Development and evaluation of the Newstage system: integrating tumor regression grade and lymph node status for improved prognostication in neoadjuvant treatment of gastric cancer.

BACKGROUND: The predictive correlation of tumor depth of invasion changes after neoadjuvant therapy, and the 8th American Joint Committee on Cancer (AJCC) ypTNM system for gastric cancer may not accurately predict patient prognosis following neoadjuvant therapy. METHODS: A retrospective analysis was conducted on a total of 258 patients who underwent radical surgery for gastric cancer after neoadjuvant therapy. The Newstage system was established based on tumor regression grade and pathological lymph node status. The 3-year survival rates of patients classified by the Newstage system were compared with those classified by the AJCC ypTNM system. RESULTS: In a cohort of 258 patients, the 3-year overall survival rates based on the Newstage system were: (I) 94.6%, (II) 79.3%, (III) 54.5%, and (IV) 30.2%. The Newstage system exhibited a lower Akaike information criterion value (902.57 vs. 912.03). Additionally, the area under the ROC curve (0.756 vs. 0.733) and the C-index (0.731 vs. 0.718) was higher than the AJCC ypTNM system. Furthermore, a multivariate analysis indicated that the Newstage system was an independent prognostic factor (p = 0.001). CONCLUSION: The Newstage system exhibits superior predictive performance in estimating survival rates for neoadjuvant therapy in gastric cancer. It also functions as an independent prognostic factor.

X-ray inhibits FUT4-mediated proliferation in A549 cells by downregulating SP1 expression.

Objective: To identify the mechanism of down-regulation of Lewis Y antigen caused by X-ray irradiation. METHODS: The present original research study was conducted at Zhejiang University City College, Hangzhou, Republic of China, from 2020 to 2022. Western blotting, Co-immunoprecipitation (CO-IP), electrophoretic mobility shift assay and Cell Counting Kit-8 (CCK8) were performed to confirm the effect of X-ray irradiation on A549 cell proliferation and its mechanism. Data was analysed using Statistical Package for Social Sciences (SPSS) 11.5. RESULTS: The expressions of fucosyltransferase IV and Lewis Y were decreased after X-ray irradiation, thus inhibiting the proliferation of A549 lung cancer cells. Deoxyribonucleic acid damage caused by the irradiation caused higher level of poly- adenosinediphosphate-ribosylated Specific Protein 1(SP1), and translocation of SP1 from the nucleus, decreasing the expression of fucosyltransferase IV and Lewis Y. Conclusion: There was a significant role of glycosylation in radiation therapy for lung cancer.

A novel glycosylation-related gene signature predicts survival in patients with lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the most common malignant tumor that seriously affects human health. Previous studies have indicated that abnormal levels of glycosylation promote progression and poor prognosis of lung cancer. Thus, the present study aimed to explore the prognostic signature related to glycosyltransferases (GTs) for LUAD. METHODS: The gene expression profiles were obtained from The Cancer Genome Atlas (TCGA) database, and GTs were obtained from the GlycomeDB database. Differentially expressed GTs-related genes (DGTs) were identified using edge package and Venn diagram. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and ingenuity pathway analysis (IPA) methods were used to investigate the biological processes of DGTs. Subsequently, Cox and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct a prognostic model for LUAD. Kaplan-Meier (K-M) analysis was adopted to explore the overall survival (OS) of LUAD patients. The accuracy and specificity of the prognostic model were evaluated by receiver operating characteristic analysis (ROC). In addition, single-sample gene set enrichment analysis (ssGSEA) algorithm was used to analyze the infiltrating immune cells in the tumor environment. RESULTS: A total of 48 DGTs were mainly enriched in the processes of glycosylation, glycoprotein biosynthetic process, glycosphingolipid biosynthesis-lacto and neolacto series, and cell-mediated immune response. Furthermore, B3GNT3, MFNG, GYLTL1B, ALG3, and GALNT13 were screened as prognostic genes to construct a risk model for LUAD, and the LUAD patients were divided into high- and low-risk groups. K-M curve suggested that patients with a high-risk score had shorter OS than those with a low-risk score. The ROC analysis demonstrated that the risk model efficiently diagnoses LUAD. Additionally, the proportion of infiltrating aDCs (p < 0.05) and Tgds (p < 0.01) was higher in the high-risk group than in the low-risk group. Spearman's correlation analysis manifested that the prognostic genes (MFNG and ALG3) were significantly correlated with infiltrating immune cells. CONCLUSION: In summary, this study established a novel GTs-related risk model for the prognosis of LUAD patients, providing new therapeutic targets for LUAD. However, the biological role of glycosylation-related genes in LUAD needs to be explored further.

Prognostic value of preoperative soluble interleukin 2 receptor α as a novel immune biomarker in epithelial ovarian cancer.

PURPOSE: Epithelial ovarian cancer (EOC) is regarded as the deadliest gynecological cancer, and the demand for novel noninvasive prognostic biomarkers remains significant. This study aimed to investigate the prognostic value of preoperative blood biomarkers in EOC patients. METHODS: In total, 73 patients who had undergone ovarian mass resection were enrolled. Serum concentration of biomarkers, including soluble interleukin 2 receptor α (sIL-2R), was measured 1-2 weeks before surgery. Independent prognostic factors for progression-free survival (PFS) were investigated with multivariate Cox regression analysis. A prognostic model was subsequently developed and evaluated by discrimination, calibration and clinical net benefit. Furthermore, transcriptome data of 376 EOC cases from The Cancer Genome Atlas (TCGA) were analyzed with ESTIMATE, CIBERSORT and Maftools algorithm to evaluate the correlation of IL2RA expression with tumor immune microenvironment and immunotherapeutic response. RESULTS: High sIL-2R concentration was found to be the only significant prognostic blood biomarker for PFS by multivariate Cox regression analysis in our center. A prognostic nomogram was developed with satisfactory discrimination, calibration and clinical net benefit. In addition, higher IL2RA expression was significantly associated with higher immune scores, activated CD4+ T cells, M2 macrophages and resting dendritic cells in TCGA data. Furthermore, IL2RA expression was closely related to TMB scores. CONCLUSIONS: sIL-2R is a potential prognostic immune biomarker for EOC patients, and a comprehensive prognostic model comprising sIL-2R with satisfactory discrimination and clinical appliance was developed. Therefore, we recommend routine sIL-2R testing in EOC patients.

Effects of neoadjuvant hyperthermic intraperitoneal chemotherapy on chemotherapy response score and recurrence in high-grade serous ovarian cancer patients with advanced disease: A multicentre retrospective cohort study.

OBJECTIVE: To investigate whether the combination of neoadjuvant hyperthermic intraperitoneal chemotherapy (NHIPEC) plus intravenous neoadjuvant chemotherapy (IV NACT) has superior efficacy to IV NACT alone. DESIGN: Retrospective cohort study. SETTING: Two tertiary referral university hospitals. POPULATION: Patients with ovarian cancer who received NACT-interval debulking surgery (IDS) between 2012 and 2020. METHODS: The tumour response to NACT was evaluated with the chemotherapy response score (CRS) system. Survival outcomes were compared. MAIN OUTCOME MEASURES: CRS 3, progression-free survival (PFS), and overall survival (OS). RESULTS: In total, 127 patients were included, and 46 received NHIPEC plus IV NACT. The addition of NHIPEC was independently associated with an increased likelihood of CRS 3 (p = 0.033). Patients who received NHIPEC + IV NACT had significantly improved PFS compared with those who received IV NACT alone (median PFS: 22 versus 16 months, p < 0.001). The use of NHIPEC was identified as an independent predictor of PFS (p < 0.0001). OS did not differ significantly between treatment groups (p = 0.062), although a trend favouring NHIPEC was noted. Incidence of grade 3-4 adverse events and the surgical complexity score of IDS were similar between the two groups. CONCLUSIONS: Compared with IV NACT alone, the combination of NHIPEC and IV NACT resulted in improved tumour response and longer PFS. The addition of NHIPEC did not increase the risk of adverse effects or affect the complexity of IDS.

Vascular endothelial cell-derived exosomal miR-30a-5p inhibits lung adenocarcinoma malignant progression by targeting CCNE2.

This study tried to explore the molecular mechanism underlying progression of lung adenocarcinoma (LUAD) and discuss the extracellular communication between cancer cells and vascular endothelial cells. Roughly, differential analysis was carried out to note that miR-30a-5p was lowly expressed in LUAD, whereas CCNE2 was highly expressed. Cell functional experiments demonstrated that overexpressed miR-30a-5p led to suppressed cell abilities in proliferation, migration and invasion. Dual-luciferase reporter gene assay and RNA immunoprecipitation verified the binding of miR-30a-5p and CCNE2, as well as decreased mRNA and protein expression of CCNE2 with miR-30a-5p overexpression. Simultaneous up-regulation of miR-30a-5p and CCNE2 reversed the promotion of CCNE2 on malignant behaviors of LUAD cells. In vivo mice experiments exhibited that high miR-30a-5p expression hindered tumor growth. Additionally, miR-30a-5p was localized on the Extracellular Vesicles microRNA (EVmiRNA) database. MiR-30a-5p was abundant in exosomes derived from vascular endothelial cells. To validate that miR-30a-5p could be delivered to LUAD cells via exosomes and then make an effect, exosomes from vascular endothelial cells were first extracted and identified by transmission electron microscopy and detection of exosomal marker proteins (Alix, CD63, TSG101). Sequentially, the extracted exosomes were labeled with DIO to note that exosomes could be internalized by cancer cells. Further experiments indicated that miR-30a-5p was increased in cancer cells co-cultured with exosomes, which in turn suppressed cell malignant behaviors and made cell cycle arrest. In all, our findings clarified that exosomes derived from vascular endothelial cells delivered miR-30a-5p to LUAD cells to affect tumor malignant progression via the miR-30a-5p/CCNE2 axis.

FUT4siRNA augments the chemosensitivity of non-small cell lung cancer to cisplatin through activation of FOXO1-induced apoptosis.

BACKGROUND: Increased fucosylation is associated with the chemoresistance phenotype. Meanwhile, fucosyltransferase IV (FUT4) amounts are frequently elevated in lung cancer and may be related to increased chemoresistance. METHODS: In the present work, FUT4's role in cisplatin-induced apoptosis was assessed in A549 and H1975 cells, respectively. To clarify whether the FUT4 gene attenuates chemosensitivity in tumor cells, we constructed FUT4siRNA and evaluated its effects on cisplatin-induced apoptosis and cell growth inhibition. Cell viability, apoptosis, migration and invasion assay were conducted to investigate cisplatin sensitivity. The activation of EGFR/AKT/FOXO1 signaling were measured by western blot. The translocation of FOXO1 was assessed by IFC using Laser Scanning Confocal Microscope. RESULTS: We found that FUT4 knockdown dose-dependently increased cisplatin-associated cytotoxicity. Furthermore, FUT4 silencing induced apoptosis and inhibited proliferation in A549 and H1975 cells by suppressing Akt and FOXO1 phosphorylation induced by cisplatin administration, which resulted in nuclear translocation of FOXO1. CONCLUSION: These results suggested FUT4 might control chemoresistance to cisplatin in lung cancer by suppressing FOXO1-induced apoptosis.

Use of Laparoscopic Slip Knot with Purse-String Suture in Surgical Management of Unruptured Heterotopic Interstitial Pregnancies.

BACKGROUND The aim of this study was to investigate the advantages and disadvantages of using laparoscopic slip knot with purse-string suture technique in the surgical management of unruptured heterotopic interstitial pregnancies compared with other surgical strategies. MATERIAL AND METHODS We retrospectively analyzed data on 13 patients with unruptured heterotopic interstitial pregnancies who underwent laparoscopy in our hospital between May 2012 and August 2018. The control group consisted of 10 patients who underwent cornual resection or cornuostomy with conventional sutures and knots. The study group consisted of 3 patients whose surgical plans involved use of the slip knot with purse-string suture technique followed by cornuostomy. We evaluated the surgical records and video to comparatively analyze their operation duration, intraoperative blood loss, and pregnancy outcomes. RESULTS The average volume of intraoperative blood loss was 76.67±25 ml in the study group and 215.00±110 ml in the control group. On average, the intraoperative blood loss volume in the study group was 138 ml less than in the control group and the difference was statistically significant (P<0.05). There was no statistically significant difference in the live birth rate and operation time between the 2 groups (P>0.05). The duration of hemostasis in the study group was 11 min shorter than in the control group, while the duration of cornual electrocoagulation in the study group was 18.5 s shorter. Both groups achieved thorough hemostasis without the help of vasopressin and avoided use of embryo-killing drugs such as methotrexate. Neither group required second surgery or developed postoperative complications such as uterus rupture or persistent ectopic pregnancy. CONCLUSIONS This strategy is safe and reliable for gestational sac clearance while simultaneously preventing any potential harm to the intrauterine embryo. It is particularly suitable for unruptured HIP patients who have a strong desire to preserve their intrauterine embryos.

Elevated CA-125 Level and ER-Negative as Prognostic Factors for Ovarian Metastasis in Patients with Endometrial Cancer: A Retrospective Cohort Study.

BACKGROUND The utility of cancer antigen 125 (CA-125), estrogen receptor (ER), and progesterone receptor (PR) in evaluation for ovarian metastasis of endometrial cancer has yet to be determined. The purpose of this study was to investigate the incidence and the possible risk factors of ovarian metastasis. MATERIAL AND METHODS A retrospective study was performed in endometrial cancer patients who accepted surgical intervention of hysterectomy and oophorectomy during 2002-2013 in Sun Yat-sen Memorial Hospital, Sun Yat-sen University, China. Clinico-pathologic characteristics and the possible risk factors were investigated. RESULTS A total of 565 patients were identified, of which 5.7% had ovarian metastasis. Univariate analysis and multivariate analysis revealed that deeper myometrial invasion, tubal involvement, and parametrial involvement were independent risk factors. In subgroup analysis, univariate analysis showed that elevated CA-125 level and negative ER were associated with ovarian metastasis (P<0.05), however multivariate analysis revealed that only high CA-125 level was an independent risk factor (P<0.05). The incidence of ovarian metastasis in patients with high CA-125 level and who were ER-negative was 24%. For patients with normal CA-125 level and who were ER-positive, the incidence was 1.19%. The optimal cutoff value that provided the best sensitivity and specificity was 110.5 U/ml. CONCLUSIONS The incidence of ovarian metastasis in endometrial cancer is low. Ovarian preservation should be considered for women without abnormal CA-125 level and who have deeper myometrial invasion, tubal involvement, parametrial involvement, and who are ER-negative. These findings may facilitate clinical decision-making.

Aldehyde Dehydrogenase 1 Expression Predicts Chemoresistance and Poor Clinical Outcomes in Patients with Locally Advanced Cervical Cancer Treated with Neoadjuvant Chemotherapy Prior to Radical Hysterectomy.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is an important treatment strategy for cervical cancer; however, few predictive markers of the response to NAC exist. Aldehyde dehydrogenase 1 (ALDH1), a cancer stem cell marker, is associated with chemoresistance in a variety of cancers. This study attempted to investigate the value of ALDH1 as a predictive marker of chemosensitivity and its prognostic value in cervical cancer patients treated with NAC. METHODS: Immunohistochemistry was used to evaluate ALDH1 expression in matched pre- and post-NAC tumor samples from 52 patients with cervical cancer. Kaplan-Meier analysis and a Cox proportional hazards regression model were applied to determine overall survival (OS) and disease-free survival (DFS). RESULTS: Fourteen patients (26.9 %) had ALDH1-positive tumors pre-NAC, and ALDH1 expression pre-NAC was significantly associated with a low clinical chemotherapy response rate and clinical non-response. Twenty-two patients (42.3 %) had ALDH1-positive tumors post-NAC, and ALDH1 expression post-NAC was associated with poor DFS and OS (both p = 0.004). Multivariate analysis revealed that ALDH1 expression post-NAC was an independent prognostic factor for OS (hazard ratio 3.513; p = 0.033). Moreover, we observed that ALDH1 expression was increased after NAC in 18 patients (36.7 %). Increased levels of ALDH1 expression after NAC predicted poor DFS and OS (p = 0.013 and p = 0.08, respectively). CONCLUSIONS: Our findings suggest that ALDH1 expression pre-NAC may be a predictive marker for response to NAC, and ALDH1 expression post-NAC could be a prognostic marker for cervical cancer.

Exposure to radiation therapy is associated with female reproductive health among childhood cancer survivors: a meta-analysis study.

BACKGROUND AND AIMS: Many epidemiological studies have revealed a positive correlation between medical radiation exposure and the reproductive health in female childhood cancer survivors. However, because of variations in the samples size, such studies showed partly inconsistent conclusions. The aim of this meta-analysis was to clarify the association between radiotherapy and the risk of reproductive health impairment for female who survived from childhood cancer. METHODS: Fourteen cohort studies involving childhood radiotherapy were selected as the exposure of interest and the impaired reproductive health condition during the childbearing age as the outcome. Among meta-analysis of observational studies found in Pubmed and Embase from 1900 to 2014, we evaluated those relevant observational studies which surveyed the association of medical radiation and reproductive health in female childhood cancer survivors. Review Manager 5.2 and STATA 12.0 software were used to perform the meta-analysis. Study-specific estimations for each outcome were combined into a pooled relative risk (RR) with 95% confidence interval (CI) by a meta-analytic approach. RESULTS: Based on a random-effects meta-analysis, significant association between infertility (RR = 1.28, 95% CI = 1.16-1.42), acute ovarian failure (AOF) (RR = 9.51, 95% CI = 5.03-17.96), low level of anti mullerian hormone (AMH) (<1 ng/mL) (RR = 14.79, 95% CI = 3.36-66.64), stillbirth (RR = 1.19, 95% CI = 1.02-1.39) and low birth weight (RR = 2.22, 95% CI = 1.55-3.17) were identified. Conversely, no significant results were found in abortion and congenital malformations. CONCLUSIONS: To the best of our knowledge, this is the first meta-analysis assessing the effect of medical radiation on female childhood cancer survivors' reproductive capability and pregnancy outcomes. Although there were some limitations, our meta-analysis further supported that radiotherapy was a risk factor for reproductive health problems of female who survived from childhood cancer.

Burdens of stomach and esophageal cancer from 1990 to 2019 and projection to 2030 in China: Findings from the 2019 Global Burden of Disease Study.

Background: Stomach and esophageal cancer exhibit high morbidity and mortality rate in China, resulting in substantial disease burdens. It is imperative to identify the temporal trends of stomach and esophageal cancer from 1990 to 2019 and project future trends until 2030, which can provide valuable information for planning effective management and prevention strategies. Methods: We collected and analysed data from the Global Burden of Disease (GBD) between 1990 and 2019, including incidence, mortality, disability-adjusted life years (DALYs), age-standardised incidence rate (ASIR), mortality rate (ASMR) and DALYs rate. We also calculated and reported the proportion of mortality and DALYs attributable to risk factors by sex in China and different regions. The Bayesian age-period-cohort model was applied to project future trends until 2030. Results: The new cases, deaths and DALYs of stomach and esophageal cancer increased from 1990 to 2019. However, the ASIR, ASMR and age-standardised DALYs rates for stomach and esophageal cancer all decreased during the same period. These changes may be related to risks, such as smoking and diet. Furthermore, we utilised the projection model to estimate that the ASIR and ASMR of stomach and esophageal cancer among females will likely follow steady downward trends, while the ASMR of stomach cancer among males is expected to exhibit a significant decline. However, the ASIR of stomach and esophageal cancer and the ASMR of esophageal cancer among males are projected to display slight upward trends until 2030. Conclusions: The analysis of stomach and esophageal cancer trends in China from 1990 to 2030 reveals a general decline. However, it is crucial to acknowledge the persistent high burden of both cancers in the country. Adopting healthy lifestyle practices, including the reduction of tobacco and alcohol intake, avoidance of moldy foods and increased consumption of fresh fruits and vegetables can contribute to mitigating the risk of stomach and esophageal cancer. Significantly, the formulation and implementation of well-founded and efficacious public health policies are imperative for alleviating the disease burden in China.

MAGOH promotes gastric cancer progression via hnRNPA1 expression inhibition-mediated RONΔ160/PI3K/AKT signaling pathway activation.

BACKGROUND: Gastric cancer (GC) is associated with high mortality and heterogeneity and poses a great threat to humans. Gene therapies for the receptor tyrosine kinase RON and its spliceosomes are attracting increasing amounts of attention due to their unique characteristics. However, little is known about the mechanism involved in the formation of the RON mRNA alternative spliceosome RONΔ160. METHODS: Fourteen human GC tissue samples and six normal gastric tissue samples were subjected to label-free relative quantitative proteomics analysis, and MAGOH was identified as a candidate protein for subsequent studies. The expression of MAGOH in clinical specimens was verified by quantitative real-time PCR and western blotting. We then determined the biological function of MAGOH in GC through in vitro and in vivo experiments. RNA pulldown, RNA sequencing and RNA immunoprecipitation (RIP) were subsequently conducted to uncover the underlying mechanism by which MAGOH regulated the formation of RONΔ160. RESULTS: Proteomic analysis revealed that MAGOH, which is located at key nodes and participates in RNA processing and mRNA splicing, was upregulated in GC tissue and GC cell lines and was associated with poor prognosis. Functional analysis showed that MAGOH promoted the proliferation, migration and invasion of GC cells in vitro and in vivo. Mechanistically, MAGOH inhibited the expression of hnRNPA1 and reduced the binding of hnRNPA1 to RON mRNA, thereby promoting the formation of RONΔ160 to activate the PI3K/AKT signaling pathway and consequently facilitating GC progression. CONCLUSIONS: Our study revealed that MAGOH could promote the formation of RONΔ160 and activate the PI3K/AKT signaling pathway through the inhibition of hnRNPA1 expression. We elucidate a novel mechanism and potential therapeutic targets for the growth and metastasis of GC based on the MAGOH-RONΔ160 axis, and these findings have important guiding significance and clinical value for the future development of effective therapeutic strategies for GC.

Tissue-location-specific transcription programs drive tumor dependencies in colon cancer.

Cancers of the same tissue-type but in anatomically distinct locations exhibit different molecular dependencies for tumorigenesis. Proximal and distal colon cancers exemplify such characteristics, with BRAFV600E predominantly occurring in proximal colon cancers along with increased DNA methylation phenotype. Using mouse colon organoids, here we show that proximal and distal colon stem cells have distinct transcriptional programs that regulate stemness and differentiation. We identify that the homeobox transcription factor, CDX2, which is silenced by DNA methylation in proximal colon cancers, is a key mediator of the differential transcriptional programs. Cdx2-mediated proximal colon-specific transcriptional program concurrently is tumor suppressive, and Cdx2 loss sufficiently creates permissive state for BRAFV600E-driven transformation. Human proximal colon cancers with CDX2 downregulation showed similar transcriptional program as in mouse proximal organoids with Cdx2 loss. Developmental transcription factors, such as CDX2, are thus critical in maintaining tissue-location specific transcriptional programs that create tissue-type origin specific dependencies for tumor development.

Optimization Co-Culture of Monascus purpureus and Saccharomyces cerevisiae on Selenium-Enriched Lentinus edodes for Increased Monacolin K Production.

Selenium-enriched Lentinus edodes (SL) is a kind of edible fungi rich in organic selenium and nutrients. Monascus purpureus with high monacolin K (MK) production and Saccharomyces cerevisiae were selected as the fermentation strains. A single-factor experiment and response surface methodology were conducted to optimize the production conditions for MK with higher contents from selenium-enriched Lentinus edodes fermentation (SLF). Furthermore, we investigated the nutritional components, antioxidant capacities, and volatile organic compounds (VOCs) of SLF. The MK content in the fermentation was 2.42 mg/g under optimal fermentation conditions. The organic selenium content of SLF was 7.22 mg/kg, accounting for 98% of the total selenium content. Moreover, the contents of total sugars, proteins, amino acids, reducing sugars, crude fiber, fat, and ash in SLF were increased by 9%, 23%, 23%, 94%, 38%, 44%, and 25%, respectively. The antioxidant test results demonstrated that 1.0 mg/mL of SLF exhibited scavenging capacities of 40%, 70%, and 79% for DPPH, ABTS, and hydroxyl radicals, respectively. Using gas chromatography-ion mobility spectrometry technology, 34 unique VOCs were identified in SLF, with esters, alcohols, and ketones being the main components of its aroma. This study showed that fungal fermentation provides a theoretical reference for enhancing the nutritional value of SL.

Exploration of tumor-suppressive microRNAs silenced by DNA hypermethylation in cervical cancer.

BACKGROUND: Multiple studies proved that miRNAs have a causal role in tumorigenesis. Some miRNAs are regulated by epigenetic alterations in their promoter regions and can be activated by chromatin- modifying drugs. METHODS: We treated cervical cancer cells with 5-aza-2'-deoxycytidine and get a microarray analysis. Dysregulation of miRNAs was measured by qPCR in cervical cell lines and methylation status of them in cervical cancer tissue were performed with MeDIP-qPCR assay. RESULTS: We found hypermethylation of miR-432, miR-1286, miR-641, miR-1290, miR-1287 and miR-95 may have some relationship with HPV infection in cervical cell lines. In primary tumors of cervix with paired normal tissue, expression levels of miRNAs were inversely correlated with their DNA methylation status in the cervical cancer cell lines treated with 5-AZA. CONCLUSIONS: Our results indicate that miRNAs might play a role in the pathogenesis of human cervical cancer with HPV and identify altered miRNA methylation as a possible epigenetic mechanism involved in their aberrant expression.

Determinants and Assessment of Menstrual Blood Flow.

Purpose of review: a)The modifiable and non-modifiable determinants and the currently available methods of assessment of menstrual blood flow will be discussed, with the goal of helping healthcare providers, researchers, and those interested in public health. Recent findings: b)Several factors can impact menstruation. The determinants include modifiable factors such as smoking, nutrition, exercise, stress, weight fluctuation, and benign gynecologic diseases, and non-modifiable factors such as age, race, and the individual's genes. The intertwined dynamic among these determinants needs more critical attention. Currently, the methods for the assessment of menstruation all have advantages and disadvantages, often with a tradeoff between practicality and accuracy. Summary: c)Considered by many as the fifth vital, menstruation provides a window to an individual's general health. The discussion of its determinants and assessment can be more appropriate for individual contexts, especially from a public health perspective as it can improve the reproductive health of the population.

Menstruation in the USA.

Purpose of review: Menstruation touches all spheres of human society, including psychology, education, business, policy, race, and religion. This narrative review aims to describe the relationship menstruation holds with these spaces. Recent findings: First, menstruation plays many roles in psychology - premenstrual syndrome affects psychological wellbeing and in turn, psychological stress impacts menstruation. Functional hypothalamic amenorrhea can result when stress hormones inhibit the Hypothalamus-Pituitary-Ovarian axis. Furthermore, menstruation has many implications for all aged individuals, especially adolescents and those who are menopausal. These implications underscore the importance of proper education surrounding menstruation, which can be achieved via social media, school systems, family, and clinicians. However, menstrual health education is highly variable depending on the state and family that someone is raised in. Additionally, menstruation can pose a financial burden as menstrual products can be expensive and access to these products is limited for those who are homeless, incarcerated, and low-income. Recent public policy measures in various states have aimed to achieve "menstrual equity," by requiring public schools to supply free menstrual products in bathrooms. Furthermore, racial disparities exist with menstrual disorders. Uterine fibroids occur more frequently in Black menstruators compared to White menstruators, and Black women experience worse outcomes overall with fibroids and endometriosis management. Finally, analysis of religion and its relationship to menstruation underscores the immense stigma and "impurity" associated with menstruation. Summary: Overall, this review highlights the universality of menstruation in society. As a "fifth vital sign", there is significant room for improvement in terms of education, research, and cultural acceptance of menstruation. Future research should explore interventions to reduce these gaps.

Oxidative Stress and Antioxidants in Uterine Fibroids: Pathophysiology and Clinical Implications.

In the last few decades, our understanding of the complex pathobiology of uterine fibroid development has grown. While previously believed to be a purely neoplastic entity, we now understand that uterine fibroids possess different and equally important aspects of their genesis. An increasing body of evidence suggests that oxidative stress, the imbalance between pro- and antioxidants, is an important factor in fibroid development. Oxidative stress is controlled by multiple, interconnecting cascades, including angiogenesis, hypoxia, and dietary factors. Oxidative stress in turn influences fibroid development through genetic, epigenetic, and profibrotic mechanisms. This unique aspect of fibroid pathobiology has introduced several clinical implications, both diagnostic and therapeutic, that can aid us in managing these debilitating tumors by using biomarkers as well as dietary and pharmaceutical antioxidants for diagnosis and treatment. This review strives to summarize and add to the current evidence revealing the relationship between oxidative stress and uterine fibroids by elucidating the proposed mechanisms and clinical implications.

Bilateral Salpingo-Oophorectomy for Intracardiac Leiomyomatosis: A Case Report.

BACKGROUND Intracardiac leiomyomatosis (ICLM) is an extremely rare tumor which is benign but presents with aggressive behavior. To date, there is still no standard of care for ICLM therapy, and treatment for complicated ICLM has obtained even less attention. Radical surgery was usually recommended to remove the patients' tumors completely. Since initial complete surgical resection cannot be performed in all cases, bilateral salpingo-oophorectomy (BSO), via its effects of estrogen deprivation, may be a feasible primary step in the treatment of premenopausal women with unresectable ICLM. CASE REPORT We describe a case of a residual mass in the inferior vena cava and right atrium that shrank dramatically after BSO. The patient was a 41-year-old woman with initially unresectable ICLM. Total hysterectomy with BSO and excision of the retroperitoneal mass was performed, but the intracaval tumor above L5 was not removed. Pathology revealed a benign leiomyoma which was strongly positive for both estrogen receptor and progesterone receptor. Two weeks after the BSO, the patient's serum estradiol level had decreased to a postmenopausal level. At the same time, the proximal end of the intracaval tumor shrank dramatically from the level of the right atrium to the level of L3 only 2 weeks after the surgery. Therefore, this may provide a therapeutic window for a second reduction surgery. CONCLUSIONS BSO, via its estrogen deprivation effect, may provide a simple but effective initial treatment choice for premenopausal women who suffer from primary unresectable ICLM.