Perturbation of macropinocytosis triggers methuosis, a non-apoptotic cell death characterized by cytoplasmic vacuolization. However, the regulatory mechanisms of methuosis remain poorly defined. Lipid metabolism dysregulation is implicated in various cell death pathways, while its role in methuosis has remained elusive. Herein, LXX-8250, an isopropanolamine derivative of β-elemene, induced a vacuolization-associated cell death in breast and liver cancer cell lines. This process was accompanied by massive macropinocytosis, thereby confirming the occurrence of methuosis. Mechanistically, hypoxia-inducible lipid droplet-associated protein (HILPDA), a key regulator that promotes intracellular triacylglycerol (TAG) accumulation, was identified as the direct target of LXX-8250. By suppressing HILPDA, LXX-8250 inhibited diacylglycerol O-acyltransferase 1 (DGAT1) and activated adipose triglyceride lipase (ATGL). Consequently, lipid droplets and cellular TAG levels were reduced, while the subsequent increased diacylglycerol (DAG) stimulated macropinosome formation, leading to methuosis in these cells. In this study, we discover a novel methuosis agonist LXX-8250, and elucidate the critical role of HILPDA repression-dysregulated lipid metabolism in methuosis. Our study highlighted the potential of targeting this pathway as a therapeutic strategy to trigger cancer cell death.

Objective: To evaluate the efficacy of different chemotherapy regimens in children with high-risk hepatoblastoma (HB). Methods: A retrospective cohort study was conducted on 99 patients under 18 years old with high-risk HB treated at Sun Yat-sen University Cancer Center between December 2004 and July 2024. The patients were divided into three groups: the PLADO regimen (cisplatin in combination with doxorubicin, n=27), the C5VD/IIV regimen (alternating cycles of cisplatin/5-flourouracil/vincristine/doxorubicin with irinotecan/ifosfamide/vincristine, n=29), and the modified SIOPEL-4 regimen (the original SIOPEL-4 regimen with omitted high-dose cisplatin on day15, n=43). Short-term efficacy, adverse effects, and long-term survival were compared among the three groups. Results: The objective response rates for the PLADO, C5VD/IIV, and modified SIOPEL-4 groups were 73.9% (17/23), 70.8% (17/24), and 88.6% (31/35), respectively, with no statistically significant difference among the three groups (P=0.190). The disease control rates were 82.6% (19/23), 83.3% (20/24), and 100.0% (35/35), the 3-year progression-free survival (PFS) rates were 19.2%, 37.0%, and 56.7%, and the 3-year overall survival (OS) rates were 69.2%, 55.6%, and 79.0%, respectively. The modified SIOPEL-4 group showed significantly better disease control rate and PFS rate compared withthe other two groups (both P＜0.05). After merging the PLADO and C5VD/IIV groups, the modified SIOPEL-4 group demonstrated significantly superior PFS and OS rates (both P＜0.05). Conclusions: The efficacy of modified SIOPEL-4 regimen in treating high-risk HB is superior compared with those of PLADO and C5VD/IIV regimens, but there remains room for further improvement in efficacy. Intensifying supportive care and pursuing aggressive local therapies, especially upfront liver transplantation for locally inoperable tumors, may further improve outcomes.

Objective: To compare the efficacy and safety of different-sized drug eluting beads preloaded with irinotrcan (DEBIRI) used in transarterial chemoembolization (TACE) as second-line therapy for colorectal cancer liver metastases (CRC-LM). Methods: A retrospective analysis was conducted on 65 patients with CRC-LM who received TACE at Yantai Yuhuangding Hospital from November 2020 to November 2022. All patients had progressed after first-line therapy. After excluding 5 lost-to-follow-up cases, 30 patients treated with 100-300 μm DEBIRI (small-size group) and 30 patients treated with 300-500 μm microspheres (large-size group) were included. Short- and long-term efficacy and adverse reactions were compared between the two groups. Univariate and multivariate Cox regression analyses were performed to identify factors influencing progression-free survival (PFS) and overall survival (OS). Results: In the small-size group, the objective response rates (ORR) at 1, 3, 6, and 12 months after treatment were 56.7%, 50.0%, 40.0%, and 30.0%, respectively, and the disease control rates (DCR) were 93.3%, 90.0%, 80.0%, and 66.7%, respectively. In the large-size group, the ORR at the same time points were 36.7%, 26.7%, 23.3%, and 16.7%, respectively, and the DCR were 86.7%, 76.7%, 76.7%, and 60.0%, respectively. None of the differences between the two groups were statistically significant (all P＞0.05). The median PFS and OS in the small-size group were 15.0 and 26.0 months, respectively, while in the large-size group they were 13.8 and 21.5 months, respectively, with no statistically significant differences between groups (all P＞0.05). The overall incidence of adverse reactions was 76.6% in the small-size group and 70.0% in the large-size group (P=0.559). The incidence of grade ≥3 adverse reactions was 23.3% and 16.7%, respectively (P=0.519). No treatment-related deaths occurred in either group. Multivariate Cox regression analysis showed that Child-Pugh grade, Eastern Cooperative Oncology Group (ECOG) score, and number of liver metastases were independent influencing factors for both PFS and OS. Conclusion: There was no significant difference in efficacy between 100-300 μm and 300-500 μm drug eluting beads preloaded with irinotrcanused in TACE for the treatment of CRC-LM, and both demonstrated good safety profiles.

Objective: To investigate the clinical value of dynamic monitoring of plasma circulating tumor DNA (ctDNA) in evaluating the efficacy of immunotherapy for esophageal squamous cell carcinoma (ESCC). Methods: Plasma samples were collected at baseline and after every 2-3 treatment cycles from 94 patients with advanced ESCC receiving second-line sintilimab monotherapy in the ORIENT-2 study. Targeted sequencing was performed to analyze somatic variants in ctDNA, and the molecular tumor burden index (mTBI) was calculated to assess dynamic changes in ctDNA. Imaging examinations were conducted synchronously with plasma sample collection, and treatment response was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Results: A total of 614 somatic mutations were detected in 93 eligible baseline plasma samples, with a median of 6 mutations per sample. Missense mutations were the most frequent mutation type. The baseline mutational profile revealed frequently mutated genes including TP53 (82%), CDKN2B (23%), and NOTCH1 (22%). In the 68 patients with both baseline and post-2-cycle plasma samples, no significant changes were observed in the variant allele frequencies (VAFs) of core driver genes before and after treatment (all P＞0.05), and no newly emerged core driver gene mutations were identified. CCND1 copy number variation was associated with shorter progression-free survival (PFS) (HR=1.88, 95% CI: 1.08-3.27), while mutations in other genes, including TP53 and NOTCH1, showed no association with PFS (all P＞0.05). None of the frequently mutated genes were associated with overall survival (OS) (all P＞0.05). Among the 68 patients, 11 (15.9%) achieved ctDNA clearance, none of whom showed tumor progression on concurrent imaging evaluation. The remaining 57 patients had ctDNA that became positive or remained persistently positive, of whom 30 (52.6%) showed tumor progression on imaging, with a statistically significant difference between groups (P=0.002). Compared with patients whose ctDNA became or remained positive, those with ctDNA clearance exhibited significantly delayed tumor progression (HR=2.05, 95% CI: 1.06-3.96), but ctDNA status after 2 cycles did not significantly affect OS (HR=1.38, 95% CI: 0.62-3.09). After 2 cycles of treatment, patients in the low mTBI group had a higher disease control rate (DCR) than those in the high mTBI group [73.5% (25/34) vs. 38.2% (13/34), P=0.007], as well as superior PFS (HR=2.80, 95% CI: 1.65-4.75) and OS (HR=3.54, 95% CI: 1.95-6.42). Dynamic changes in mTBI were highly consistent with concurrent imaging response assessments. The molecular response group had a significantly higher DCR than the non-response group [87.5% (21/24) vs. 42.2% (19/45), P＜0.001], as well as superior PFS (HR=2.39, 95% CI: 1.41-4.06) and OS (HR=2.77, 95% CI: 1.46-5.22). Among 32 patients with stable disease (SD) at the first imaging evaluation after 2 cycles, those in the molecular response group had comparable PFS with the non-response group (HR=1.03, 95% CI: 0.51-2.08, P=0.942), but significantly longer OS (HR=3.12, 95% CI: 1.20-8.06). Conclusion: Dynamic monitoring of the ctDNA-based molecular tumor burden index (mTBI) provides real-time and sensitive molecular information for evaluating the efficacy of immunotherapy in advanced ESCC, demonstrating definite clinical value for personalized treatment management.

Objective: To evaluate the prostate cancer (PCa) detection rates of targeted biopsy (TB) alone versus TB combined with systematic biopsy (SB) in patients with prostate imaging reporting and data systemv2.1 (PI-RADS v2.1) 4-5 lesions on biparametric magnetic resonance imaging. Methods: Clinical data were retrospectively collected from 1 060 patients who underwent combined prostate TB and SB at the First Affiliated Hospital of Nanjing Medical University between March 2018 and December 2023. All patients had pre-biopsy biparametric magnetic resonance imaging with PI-RADS v2.1 category 4 or 5 lesions. A comparative analysis was performed to evaluate the PCa detection rate and clinically significant prostate cancer (csPCa) detection rate between the two biopsy strategies. Using the postoperative pathological findings from 730 patients who underwent radical prostatectomy as the reference standard, a comparison of the pathological upgrading rates between TB alone and the combined biopsy approach was performed. Results: TB alone yielded detection rates of 79.6% (844/1 060) for PCa and 67.9% (720/1 060) for csPCa. The combined biopsy approach yielded detection rates of 82.2% (871/1 060) for PCa and 69.7% (739/1 060) for csPCa. The two strategies demonstrated no significant difference in detection rates of PCa and csPCa (P=0.136 and P=0.373) and showed substantial agreement (Kappa=0.918 for PCa and 0.958 for csPCa, both P＜0.001). This diagnostic alignment persisted across subgroups: among patients with PI-RADS category 4 lesions, the csPCa detection rates for TB alone and combined biopsy were 59.2% (395/667) and 61.5% (410/667), respectively, demonstrating high concordance (Kappa=0.953, P＜0.001). Among patients with PI-RADS category 5 lesions, the csPCa detection rates for TB alone and combined biopsy were 82.7% (325/393) and 83.7% (329/393), respectively, also demonstrating a high level of agreement (Kappa=0.964, P＜0.001). When compared with postoperative pathology, the overall pathological upgrading rates were 30.5% (223/730) for TB alone and 25.9% (189/730) for combined biopsy. The rates of upgrading specifically from biopsy-negative or ciPCa to csPCa were 12.3% (90/730) and 9.9% (72/730), respectively. Conclusion: For patients with PI-RADS 4-5 lesions, TB may serve as a clinically equivalent alternative to combined biopsy, achieving comparable diagnostic efficacy while reducing procedural burden on both patients and healthcare systems.

Objectives: To investigate the relationship between CD8+ tissue-resident memory T cells (TRM) and CD8+ bystander T cells (Tbys) in the tumor center (TC) and invasive margin (IM) regions of primary non-small cell lung cancer (NSCLC) and recurrence, and to perform stratified analysis based on lymph node status to guide individualized treatment. Methods: A retrospective review was conducted of patients with stage IA-IIIB non-small cell lung cancer (NSCLC) who underwent radical surgery at Shandong Provincial Cancer Hospital between January 1, 2014 and December 31, 2018. Tissue microarrays containing TC and IM regions were prepared, and multicolor immunofluorescence staining was applied to quantify the density of CD8+ T cells (CK- CD8+), tissue-resident memory T cells (CK- CD103+ CD8+), and bystander T cells (CK- CD103- CD8+). Kaplan-Meier and Cox proportional hazards models were used to identify factors associated with recurrence. Results: In the TC region, TRM/CD8+ T cells, Tbys/CD8+ T cells, and TRM/Tbys accounted for 34.3%, 67.9%, and 50.5% of CD8+ T cells, respectively. In the IM region, TRM/CD8+ T cells accounted for 29.6%, Tbys/CD8+ T cells for 70.7%, and TRM/Tbys for 41.9%. At a median follow-up of 37.9 months, recurrence occurred in 87 patients (34.0%). In all 256 patients, TRM/CD8+ T cells, Tbys/CD8+ T cells, and TRM/Tbys in both IM and TC regions were unrelated to RFS (all P＞0.05). Among the 172 N0 patients, the high Tbys/CD8+ T cell group in the IM region showed higher RFS rates than the low group (P=0.050), while the high-level groups for TRM/CD8+ T cells and TRM/Tbys in the TC region showed lower RFS rates than their low-level counterparts (all P＜0.05). Conversely, the high-level group for Tbys/CD8+ T cells in the TC region demonstrated a higher RFS rate than the low-level group (P=0.005). Multivariate Cox analysis revealed that high TC TRM/CD8+ T cells and high TC TRM/Tbys were independent risk factors for postoperative recurrence in N0 NSCLC patients (HR=2.772, 95% CI: 1.260-6.098; HR=2.656, 95% CI: 1.205-5.855), while high TC Tbys/CD8+ T cells was an independent protective factor for postoperative recurrence in N0 NSCLC patients (HR=0.324, 95% CI: 0.147-0.711). Among the 84 N1-2 patients, TRM/CD8+ T cells, Tbys/CD8+ T cells, and TRM/Tbys in the IM and TC regions were not associated with RFS (all P＞0.05). Conclusions: Specific CD8+ T cell subsets in the TC region of the primary tumor in NSCLC patients are associated only with recurrence after curative surgery in N0 patients. Elevated TRM/CD8+ T and TRM/Tbys ratios, coupled with reduced Tbys/CD8+ T ratios, correlate with heightened recurrence risk. This may aid in stratifying the risk of recurrence in N0 patients after surgery and guide treatment strategies.

Objective: To investigate the anti-colorectal cancer effect of tremella fuciformis polysaccharides (TFP) via the gut microbiota-metabolite axis. Methods: Colorectal cancer was induced in C57BL/6J mice using azoxymethane/dextran sulfate sodium. TFP or distilled water was administered by gavage for 3 weeks. Disease activity index (DAI), colon length, tumor burden, histopathology, gut microbiota (metagenomics), fecal metabolites (untargeted metabolomics), and colonic protein expression (Western blot) were assessed. Pyridoxic acid's effect on HT-29 cells was tested in vitro. Results: TFP significantly reduced DAI [2.0(1.8, 3.3) vs. 3.5(2.8, 4.5), P＜0.01], increased colon length [(7.2±1.1) vs. (5.5±0.5) cm, P＜0.05], lowered pathological score [6(3, 8) vs. 9(8, 10), P＜0.05], and decreased tumor number [2(1, 3) vs. 4(3, 4), P＜0.05] and volume [(11.02±7.88) vs. (24.99±3.38), P＜0.01]. Metagenomics revealed that TFP significantly reshaped gut microbiota (R²=0.173, P=0.027), enriching Candidatus Amulumruptor, Helicobacter, and Akkermansia. Metabolomics showed distinct profiles (R²=0.159, P=0.004), with pyridoxic acid elevated 1.20 fold (P＜0.001). Pyridoxic acid suppressed HT-29 cell viability and migration, and correlated positively with several upregulated bacteria, suggesting a microbiota-metabolite axis underlying its anti-tumor effect. TFP downregulated nuclear factor-κB (NF-κB) (P＜0.01) and upregulated phosphorylated AMP-activated protein kinase alpha (p-AMPKα) (P＜0.001), BAX (P＜0.001), and cleaved caspase-3 (P＜0.05). Conclusion: TFP inhibits colorectal cancer progression by modulating gut microbiota, elevating pyridoxic acid, suppressing NF-κB, and activating AMPK-mediated apoptosis.

Objective: To investigate the expression profile of Centromere Protein N (CENPN) in invasive breast cancer (BRCA), evaluate its prognostic significance, and assess its involvement in immune regulation. Methods: The expression, prognostic value, and correlation with tumor immunogenicity of CENPN in BRCA tissues were analyzed based on The Cancer Genome Atlas (TCGA) database. Verification was conducted using cancerous and adjacent normal tissues from BRCA patients who underwent surgical treatment at Yantai Mountain Hospital between January 2022 and April 2023. CENPN expression in various immune cells in the blood was examined using the Human Protein Atlas (HPA) database. Genetic alterations of CENPN in breast cancer tissues were analyzed via the cBioPortal database. CENPN-related genes were screened using the GEPIA 2.0 database, and the interaction network between CENPN and similar genes was visualized with the STRING database. Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and Gene Set Enrichment Analysis (GSEA) were employed to explore the potential biological functions of CENPN. The correlation between CENPN expression and immune cell infiltration, as well as immune cell markers in BRCA tissues, was assessed using the TIMER 2.0 database. The effect of CENPN on the proliferation ability of breast cancer MCF-7 cells was detected by the CCK-8 assay, and its impact on the migration ability of MCF-7 cells was evaluated by a wound healing assay. Results: Analysis of TCGA database data revealed that CENPN expression was significantly higher in BRCA tissues compared to adjacent normal tissues (P＜0.05). Validation in our institutional cohort demonstrated a significantly higher positivity rate for CENPN in the 17 breast cancer tissues (82.4%) than in the paired paracancerous tissues (5.9%, P＜0.001). According to the HPA database, elevated CENPN expression was observed in T-reg cells, naïve B cells, and myeloid dendritic cells. Kaplan-Meier survival analysis indicated that patients with high CENPN expression had poorer overall survival (HR=1.39, P＜0.001), recurrence-free survival (HR=1.31, P＜0.001), post-progression survival (HR=1.28, P=0.036), and distant metastasis-free survival (HR=1.6, P＜0.001). Correlation analysis revealed a negative association between CENPN expression and tumor mutational burden in BRCA patients (r=-0.196, P＜0.001). Furthermore, CENPN expression was positively correlated with 5 out of 20 common immune checkpoint genes and negatively correlated with the remaining 15, suggesting its potential for predicting immunotherapy response. Analysis via the cBioPortal database showed that invasive lobular breast carcinoma had the highest CENPN alteration frequency, with amplification being the most common alteration in BRCA. Invasive mixed mucinous breast carcinoma exhibited the highest mutation frequency, and a key missense mutation (K329N) was identified as a potential driver in BRCA.GO enrichment analysis demonstrated that CENPN-related genes were primarily involved in cell cycle, DNA metabolic processes, cell division, nuclear lumen, chromosomes, nucleoplasm, and functions related to ATP, nucleotide, and small molecule binding. KEGG pathway analysis indicated significant enrichment in DNA replication, cellular senescence, mismatch repair, homologous recombination, p53 signaling pathway, and FOXO signaling pathway. Correlation analysis using the TIMER 2.0 database established associations between CENPN expression and the infiltration levels of B cells, CD4+ T cells, CD8+ T cells, macrophages, neutrophils, and dendritic cells in BRCA. Positive correlations were also found with markers for CD8+ T cells, B cells, T cells, and T-cell exhaustion.CCK-8 assay and wound healing experiments confirmed that CENPN knockdown significantly suppressed malignant phenotypes, including proliferation and migration, in MCF-7 cells. Additionally, CENPN knockdown was found to enhance the chemosensitivity of MCF-7 cells to the anti-tumor agents 5-fluorouracil and gemcitabine. Conclusion: CENPN serves as a potential prognostic biomarker and a novel target for immunotherapy in BRCA.

Objective: This study aims to investigate the expression characteristics of GLUT10 in breast cancer and its role in mediating cisplatin resistance, with the goal of providing a new molecular target for personalized breast cancer treatment. Methods: Data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases were analyzed using the GEPIA2 platform to assess pan-cancer expression, while the UALCAN platform was used to analyze expression differences between breast cancer and normal breast tissues. In vitro, SK-BR-3 cells were divided into three groups: shScr (transfected with non-targeting scrambled shRNA), shSLC2A10#1, and shSLC2A10#2. MDA-MB-231 cells were divided into a vector control group and an SLC2A10 overexpression group. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect SLC2A10 mRNA expression. Western blotting was used to detect GLUT10 and cleaved caspase-3 protein expression. The CM-H2DCFDA probe was used to measure intracellular reactive oxygen species (ROS) levels. Drug sensitivity and colony formation assays were performed to evaluate cisplatin sensitivity, and flow cytometry was used to detect apoptosis rates. Results: GEPIA2 analysis showed that GLUT10 expression was downregulated in adrenocortical carcinoma, cervical squamous cell carcinoma and adenocarcinoma, and kidney chromophobe tumor tissues compared to normal tissues, whereas it was upregulated in invasive breast cancer, glioma, skin melanoma, and thymoma. UALCAN analysis revealed that SLC2A10 mRNA levels in breast cancer tissues were 1.85-fold higher than in normal breast tissues (P＜0.001). RT-qPCR results showed that SLC2A10 mRNA expression levels in breast cancer cell lines, ranked from high to low, were Hs 578T (160.5±12.3), SK-BR-3 (115.2±10.5), MDA-MB-468 (50.1±5.2), T-47D (35.4±4.1), and MCF7 (25.6±3.8), all significantly higher than in normal breast epithelial cells (P＜0.001). In SK-BR-3 cells, compared with the shScr group, the shSLC2A10#1 and shSLC2A10#2 groups exhibited increased intracellular ROS levels (relative fluorescence intensity: 1.78±0.12 and 2.05±0.15, respectively; P＜0.05), increased cisplatin sensitivity, reduced colony numbers, and promoted cisplatin-induced ROS accumulation and apoptosis. In MDA-MB-231 cells, compared with the vector control group, the SLC2A10 overexpression group showed decreased intracellular ROS levels (relative fluorescence intensity: 0.58±0.09, P＜0.05), decreased cisplatin sensitivity, and inhibited cisplatin-induced ROS accumulation and apoptosis. Conclusion: GLUT10 is highly expressed in breast cancer and mediates cisplatin resistance by regulating ROS levels, suggesting it may serve as a novel therapeutic target for reversing drug resistance in breast cancer.

Objective: To investigate the expression and function of Zeste 12 homolog (SUZ12) in hepatocellular carcinoma (HCC), and to preliminarily explore its biological role and underlying molecular mechanisms in HCC. Methods: This cell-based experimental study was conducted at the Basic Laboratory of the General Hospital of Southern Theater Command of the PLA from June 2024 to June 2025. The mRNA and protein expression levels of SUZ12 in HCC tissues and their correlations with clinicopathological features were analyzed using The Cancer Genome Atlas (TCGA). The prognostic impact of SUZ12 on HCC patients was evaluated using the K-M plotter database. SUZ12 overexpression and knockdown models were established in human hepatocellular carcinoma cells (HepG2). Transfection efficiency was verified by quantitative real-time polymerase chain reaction (qPCR) and Western blot. The effects of SUZ12 on HCC cell proliferation, invasion, and migration were assessed via Cell Counting Kit-8 assay (CCK-8), colony formation assay, and Transwell assay. The interaction between SUZ12 and enhancer of Zeste homolog 2 (EZH2) was validated by Co-Immunoprecipitation (Co-IP). Western blot was further used to preliminarily examine the effects of SUZ12 on the protein expression levels of H3K27me3 and CDKN1A. Statistical analyses were performed using two independent-sample t-tests.Results: In HCC tissues, SUZ12 mRNA levels were significantly higher than those in normal liver tissues (TPM=7.644 vs. 4.643, t=-6.648, P<0.001), and SUZ12 protein expression levels were also significantly elevated (Z-score=0.004 vs.-1.621, t=-9.815, P<0.001). The mRNA expression level of SUZ12 showed an increasing trend with higher clinical stage (normal: 4.643; stage Ⅰ: 7.071; stage Ⅱ: 7.085; stage Ⅲ: 8.677 TPM,H=36.700, P<0.001) and pathological grade (normal: 4.643; grade 1: 5.589; grade 2: 7.032; grade 3: 8.586 TPM, H=38.200, P<0.001). In the CCK-8 assay, the cell viability value in the SUZ12 overexpression group was higher than that in the control group; the relative absorbance at 450 nm on day 1(0.370±0.020 vs. 0.379±0.010, t=0.376, P=0.725), day 2 (0.477±0.016 vs. 0.370±0.069, t=-4.391, P=0.005), day 3 (0.900±0.022 vs. 0.816±0.024, t=-6.577, P=0.001), day 4 (1.601±0.017 vs. 1.390±0.026, t=-2.477, P=0.048). The cell viability value in the SUZ12 knockdown group was lower than that in the control group; the relative absorbance at 450 nm on day 1 (0.277±0.005 vs. 0.287±0.001, t=1.737, P=0.133), day 2 (0.344±0.002 vs. 0.377±0.006, t=4.677, P=0.010), day 3 (0.643±0.006 vs. 0.720±0.006, t=4.142, P=0.012), day 4 (1.065±0.015 vs. 1.210±0.031, t=8.941, P<0.001). In the colony formation assay, the number of colonies formed in the SUZ12 overexpression group was significantly higher than that in the control group [(775.000±51.884) colonies vs. (429.333±16.756 )colonies, t=-6.340, P=0.003]; the number of colonies decreased in the knockdown group [(150.666±4.055) colonies vs. (272.666±7.172) colonies, t=13.917, P<0.001]. In the Transwell assay, the invasion ability [(329.000±33.291) cells vs. (229.333±12.732) cells, t=-4.564, P=0.010] and migration ability [(325.333±7.310) cells vs. (217.333±1.732) cells, t=-14.120, P<0.001)] were significantly enhanced in the SUZ12 overexpression group compared to the control group; the invasion ability [(269.000±19.467) cells vs. (374.000±22.500) cells, t=3.529, P=0.024] and migration ability [(163.333±8.412) cells vs. (272.333±19.220) cells, t=6.194, P=0.020] were significantly weakened in the SUZ12 knockdown group compared to the control group. Western blot results suggested that high expression of SUZ12 downregulated the protein expression level of CDKN1A. Conclusion: SUZ12 high expression is associated with malignant biological behaviors of HCC cells. The SUZ12/EZH2/CDKN1A axis may represent a potential therapeutic target for patients with advanced HCC.

Objective: To develop a prediction model for colorectal cancer liver metastasis (CRLM) using machine learning algorithms based on routine clinical laboratory data. Methods: A retrospective case-control study was performed on 5 026 patients with colorectal cancer admitted to Qilu Hospital of Shandong University from January 2019 to August 2023. Clinical information and 70 routine laboratory indicators at admission were collected. Patients were randomly divided into training and validation sets in a 7∶3 ratio. Feature selection was performed stepwise using LASSO regression followed by multivariate logistic regression. A random forest (RF) prediction model was constructed in the training set. The model performance was comprehensively evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, decision curve analysis (DCA), calibration curve, and Brier score, and further validated in the validation set. SHapley Additive exPlanations (SHAP) analysis was used to interpret the feature importance of the final model. Results: 11 laboratory indicators were screened to develop an RF predictive model, including AFP, CEA, CA19-9, ADA, HDL-C, LDH, Cys C, GLDH, Hcy, PT, and lymphocyte ratio. The AUC of the RF model, CEA, CA19-9, and combined detection of the two markers was 0.867, 0.737, 0.738, and 0.786, respectively. Delong test revealed that the predictive performance of the RF model was superior to that of the other detection methods (all P<0.05). Model interpretation using the SHAP algorithm revealed that carcinoembryonic antigen, carbohydrate antigen 19-9, and other indicators were key predictors of CRLM. Conclusion: An interpretable machine learning model is developed for the early prediction of liver metastasis and personalized treatment regimens in colorectal cancer patients through the effective integration of clinical laboratory data, providing valuable clinical decision support to clinicians and improving patient prognosis.

Epignathus, a teratoma arising from the palate or pharynx, is extremely rare and palatal fetus-in-fetu represents an even rarer anomaly. We report a prenatally diagnosed palatal fetus-in-fetu successfully managed with ex utero intrapartum treatment (EXIT). A 4 cm oral mass detected at 23 weeks caused polyhydramnios and gastric shrinkage, suggesting impaired swallowing and potential airway obstruction. Multidisciplinary evaluation determined the need for EXIT to secure the airway under placental circulation. At 34+5 weeks of gestation, caesarean delivery with EXIT was performed; a 14 cm tumour was delivered and tracheostomy followed by staged resection was undertaken. Histopathology revealed multiple differentiated tissues-including nerve, gastrointestinal tract, adrenal gland, skin, bone and teeth-meeting Spencer's criteria for fetus-in-fetu. The infant recovered well and was discharged 96 days postnatally. EXIT proved invaluable for airway management in high-risk epignathus, and fetus-in-fetu differs from teratoma by its lower malignant potential, emphasising individualised prenatal planning and team collaboration.

The urethral caruncle is the most common lesion arising from the posterior lip of the urethral meatus in women; however, various benign and malignant tumours may mimic this condition. We report a case of a solitary fibrous tumour (SFT) presenting as a urethral caruncle. A woman in her late 60s presented with a progressively enlarging urethral mass that was accompanied by urinary spraying. Physical examination revealed a smooth spherical mass measuring 1.2 cm at the posterior urethral meatus. The lesion was completely excised under local anaesthesia. Histologically, the tumour consisted of spindle cells within collagenous stroma. Immunohistochemically, the tumour cells showed nuclear expression of STAT6 with focal CD34 positivity, supporting the diagnosis of SFT. No recurrence was observed during the 9-month follow-up period. This case highlights that lesions clinically resembling urethral caruncle may include mesenchymal tumours such as SFT, underscoring the importance of histopathological evaluation.

Metabolic reprogramming through enhanced glycolysis is a hallmark of cancer that supports tumor progression and promotes protumor immune responses. Methylglyoxal (MG), a reactive by-product of glycolysis, has recently emerged as an oncometabolite implicated in cancer progression and therapy resistance. Our previous work demonstrated that an imbalance between MG production and detoxification by the glyoxalase system, referred to as MG stress, contributes to progression and metastatic dissemination in triple-negative breast cancer (TNBC). However, the impact of MG stress on the tumor immune microenvironment remains poorly understood.

Immunotherapeutic approaches for cutaneous squamous cell carcinoma (cSCC) remain limited to programmed cell death protein 1 (PD-1) blockade. Although genomics studies have characterized key driver mutations in cSCC, preclinical models that faithfully recapitulate both the genetic landscape and immune microenvironment of the human disease, that could drive the development of novel, effective therapies, are lacking.

This study aims to elucidate the molecular mechanisms by which Polyphyllin I (PPI), a potent steroidal saponin, attenuates non-small cell lung cancer (NSCLC) progression via mechanistic reprogramming of an autophagy-dependent immunogenic response.

Robot-assisted radical nephroureterectomy (RANU) is increasingly used for upper tract urothelial carcinoma (UTUC), yet most published series are selected and real-world data from consecutive, unselected practice are scarce. We reviewed 100 consecutive RANU performed at a single institution between April 2022 and March 2026, including six cases with a concomitant procedure. Median age was 77 years and 39 patients had pT3-4 disease. Median estimated blood loss was 29 mL, operative time 200 min, and console time 141 min; three patients required transfusion. Clavien-Dindo grade II or higher complications occurred within 90 days in 13 patients, with only one grade III event. At a median follow-up of 15.5 months, the cumulative incidence of intravesical and of distant or local recurrence was approximately 17% and 18% at 12 months, and overall survival was approximately 86% at 24 months. RANU was feasible with favorable perioperative outcomes in this elderly, frequently advanced cohort.

Rectal cancer with mesorectal fascia involvement (MRF+) requires neoadjuvant downstaging and/or induction therapy, followed by (beyond) total mesorectal excision and/or multivisceral resection (MVR) depending on response. Decisions on the need for MVR and plane of dissection vary. This nationwide cross-sectional study aimed to evaluate treatment and oncological outcomes in MRF+ primary rectal cancer and the impact of MVR types.

HLA-G is a non-classical MHC class I molecule with potent immunoregulatory functions that is aberrantly expressed in multiple malignancies, yet its tumor-intrinsic role remains poorly defined. To characterize this potential oncogenic role of HLA-G in clear cell renal cell carcinoma (ccRCC), we utilized integrated transcriptomic, in vitro, and in vivo approaches. Analysis of the Cancer Genome Atlas (TCGA) ccRCC cohort revealed that elevated HLA-G expression was associated with immunosuppressive programs and cell populations. Interrogation of a publicly available ccRCC single-cell RNA sequencing dataset revealed that HLA-G expression within tumor epithelial clusters is associated with hypoxia-driven, metabolic transcriptional programs. Multiplex immunofluorescence of human ccRCC specimens confirmed the presence of tumor cell-intrinsic HLA-G expression in advanced disease. Functional studies using RCC7 cells expressing the full-length canonical HLA-G isoform (RCC7/HLA-G1) demonstrated increased proliferation, migration, clonogenicity, cell-cycle progression, and resistance to apoptosis compared with HLA-G-negative RCC7wt cells. RCC7/HLA-G1 xenografts exhibited accelerated tumor growth accompanied by the activation of proliferative, stemness-related, and metabolic programs. Multi-omics analyses further revealed enhanced mitochondrial activity and redox metabolic adaptation in HLA-G-expressing tumors. Mechanistically, HLA-G expression was associated with increased VEGF-C expression and enhanced VEGFR3 signaling, suggesting the activation of a VEGF-C/VEGFR3-associated pro-survival pathway. In three-dimensional tumor spheroid immune cell co-culture models, HLA-G expression reduced CD8⁺ T-cell-mediated cytotoxicity while promoting regulatory T-cell expansion and macrophage polarization toward an immunosuppressive M2-like phenotype. Collectively, these findings establish HLA-G as a key contributor to tumor progression and immune suppression in ccRCC and support HLA-G as a promising therapeutic target.

Primary breast neuroendocrine carcinomas (NECs) are rare, high-grade malignancies that are frequently grouped with invasive breast carcinomas with neuroendocrine differentiation (IBC-NED), despite uncertain biological equivalence. We sought to define the clinicopathologic, immunophenotypic, and genomic features of breast NEC and to determine whether they represent a biologically distinct entity.