Knowledge, attitudes, and practices of human papillomavirus and self-sampling among adult women: a cross-sectional study.

Background: This study aimed to investigate the knowledge, attitude, and practice (KAP) of human papillomavirus (HPV) and self-sampling among adult women. Methods: The cross-sectional, questionnaire-based study included adult women at Shanghai Pudong Hospital from October 14, 2022, to March 31, 2023. The questionnaire contained demographic information, knowledge, attitude and practice dimensions. Factors associated with KAP and self-sampling were identified by multivariate logistic regression. Results: A total of 1843 valid questionnaires were collected. The average knowledge, attitude, and practice score was 10.09 ± 5.60, 26.76 ± 3.80, and 6.24 ± 2.20, respectively. Urban residents (estimate = 0.705, p < 0.001), suburban residents (estimate = 0.512, p < 0.001), as well as individuals with undergraduate degrees and higher (estimate = 0.535, p < 0.001), were associated with good knowledge, while individuals lacking a history of HPV infection (estimate = -0.461, p < 0.001) and married individuals (estimate = -0.185, p < 0.001) were less likely to have good knowledge. Higher knowledge scores (estimate = 0.087, p < 0.001) and individuals with undergraduate education and above (estimate = 1.570, p < 0.001) were associated with a positive attitude. Being married (estimate = 0.291, p = 0.049) was associated with good practice, whereas not engaging in sexual activity (estimate = -0.959, p < 0.001) or lacking a history of HPV infection (estimate = -0.499, p = 0.011) were associated with unfavorable practices. Minorities (OR = 2.787, p = 0.038) and individuals with multiple sexual partners (OR = 2.297 for two partners, OR = 2.767 for three or more partners, p = 0.020 and p = 0.022) were positively associated with self-sampling. However, higher knowledge (OR = 0.952, p = 0.026) and attitude scores (OR = 0.929, p = 0.015) were negatively associated with self-sampling. Conclusion: Demographic and behavioral factors significantly influenced KAP scores and self-sampling behaviors regarding HPV. Urban residency, higher education levels, positive attitudes, and minority status correlated with favorable outcomes, while factors like marriage and lack of sexual activity were associated with less favorable practices.

An androgen receptor-based signature to predict prognosis and identification of ORC1 as a therapeutical target for prostate adenocarcinoma.

Background: Aberrant activation of androgen receptor (AR) signaling plays a crucial role in the progression of prostate adenocarcinoma (PRAD) and contributes significantly to the development of enzalutamide resistance. In this study, we aimed to identify a novel AR-driven signature that can predict prognosis and endows potentially reveal novel therapeutic targets for PRAD. Methods: The Seurat package was used to preprocess the single-cell RNA sequencing (scRNA-seq). Differentially expressed genes were visualized using limma and pheamap packages. LASSO and multi-variate Cox regression models were established using glmnet package. The package "Consensus Cluster Plus" was utilized to perform the consensus clustering analysis. The biological roles of origin recognition complex subunit 1 (ORC1) in PRAD were determined by gain- and loss-of-function studies in vitro and in vivo. Result: We characterized the scRNA-seq data from GSE99795 and identified 10 AR-associated genes (ARGs). The ARGs model was trained and validated in internal and external cohorts. The ARGs were identified as an independent hazard factor in PRAD and correlated with clinical risk characteristics. In addition, the ARGs were found to be correlated with somatic tumor mutation burden (TMB) levels. Two groups that have distinct prognostic and molecular features were identified through consensus clustering analysis. ORC1 was identified as a critical target among these ARGs, and it ORC1 promoted proliferation and stem-like properties of PRAD cells. Chromatin immunoprecipitation (ChIP)-qPCR assay confirmed that AR could directly bind the promoter of ORC1. Activated AR/ORC1 axis contributed to enzalutamide resistance, and targeting ORC1 rendered PRAD cells more susceptible to enzalutamide. Conclusions: This study defines an AR-driven signature that AR activates ORC1 expressions to promote PRAD progression and enzalutamide resistance, which may provide novel targets for PRAD treatment.

SMAD4 inhibits glycolysis in ovarian cancer through PI3K/AKT/HK2 signaling pathway by activating ARHGAP10.

BACKGROUND: ARHGAP10 is a tumor-suppressor gene related to ovarian cancer (OC) progression; however, its specific mechanism is unclear. AIMS: To investigate the effect of ARHGAP10 on OC cell migration, invasion, and glycolysis. METHODS AND RESULTS: Quantitative real-time PCR (qRT-PCR) quantified mRNA and protein expressions of AKT, p-AKT, HK2, and SMAD4 were tested by Western blot. EdU, Wound healing, and Transwell assay were utilized to evaluate OC cell proliferation, migration, and invasion. We used a Seahorse XF24 Extracellular Flux Analyzer to monitor cellular oxygen consumption rates (OCR) and extracellular acidification rates (ECAR). Chromatin immunoprecipitation (ChIP) was used to analyze the transcriptional regulation of ARHGAP10 by SMAD4. ARHGAP10 expression in OC tissues was detected by immunohistochemistry. Our results showed that ARHGAP10 expression was negatively related to lactate levels in human OC tissues. ARHGAP10 overexpression can inhibit the migration, proliferation, and invasion of OC cells, and this function can be blocked by 2-Deoxy-D-glucose. Moreover, we found that ARHGAP10 expression can be rescued with the AKT inhibitor LY294002. CONCLUSIONS: This study revealed that the antitumor effects of ARHGAP10 in vivo and in vitro possibly suppress oncogenic glycolysis through the PI3K/AKT/HK2-regulated glycolysis metabolism pathway.

Serum Galectin-3 Predicts Mortality in Venoarterial Extracorporeal Membrane Oxygenation Patients.

Objective: We investigated the potential use of galectin-3 (Gal-3) as a prognostic indicator for patients with cardiogenic shock and developed a predictive mortality model for venoarterial extracorporeal membrane oxygenation (VA-ECMO). Methods: We prospectively studied patients (survivors and nonsurvivors) who received VA-ECMO for cardiogenic shock from 2019 to 2021. We recorded baseline data, Gal-3, and B-type natriuretic peptide (BNP) before ECMO and 24-72 h after ECMO. We used multivariable logistic regression to analyze significant risk factors and construct a VA-ECMO death prediction model. Receiver operating characteristic (ROC) curves were plotted to assess the predictive efficacy of the model. Results: We enrolled 73 patients with cardiogenic shock who received VA-ECMO support; 38 (52.05%) died in hospital. The median age was 57 years (interquartile range (IQR): 48-67 years); the median duration of ECMO therapy was 5.8 days (IQR: 4.62-7.57 days); and the median intensive care unit stay was 19.04 days (IQR: 13.92-26.15 days). Compared with the nonsurvivors, survivors had lower acute physiology and chronic health evaluation (APACHE) II scores (p < 0.001), increased left ventricular ejection fraction (p < 0.05), lower Gal-3 levels at 24 and 72 h (both p = 0.001), lower BNP levels at 24 and 72 h (both p = 0.001), and higher platelet counts (p = 0.009). Further multivariable analysis showed that APACHE II score, BNP-T72, and Gal-3-T72 were independent risk factors for death in VA-ECMO patients. Gal-3 and BNP were positively correlated (p < 0.05) and decreased significantly during ECMO treatment. The areas under the ROC curve (AUC) for APACHE II score, Gal-3-T72, and BNP-T72 were 0.687, 0.799, and 0.723, respectively. We constructed a combined prediction model with an AUC of 0.884 (p < 0.01). Conclusion: Gal-3 may serve as a prognostic indicator for patients receiving VA-ECMO for cardiogenic shock. The combined early warning score is a simple and effective tool for predicting mortality in VA-ECMO patients.

Association of inactivated COVID-19 vaccination with maternal coagulation function in early pregnancy.

Reports of rare but severe thrombotic events after receiving some COVID-19 vaccines brought concerns for the possibility of vaccine-induced coagulation abnormality. However, no study has reported the impacts of COVID-19 vaccination on coagulation function in pregnant women. We aimed to explore whether vaccination with inactivated COVID-19 vaccines before pregnancy was associated with coagulation changes in pregnant women. We conducted a retrospective cohort study in a tertiary-care hospital in Shanghai, China. A total of 5166 pregnant women were included, of whom 2721 (52.7%) completed vaccination before conception. Compared with unvaccinated women, the mean serum levels of prothrombin time (PT) and fibrinogen (FIB) were lower in vaccinated women by 0.09 (ß = -0.09, 95% confidence interval [CI], -0.13, -0.05) mg/L and 0.11 (ß = -0.11, 95% CI, -0.15, -0.07) mg/L, and the mean D-Dimer (D-D) levels were higher by 0.12 (ß = 0.12, 95% CI, 0.09, 0.15) mg/L. However, no significant association was observed between COVID-19 vaccination and serum levels of activated partial thromboplastin time (APTT), fibrinogen degradation product (FDP) or thrombin time (TT). Our findings suggested that inactivated COVID-19 vaccination before conception resulted in a small change in maternal coagulation function, but this might not have clinical significance.

p16INK4A flow cytometry of exfoliated cervical cells: Its role in quantitative pathology and clinical diagnosis of squamous intraepithelial lesions.

BACKGROUND: P16INK4A is a surrogate signature compensating for the specificity and/or sensitivity deficiencies of the human papillomavirus (HPV) DNA and Papanicolaou smear (Pap) co-test for detecting high-grade cervical squamous intraepithelial lesions or worse (HSIL+). However, traditional p16INK4A immunostaining is labour intensive and skill demanding, and subjective biases cannot be avoided. Herein, we created a high-throughput, quantitative diagnostic device, p16INK4A flow cytometry (FCM) and assessed its performances in cervical cancer screening and prevention. METHODS: P16INK4A FCM was built upon a novel antibody clone and a series of positive and negative (p16INK4A -knockout) standards. Since 2018, 24 100-women (HPV-positive/-negative, Pap-normal/-abnormal) have been enrolled nationwide for two-tier validation work. In cross-sectional studies, age- and viral genotype-dependent expression of p16INK4A was investigated, and optimal diagnostic parameter cut-offs (using colposcopy and biopsy as a gold standard) were obtained. In cohort studies, the 2-year prognostic values of p16INK4A were investigated with other risk factors by multivariate regression analyses in three cervicopathological conditions: HPV-positive Pap-normal, Pap-abnormal biopsy-negative and biopsy-confirmed LSIL. RESULTS: P16INK4A FCM detected a minimal ratio of 0.01% positive cells. The p16INK4A -positive ratio was 13.9 ± 1.8% among HPV-negative NILM women and peaked at the ages of 40-49 years; after HPV infection, the ratio increased to 15.1 ± 1.6%, varying with the carcinogenesis of the viral genotype. Further increments were found in women with neoplastic lesions (HPV-negative: 17.7 ± 5.0-21.4 ± 7.2%; HPV-positive: 18.0 ± 5.2-20.0 ± 9.9%). Extremely low expression of p16INK4A was observed in women with HSILs. As the HPV-combined double-cut-off-ratio criterion was adopted, a Youden's index of 0.78 was obtained, which was significantly higher than that (0.72) of the HPV and Pap co-test. The p16INK4A -abnormal situation was an independent HSIL+ risk factor for 2-year outcomes in all three cervicopathological conditions investigated (hazard ratios: 4.3-7.2). CONCLUSIONS: FCM-based p16INK4A quantification offers a better choice for conveniently and precisely monitoring the occurrence of HSIL+ and directing risk-stratification-based interventions.

Mitonuclear Interactions and the Origin of Macaque Societies.

In most eukaryotes, aerobic respiration requires interactions between autosomally encoded genes (Ninteract genes) and mitochondrial DNA, RNA, and protein. In species where females are philopatric, contrasting distributions of genetic variation in mitochondrial and nuclear genomes create variation in mitonuclear interactions that may be subject to natural selection. To test this expectation, we turned to a group with extreme female philopatry: the macaque monkeys. We examined four genomic data sets from (1) wild caught and (2) captive populations of rhesus macaque, which is the most widely distributed nonhuman primate, and (3) the stump-tailed macaque and (4) a subspecies of longtail macaque, both of whose mitochondrial DNA is introgressed from a highly diverged ancestor. We identified atypically long runs of homozygosity, low polymorphism, high differentiation, and/or rapid protein evolution associated with Ninteract genes compared with non-Ninteract genes. These metrics suggest a subset of Ninteract genes were independently subject to atypically pervasive natural selection in multiple species. These findings suggest that natural selection on mitonuclear interactions could have influenced several aspects of macaque societies including species diversity, ecological breadth, female-biased adult sex ratio and demography, sexual dimorphism, and mitonuclear phylogenomics.

m6A-related long noncoding RNAs predict prognosis and indicate therapeutic response in endometrial carcinoma.

BACKGROUND: N6-methyladenosine (m6A) has been identified as the most common, abundant, and conserved internal transcriptional modification. Long noncoding RNAs (lncRNAs) are noncoding RNAs consisting of more than 200 nucleotides, and the expression of various lncRNAs may affect cancer prognosis. The impact of m6A-associated lncRNAs on uterine corpus endometrial carcinoma (UCEC) prognosis is unknown. METHODS: In this study, UCEC prognosis-related m6A lncRNAs were screened, bioinformatics analysis was performed, and experimental validation was conducted. Endometrial carcinoma (EC) and normal tissue samples were obtained from The Cancer Genome Atlas. The prognosis-related m6A lncRNAs screened by the least absolute shrinkage and selection operator method were used for multivariate Cox proportional risk regression modeling. Principal component analysis and Gene Ontology, immune function difference, and drug sensitivity analyses of the prognostic models were performed. Prognostic analysis was conducted for m6A-associated lncRNAs. The immune infiltration relationship of m6A-associated lncRNAs in EC was identified using the ssGSEA immune infiltration algorithm. A competing endogenouse RNA network was constructed using the LncACTdb database. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) assays were used to validate the differences in m6A-related lncRNA expression in normal and EC cells. RESULTS: CDKN2B-AS1 and MIR924HG were found to be risk factors for EC. RAB11B-AS1 was a protective factor in EC patients. MIR924HG expression was upregulated in KLE and RL95-2 endometrial cancer cell lines. Prognostic models involved RAB11B-AS1, LINC01812, HM13-IT1, TPM1-AS, SLC16A1-AS1, LINC01936, and CDKN2B-AS1. The high-risk group was more sensitive to five compounds (ABT.263, ABT.888, AP.24534, ATRA, and AZD.0530) than the low-risk group. CONCLUSION: These findings contribute to understanding of the function of m6A-related lncRNAs in UCEC and provide promising therapeutic strategies for UCEC.

Herpesvirus entry mediator regulates the transduction of Tregs via STAT5/Foxp3 signaling pathway in ovarian cancer cells.

The ratio of regulatory T cells (Treg) in peripheral blood of cancer patients has a closely correlation to the occurrence and development of ovarian cancer. In this study, our aim to explore the expression of herpesvirus entry mediator (HVEM) in ovarian cancer and its correlation with Tregs. The expression of HVEM in peripheral blood of ovarian cancer patients was detected by ELISA, and the ratio of CD4+ CD25 + Foxp3 positive Tregs cells was detected by flow cytometry. Ovarian cancer cell lines with high- and low-HVEM expression were constructed. CD4+ cells were co-cultured with ovarian cancer (OC) cells, and the expressions of IL-2 and TGF-ß1 in the supernatant of cells were detected by ELISA, and western blot was used to detect the expressions of STAT5, p-STAT5, and Foxp3. The results indicated that the number of Treg cells in the peripheral blood of OC patients increased, and the expression of HVEM increased, the two have a certain correlation. At the same time, the overexpression of HVEM promoted the expression of cytokines IL-2 and TGF- ß1, promoted the activation of STAT5 and the expression of Foxp3, leading to an increase in the positive rate of Treg, while the HVEM gene silence group was just the opposite. Our results showed that the expression of HVEM in OC cells has a positive regulation effect on Tregs through the STAT5/Foxp3 signaling pathway. To provide experimental basis and related mechanism for the clinical treatment of ovarian cancer.

Anterior Gradient 2 is a Significant Prognostic Biomarker in Bone Metastasis of Breast Cancer.

Background: The study aimed to detect DEGs associated with BRCA bone metastasis, filter prognosis biomarkers, and explore possible pathways. Methods: GSE175692 dataset was used to detect DEGs between BRCA bone metastatic cases and non-bone metastatic cases, followed by the construction of a PPI network among DEGs. The main module among the PPI network was then determined and pathway analysis on genes within the module was performed. Through performing Cox regression, Kaplan-Meier, nomogram, and ROC curve analyses using GSE175692 and GSE124647 datasets at the same time, the most significant prognostic biomarker was gradually filtered. Finally, important pathways associated with prognostic biomarkers were explored by GSEA analysis. Results: The 74 DEGs were detected between bone metastasis and non-bone metastasis groups. A total of 15 nodes were included in the main module among the whole PPI network and they mainly correlated with the IL-17 signaling pathway. We then performed Cox analysis on 15 genes using two datasets and only enrolled the genes with p < 0.05 in Cox analysis into the further analyses. Kaplan-Meier analyses using two datasets showed that the common biomarker AGR2 expression was related to the survival time of BRCA metastatic cases. Further, the nomogram determined the greatest contribution of AGR2 on the survival probability and the ROC curve revealed its optimal prognostic performance. More importantly, high expression of AGR2 prolonged the survival time of BRCA bone metastatic patients. These results all suggested the importance of AGR2 in metastatic BRCA. Finally, we performed the GSEA analysis and found that AGR2 was negatively related to IL-17 and NF-kß signaling pathways. Conclusion: AGR2 was finally determined as the most important prognostic biomarker in BRCA bone metastasis, and it may play a vital role in cancer progression by regulating IL-17 and NF-kB signaling pathways.