Development and validation of a circulating tumor DNA-based optimization-prediction model for short-term postoperative recurrence of endometrial cancer.

BACKGROUND: Endometrial cancer (EC) is a common gynecological malignancy that typically requires prompt surgical intervention; however, the advantage of surgical management is limited by the high postoperative recurrence rates and adverse outcomes. Previous studies have highlighted the prognostic potential of circulating tumor DNA (ctDNA) monitoring for minimal residual disease in patients with EC. AIM: To develop and validate an optimized ctDNA-based model for predicting short-term postoperative EC recurrence. METHODS: We retrospectively analyzed 294 EC patients treated surgically from 2015-2019 to devise a short-term recurrence prediction model, which was validated on 143 EC patients operated between 2020 and 2021. Prognostic factors were identified using univariate Cox, Lasso, and multivariate Cox regressions. A nomogram was created to predict the 1, 1.5, and 2-year recurrence-free survival (RFS). Model performance was assessed via receiver operating characteristic (ROC), calibration, and decision curve analyses (DCA), leading to a recurrence risk stratification system. RESULTS: Based on the regression analysis and the nomogram created, patients with postoperative ctDNA-negativity, postoperative carcinoembryonic antigen 125 (CA125) levels of < 19 U/mL, and grade G1 tumors had improved RFS after surgery. The nomogram's efficacy for recurrence prediction was confirmed through ROC analysis, calibration curves, and DCA methods, highlighting its high accuracy and clinical utility. Furthermore, using the nomogram, the patients were successfully classified into three risk subgroups. CONCLUSION: The nomogram accurately predicted RFS after EC surgery at 1, 1.5, and 2 years. This model will help clinicians personalize treatments, stratify risks, and enhance clinical outcomes for patients with EC.

LYAR promotes the proliferation of non-small cell lung cancer and is associated with poor prognosis.

INTRODUCTION: The aim of the study was to investigate the clinical significance of Ly-1 antibody reactive clone (LYAR) in non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: The expressions of LYAR at the protein level in representative paired NSCLC tumor tissues and adjacent non-tumor tissues were measured by Western blot and immunohistochemistry. Kaplan-Meier method was used to calculate the survival curve of patients with NSCLC. Cell Counting Kit-8 assay and flow cytometry were used to estimate the cell proliferation and cell cycle, respectively. Terminal-deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay was performed to detect cell apoptosis. RESULTS: LYAR was dramatically overexpressed in NSCLC tissues which were closely related to the survival of patients with NSCLC. In clinical studies, the expression of LYAR was related to the clinical stage, histological differentiation, and Ki-67 expression. A positive correlation was found between LYAR and Ki-67 expression by Spearman's correlation test. After serum starvation for 72 h, serum re-addition significantly increased the expression of LYAR, PCNA, and Cyclin A and promoted the cell cycle progression. LYAR knockdown inhibited the proliferation and induced the G0/G1 cell cycle arrest and apoptosis of A549 cells. CONCLUSIONS: The present study revealed the clinical significance of LYAR in NSCLC. LYAR might serve as a tumor promoter in NSCLC progression by promoting the proliferation and inhibiting the apoptosis of NSCLC cells. Inhibiting the expression of LYAR was considered as a potential novel therapeutic strategy for NSCLC.

Cervical neoplastic lesions in relation to CD4 T-lymphocyte counts and antiretroviral therapy among women with clinical stage 1 HIV in Yunnan, China.

China lacks data demonstrating associations of cervical neoplastic lesions with CD4 T-lymphocyte (CD4 cell) counts and antiretroviral therapy (ART) among HIV-infected women, suggesting relevant investigations are needed. A total of 545 HIV-infected women were enrolled in Yunnan, China, between 2011 and 2013. CD4 cell counts and ART were measured via medical records and cervical neoplastic lesions were measured by professional pathologists. Multivariable logistic models, which treated cervical intraepithelial neoplasia (CIN) 1+ and CIN2+ as outcomes, calculated adjusted odds ratio (aOR) of CD4 cell counts and ART. Subgroup analysis treating CIN1+ as the outcome was conducted by HIV infection duration (<4 vs ≥4 years), ethnicity (Han vs non-Han), and study site (Mangshi vs Kunming). The prevalence of CIN1+ and CIN2+ was 17.4% and 7.3%, respectively. Overall, 243 (44.6%) women had CD4 cell counts ≥500 cell/µL, 187 (34.3%) used ART for less than 2 years, and 236 (43.3%) used ART for at least 2 years. We found inverse associations of CIN1+ with CD4 cell counts (≥500 compared to <500 cells/µL: aOR = 0.46, 95% CI = 0.27-0.79) and ART use (<2 years: aOR = 0.43, 95% CI = 0.21-0.87; ≥2 years: aOR = 0.54, 95% CI = 0.27-1.10). Point estimates did not change substantially for CIN2+ but aORs of ART became nonsignificant. No significant interaction was observed for HIV infection duration. We found significant interaction between CD4 cell counts and ethnicity and study site in relation to CIN1+. Our study suggests potential protective effects of high CD4 cell counts against cervical neoplastic lesions among HIV-infected women, whereas associations of ART are less consistent.

DISC1 overexpression promotes non-small cell lung cancer cell proliferation.

Neuropsychiatric disorder-associated disrupted-in-schizophrenia-1 (DISC1) activates Wnt/ß-catenin signaling by inhibiting glycogen synthase kinase 3 beta (GSK3ß) phosphorylation, and may promote neural progenitor cell and pancreatic ß-cell proliferation. The present study found that DISC1 promotes non-small cell lung cancer (NSCLC) cell growth. Western blotting and immunohistochemistry analyses showed that DISC1 was highly expressed in NSCLC cell lines and patient tissues. DISC1 expression was negatively associated with phosphorylated (p-) GSK3ß, but positively correlated with a more invasive tumor phenotype and predicted poor NSCLC patient prognosis. siRNA-mediated DISC1 silencing increased p-GSK3ß expression and decreased expression of ß-catenin and Cyclin D1, while DISC1 upregulation produced the opposite results. DISC1 knockdown also reduced NSCLC cell proliferation rates in vitro. These results suggest that DISC1 promotes NSCLC growth, likely through GSK3ß/ß-catenin signaling, and that DISC1 may function as an oncogene and novel anti-NSCLC therapeutic target.

Oxidative damage of the male reproductive system induced by paraquat.

The effects of paraquat (PQ) on the male reproductive system are unclear. In this study, male rats were divided into four groups (0, 0.5, 2, and 8 mg/kg) and treated with PQ by oral gavage for 8 weeks. At the end of the experiment, a significant decline in sperm count, motility, and viability and an increase in teratospermia were observed in the PQ-treated group (P < 0.05). Further investigation found that PQ resulted in enhanced lipid peroxidation and more apoptosis in the testis tissues, and apoptosis was likely to be associated with activation of the mitochondrial pathway. In summary, our study demonstrated oxidative damage due to PQ on the male reproductive system.

[Effects of Long-term Implementation of the Flow-Sediment Regulation Scheme on Grain and Clay Compositions of Inshore Sediments in the Yellow River Estuary].

Based on the laser particle size and X-ray diffraction (XRD) analysis, 28 sediment samples collected from the inshore region of the Yellow River estuary in October 2013 were determined to discuss the influence of long-term implementation of the flow-sediment regulation scheme (FSRS, initiated in 2002) on the distributions of grain size and clay components (smectite, illite, kaolinite and chlorite) in sediments. Results showed that, after the FSRS was implemented for more than 10 years, although the proportion of sand in inshore sediments of the Yellow River estuary was higher (average value, 23.5%) than those in sediments of the Bohai Sea and the Yellow River, silt was predominated (average value, 59.1%) and clay components were relatively low (average value, 17.4%). The clay components in sediments of the inshore region in the Yellow River estuary were close with those in the Yellow River. The situation was greatly changed due to the implementation of FSRS since 2002, and the clay components were in the order of illite > smectite > chlorite > kaolinite. This study also indicated that, compared to large-scale investigation in Bohai Sea, the local study on the inshore region of the Yellow River estuary was more favorable for revealing the effects of long-term implementation of the FSRS on sedimentation environment of the Yellow River estuary.