPTW adjustment, baseline covariate balance was substantially improved, although residual imbalances remained for FIGO stage, depth of stromal invasion, neoadjuvant chemotherapy, and tumor differentiation. Weighted survival analysis showed no consistent survival advantage associated with preoperative conization. In pairwise OS comparisons, the laparotomy with conization group appeared to have superior OS compared with the other groups; however, this finding should be interpreted cautiously because no death events occurred in this group, resulting in non-estimable hazard ratios for comparisons involving this group. For PFS, no significant differences were observed between groups, including laparotomy with versus without conization (HR = 2.61, 95% CI: 0.62-11.02, P = 0.54), laparoscopic surgery without conization versus laparotomy without conization (HR = 1.97, 95% CI: 0.98-3.94, P = 0.21), laparoscopic surgery with conization versus laparotomy without conization (HR = 0.84, 95% CI: 0.21-3.49, P = 1.00), laparoscopic surgery without conization versus laparotomy with conization (HR = 0.75, 95% CI: 0.18-3.08, P = 0.98), laparoscopic surgery with conization versus laparotomy with conization (HR = 0.32, 95% CI: 0.05-2.02, P = 0.60), and laparoscopic surgery with versus without conization (HR = 0.43, 95% CI: 0.12-1.59, P = 0.56). CONCLUSION: Preoperative conization was not associated with improved OS or PFS in patients with FIGO 2018 stage IB cervical cancer undergoing radical surgery. The apparent OS advantage observed in the laparotomy with conization group was based on zero death events and non-estimable hazard ratios, and therefore should not be interpreted as definitive evidence of a survival benefit. Further prospective multicenter studies with larger conization cohorts and longer follow-up are warranted.

BACKGROUND: Osteosarcoma is the most prevalent primary malignant bone tumor predominantly affecting children and adolescents, yet prognosis for metastatic disease remains dismal. Understanding the cellular complexity within the tumor microenvironment is essential for developing targeted therapeutic strategies. METHODS: We performed comprehensive single-cell RNA sequencing analysis on an osteosarcoma tissue sample (GSM4952363) using the Seurat pipeline (v4.3.0). Following rigorous quality control (200-6000 genes per cell, < 15% mitochondrial reads), cells were filtered for downstream analysis. Dimensionality reduction (PCA and UMAP) and unsupervised clustering (Louvain algorithm, resolution = 0.8) identified seven distinct cellular clusters. Differential expression analysis (Wilcoxon rank-sum test, |log₂FC| > 0.25, adjusted < 0.05) identified cluster-specific markers, while Gene Ontology and KEGG pathway enrichment analyses (clusterProfiler, adjusted < 0.05) revealed functional programs. Four candidate genes (F11, ACRP2, LEPR, and POSTN) were selected for validation by quantitative real-time PCR (mRNA level) and ELISA (protein level) in MG-63 osteosarcoma cells compared to hFOB 1.19 normal osteoblasts. RESULTS: Single-cell transcriptomic profiling identified seven distinct cellular clusters within the osteosarcoma microenvironment, including macrophages (Cluster 0, 28.0%), osteoblasts (Cluster 1, 24.2%), fibroblasts (Cluster 2, Fibro_COMP, 14.7%), proliferating cells (Cluster 3, 12.3%), osteoclasts (Cluster 4, 11.6%), monocytes (Cluster 5, 6.3%), and T cells (Cluster 6, 2.9%). Functional enrichment analysis highlighted activation of PI3K-Akt signaling, focal adhesion, and extracellular matrix organization as core pathways. qRT-PCR validation (mRNA level) demonstrated that F11 was significantly downregulated (0.31 ± 0.04 vs. 1.00 ± 0.07, 69% reduction, < 0.001), whereas ACRP2 (2.87 ± 0.33-fold), LEPR (4.52 ± 0.48-fold), and POSTN (6.23 ± 0.57-fold) were significantly upregulated (all < 0.001). ELISA validation (protein level) confirmed consistent trends: F11 protein decreased by 65% (0.35 ± 0.05 vs. 1.00 ± 0.08, < 0.001), whereas ACRP2 (2.64 ± 0.29-fold), LEPR (4.18 ± 0.44-fold), and POSTN (5.89 ± 0.53-fold) protein levels were elevated (all < 0.001). Among the four candidates, POSTN exhibited the most pronounced changes at both mRNA and protein levels, suggesting its involvement in osteosarcoma matrix remodeling. CONCLUSIONS: This study provides a single-cell transcriptomic atlas of the osteosarcoma microenvironment, revealing substantial cellular heterogeneity. The differentially expressed genes F11, ACRP2, LEPR, and POSTN represent candidate biomarkers that warrant further investigation for their potential roles in osteosarcoma biology and as putative therapeutic targets.

BACKGROUND: Ovarian cancer is one of the most common gynecological cancers in women. Its diagnosis and treatment often cause significant psychological distress, mainly reflected in depression and anxiety, which arise from multiple interacting factors. This study, grounded in Lazarus's Stress and Coping Model and from the perspective of set theory, aimed to investigate the correlates and configurational pathways of high and low levels of depression and anxiety symptoms in ovarian cancer patients by integrating stress sources, coping styles, and coping resources. METHODS: The study recruited ovarian cancer patients from a tertiary general hospital in Shenyang, China. The analysis included 169 ovarian cancer patients. The configurational factors included self-perceived burden (SPB), positive and negative coping styles, self-esteem, and general self-efficacy. Multiple linear regression and fuzzy-set qualitative comparative analysis (fsQCA) were used to explore the factors and configurational pathways related to depression and anxiety symptoms. RESULTS: The fsQCA identified six configurational pathways linked to high and low levels of depression symptoms. Similarly, the fsQCA identified two configurations linked to high anxiety symptoms and four configurations related to low anxiety symptoms. Moreover, the configurations associated with low psychological symptoms did not stand in opposition to those associated with high psychological symptoms. Substitutability and complementarity were observed among the various elements in the configuration. CONCLUSION: The study generated multiple configurational pathways for depression and anxiety symptoms in ovarian cancer patients by examining the combined effects of stress sources, coping styles, and coping resources. The configuration allows caregivers and medical staff to implement targeted measures to reduce burden perception and negative coping, enhance positive coping and self-esteem considering their substitutability and complementarity.

PURPOSE: To evaluate whether oliceridine, a G protein-biased μ-opioid receptor agonist, reduces postoperative nausea and vomiting (PONV) compared with sufentanil in women undergoing gynecological laparoscopic surgery. PATIENTS AND METHODS: This prospective, double-blind, randomized controlled trial recruited 260 female patients, ASA physical status I-III, undergoing elective gynecological laparoscopic surgery under general anesthesia at Shanghai East Hospital, Shanghai, People's Republic of China. Patients were randomized to receive oliceridine (induction 0.05 mg/kg; postoperative infusion 0.4 mg/kg) or sufentanil (induction 0.5 μg/kg; postoperative infusion 2.0 μg/kg), with standardized general anesthesia and prophylactic antiemetics. The primary outcome was 48-hour cumulative PONV incidence. Secondary outcomes included PONV severity, opioid-induced respiratory depression (OIRD), adverse events, pain scores, 15-item Quality of Recovery (QoR-15) score, and patient satisfaction. All analyses were performed on the modified intention-to-treat population. RESULTS: The 48-hour PONV incidence was significantly lower with oliceridine (22.5% vs 43.0%; odds ratio 0.38; 95% CI 0.22-0.66; < 0.001), with consistent findings after multivariate adjustment. The absolute risk reduction was 20.5%, with a relative risk of 0.52, and a number needed to treat of 5, representing a clinically meaningful antiemetic advantage. Severe PONV was reduced (3.9% vs 15.6%, = 0.02). No significant differences were observed in pain scores or rescue analgesia. Oliceridine patients reported higher QoR-15 scores (median 123 vs 116, = 0.002) and greater satisfaction (69.0% vs 50.8%, = 0.02). OIRD and dizziness trended lower but were not significant after multiplicity correction. CONCLUSION: Oliceridine significantly reduced PONV incidence and improved recovery quality and patient satisfaction compared with sufentanil, without compromising analgesia, in women undergoing gynecological laparoscopic surgery.

A major limitation of conventional two and three-dimensional preclinical in vitro cancer models is their inability to reproduce the drug-delivery barriers. Tumor assembloids, which integrate patient-derived cancer cells with stromal, endothelial, and immune components in three-dimensional architectures, provide a manipulable framework for simulating these multicellular impediments. This review specifically examines the application of tumor assembloids to investigate drug delivery constraints, including stromal exclusion, vascular transport, immune-mediated resistance, penetration gradients, and spatially heterogeneous drug exposure. We compared three major construction strategies, including self-assembly, 3D bioprinting, and microfluidic compartmentalization, and evaluated their respective strengths for drug assessment. We also discussed assembloids' current limitations, including reproducibility, incomplete physiological dynamics, insufficient spatial analytics, and the need for standardized benchmarking. Overall, tumor assembloids represent promising mechanistic platforms for studying tumor drug delivery barriers. However, broader clinical application will necessitate rigorous validation and harmonized assay standards.

BACKGROUND: Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph + B-ALL) is a high-risk subtype of ALL characterized by the presence of the BCR-ABL1 fusion gene and typically presents with diffuse bone marrow involvement, circulating blasts, and systemic symptoms. While extramedullary disease may occur, it is rarely the dominant or sole feature at diagnosis. Isolated skeletal involvement with a normal bone marrow evaluation is exceedingly rare and diagnostically challenging. CASE PRESENTATION: We report the case of a 56-year-old Caucasian female who presented with progressive left hip pain and extensive lytic skeletal lesions, initially raising concern for multiple myeloma or metastatic cancer. Imaging revealed multifocal FDG-avid lesions in the skeleton without evidence of a systemic disease. Bone biopsy confirmed precursor B-lymphoblastic leukemia with expression of CD45, CD34, CD79a, TdT, and CD99, and eventually detection of BCR::ABL1 p190 transcript, consistent with Ph + B-ALL. Surprisingly, bone marrow aspirate and biopsy showed normocellular trilineage hematopoiesis without morphologic or immunophenotypic evidence of leukemia. The patient was treated with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with high dose methotrexate and cytarabine (HyperCVAD/MA) plus dasatinib followed by allogeneic stem cell transplantation, achieving complete molecular and metabolic remission. CONCLUSION: This case highlights an atypical presentation of Ph + B-ALL with isolated extramedullary skeletal involvement and a normal bone marrow at diagnosis. Such presentations, although rare, underscore the importance of maintaining a broad differential diagnosis in patients with unexplained lytic bone lesions and unremarkable hematologic findings. Early biopsy and appropriate molecular testing of affected tissue are essential for timely diagnosis and initiation of appropriate targeted therapy.

INTRODUCTION: With the advent of modern therapies, including rituximab and novel oral targeted agents such as BTK inhibitors, the survival of lymphoma patients has significantly improved. However, the risk of secondary primary malignancies (SPMs) remains a critical concern. This study aims to evaluate the incidence, risk factors, latency, and survival outcomes of SPMs in lymphoma patients treated in the era of targeted therapies. METHODS: A retrospective cohort study was conducted on 1,715 lymphoma patients diagnosed between October 2011 and October 2024 at Shanxi Bethune Hospital, China. Patients with incomplete records, pediatric cases, or immunodeficiency were excluded. Data on demographics, lymphoma characteristics, treatment modalities, and SPMs were collected. SPMs were classified as synchronous (diagnosed within 6 months of lymphoma) or metachronous (diagnosed after 6 months). Statistical analyses included Cox regression for risk factors and Kaplan-Meier for survival analysis. RESULTS: Among 1,715 lymphoma patients, 65 (3.8%) developed SPMs, including 10 synchronous (0.6%, descriptive enumeration only), while 55 (3.2%) developed metachronous SPMs that constituted the primary analytic cohort. Aggressive B-cell non-Hodgkin lymphoma (43.6%) was the most common lymphoma subtype among patients who developed SPMs, followed by indolent B-cell non-Hodgkin lymphoma (38.2%). Digestive and respiratory system tumors were the predominant SPMs (34.5% and 23.6%, respectively). Multivariate analysis identified male sex, ECOG performance status ≥2, extranodal involvement, bone marrow infiltration, BTK inhibitor use, and radiotherapy as independent risk factors for SPMs. Competing-risk analysis showed a higher cumulative incidence of SPMs in patients exposed to BTK inhibitors than in those not exposed to BTK inhibitors (5-year CIF, 7.92% vs 2.57%; Gray's test [Formula: see text] =0.007). Kaplan-Meier analysis showed that patients with SPMs had significantly worse OS than those without SPMs (median OS, 10.3 years; 5-year OS, 69.6% vs 89.6%; log-rank [Formula: see text]<0.0001). No significant difference in OS was observed between patients with solid and hematologic SPMs (median OS, 12.8 vs 6.0 years; [Formula: see text]=0.76). DISCUSSION: In the transitional era of conventional and targeted therapies, although data are limited.This exploratory analysis confirmed that gastrointestinal and respiratory SPMs predominated in this Asian cohort, and identified male sex, ECOG ≥2, extranodal involvement, bone marrow infiltration, radiotherapy, and BTK inhibitor use as independent risk factors. The association with BTK inhibitors (HR=2.56) warrants cautious interpretation and prospective validation. Early detection and tailored surveillance (prioritizing gastrointestinal screening) are essential for improving long-term outcomes.

BACKGROUND: Systemic inflammation and nutritional status are key determinants of tumor progression in advanced hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic significance of inflammation and nutrition based indices in patients with BCLC stage C HCC treated with sorafenib. METHODS: This retrospective cohort study included 109 patients with Barcelona Clinic Liver Cancer (BCLC) stage C HCC who received sorafenib as first line systemic therapy. A complete-case approach was used for multivariate Cox regression analysis. Progression-free survival (PFS) was defined according to RECIST version 1.1. Kaplan-Meier survival analysis and Cox proportional hazards regression models were used to assess prognostic factors. RESULTS: In Kaplan-Meier and univariate Cox analyses, several inflammation- and nutrition-based indices, including NLR, PLR, SII, mGPS, PI, and ALBI grade, were significantly associated with PFS. Although the total cohort included 109 patients, the final multivariate Cox regression model for PNI included 78 complete-case patients. In this model, low prognostic nutritional index (PNI) (HR: 2.36, 95% CI: 1.14-4.87, p=0.020) and prior local ablative treatment (HR: 0.45, 95% CI: 0.24-0.83, p=0.011) remained independently associated with PFS. CONCLUSION: Pretreatment low PNI was independently associated with shorter progression-free survival in patients with BCLC stage C HCC treated with sorafenib. Other inflammation and nutrition-based indices were associated with PFS in univariate analyses but did not retain independent prognostic significance after adjustment. PNI may serve as a simple prognostic marker for risk stratification in real-world settings, although external validation is required.

UNLABELLED: Pyrogallol, a polyphenolic compound, exhibits diverse activities, including antibacterial, antifungal, and antiviral effects; however, its anticancer potential has only been examined in a very few cancers and remains unexplored in T cell lymphoma. Hence, the present study is designed to elucidate the antitumor potential of pyrogallol against T cell lymphoma along with possible implication of modulated glucose metabolism and immune evasion. The experimental findings of this investigation show tumor-specific cytotoxicity of pyrogallol against T lymphoma cells. Further, pyrogallol has been shown to mediate G2/M cell cycle arrest by downregulating cyclin B1 and c-Myc expression, and induce apoptosis by altering ROS levels, mitochondrial membrane potential, and the expression of apoptosis regulators, namely Bcl2 and cleaved caspase 3, in T lymphoma cells. Furthermore, pyrogallol is observed to shift glucose metabolism towards oxidative phosphorylation by suppressing GLUT1, GLUT3, HKII, PKM2, PDK1, PDK3, and HIF-1α levels. Moreover, it suppresses the immune evasion ability of T lymphoma cells through deregulating 'do not eat me' and 'find me' signals, specifically PD-L1, CD-24 and CD-47, and S1P and LPC, respectively. Notably, the disrupted AKT pathway was found to play a critical role in pyrogallol-mediated T cell lymphoma growth inhibition. Overall, our investigation demonstrates that pyrogallol exerts tumor growth inhibitory effect in T lymphoma cells by modulating the cell cycle, apoptosis, glucose metabolism, and immune evasion in an AKT-dependent manner. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10616-026-01034-3.