Low PDE4A expression promoted the progression of ovarian cancer by inducing Snail nuclear translocation.

Widespread metastasis is the primary reason for the high mortality associated with ovarian cancer (OC), and effective targeted therapy for tumor aggressiveness is still insufficient in clinical practice. Therefore, it is urgent to find new targets to improve prognosis of patients. PDE4A is a cyclic nucleotide phosphodiesterase that plays a crucial role in the occurrence and development in various malignancies. Our study firstly reported the function of PDE4A in OC. Expression of PDE4A was validated through bioinformatics analysis, RT-qPCR, Western blot, and immunohistochemistry. Additionally, its impact on cell growth and motility was assessed via in vitro and in vivo experiments. PDE4A was downregulated in OC tissues compared with normal tissues and low PDE4A expression was correlated with poor clinical outcomes in OC patients. The knockdown of PDE4A significantly promoted the proliferation, migration and invasion of OC cells while overexpression of PDE4A resulted in the opposite effect. Furthermore, smaller and fewer tumor metastatic foci were observed in mice bearing PDE4A-overexpressing OVCAR3 cells. Mechanistically, downregulation of PDE4A expression can induce epithelial-mesenchymal transition (EMT) and nuclear translocation of Snail, which suggests that PDE4A plays a pivotal role in suppressing OC progression. Notably, Rolipram, the PDE4 inhibitor, mirrored the effects observed with PDE4A deletion. In summary, the downregulation of PDE4A appears to facilitate OC progression by modulating the Snail/EMT pathway, underscoring the potential of PDE4A as a therapeutic target against ovarian cancer metastasis.

Lymphadenectomy and optimal excise lymph nodes count for early-stage primary fallopian tube cancer: a SEER-based study.

BACKGROUNDS: There is still no consensus on the significance of Lymphadenectomy (LD) and the number of lymph nodes that need to be excised (ELNs) for adequate LD in patients with early-stage primary fallopian tube cancer (PFTC). Our endeavor is geared towards deepening comprehension of LD in early-stage PFTC and identify the optimal cut-off of ELNs. METHODS: This SEER-based study analyzed the clinical data of patients with early-stage PFTC between 2000 and 2018. X-tile was employed to confirm the optimal cut-off of ELNs. The survival data between groups were analyzed by the Kaplan-Meier estimates, Log-rank test and Cox proportional hazards model. RESULTS: There was significant improvement in both mean cancer-specific survival (CSS, p < 0.001) and overall survival (OS, p < 0.001) in LD group. Regardless of matched or not, LD was identified as an independent protective factor of CSS and OS. The optimal 3-year CSS-based cutoff of ELNs was 11 (p = 0.026) as determined by X-tile. Both the mean CSS (p = 0.001) and mean OS (p = 0.002) in adequate LD group (ELNs > 11, n = 574) were significantly longer than these in inadequate LD group (ELNs ≤ 11, n = 738). Adequate LD, FIGO stage, tumor grade and histology were significant prognostic factors for CSS and OS. CONCLUSION: LD is an independent protective prognostic factor of patients with early-stage PFTC. The association between ELNs > 11 and an improved prognosis is evident. Future studies are needed to further clarify the results above.

Do plaque-related factors affect the diagnostic performance of an artificial intelligence coronary-assisted diagnosis system? Comparison with invasive coronary angiography.

OBJECTIVE: The aim of this study was to investigate the effects of plaque-related factors on the diagnostic performance of an artificial intelligence coronary-assisted diagnosis system (AI-CADS). METHODS: Patients who underwent coronary computed tomography angiography (CCTA) and invasive coronary angiography (ICA) were retrospectively included in this study. The degree of stenosis in each vessel was collected from CCTA and ICA, and the information on plaque-related factors (plaque length, plaque type, and coronary artery calcium score (CAC)) of the vessels with plaques was collected from CCTA. RESULTS: In total, 1224 vessels in 306 patients (166 men; 65.7 ± 10.1 years) were analyzed. Of these, 391 vessels in 249 patients showed significant stenosis using ICA as the gold standard. Using per-vessel as the unit, the area under the curves of coronary stenosis ≥ 50% for AI-CADS, doctor, and AI-CADS + doctor was 0.764, 0.837, and 0.853, respectively. The accuracies in interpreting the degree of coronary stenosis were 56.0%, 68.1%, and 71.2%, respectively. Seven hundred fifty vessels showed plaques on CCTA; plaque type did not affect the interpretation results by AI-CADS (chi-square test: p = 0.0093; multiple logistic regression: p = 0.4937). However, the interpretation results for plaque length (chi-square test: p < 0.0001; multiple logistic regression: p = 0.0061) and CACs (chi-square test: p < 0.0001; multiple logistic regression: p = 0.0001) were significantly different. CONCLUSION: AI-CADS has an ability to distinguish ≥ 50% coronary stenosis, but additional manual interpretation based on AI-CADS is necessary. The plaque length and CACs will affect the diagnostic performance of AI-CADS. KEY POINTS: • AI-CADS can help radiologists quickly assess CCTA and improve diagnostic confidence. • Additional manual interpretation on the basis of AI-CADS is necessary. • The plaque length and CACs will affect the diagnostic performance of AI-CADS.

Nonconforming gender expression and adolescent anabolic-androgenic steroids misuse.

BACKGROUND: Gender nonconformity (GNC) is an under-researched area of adolescent health that is of increasing interest to researchers and general public. However, little is known about whether it is associated with anabolic-androgenic steroids (AAS) misuse. We aimed to investigate the association among high school students using a cross-sectional design. METHODS: We pooled the 6 school districts data from the Youth Risk Behavior Survey in 2017 and 2019. We compared the prevalence of AAS misuse among gender nonconforming and conforming students. AAS misuse was determined on the reported experience of lifetime non-prescription steroid use. GNC was derived from perceived gender expression and sex. We estimated the sex-stratified adjusted odds ratios (AORs) for the association of GNC with AAS misuse after adjusting for race/ethnicity, grade, and sexual orientation. RESULTS: The study population consisted of 17,754 US high school students including 9143 (49.67%) female students. Among female students, GNC was significantly associated with moderate (AOR, 3.69; 95% CI 1.28-10.62; P = 0.016) and severe (AOR, 5.00; 95% CI 1.05-23.76; P = 0.043) AAS misuse, but not with any AAS misuse (AOR, 0.85; 95% CI 0.34-2.14; P = 0.734). Among male students, GNC was significantly associated with any (AOR, 4.75; 95% CI 2.93-7.69; P < 0.001), moderate (AOR, 4.86; 95% CI 2.66-8.89; P < 0.001) and severe (AOR, 4.13; 95% CI 1.43-11.95; P = 0.009) AAS misuse. We did not observe a dose-response relationship between GNC and any AAS misuse in female and male students. CONCLUSIONS: This study suggests that AAS misuse is associated with GNC among female and male adolescents.

Prognostic Value of Ki67 in Epithelial Ovarian Cancer: Post-Neoadjuvant Chemotherapy Ki67 Combined with CA125 Predicting Recurrence.

Purpose: To evaluate Ki67 expression and prognostic value during neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (EOC). Patients and Methods: 95 patients with advanced EOC receiving NACT followed by interval debulking surgery (IDS) were available for tissue samples from matched pre- and post-therapy specimens. The expression of Ki-67 was evaluated by immunohistochemistry and classified by percentage of stained cells. The optimal cutoff values of the Ki67 were assessed by receiver operating characteristic analysis. Kaplan-Meier analysis, the Log rank test, and Cox regression analysis were carried out to analyze survival. Results: Post-NACT Ki67 was an independent prognostic factor for recurrence by univariate (HR: 1.8, 95% CI: 1.1-3.0, P-value: 0.023) and multivariate (HR: 1.88, 95% CI: 1.08-3.26, P-value: 0.025) analysis. Residual disease >1cm (HR: 2.69, 95% CI: 1.31-5.54, P-value: 0.0070) and pre-treatment CA125 ≥ 1432 U/mL (HR: 2.00, 95% CI: 1.13-3.55, P-value: 0.017) were also independent risk factors for progression-free survival (PFS) in multivariate analysis. Post-NACT Ki67 ≥ 20% was an independent risk factor for PFS, however, baseline Ki67 and Ki67 change did not suggest prognostic significance. In patients with high CA125, the median PFS for patients with high postKi67 (median PFS: 15.0 months, 95% CI: 13.4-16.6 months) was significantly (P-value: 0.013) poorer compared to patients with low postKi67 (median PFS: 30.0 months, 95% CI: 13.5-46.5 months). Conclusion: Post-NACT Ki67 ≥ 20% was an independent factor associated with poorer PFS in patients with advanced-stage EOC undergoing NACT followed by IDS. The combination of post-NACT Ki67 and pretreatment CA125 could better identify patients with poorer PFS in NACT-administered patients.

Neoadjuvant chemotherapy in advanced epithelial ovarian cancer by histology: A SEER based survival analysis.

To evaluate the prognostic effect of neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (EOC) patients with different histological subtype. Stage III/IV EOC patients diagnosed between 2010 and 2018 were identified from the surveillance, epidemiology, and end results database (SEER) database and stratified by histological subtype. Kaplan-Meier analysis was used for the assessment of overall survival (OS) cause-specific survival (CSS) before and after matching for baseline characteristics between NACT and primary debulking surgery (PDS) groups. Cox proportional risk model was conducted to identify independent prognostic factors. A total of 13,582 patients were included in the analysis. Of them, 9505 (74.50%) received PDS and 3253 (25.50%) received NACT. Overall, an inferior OS and CSS was observed among patients with high-grade serous carcinoma (HGSC) receiving NACT, while NACT served as a protective factor in clear cell carcinoma and carcinosarcoma in both original cohorts and adjusted cohorts. For other histo-subtypes, PDS showed survival benefit over NACT in certain cohorts of models. Prognostic effect of NACT in advanced EOC differed from pathological subtypes. Although it served as a risk factor for HGSC, patients with less common subtypes may benefit from NACT.

Survival impact of bowel resection in patients with FIGO stage II-IV ovarian cancer.

INTRODUCTION: To compare the effect of bowel resection vs stripping on the clinical outcomes of patients with FIGO II-IV ovarian cancer. METHODS: We retrospectively analyzed patients with FIGO II-IV ovarian cancer who suffered from bowel involvement and underwent cytoreductive surgery between January 2014 and March 2022. Patients' survival was compared by Kaplan-Meier survival analysis and Cox proportional hazards models. RESULTS: Four hundred and twelve patients were included. 48 patients underwent bowel resection (BR), and 364 patients underwent bowel tumor stripping (BTS). The BR group had longer operative duration, hospital stay, time to post-operative chemotherapy, and more intraoperative bleeding. The median PFS was 37 months (95% CI 12-62) in BTS compared to 25 months (95% CI 10-40) in BR among patients who achieved R0 resection (p = 0.590). Among those with R1 resection, the median PFS in BST was 23 months (95% CI 16-30) and that in BR was 15 months (95% CI 12-18, p = 0.136); moreover, a favorable median PFS was observed in BTS with residual bowel lesions (23 months, 95% CI 14-32), compared to BR (15 months, 95% CI 12-18, p = 0.144). Multivariate analysis indicated that FIGO stage, PCI, cytoreduction time and residual lesions were independent prognostic factors of PFS. CONCLUSION: For patients with FIGO stage II-IV ovarian cancer with bowel implicated, bowel resection is necessary to achieve complete removal to improve the survival. If complete resection was judged unfeasible, cautious decision of bowel resection is required. Neoadjuvant chemotherapy might reduce the ratio of bowel resection for some with mesenteric involvement.

LLGL2 Inhibits Ovarian Cancer Metastasis by Regulating Cytoskeleton Remodeling via ACTN1.

Epithelial ovarian cancer is the most lethal gynecological malignant tumor. Although debulking surgery, chemotherapy, and PARP inhibitors have greatly improved survival, the prognosis for patients with advanced EOC without HRD is still poor. LLGL2, as a cell polarity factor, is involved in maintaining cell polarity and asymmetric cell division. In the study of zebrafish development, LLGL2 regulated the proliferation and migration of epidermal cells and the formation of cortical F-actin. However, the role of LLGL2 in ovarian cancer has not been described. Our study found, through bioinformatics analysis, that low expression of LLGL2 was significantly associated with a more advanced stage and a higher grade of EOC and a poorer survival of patients. Functional experiments that involved LLGL2 overexpression and knockdown showed that LLGL2 inhibited the migration and invasion abilities of ovarian cancer cells in vitro, without affecting their proliferation. LLGL2-overexpressing mice had fewer metastatic implant foci than the controls in vivo. Mechanistically, immunoprecipitation combined with mass spectrometry analysis suggested that LLGL2 regulated cytoskeletal remodeling by interacting with ACTN1. LLGL2 altered the intracellular localization and function of ACTN1 without changing its protein and mRNA levels. Collectively, we uncovered that LLGL2 impaired actin filament aggregation into bundles by interacting with ACTN1, which led to cytoskeleton remodeling and inhibition of the invasion and metastasis of ovarian cancer cells.

Lymphadenectomy in Primary Fallopian Tube Cancer is Associated with Improved Survival.

BACKGROUND AND OBJECTIVES: Primary fallopian tube cancer (PFTC) shares the same diagnostic and management guidelines with epithelial ovarian cancer (EOC). The LION trail raised concerns regarding the role of systematic pelvic and para-aortic lymphadenectomy during debulking surgery. We aimed to evaluate the significance of lymphadenectomy in PFTC survival. METHODS: This retrospective study analyzed the clinical features and survival of patients with PFTC who underwent primary surgery in our center between January 2013 and October 2020. RESULTS: Sixty-one patients diagnosed with PFTC were included in the study. Twenty-five (41.0%, 25/61) were diagnosed with FIGO (International Federation of Gynecology and Obstetrics) stages I/II and 36 (59.0%, 36/61) were diagnosed with stage III/IV. Twenty-nine (47.5%, 29/61) underwent pelvic lymphadenectomy with or without para-aortic lymphadenectomy, among which 12 (41.4%, 12/29) had lymph node metastasis confirmed by postoperative pathology. The mean progression-free survival was 60.4 months in the lymphadenectomy group and 37.8 months in the no-lymphadenectomy group (p = 0.042, HR 0.374, 95% CI 0.145-0.966). CONCLUSIONS: PFTC is often diagnosed earlier and has a better prognosis than EOC. Most patients with PFTC would benefit from lymphadenectomy. However, the extent to which this association translates to a more diverse population needs to be further identified.

Computed tomographic enterography (CTE) in evaluating bowel involvement in patients with ovarian cancer.

PURPOSE: To explore the utility of CTE in the evaluation of bowel invasion in patients with primary ovarian, fallopian tube, and peritoneal cancer. METHODS: This observational study included 73 patients who received CTE before operation between September 2019 and December 2021. Two radiologists reviewed CTE images, focusing on the sites and depth of bowel involvement. Based on the findings during surgical exploration, we evaluated the diagnostic power, like sensitivity, specificity, accuracy, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (+ LR), and negative likelihood ratio (- LR) of CTE. Additionally, the characteristic images of bowel involvement on CTE corresponding to surgical findings were shown in the study. RESULTS: The rate of macroscopic bowel invasion in this cohort was 49.31% (36/73), of which eight patients had small bowel involvement, 17 patients had colon involvement and 27 patients had sigmoid-rectum involvement. CTE detected bowel invasion in the small intestine with a sensitivity, specificity, PPV, NPV, and accuracy of 87.50%, 92.31%, 58.33%, 98.36%, 91.78%; for colon, the statistics were 58.82%, 96.43%, 83.33%, 88.52%, 87.67% and for sigmoid-rectum 62.96%, 82.61%, 68.00%, 79.17%, 75.34%, respectively. CONCLUSION: CTE appeared a preferable diagnostic power on the small bowel and colon invasion in patients with primary ovarian, fallopian tube, and peritoneal cancer.

Online study on the co-pyrolysis of coal and corn with vacuum ultraviolet photoionization mass spectrometry.

With the aim to support the experimental tests in a circulating fluidized bed pilot plant, the pyrolysis processes of coal, corn, and coal-corn blend have been studied with an online pyrolysis photoionization time-of-flight mass spectrometry (Py-PI-TOFMS). The mass spectra at different temperatures (300-800°C) as well as time-evolved profiles of selected species were measured. The pyrolysis products such as alkanes, alkenes, phenols, aromatics, as well as nitrogen- and sulfur-containing species were detected. As temperature rises, the relative ion intensities of high molecular weight products tend to decrease, while those of aromatics increase significantly. During the co-pyrolysis, coal can promote the reaction temperature of cellulose in corn. Time-evolved profiles demonstrate that coal can affect pyrolysis rate of cellulose, hemicellulose, and lignin of corn in blend. This work shows that Py-PI-TOFMS is a powerful approach to permit a better understanding of the mechanisms underlying the co-pyrolysis of coal and biomass.

Interaction of tryptophan hydroxylase 2 gene and life events in susceptibility to major depression in a Chinese Han population.

BACKGROUND: Major depression (MD) results from a complex synergy between genetic and environmental factors. The aim of this study is to analyze the interaction of tryptophan hydroxylase 2 gene (TPH2) variation and negative life events in the pathogenesis of MD. Three TPH2 polymorphisms, -703G/T (rs4570625), -473T/A (rs11178997), and 1463G/A (rs120074175), were selected based on previous findings of associations with MD. METHODS: In this study, 289 patients with MD and 289 age- and sex-matched control subjects were genotyped. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). Gene-environment interactions (G×E) were assessed using the generalized multifactor dimensionality reduction (GMDR) method. RESULTS: Differences in rs11178997 and rs120074175 allele frequencies and genotype distributions were observed between MD patients and controls. Significant G×E interactions between negative life events and allelic variation of rs4570625, rs11178997, and rs120074175 were also observed. Individuals carrying the T(-) genotype of rs4570625 (GG), T(-) genotype of rs11178997 (AA), or A(-) genotype of rs120074175 (GG) were susceptible to MD only when exposed to high-negative life events. However, individuals with the T(+) genotypes of rs11178997 (TA, TT) and A(+) genotypes of rs120074175 (AG, AA) were susceptible to MD when exposed to low-negative life events. LIMITATION: Assessment of negative life events was influenced by subjective interpretation. CONCLUSIONS: Interactions between multiple TPH2 gene alleles and negative life events were revealed by GMDR analysis. Chinese Han individuals with at least one rs11178997 T allele or rs120074175 A allele are susceptible to MD even in the relative absence of high-negative life events.