Cesarean hysterectomy for placenta accreta spectrum: Surgeon specialty-specific assessment.

OBJECTIVE: To assess (i) clinical and pregnancy characteristics, (ii) patterns of surgical procedures, and (iii) surgical morbidity associated with cesarean hysterectomy for placenta accreta spectrum based on the specialty of the attending surgeon. METHODS: The Premier Healthcare Database was queried retrospectively to study patients with placenta accreta spectrum who underwent cesarean delivery and concurrent hysterectomy from 2016 to 2020. Surgical morbidity was assessed with propensity score inverse probability of treatment weighting based on surgeon specialty for hysterectomy: general obstetrician-gynecologists, maternal-fetal medicine specialists, and gynecologic oncologists. RESULTS: A total of 2240 cesarean hysterectomies were studies. The most common surgeon type was general obstetrician-gynecologist (n = 1534, 68.5%), followed by gynecologic oncologist (n = 532, 23.8%) and maternal-fetal medicine specialist (n = 174, 7.8%). Patients in the gynecologic oncologist group had the highest rate of placenta increta or percreta, followed by the maternal-fetal medicine specialist and general obstetrician-gynecologist groups (43.4%, 39.6%, and 30.6%, P < .001). In a propensity score-weighted model, measured surgical morbidity was similar across the three subspecialty groups, including hemorrhage / blood transfusion (59.4-63.7%), bladder injury (18.3-24.0%), ureteral injury (2.2-4.3%), shock (8.6-10.5%), and coagulopathy (3.3-7.4%) (all, P > .05). Among the cesarean hysterectomy performed by gynecologic oncologist, hemorrhage / transfusion rates remained substantial despite additional surgical procedures: tranexamic acid / ureteral stent (60.4%), tranexamic acid / endo-arterial procedure (76.2%), ureteral stent / endo-arterial procedure (51.6%), and all three procedures (55.4%). Tranexamic acid administration with ureteral stent placement was associated with decreased bladder injury (12.8% vs 23.8-32.2%, P < .001). CONCLUSION: These data suggest that patient characteristics and surgical procedures related to cesarean hysterectomy for placenta accreta spectrum differ based on surgeon specialty. Gynecologic oncologists appear to manage more severe forms of placenta accreta spectrum. Regardless of surgeon's specialty, surgical morbidity of cesarean hysterectomy for placenta accreta spectrum is significant.

Comparing survival of older ovarian cancer patients treated with neoadjuvant chemotherapy versus primary cytoreductive surgery: Reducing bias through machine learning.

OBJECTIVE: To develop and evaluate a multidimensional comorbidity index (MCI) that identifies ovarian cancer patients at risk of early mortality more accurately than the Charlson Comorbidity Index (CCI) for use in health services research. METHODS: We utilized SEER-Medicare data to identify patients with stage IIIC and IV ovarian cancer, diagnosed in 2010-2015. We employed partial least squares regression, a supervised machine learning algorithm, to develop the MCI by extracting latent factors that optimally captured the variation in health insurance claims made in the year preceding cancer diagnosis, and 1-year mortality. We assessed the discrimination and calibration of the MCI for 1-year mortality and compared its performance to the commonly-used CCI. Finally, we evaluated the MCI's ability to reduce confounding in the association of neoadjuvant chemotherapy (NACT) and all-cause mortality. RESULTS: We included 4723 patients in the development cohort and 933 in the validation cohort. The MCI demonstrated good discrimination for 1-year mortality (c-index: 0.75, 95% CI: 0.72-0.79), while the CCI had poor discrimination (c-index: 0.59, 95% CI: 0.56-0.63). Calibration plots showed better agreement between predicted and observed 1-year mortality risk for the MCI compared with CCI. When comparing all-cause mortality between NACT with primary cytoreductive surgery, NACT was associated with a higher hazard of death (HR: 1.13, 95% CI: 1.04-1.23) after controlling for tumor characteristics, demographic factors, and the CCI. However, when controlling for the MCI instead of the CCI, there was no longer a significant difference (HR: 1.05, 95% CI: 0.96-1.14). CONCLUSIONS: The MCI outperformed the conventional CCI in predicting 1-year mortality, and reducing confounding due to differences in baseline health status in comparative effectiveness analysis of NACT versus primary surgery.

Structurally diverse cucurbitane-type triterpenoids from the tubers of Hemsleya chinensis with cytotoxic activity.

Ten previously undescribed cucurbitane-type triterpenoids, namely hemslyencins A-F (1-6) and hemslyencosides A-D (7-10), together with twenty previously reported compounds (11-30), were isolated from the tubers of Hemsleya chinensis. Their structures were elucidated by unambiguous spectroscopic data (UV, IR, HR-ESI-MS, 1D and 2D NMR data). Hemslyencins A and B (1 and 2) possessing unique 9, 11-seco-ring system with a six-membered lactone moiety, were the first examples among of the cucurbitane-type triterpenoids, and hemslyencins C and D (3 and 4) and hemslyencoside D (10) are the infrequent pentacyclic cucurbitane triterpenes featuring a 6/6/6/5/6 fused system. The cytotoxic activities of all isolated compounds were evaluated against MCF-7, HCT-116, HeLa, and HepG2 cancer cells, and their structure-activity relationships (SARs) was discussed as well. Compounds 17, 25, and 26 showed significant cytotoxic effects with IC50 values ranging from 1.31 to 9.89 µM, among which compound 25 induced both apoptosis and cell cycle arrest at G2/M phase in a dose dependent manner against MCF-7 cells.

Survival rates in Hispanic/Latinx subpopulations with cervical cancer associated with disparities in guideline-concordant care.

BACKGROUND: Failure to deliver guideline-concordant treatment may contribute to disparities among Hispanic/Latinx cervical cancer patients. This study investigated the association between survival rates in Hispanic/Latinx subpopulations and the provision of guideline-concordant care. METHODS: We analyzed patients with primary cervical cancer from 2004 to 2019 (National Cancer Database). We developed nine quality metrics based on FIGO staging (2009). Clinical and demographic covariates were analyzed using Chi-squared tests. Adjusted associations between receipt of guideline-concordant care and races and ethnicities were analyzed using multivariable marginal Poisson regression models. Adjusted Cox proportional hazard models were utilized to evaluate survival probability. RESULTS: A total of 95,589 patients were included. Hispanic/Latinx and Non-Hispanic Black (NHB) populations were less likely to receive guideline-concordant care in four and five out of nine quality metrics, respectively. Nonetheless, the Hispanic/Latinx group exhibited better survival outcomes in seven of nine quality metrics. Compared to Mexican patients, Cuban patients were 1.17 times as likely to receive timely initiation of treatment in early-stage disease (RR 1.17, 95% CI 1.04-1.37, p < 0.001). Puerto Rican and Dominican patients were, respectively, 1.16 (RR 1.16, 95% CI 1.07-1.27, p < 0.001) and 1.19 (RR 1.19, 95% 1.04-1.37, p > 0.01) times as likely to undergo timely initiation of treatment in early-stage disease. Patients of South or Central American (RR 1.18, 95% CI 1.10-1.27, p < 0.001) origin were more likely to undergo timely initiation of treatment in locally advanced disease. CONCLUSION: Significant differences in survival were identified among our cohort despite the receipt of guideline concordant care, with notably higher survival among Hispanic/Latinx populations.

Synergistic suppression of ovarian cancer by combining NRF2 and GPX4 inhibitors: in vitro and in vivo evidence.

Ovarian cancer is a significant challenge in women's health due to the lack of effective screening and diagnostic methods, often leading to late detection and the highest mortality rate among all gynecologic tumors worldwide. Recent research has shown that ovarian cancer has an "iron addiction" phenotype which makes it vulnerable to ferroptosis inducers. We tested the combination of NRF2-targeted inhibitors with GPX4-targeted inhibitors in ovarian cancer through in vitro and in vivo experiment. The data showed that combination treatment effectively suppressed adherent cell growth, inhibited suspended cell spheroid formation, and restrained the ability of spheroid formation in 3D-culture. Mechanistically, the combination induced accumulation of ROS, 4-HNE, as well as activation of caspase-3 which indicates that this combination simultaneously increases cell ferroptosis and apoptosis. Notably, inhibition of GPX4 or NRF2 can suppress ovarian cancer spreading and growth in the peritoneal cavity of mice, while the combination of NRF2 inhibitor ML385 with GPX4 inhibitors showed a significant synergistic effect compared to individual drug treatment in a syngeneic mouse ovarian cancer model. Overall, these findings suggest that combining NRF2 inhibitors with GPX4 inhibitors results in a synergy suppression of ovarian cancer in vitro and in vivo, and maybe a promising therapeutic strategy for the treatment of ovarian cancer.

Does the Adoption of Molecular Testing Cause Decreased Thyroidectomy Rates in a National Cohort? A Quasiexperimental Study of High- Versus Low-Adoption States.

Background: Over the last decade, the utilization of molecular testing (MT) for the evaluation of thyroid nodules has increased. Rates and patterns of adoption of MT and its effect on thyroidectomy rates nationally are unknown. Varying rates of MT adoption at the state level provide an opportunity to study the effects of MT on thyroidectomy rates using a quasiexperimental study design. Methods: We performed a retrospective analysis of American adult patients in the Merative™ MarketScan® Research Databases who underwent thyroid fine-needle aspiration (FNA) from 2011 to 2021. MT included commercially available DNA and RNA platforms and traditional targeted mutational analysis. Interrupted time series analysis was used to evaluate the inflection of MT adoption and thyroidectomy rates after 2015. Difference-in-differences (DID) analysis was used to causally analyze the effect of MT adoption on thyroidectomy rates in high-adoption (at least a 10% increase in MT utilization) versus low-adoption states (no more than 5% increase in MT utilization) from 2015 to 2021. Results: We identified 471,364 patients who underwent thyroid FNA. The utilization of MT increased over the study period from 0.01% [confidence interval, CI: 0.00% to 0.02%] to 10.1% [CI: 9.7% to 10.5%], in 2021, with an immediate (ß2 = 1.61, p = 0.002) and deeper (ß3 = 0.6, p < 0.001) increase in MT adoption after 2015. Utilization of MT was lower in black patients, the elderly, rural areas, and patients with Medicaid (p < 0.05). Thyroidectomy rates were inversely correlated with MT utilization (r = -0.98, p < 0.0001). From 2015 to 2021, the average MT utilization rate increased from 2.4% to 15.3% in high-adoption states and 1.6% to 5.6% in low-adoption states. In low-adoption states, thyroidectomy rates decreased more but to similar levels (18.5-13.2%) compared with high-adoption states (15.9-13.4%) with an adjusted DID rate of -3.3% [CI -5.6% to -0.8%]. Conclusions: The acceleration in adoption of MT after 2015 likely coincides with the publication of American Thyroid Association guidelines. Black, elderly, and rural patients are less likely to receive MT. Although thyroidectomy rates were inversely correlated with MT utilization, our study suggests that this correlation is not causal. The effect of MT on thyroidectomy rates may be overshadowed by decreasing aggressiveness of thyroid nodule evaluation.

Hospital Volume and Quality of Care for Emergency Gynecologic Care.

OBJECTIVE: To evaluate the association between hospital volume and the quality of gynecologic emergency care for tubal ectopic pregnancies, ovarian torsion, and pelvic inflammatory disease (PID). METHODS: In this cross-sectional analysis, we analyzed patients who presented for emergency care for tubal ectopic pregnancies, ovarian torsion, and PID using the Premier Healthcare Database from 2006 to 2020. We measured the following outcomes: methotrexate use for ectopic pregnancy, ovarian cystectomy for torsion, and guideline-based antibiotic use for PID. For each condition, we measured outlier hospitals that performed the above interventions at below the 10th percentile. Multivariable logistic regression models were used to analyze associations between outlier care and hospital factors such as annualized mean case volume, urban or rural location, teaching status, bed capacity, and geographic region, as well as hospital-level patient population factors, including age, insurance status, and race. RESULTS: A total of 602 hospitals treated patients with tubal ectopic pregnancies, of which 21.9% were outliers, with no cases managed with methotrexate. Of 512 hospitals treating patients with ovarian torsion, 17.4% were outliers, with no cases managed with cystectomy. Of 929 hospitals that treated patients with PID, 9.9% were deemed outliers with low rates of guideline-adherent antibiotic administration. Low-volume hospitals were more likely to be outliers with low rates of use of methotrexate for ectopic pregnancy (6.7% of high-volume hospitals vs 49.7% of low-volume hospitals were outliers; adjusted odds ratio [aOR] 0.13, 95% CI, 0.05-0.31 for high-volume hospitals) and cystectomy for torsion (34.9% of low-volume vs 2.4% of high-volume hospitals were outliers; aOR 0.05, 95% CI, 0.01-0.18 for high-volume hospitals). There was no association between hospital volume and lower rates of guideline-based antibiotic use for PID. CONCLUSION: Higher hospital volume is associated with use of conservative, fertility-preserving treatment of emergency gynecologic conditions, including ectopic pregnancy and ovarian torsion.

Ambient particulate matter air pollution exposure and ovarian cancer incidence in the USA: An ecological study.

OBJECTIVE: To investigate associations between air particulate matter of ≤2.5 µm in diameter (PM2.5 ) and ovarian cancer. DESIGN: County-level ecological study. SETTING: Surveillance, epidemiology, and end results from a collection of state-level cancer registries across 744 counties. Data from the Environmental Protection Agency's network for PM2.5 monitoring was used to calculate trailing 5- and 10-year PM2.5 county-level values. County-level data on demographic characteristics were obtained from the American Community Survey. POPULATION: A total of 98 751 patients with histologically confirmed ovarian cancer as a primary malignancy from 2000 to 2016. METHODS: Generalised linear regression models were developed to estimate the association between PM2.5 and PM10 levels, over 5- and 10-year periods of exposure, and ovarian cancer risk, after accounting for county-level covariates. MAIN OUTCOME MEASURES: Risk ratios for associations between ovarian cancer (both overall and specifically epithelial ovarian cancer) and PM2.5 levels. RESULTS: For the 744 counties included, the average PM2.5 level from 1990 through 2018 was 11.75 µg/m3 (SD = 3.7) and the average PM10 level was 22.7 µg/m3 (SD = 5.7). After adjusting for county-level covariates, the overall annualised ovarian cancer incidence was significantly associated with increases in 5-year PM2.5 (RR = 1.11 per 10 units (µg/m3 ) increase, 95% CI 1.06-1.16). Similarly, when the analysis was limited to epithelial cell tumours and adjusted for county-level covariates there was a significant association with trailing 5-year PM2.5 exposure models (RR = 1.12 per 10 units increase, 95% CI 1.08-1.17). Likewise, 10-year PM2.5 exposure was associated with ovarian cancer overall and with epithelial ovarian cancer. CONCLUSIONS: Higher county-level ambient PM2.5 levels are associated with 5- and 10-year incidences of ovarian cancer, as measurable in an ecological study.

Analysis of the correlation between skin barrier function and age in rosacea patients in Qinghai region.

OBJECTIVE: This study aims at investigating the difference in facial skin barrier function between rosacea patients and the healthy population of different ages in the Qinghai region and its correlation with age, providing a basis for clinical nursing and treatment. METHODS: The data of 216 rosacea patients were collected, and 211 healthy testers were selected as the control group. The skin barrier characteristics of rosacea patients of different ages were evaluated by comparing transepidermal water loss (TEWL), stratum corneum hydration (SCH), sebum content (SC), and pH values between the two groups. Then, the correlation between skin barrier function and age in rosacea patients and the healthy population was analyzed. RESULTS: In all four age groups, the TEWL of the rosacea group was higher than that of the healthy control group, and the epidermal hydration was lower than the healthy control group. In the population aged over 40, the sebum content in rosacea was lower than that in the healthy control group. In the age group of 40-59, the pH value of the rosacea group was higher than the healthy control group. In both the rosacea and the control groups, TEWL was positively correlated with age, and epidermal hydration was negatively correlated with age. The sebum content in rosacea group was negatively correlated with age (p < 0.05). CONCLUSION: As age increases, the facial epidermal function of both rosacea patients and the healthy population declines. Therefore, with increasing age, attention should be paid to enhance the epidermal function to slow down the skin aging process.

High-throughput virtual screening to identify potential small molecule inhibitors of the Zα domain of the adenosine deaminases acting on RNA 1(ADAR1).

Changes in RNA editing are closely associated with diseases such as cancer, viral infections, and autoimmune disorders. Adenosine deaminase (ADAR1), which acts on RNA 1, plays a key role in adenosine to inosine editing and is a potential therapeutic target for these various diseases. The p150 subtype of ADAR1 is the only one that contains a Zα domain that binds to both Z-DNA and Z-RNA. The Zα domain modulates immune responses and may be suitable targets for antiviral therapy and cancer immunotherapy. In this study, we attempted to utilize molecular docking to identify potential inhibitors that bind to the ADAR1 Zα domain. The virtual docking method screened the potential activity of more than 100,000 compounds on the Zα domain of ADAR1 and filtered to obtain the highest scoring results.We identified 71 compounds promising to bind to ADAR1 and confirmed that two of them, lithospermic acid and Regaloside B, interacts with the ADAR1 Zα domain by surface plasmonic resonance technique. The molecular dynamics calculation of the complex of lithospermic acid and ADAR1 also showed that the binding effect of lithospermic acid to ADAR1 was stable.This study provides a new perspective for the search of ADAR1 inhibitors, and further studies on the anti-ADAR11 activity of these compounds have broad prospects.

An Exosome-Related Long Non-coding RNA (lncRNA)-Based Signature for Prognosis and Therapeutic Interventions in Lung Adenocarcinoma.

Background The poor prognosis of lung adenocarcinoma (LUAD) has been confirmed by a large number of studies, so it is necessary to construct a prognosis model. In addition, exosome is closely related to tumors, but there are few studies on exosome-related long non-coding RNA (lncRNA) (ExolncRNA). Methods In this study, we designed a prognostic model, exosome-related lncRNA-based signature (ExoLncSig), using ExolncRNA expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA). ExolncRNAs were identified through univariate and multivariate and Lasso analyses. Subsequently, based on the ExoLncSig, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, immune function and immunotherapy analysis, drug screening, and so on were performed. Results AC026355.2, AC108136.1, AL590428.1, and LINC01312 were examined to establish the ExoLncSig. Gene enrichment analysis identified potential prognostic markers and therapeutic targets, including human leukocyte antigen (HLA), parainflammation, chemokine receptor (CCR), antigen-presenting cell (APC) co-inhibition, cancer-associated fibroblast (CAF), and myeloid-derived suppressor cell (MDSC). Moreover, we ascertained that the high-risk subgroup exhibits heightened susceptibility to pharmaceutical agents. Conclusion Our findings indicate that ExoLncSig holds promise as a valuable prognostic marker in LUAD. Furthermore, the immunogenic properties of ExolncRNAs may pave the way for the development of a therapeutic vaccine against LUAD.

Overview of distinct 5-methylcytosine profiles of messenger RNA in normal and knock-down NSUN2 colorectal cancer cells.

Background: Colorectal cancer (CRC) is a harmful cancer with high morbidity and poor prognosis. There is growing evidence that RNA methylation is closely related to the occurrence of cancer and its malignant biological behavior. N6-methyladenosine (m6A) methylation is the most common RNA modification in eukaryotes, and its multiple regulatory mechanisms in CRC have been elucidated from multiple perspectives. At the same time, the role of 5-methylcytosine (m5C), another important and widely distributed methylation modification, in CRC is far from being elucidated. Methods: In this study, we used RNA immunoprecipitation sequencing combined with bioinformatics methods to identify the m5C peaks on messenger RNA (mRNA) in HCT15 cells and sh-NSUN2 HCT15 cells, understand which transcripts are modified by m5C, and characterize the distribution of m5C modifications. In addition, we performed further bioinformatics analysis of the detected data to initially clarify the potential function of these m5C-modified transcripts. Results: We found significant differences in the distribution of m5C between HCT15 cells and sh-NSUN2 HCT15 cells, suggesting that m5C is likely to play a key role in the occurrence and development of CRC. Furthermore, Gene Ontology (GO) enrichment analysis showed that genes altered by m5C were mainly enriched in phylogeny, synaptic membrane, and transcription factor binding. The Kyoto Encyclopedia of Genes and Genomes (KEGG)pathway analysis showed that the genes altered by m5C are enriched in ECM receptor interaction pathway, the circadian pathway, and the cAMP signaling pathway. Conclusion: Here, our study preliminarily revealed the different distribution patterns of m5C between HCT15 cell and sh-NSUN2 HCT15 cell. Our results open a new window to understand the role of m5C RNA methylation of mRNA in the development of CRC.

Corrigendum to "Adjuvant and first line chemotherapy use for endometrial cancer" [Gynecol. Oncol. Rep. 41 (2022) 101002].

[This corrects the article DOI: 10.1016/j.gore.2022.101002.].

Risk score = LncRNAs associated with doxorubicin metabolism can be used as molecular markers for immune microenvironment and immunotherapy in non-small cell lung cancer.

Doxorubicin is the most effective anthracycline chemotherapy drug in the treatment of cancer, and it is an effective single agent in the treatment of non-small cell lung cancer (NSCLC). There is a lack of studies on the differentially expressed doxorubicin metabolism-related lncRNAs in NSCLC. In this study, we extracted related genes from the TCGA database and matched them with lncRNAs. Doxorubicin metabolism-related lncRNA-based gene signatures (DMLncSig) were gradually screened from univariate regression, LASSO regression, and multivariate regression analysis, and the risk score model was constructed. These DMLncSig were subjected to a GO/KEGG analysis. We then used the risk model to construct the TME model and analyze drug sensitivity. The IMvigor 210 immunotherapy model was cited for validation. Eventually, we performed tumor stemness index differences, survival, and clinical correlation analyses.

Five New C21 -Steroidal Sapogenins from the Acid Hydrolysate of Cynanchum otophyllum Roots.

Five new C21 -steroidal sapogenins (1-5) named cynotogenins J-N, were isolated from the acid hydrolysate of Cynanchum otophyllum roots. Their structures were established by extensive spectroscopic analysis (UV, IR, HR-ESI-MS, and NMR). Most notably, compounds 1-3 harboring a rare 5ß,6ß-epoxy group in the C21 -steroidal skeleton of Cynanchum plants. All compounds were evaluated for their cytotoxicities against multiple cancer cell lines, in which compounds 5 showed weak cytotoxicity against HepG2 cancer cells with IC50 values of 44.90 µM.

Histone Deacetylase 1 Expression and Regulatory Network in Lung Adenocarcinoma Based on Data Mining and Implications for Targeted Treatment.

Background and Aims: Histone deacetylase 1 (HDAC1) codes a protein that is a component of the histone deacetylase complex. The abnormal expression of HDAC1 is strongly correlated with cell proliferation, differentiation, transcription, and translation. Through continuous screening of genes associated with changes in lung adenocarcinoma (LUAD), gene networks are formed to explore tumor pathogenesis and new therapeutic targets. Methods: We evaluated HDAC1 gene survival analysis and its expression of LUAD using relevant websites and databases (TCGA and GEO databases). Through data mining, we determined the frequency and type of HDAC1 mutation, obtained the relevant heat map of the gene interaction network, completed the analysis of gene ontology and function enrichment, and understood the pharmaceutic of HDAC1. Results: We found that HDAC1 expression was associated with the prognosis of patients with LUAD. In gene expression analysis, HDAC1 was highly expressed in LUAD, and the HDAC1 interaction gene network (MARCKSL, eIF3I) was closely related to cellular gene expression. Functional network analysis shows that the expression of HDAC1 is related to the monitoring point of the G1-S phase of the cell cycle and the activation of the Notch signaling pathway (CSL transcription factor), which is involved in the process of cell proliferation and differentiation and gene expression associated with new therapeutic targets. Conclusion: Our data revealed the expression and potential regulatory factors of HDAC1 in LUAD of data mining, which laid a foundation for the study of the occurrence, development, and treatment of HDAC1 in LUAD.

New insights on the interaction between m6A modification and non-coding RNA in cervical squamous cell carcinoma.

BACKGROUND: N6-Methyladenosine (m6A) and long non-coding RNAs (lncRNAs) are both crucial regulators in human cancer growth and metastasis. However, their regulation on cervical squamous cell carcinoma (CSCC) is largely unclear. The present study aimed to explore the role of m6A-associated lncRNAs in CSCC. METHODS: We screened the expression of methylation modification-related enzymes in CECC samples from TCGA. The qRT-PCR was used to detect METTL3 and lncRNA METTL4-2 expression. The biological activities of METTL3 in CSCC cells were evaluated by CCK-8, colony formation, transwell, wound healing, and xenograft tumor assays, respectively. The SRAMP tool was used to screen m6A modification sites of METTL4-2. Finally, the quantitative analysis of m6A modification was carried out by MeRIP. RESULTS: METTL3 expression was upregulated in CSCC cells and tissues. Biological function and function loss analysis indicated that METTL3 promoted the migration and proliferation of CSCC cells. In addition, METTL3 promoted CSCC tumor growth in vivo. Mechanically, METTL3 installed the m6A modification and enhanced METTL4-2 transcript stability to increase its expression. Meanwhile, the m6A "reader" YTHDF1 recognized METTL4-2 installed by METTL3 and facilitated the translation of METTL4-2. CONCLUSIONS: In conclusion, our study highlights the function and mechanism of METTL3-induced METTL4-2 in CSCC. These findings support that METTL3-stabilized METTL4-2 promoted CSCC progression via a m6A-dependent modality, which provides new insights into therapeutic strategies for CSCC.

Prescription of hormone replacement therapy among cervical cancer patients with treatment-induced premature menopause.

OBJECTIVE: To examine the utilization of hormone replacement therapy (HRT) among newly diagnosed cervical cancer patients who experienced premature menopause due to primary treatment. METHODS: The MarketScan Databases were used to identify newly diagnosed cervical cancer patients <50 years of age with premature menopause after hysterectomy with bilateral salpingo-oophorectomy (primary surgery) or primary external beam pelvic radiation (primary radiotherapy). We examined the cumulative utilization of HRT until 24 months after the loss of ovarian function. Fine-Gray subdistribution hazard models were developed to examine the factors associated with cumulative HRT use. The duration of HRT use was analyzed by Kaplan-Meier curves. RESULTS: A total of 1826 patients, including 352 (19.3%) who underwent primary surgery and 1474 (80.7%) who received primary radiotherapy, were identified. Overall, 39.0% of patients received HRT within 24 months of primary treatment. HRT was used in 49.4% of those who underwent primary surgery and in 36.6% of those who received primary radiotherapy (p<0.0001). The median duration of HRT use was 60 days among the entire cohort and was significantly shorter for the primary radiotherapy group than the primary surgery group (35 vs 90 days, p<0.0001). Primary radiotherapy, older age, residency in the Northeastern USA, and Black race were associated with a lower likelihood of HRT use. CONCLUSIONS: HRT was prescribed to less than half of patients with newly diagnosed cervical cancer under the age of 50 who experienced premature menopause due to primary treatment. Among those who used HRT the duration of use was short.

Heterogeneity of outcomes of endometrial cancer patients included in prospective clinical trials.

OBJECTIVE: To assess heterogeneity in five-year overall survival of patients with endometrial cancer using a large retrospective database with cohorts defined by recent prospective clinical trials. METHODS: The National Cancer Database was used to identify patients with endometrial cancer who underwent hysterectomy from 2004 to 2016. The reported inclusion criteria for GOG-249, PORTEC-3, and GOG-258 were used to define the respective cohorts. Five-year overall survival for each cohort was stratified by tumor characteristics and adjuvant therapy regimens. RESULTS: A total of 89,133 patients were identified who would have fulfilled the entry criteria to GOG-249, PORTEC-3, or GOG-258. When stratified by tumor characteristics, irrespective of adjuvant therapy, five-year overall survival ranged from 59.9%-81.7% for patients meeting GOG-249 inclusion criteria, 40.2%-81.8% for patients meeting PORTEC-3 inclusion criteria, and 17.5%-75.0% for those meeting GOG-258 inclusion criteria. Analysis of subgroups by adjuvant therapy regimen revealed significant improvement in five-year overall survival for chemoradiotherapy compared to chemotherapy or radiotherapy alone for endometroid stage III and stage IVA disease and for some stages of serous and clear cell histology. CONCLUSIONS: Recent prospective trials of adjuvant therapy for endometrial cancer have included heterogeneous cohorts of patients based on five-year overall survival rates when the populations are stratified by tumor characteristics. The variation in expected five-year overall survival for subsets of patients may result in underpowered studies or misleading results.