Lymph node dissection is a standardized procedure in gastric cancer surgery. Typically, lymph node metastasis begins in the perigastric (PG) region and then extends to the extraperigastric (EP) region. However, in some circumstances, skip lymph node metastasis occurs in the EP region without involvement of the PG lymph nodes. This study aims to investigate the clinical significance of skip lymph node metastasis in gastric cancer.

A total of 1,055 patients who underwent curative gastrectomy for primary gastric cancer with pathological lymph node metastasis were analyzed. Patients were categorized into three groups: the PG-only group, the PG + EP group, and the skip group. The clinicopathologic characteristics and prognosis were analyzed.

The incidence of skip lymph node metastasis was 3.9% (41 of 1,055 patients). The skip group had a higher proportion of females compared to both the PG-only group (43.9% vs. 27.5%, p = 0.025) and the PG + EP group (43.9% vs. 26.5%, p = 0.017). Additionally, the skip group showed a higher proportion of intestinal-type tumors compared to the PG-only group (68.3% vs. 50.6%, p = 0.029) and the PG + EP group (68.3% vs. 40.2%, p = 0.001). Disease-free survival and overall survival in the skip group were similar to those in the PG-only group but significantly better than those in the PG + EP group.

Skip lymph node metastasis is uncommon, and it is associated with a higher proportion of females and intestinal-type tumors. The prognosis of the skip group was comparable to the PG-only group and significantly better than that of the PG + EP group.

Comprehensive analysis of single-cell transcriptome and chromatin accessibility will contribute to interpret the heterogeneity of acute myeloid leukemia (AML). We hypothesize that integrating single-cell transcriptomic and chromatin accessibility landscapes underlying t(8;21) AML will provide valuable insights into its heterogeneous cellular properties and gene regulatory programs.

Here, we conducted paired single-cell RNA-sequencing (scRNA-seq) and single-cell ATAC sequencing on bone marrow samples from newly diagnosed t(8;21) AML patients and healthy controls. Genetic signatures extracted from scRNA-seq were built and validated across three independent cohorts (German AMLCG1999, GSE106291 and TCGA LAML).

We identified TCF12, a core component of AML1-ETO-containing transcription factor complex (AETFC), as the most active transcription factor in blast cells, driving a universally repressed chromatin state. Furthermore, we delineated two functionally distinct T cell subsets, revealing that EOMES-mediated transcriptional regulation promotes the expansion of a cytotoxic T cell population (T cells_2; high GNLY, NKG7 and GZMB expression), with an increased clonality and a tendency for drug resistance. In addition, we discovered a novel leukemic CMP-like cluster characterized by high TPSAB1, HPGD and FCER1A expression. Leveraging machine learning-based integration of multi-omic profiles, we identified a robust 9-gene prognostic signature, which demonstrated significant predictive value for AML outcomes across three independent cohorts.

This multi-omics study provides unprecedented insights into the transcriptional and epigenetic heterogeneity of t(8;21) AML, providing a potential actionable tool for clinical risk stratification.

While systemic cholesterol levels are generally associated with cancer risk and progression in various tumors, studies of cholesterol de novo synthesis by cancer cells in various tumor settings were limited. This meta-analysis aims to provide a comprehensive understanding of the role of cholesterol de novo synthesis pathway in cancer, focusing on key markers related with this metabolic reprogramming in cancer tissues.

A systematic review and meta-analysis were conducted using data from multiple databases, including PubMed, EMBASE, and Cochrane Library. Studies were included if they examined the expression of cholesterol synthesis markers in solid tumors and reported hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS), or recurrence-free survival (RFS). Data extraction and quality assessment were performed by two independent researchers. Pooled HRs and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models.

Twenty studies involving 4,343 patients were included. High expression of cholesterol metabolism and esterification markers was significantly associated with worse prognosis in overall survival (OS: HR 2.38, 95% CI 1.97-2.87, p < 0.0001) and disease-free survival (DFS: HR 2.44, 95% CI 1.69-3.51, p < 0.0001). However, no significant association was observed for recurrence-free survival (RFS: HR 0.95, 95% CI 0.28-3.24, p = 0.9), with substantial heterogeneity (I² = 89%). Elevated expressions of enzymes correlated with more aggressive tumor characteristics, including lymph node metastasis and larger tumor size.

High expression of cholesterol metabolism markers in solid tumors is linked to poorer survival and aggressive disease features. Among these, SQLE and SOAT1 stand out as the most robust predictors and potential therapeutic targets, emphasizing the critical role of cholesterol metabolic reprogramming in cancer progression.

The B-aggressive lymphoma (BAL) proteins, including BAL1, BAL2, and BAL3, constitute a conserved protein family characterized by their N-terminal macro domains and putative C-terminal poly (ADP-ribose) polymerase (PARP) active site. Dysregulation of BALs has been closely associated with the progression of various cancers. However, there is limited understanding of their precise expression profile, prognostic significance, and role in breast cancer (BC).

The expression patterns of BALs were evaluated utilizing multiple databases, including Ualcan, Gene Set Cancer Analysis (GSCA), Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and Gene Expression Profiling Interactive Analysis (GEPIA). The prognostic significance of BALs was assessed via Kaplan-Meier plotter analysis. Furthermore, the potential mechanisms underlying the contribution of BC progression were predicted through GO and KEGG pathway enrichment analysis. Additionally, the effect of BALs on the malignant behaviors of BC cells was determined using CCK-8 assay, Transwell assay, and TUNEL assay.

The data revealed that the expression levels of both BAL1 and BAL2 were upregulated in BC, whereas no significant change was observed for BAL3. Survival analysis demonstrated a strong association between the overexpression of both BAL1 and BAL2 and favorable prognosis in patients with various subtypes of BC, including estrogen receptor (ER)-positive, ER-negative, Basal, luminal B, HER2-, and HER2 + subtypes. Additionally, the knockdown of BAL1 and BAL2 inhibited the proliferation and migration of BC cells while facilitating apoptosis.

These findings suggest that both BAL1 and BAL2 hold great potential as significant prognostic biomarkers and therapeutic targets for patients with BC.

Polycystic ovary syndrome (PCOS) is the most common metabolic disorder in women and is characterized by chronic oligomenorrhea and hyperandrogenism, often accompanied by insulin resistance. In women with PCOS, insulin resistance, hyperandrogenism, and impaired lipid metabolism contribute to an increased risk of atherogenesis.

Our study was conducted retrospectively on 347 women with PCOS and 132 healthy women who presented at our clinic. The impact of PCOS on the atherogenic plasma index (AIP) was assessed using multivariable linear regression analysis.

The AIP was significantly greater in women with PCOS than in controls (p-value < 0.001). A marked increase in AIP was observed when the body mass index (BMI) was ≥ 35 kg/m² (p-value < 0.001). AIP was positively correlated with BMI (r = 0.174, p-value = 0.001) and the homeostatic model assessment for insulin resistance (HOMA-IR) score (r = 0.294, p-value < 0.001). In the multivariable linear regression model including all participants, PCOS diagnosis (B = 0.146, 95% CI = 0.082-0.210; p-value < 0.001) and HOMA-IR (B = 0.017, 95% CI = 0.011-0.022; p-value < 0.001) independently predicted higher AIP. These findings identify PCOS and insulin resistance as independent risk factors for increased atherogenicity.

PCOS diagnosis and HOMA-IR are independent risk factors for increased atherogenicity. The increased atherogenic burden in women with PCOS can be assessed by the AIP. A significant increase in atherogenicity was observed in patients with a BMI of 35 kg/m² or higher.

This study aimed to compare the benefits and identify the best second-line treatment regimen for gemcitabine-refractory unresectable pancreatic cancers.

This retrospective analysis included 144 patients with unresectable pancreatic cancer who underwent a gemcitabine-based regimen as the first-line treatment. 57, 37, and 50 patients received oxaliplatin-, irinotecan-based, and modified FOLFIRINOX (mFFX) regimens, respectively. The primary endpoint of this study was progression-free survival (PFS) and the secondary endpoints were overall survival (OS), response rate, and treatment-related toxicity.

There were no significant differences in median PFS (mPFS) (4.6 months vs. 2.9 months, P = 0.627, HR = 1.128, 95%CI 0.693-1.836) and median OS (mOS) (6.5 months vs. 10.2 months, P = 0.108, HR = 0.664, 95%CI 0.392-1.125) between irinotecan- and oxaliplatin-based groups. The mOS was significantly longer in the mFFX group than in the Iri/Oxa group (pooled the irinotecan- and oxaliplatin-based groups) (10.7 months vs. 8.8 months, P = 0.035, HR = 1.560, 95%CI 1.037-2.347), whereas no statistical difference was observed in mPFS between the two groups (4.4 months vs. 4.2 months, P = 0.222, HR = 1.247, 95%CI 0.866-1.797). However, after propensity score matching adjustment, no significant differences were found in mPFS (3.5 months vs. 4.2 months, P = 0.290, HR = 0.763, 95%CI 0.448-1.297) and mOS (8.5 months vs. 12.4 months, P = 0.464, HR = 1.262, 95%CI 0.673-2.367) between mFFX and Iri/Oxa groups. Survival analysis by performance status showed that patients with good performance status lived longer than those with poor performance status (10.8 months vs. 7.7 months, P = 0.000, HR = 2.194, 95%CI 1.408-3.420), suggesting that patient performance status, rather than the treatment regimen, was the primary factor affecting overall survival during second-line treatment.

In the second-line treatment of pancreatic cancer, the efficacy of common treatment regimens is not significantly different, while a good performance status is the key factor influencing survival. Thus, it is recommended that supportive care be enhanced concurrently with systemic therapy in patients with pancreatic cancer.

To establish and validate a droplet digital PCR (ddPCR) assay for quantifying FRS2 gene copy number in formalin-fixed paraffin-embedded (FFPE) bladder cancer tissue samples, and to evaluate its analytical performance.

The ddPCR assay was developed using FRS2 as the target gene and RPP30 as the reference gene. Artificial plasmids, genomic DNA from urinary sediment of healthy individuals and cell lines were used as templates to assess the assay's precision, minimum reliable input DNA, and linearity. Fluorescence in situ hybridization (FISH) was employed to validate the accuracy of the ddPCR results.

One-dimensional fluorescence amplitude plots showed clear separation between positive and negative droplets for both FRS2 and RPP30. Duplex detection of FRS2 and RPP30 within the same reaction showed no interference between primers or probes. The assay exhibited excellent repeatability and precision, with intra-assay coefficient of variation (CV)% of 2.58% and 3.75%, and inter-assay CV% of 2.68% and 3.79%, across 20 ng and 2 ng input levels, respectively. The minimum reliable input DNA amount was determined to be 2 ng, and a strong linear relationship was observed (R² >0.99). Compared to FISH, the ddPCR assay showed 100% sensitivity, 100% specificity, and a kappa value of 1.

The developed ddPCR assay enables accurate and reliable quantification of FRS2 copy number in FFPE samples, offering a promising tool for auxiliary diagnosis and prognostic assessment in bladder cancer.

To explore the predictive value of vaginal lactic acid bacteria changes on the occurrence of HR-HPV infected cervical intraepithelial neoplasia (CIN), and to construct and validate Nomogram model.

The community composition, quantitative distribution and other indicators of vaginal lactic acid bacteria in patients with and without CIN were detected and analyzed. The key lactic acid bacteria characteristics and other potential risk factors related to CIN were screened out using statistical methods, and then the Nomogram prediction model was constructed. The model discrimination was assessed by the receiver operating characteristic (ROC) and the calibration curves, and decision curves analysis (DCA) was performed to verify the reliability of the model.

There was no significant difference in the incidence of CIN, baseline data and vaginal lactic acid bacteria parameters between the training set and the verification set (P > 0.05). Univariate analysis identified significant differences in clinical factors (e.g., age of first sexual activity, safety measures) and vaginal lactobacilli (e.g., L. acidophilus, L. jenseni, L. gasseri, L. rhamnosus) between groups (P < 0.05). Multivariate Logistic regression confirmed safety measures, serum progesterone levels, and relative abundances of L. acidophilus, L. crispatus, L. jenseni, and L. rhamnosus as independent risk factors for CIN (P < 0.05). Further, the nomogram prediction model was constructed, and the nomogram model had good calibration and fit between prediction and reality in the training set and the verification set, and the nomogram demonstrated excellent discrimination in the training set and validation set, with calibration curves showing minimal absolute error (0.048 vs. 0.046) and DCA confirming clinical utility across a threshold probability of 0.05-0.95.

Changes in vaginal lactobacilli (e.g., reduced L. acidophilus, L. jenseni, L. gasseri, and L. rhamnosus) are significantly associated with CIN risk, potentially reflecting dysbiosis-driven vulnerability to HR-HPV persistence The Nomogram model demonstrated high accuracy in internal validation, suggesting its potential utility as a clinician-friendly tool for individualized risk assessment. However, external validation in prospective cohorts is required before clinical implementation.

This study aims to compare the therapeutic efficacy of whole brain radiotherapy (WBRT) versus WBRT plus simultaneous integrated boost (WBRT + SIB) in patients with brain metastases (BMs) from small cell lung cancer (SCLC).

A retrospective analysis was conducted on 127 patients with BMs from SCLC who received brain radiotherapy between 2014 and 2023 at the Cancer Hospital of the Chinese Academy of Medical Science. Among them, 71 patients underwent WBRT (25.0-54.0 Gy in 10-21 fractions), while 56 patients received WBRT + SIB (SIB to metastases: 18.0-60.0 Gy in 5-20 fractions). The overall survival (OS), intracranial progression-free survival (iPFS), objective response rate (ORR), and local control rate (LCR) were evaluated to assess the efficacy of the treatments.

With a median follow-up of 14.9 months, the median OS was significantly longer in the WBRT + SIB group compared to the WBRT group (18.0 vs. 11.7 months). Similarly, the iPFS was extended in the WBRT + SIB group (12.2 vs. 7.6 months). Kaplan-Meier analysis revealed that WBRT + SIB significantly improved OS in patients with SCLC of BMs (P = 0.009). Subgroup analysis indicated that male patients, age < 60 years old, and multiple intracranial metastases benefited more from WBRT + SIB. Interaction tests suggested that age significantly influence the efficacy of WBRT + SIB, with patients < 60 years old deriving more benefit (P = 0.049). Concurrent WBRT + SIB with anti-angiogenic targeted therapy significantly improved iPFS (P < 0.001).

WBRT + SIB can prolong the OS in SCLC patients with BMs, with younger age and those receiving anti-angiogenesis therapy potentially achieving additional survival benefits.

Over-/undertreatment are pervasive in older adults with cancer, and challenges arise in applying the principles of bioethics: beneficence, nonmaleficence, justice, and patient autonomy. The objective of this study was to determine whether these ethical principles relate to over-/undertreatment for older adults, and how tensions among the principles may contribute.

We conducted a modified Delphi study with 13 experts in biomedical ethics for iterative rounds of data collection. In the first round, we presented via electronic questionnaire our previously published definitions of over-/undertreatment in older adults with cancer. We then asked which ethical principles related to each definition, followed by how over-/undertreatment might arise from conflicts among different ethical principles. Consensus for each question was defined as ≥ 75% of experts answering "agree" or "strongly agree". The second round consisted of a virtual discussion with nine of the panel experts led by a qualitative researcher to summarize round one results and review questions that did not reach consensus, followed by a second questionnaire including those questions.

Experts reached consensus that beneficence, non-maleficence, and autonomy were related to over-/undertreatment in older adults with cancer. Consensus was reached (92%) that overtreatment can occur when oncologists overemphasize beneficence valuing the potential benefit of cancer treatments, while underemphasizing non-maleficence with respect to treatment toxicities. Consensus was also reached (85%) that undertreatment reflects a lack of justice in equitable consideration of cancer treatments that could provide similar net benefits in older adults compared to younger adults. Lastly, consensus was reach that, in most cases, it is unethical to make a treatment recommendation without (1) formal assessment of patient frailty (e.g., via a geriatric assessment) or (2) the opportunity for the patient to share their values, goals, and preferences.

Our findings elucidate the ethical principles underpinning over- and undertreatment in older adults with cancer.