A genome-wide study identified tumor suppressor P53 (TP53), BRAF, KRAS, COL-3A1, and SOCS-2 as key drivers of tumorigenesis in human colorectal cancers (CRC). We investigated the association between these molecules' expression levels and the progression of clinical stage as well as the occurrence of distant metastasis in CRC.

We recruited adult patients who underwent colonoscopy and had a histologically confirmed diagnosis of CRC. Clinical staging was determined following extensive workups. Immunohistochemistry (IHC) was used to evaluate the expression level of TP53, KRAS, BRAF, COL-3A1 and SOCS-2 in tumor biopsies.

The study involved 63 CRC patients, with a distribution across different stages: 1 (1.6%) in stage I, 6 (9.5%) in stage II, 30 (47.6%) in stage III, and 26 (41.3%) in stage IV. The expression level of TP53 gene were inversely correlated with clinical stages (ρ -0.260, p<0.05). Patients with distant metastases had a significantly lower expression of TP53 compared to those without (0.00 [1.00] vs. 1.00 [23.00], p<0.05). Subanalysis of patients with left-sided tumors demonstrates a significantly reduced expression level of TP53 in both lung (0.00 [0.00] vs. 1.00 [5.25], p<0.05) and overall (0.00 [1.00] vs. 1.00 [21.50], p<0.05) metastases. The expression of TP53 was also positively correlated with BRAF, KRAS, COL-3A1, and SOCS-2 (ρ -0.617, p<0.05; ρ -0.272, p<0.05; ρ 0.348, p<0.05; ρ 0.571, p<0.05).

TP53 is downregulated in advanced clinical stages and distant metastases, demonstrating its role in aggressive nature of CRC.

The widespread use of screening endoscopy has increased the detection rate of ampullary neoplasms. Most of these lesions are adenomas or carcinomas. The recurrence rates after an endoscopic papillectomy have been reported to range from 5% to 40%, even in cases with pathologically confirmed complete resection. An endoscopic mucosal resection (EMR) is commonly performed for residual or recurrent lesions, and endoscopic ablation therapies, such as argon plasma coagulation, may be used either as an alternative to or in conjunction with EMR. Recently, radiofrequency ablation (RFA) has garnered attention as a potential alternative to surgical treatment for intraductal residual or recurrent ampullary neoplasms after an endoscopic papillectomy, showing a 75.7% clinical success rate. In cases of recurrence after initial RFA, additional RFA has enabled oncologic control in nearly all patients without the need for surgery. Nevertheless, further prospective studies and accumulation of evidence are necessary to establish the efficacy and safety of RFA in this setting.

Robust methods for analysis and prediction of local cell survival after spatially fractionated radiotherapy (SFRT) in vitro remain limited. We present a methodology integrating spatial dosimetry with colony formation assessment and modelling to improve prediction of SFRT-induced responses. Patient/material and methods: A549 lung cancer cells were irradiated with 220 kV X-rays in three field patterns: open, striped, and dotted. Colony centroid locations were mapped from scanned images of culture flasks. Dose distributions were measured using radiochromic film dosimetry. Digital images with colony locations and dose maps were divided into 1 mm² quadrats. A Poisson regression model was fitted to colony counts per quadrat, incorporating linear-quadratic (LQ) model parameters α and β. A modified LQ (MLQ) model included an additional interaction between dose and nearest distance to a peak region, with parameter δ.

The methodology was successfully implemented. LQ fitting across all quadrats and patterns yielded α = 0.254 Gy-¹ and β = 0.039 Gy-², while the MLQ model gave α = 0.249 Gy-¹, β = 0.032 Gy-², and δ = -0.040 Gy-¹ cm-¹. Parameter uncertainty was below 0.5%. The MLQ model showed slightly lower fitting errors than the LQ model, indicating improved predictive accuracy.

We introduce a novel analysis pipeline for 2D localization of colonies and SFRT survival modelling in vitro. Findings suggest that distance to peak dose regions significantly influences local SFRT effects. Incorporating this spatial factor via an MLQ model may enhance understanding and prediction of SFRT-induced survival.

Multiple myeloma (MM) is a malignant neoplasm of plasma cells leading to bone destruction and marrow failure. Prognosis and management of MM rely on cytogenetic determination of copy number alterations (CNAs). Nevertheless, karyotype analysis difficult due to the presence of few plasma cells and their low proliferative activity. A shallow whole-genome sequencing (sWGS) technology named LeukoPrint was used to detect genome-wide CNAs in MM patients (n = 128), which can cover the entire genome without involving cell culture. Compared with karyotyping and fluorescent in situ hybridization (FISH), LeukoPrint demonstrated a significantly higher detection rate of copy number alterations (CNAs), increasing from 8.0% (karyotyping) and 44.2% (FISH) to 75.0% (n = 96), provided new CNA information and redefined the prognostic stratification in 20.3% of patients according to mSMART guidelines. Hyperdiploidy was the most common CNA feature (39.6%) in this cohort. A high concordance of 90.7% was observed in CNA between matched bone marrow and peripheral blood samples. LeukoPrint can be regarded as an automated, convenient and cost-effective approach to describe genomic CNA profiles. With the advantage of detecting CNAs of short segments and incorporating routine diagnostic methods, LeukoPrint can add value to conventional karyotyping with improved prognostic stratification.

To assess the necessity of restaging surgery for patients with suspected International Federation of Gynecology and Obstetrics (FIGO) stage I-II epithelial ovarian cancer (EOC) following incomplete surgical staging.

This multicenter retrospective study evaluated patients with early-stage EOC referred for restaging. These patients were diagnosed with suspected FIGO stage I-II EOC between January 2007 and November 2022 after incomplete surgical staging, and no residual region was confirmed by radiological evaluation. Progression-free survival (PFS) and overall survival (OS) were examined.

Among the 173 patients included in the study, 56 were assigned to the no restaging surgery group, and 117 to the restaging surgery group. After restaging, 23 were upstaged to other main stage. However, PFS and OS were not significantly different between the groups, also, dividing the groups into 4 groups who underwent chemotherapy and those who did not also did not show significant differences. In multivariate analysis, histologic grade independently influenced PFS outcomes.

While restaging surgery resulted in upstaging in some patients, it was not associated with significant differences in PFS or OS in this retrospective analysis. However, the omission of any additional treatment warrants careful consideration and further discussion. Nevertheless, the observation that patients who did not undergo restaging surgery but received adjuvant chemotherapy did not show significantly different prognoses highlights the need for further research to establish appropriate treatment strategies tailored to diverse patient contexts.

Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson tumor, is a rare vascular benign tumor of blood vessels. It may occur in any part of the body, especially the deep dermis and subcutaneous tissue of the head, neck, fingers and trunk. The imaging and histopathology of IPEH are similar to hemangiosarcoma, especially in the case of active vascular endothelial hyperplasia. IPEH is a reactive proliferative lesion of vascular intima. The etiology is still unclear. After some studies showed that IPEH was a benign lesion, few reports on the etiology of it were reported. IPEH is usually limited to the thrombotic vessels or lumens of vascular malformations, usually accompanied by a clear history of trauma. IPEH usually does not cause any symptoms. It looks like a slow-growing lump. Some cases have been reported with pain and swelling. Although IPEH is relatively rare, its accurate diagnosis is crucial because it may be similar to malignant angiogenic lesions in clinical practice. There were few reports of cases related to intravascular papillary endothelial hyperplasia located in the sternocleidomastoid muscle after reviewing the domestic and foreign literature in recent 10 years. This case reports that a young male, who was admitted to the hospital one month after finding a subcutaneous tumor in the left neck. After admittance, relevant preoperative examinations were completed. After multi-disciplinary discussion and elimination of surgical contraindications, a specific surgical plan was formulated. The tumor was removed under local anesthesia on the second day after admission. During the operation, it was found that the tumor was located between the sternocleidomastoid muscle bundles, and it was sent for pathologic examination. Paraffin section pathology was reported after operation. Histological examination showed that the morphology was consistent with vascular endothelial papillary hyperplasia. There were no related surgical complications and recurrence in the 3-month follow-up. The purpose of this paper is to provide clinicians with a certain understanding of this rare disease through the report of this case of IPEH, and to identify it in later clinical work, and at the same time, to avoid confusion with malignant diseases, such as hemangiosarcoma, leading to unnecessary treatment and increase the cost of treatment.

Gastric cancer is a high-incidence malignancy that poses a serious threat to public health in China, ranking among the top three cancers in both incidence and mortality. The majority of patients are diagnosed at an advanced stage, resulting in limited treatment options and poor prognosis. To address key challenges in gastric cancer diagnosis and treatment, a research team led by Professor Jiafu Ji at Peking University Cancer Hospital has focused on the project "Development and Dissemination of Precision Medicine Approaches in Gastric Cancer Management". Through a series of high-quality multicenter clinical studies, the team established a set of new international standards in perioperative treatment, individua-lized drug selection, intelligent noninvasive diagnostics, and novel immunotherapy strategies. These advances have significantly improved treatment efficacy and reduced surgical trauma, achieving key technological breakthroughs in diagnosis, therapy, and mechanistic understanding, and systematically enhancing outcomes for gastric cancer patients. The project ' s findings had a broad international impact, including hosting China ' s first International Gastric Cancer Congress. Through nationwide dissemination, they have promoted the development of precision diagnosis and treatment of gastric cancer as a discipline, and led the formulation of the National Health Commission's guidelines for gastric cancer diagnosis and treatment. In recognition of its achievements, the project was awarded the First Prize of the 2024 Chinese Medical Science and Technology Award.

Hemophagocytic lymphohistiocytosis is rare and does not have any distinct clinical features or laboratory abnormalities, whereby a high index of suspicion is required for diagnosis. Hemophagocytic lymphohistiocytosis can be divided into primary/genetic or secondary causes that can be immunotherapy-induced. With the increasing use of immune checkpoint inhibitors for treatment of multiple solid tumor malignancies, the incidence of rare complications such as hemophagocytic lymphohistiocytosis can be expected to rise.

We describe a fatal case of immunosuppression-refractory pembrolizumab-induced hemophagocytic lymphohistiocytosis complicated by secondary disseminated fungal infection. A 75-year-old white Australian man with resected stage IIC melanoma who received four cycles of adjuvant pembrolizumab presented 11 weeks after commencement with febrile neutropenia, elevated C-reactive protein, and nonspecific symptoms. He developed progressive transaminitis, acute kidney injury, pancytopenia, hyperferritinemia, and hypofibrinogenemia. In addition, a bone marrow aspiration and trephine biopsy demonstrated hemophagocytosis. Treatment was commenced with high-dose corticosteroids and mycophenolate mofetil initially for suspected immune-related side effects, followed by tocilizumab and anakinra once a diagnosis of hemophagocytic lymphohistiocytosis was made. Unfortunately, his disease was refractory to treatment with development of multiorgan failure secondary to hemophagocytic lymphohistiocytosis, complicated by disseminated candidemia from prolonged immunosuppression, leading to death 26 days after admission.

This case underscores the diagnostic complexities of hemophagocytic lymphohistiocytosis, the importance of a multidisciplinary approach to management, and the fatal side effects of extended immunosuppression. This also highlights the importance of the discussion of risks versus benefits of treatment, particularly in the adjuvant setting, emphasizing the rare but real risk of fatal toxicities. Prolonged immunosuppression can lead to severe complications, and judicious use of corticosteroids with intensive prophylaxis is crucial. Further research into the mechanism of checkpoint inhibitor-induced toxicities is critical in the era of immunotherapy to allow personalized immunosuppressive and steroid-sparing strategies in complex cases.

Prostate cancer (PCa) is one of the prevalent cancers in men. Although deubiquitinating enzymes are implicated in tumorigenesis and progression, the specific role of ubiquitin specific peptidase 21 (USP21) in PCa remains unclear. This study provides the first comprehensive analysis of USP21 as a key oncogene driving PCa progression.

Prognosis-related deubiquitinating enzymes in PCa were initially identified through PCa cohorts from TCGA and GEO databases, followed by experimental validation. USP21 expression in PCa tissues and cell lines using tissue microarray immunohistochemistry, western blotting, and RT-qPCR. The biological functions of USP21 were evaluated through patient-derived organoids, in vitro and in vivo experiments. USP21 substrate proteins were identified by co-immunoprecipitation (Co-IP) coupled with mass spectrometry, revealing Y-box binding protein 1 (YBX1) as the primary target. YBX1 transcriptional activity was quantified using dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP). The effect of USP21 inhibition was evaluated using the USP21-targeted inhibitor Bay-805 in PCa cells.

USP21 is upregulated in PCa and correlates with poor prognosis. Functional assays demonstrated that USP21 knockdown significantly inhibited PCa cells proliferation, migration, and invasion. RNA-sequencing further revealed that USP21 modulates the HIF1 signaling pathway. Mechanistically, USP21 deubiquitinates and stabilizes YBX1, which in turn enhances HIF1A (encoding HIF1-α) transcription. Notably, pharmacological inhibition of USP21 with Bay-805 suppressed PCa progression, highlighting its therapeutic potential.

USP21 promotes PCa malignancy by interacting with YBX1 to upregulate HIF1-α expression. These findings suggest Bay-805 as a promising therapeutic candidate for PCa.

Hepatocellular carcinoma (HCC) is one of the most common aggressive malignant tumors worldwide with poor clinical outcomes and high mortality rates, highlighting the pressing need to identify reliable biomarkers. Nucleolar protein 11 (NOL11), as an essential element for ribosomal biosynthesis, has been implicated in the development and progression of various diseases. However, the potential role of NOL11 in HCC remains elusive.

The expression level of NOL11 was investigated by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the correlation between NOL11 and the clinical characteristics was analyzed. Furthermore, spatial-temporal expression patterns of NOL11 were delineated based on single-cell and spatial transcriptomics. Cox regression and ROC analyses were performed to evaluate the prognostic and diagnostic value of NOL11. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and gene set enrichment analysis (GSEA) were conducted to elucidate the functional pathways and potential mechanisms associated with NOL11. The association of NOL11 with immune infiltration was also explored using single-sample Gene Set Enrichment Analysis (ssGSEA). The integrated bioinformatics analysis was utilized to identify the drug sensitivity, and further drug validation was employed via molecular docking. Finally, the biological function of NOL11 was validated through in vitro experiments.

The expression of NOL11 was significantly upregulated in HCC, especially in tumor cells. Elevated NOL11 levels closely correlated with worse clinicopathological features, poor prognosis, and immune infiltration. Functional enrichment analysis revealed NOL11's potential involvement in multiple cancer-associated signaling pathways, including the cell cycle, DNA replication, and cell metabolism. Furthermore, we found that common chemotherapy drugs, such as gemcitabine, trametinib, and paclitaxel were sensitive to the expression of NOL11 and exhibited a strong molecular combination with NOL11. Lastly, NOL11 knockdown suppressed the proliferation, migration, and invasion of HCC cells.

Our findings suggest that NOL11 is a promising diagnostic and prognostic biomarker for HCC, providing new insights into the treatment decisions for HCC patients.