Effectiveness of TruScreen for detecting CIN2+ in women with ThinPrep cytologic test results indicating atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions.

Objective: To evaluate the effectiveness of TruScreen (TS) for detecting cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in women with abnormal ThinPrep cytologic test (TCT) results. Methods: 466 women with atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) were enrolled and underwent TS, colposcopy and biopsy examination. Results: Compared with the high-risk human papillomavirus (hrHPV) test for CIN2+, significantly higher specificity of TS, combined TS and hrHPV (69.6 and 75.0 vs 36.8% in ASCUS; 59.0 and 69.9 vs 30.1% in LSIL), significantly higher positive predictive value of combined TS and hrHPV were observed (32.7 vs 24.6% in ASCUS; 47.9 vs 35.6% in LSIL). Conclusion: TS combined with hrHPV showed better performance in diagnosing CIN2+ in ASCUS/LSIL.

Efficacy and Safety of Ultrasound-Guided High-Intensity Focused Ultrasound Ablation in Women With Multiple Uterine Fibroids: An Exploratory Study.

OBJECTIVE: The aim of the work described here was to explore the clinical efficacy and safety of ultrasound-guided high-intensity focused ultrasound (USg-HIFU) treatment in women with multiple fibroids and identify the characteristic parameters predicting USg-HIFU efficacy in multiple fibroids. METHODS: From February 2021 to August 2022, 138 patients with multiple fibroids (group A comprising 125 patients with two to four fibroids and 13 patients with five or more fibroids) and 149 patients with solitary fibroids (group B) were included. HIFU treatment information, efficacy comparisons and adverse events were recorded. A nomogram model of the characteristic parameters used to predict the efficacy of USg-HIFU in multiple fibroids was established. RESULTS: After USg-HIFU treatment, the statistical comparison of pre-operative versus post-operative symptom scores and fibroid volume in the two groups indicated obvious symptom relief and substantial shrinkage of fibroid volume (all p values <0.001). Nevertheless, group A required more energy and longer treatment and sonication times to achieve a 70% non-perfused volume (NPV) ratio, and had a lower energy efficiency factor than group B (all p values <0.05). No severe complications were observed in either group. The nomogram model included fibroid volume, fibroid location and signal intensity on T2-weighted imaging (T2WI). The area under the receiver operating characteristic curve and the accuracy of the model were 0.698 and 0.686, respectively. CONCLUSION: USg-HIFU appears to be an effective and safe treatment option for multiple fibroids. Knowledge of the fibroid volume, location and signal intensity on T2WI may help determine the efficacy of USg-HIFU in multiple fibroids.

Promoter hypermethylation analysis of host genes in cervical intraepithelial neoplasia and cervical cancers on histological cervical specimens.

BACKGROUND: DNA methylation is an essential factor in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer. The aim was to investigate the diagnostic value provided by methylation biomarkers of six tumor suppressor genes (ASTN1, DLX1, ITGA4, RXFP3, SOX17 and ZNF671) for cervical precancerous lesions and cervical cancer. METHODS: The histological cervical specimens of 396 cases including 93 CIN1, 99 CIN2, 93 CIN3 and 111 cervical cancers were tested for methylation-specific PCR assay (GynTect®) of score and positive rate. Among them, 66 CIN1, 93 CIN2, 87 CIN3 and 72 cervical cancers were further used for paired analysis. A chi-square test was used to analyze the difference of methylation score and positive rate in cervical specimens. The paired t-test and paired chi-square test were for analyzing the methylation score and positive rate in paired CIN and cervical cancer cases. The specificity, sensitivity, odds ratio (OR) and 95% confidence interval (95% CI) of the GynTect® assay for CIN2 or worse (CIN2 +) and CIN3 or worse (CIN3 +) were evaluated. RESULTS: According to the chi-square test trend, hypermethylation increased with severity of the lesions as defined by histological grading (P = 0.000). The methylation score above 1.1 was more common in CIN2 + than in CIN1. The DNA methylation scores in the paired groups of CIN1, CIN3 and cervical cancer were significant differences (P = 0.033, 0.000 and 0.000, respectively), except for CIN2 (P = 0.171). While the positive rate of GynTect® in each paired group had no difference (all P > 0.05). The positive rate of every methylation marker in the GynTect® assay showed differences in four cervical lesion groups (all P < 0.05). The specificity of GynTect® assay for detection of CIN2 + /CIN3 + were higher than high-risk human papillomavirus test. With CIN1 as a reference, the positive status of GynTect®/ZNF671 were significantly higher in CIN2 + : odds ratio (OR) 5.271/OR 13.909, and in CIN3 + : OR 11.022/OR 39.150, (all P < 0.001). CONCLUSION: The promoter methylation of six tumor suppressor genes is related to the severity of cervical lesions. The GynTect® assay based on cervical specimens provides diagnostic values for detecting CIN2 + and CIN3 + .

The reduction of oocytes and disruption of the meiotic prophase I in Fanconi anemia E-deficient mice.

In brief: Fanconi anemia results in subfertility and primary ovarian deficiency in females. This study reveals that disrupted meiosis in oocytes is one of the mechanisms involved. Abstract: Fance is an important factor participating in the repair of DNA interstrand cross-links and its defect causes severe follicle depletion in female mice. To explore the underlying mechanisms, we investigated the effects of Fance on ovarian development in embryonic and newborn mice. We found that the number of oocytes was significantly decreased in Fance-/- mice as early as 13.5 days post coitum (dpc). The continuous decrease of oocytes in Fance-/- mice compared with the Fance+/+ mice led to the primordial follicles being almost exhausted at 2 days postpartum (dpp). The mitotic-meiotic transition occurred normally, but the meiotic progression was arrested in pachytene in Fance-/- oocytes. We detected the expressions of RAD51 (homologous recombination repair factor), 53BP1 (non-homologous end-joining repair factor), and γH2AX by immunostaining analysis and chromosome spreads. The expressions of 53BP1 were increased and RAD51 decreased significantly in Fance-/- oocytes compared with Fance+/+ oocytes. Also, the meiotic crossover indicated by MLH1 foci was significantly increased in Fance-/- oocytes. Oocyte proliferation and apoptosis were comparable between Fance-/- and Fance+/+ mice (P > 0.05). The aberrant high expression at 17.5 dpc and low expressions at 1 and 2 dpp indicated that the expression pattern of pluripotent marker OCT4 (POU5F1) was disordered in Fance-/- oocytes. These findings elucidate that Fance mutation leads to a progressive reduction of oocytes and disrupts the progression of meiotic prophase I but not the initiation. And, our study reveals that the potential mechanisms involve DNA damage repair, meiotic crossover, and pluripotency of oocytes.

Diagnostic accuracy of dual-energy computed tomography angiography in the differentiation of benign and malignant pelvic masses.

PURPOSE: The dual-energy computed tomography(CT) angiography can accurately display subtle details of blood vessels and their surroundings. We aimed to apply dual-energy CT angiography and virtual monochromatic spectral(VMS) images to pelvic mass imaging and evaluate its value of distinguishing between benign and malignant pelvic masses. METHODS: The prospective study was approved by the Institutional Review Board and all participants signed informed consent forms. From August 2018 to July 2020, consecutive female patients with pelvic mass undergone dual-source third-generation CT angiography. The 40 keV VMS images were reconstructed to display mass morphology and corresponding feeding arteries. All images were evaluated by two radiologists blinded to diagnosis(with 9 years and 10 years of experience in CT reading).Disagreements were solved by consensus. The final diagnosis was using histopathology results as the gold standard. Interobserver variability was calculated using Cohen's kappa and Quadratic Weighted Kappa. The differences between benign and malignant masses were compared using the chi-square test. Accuracy rate, sensitivity, specificity, and the area under the curve (AUC) were calculated as the primary indices for diagnostic accuracy. McNemar test was used to evaluate the difference in diagnostic accuracy between dual-energy CT angiography images and original CT images. A two-tailed P < 0.05 was considered statistically significant. RESULTS: A total of 64 patients with 28 malignant masses and 47 benign masses were included. The characteristics of malignant masses showed the branch number of the main feeding artery was ≥ 3(71.4%, 20/28), the course of feeding artery(100%, 28/28) and the mass shape(85.7%, 24/28) were both irregulars. Those characteristics all had statistical differences between benign and malignant masses(all P = 0.000). The Models using the course of feeding artery as a predictor, the accuracy, sensitivity and positive likelihood ratio were 89.3% (95 % CI: 0.801, 0.947), 100% (95 % CI: 0.850, 1) and 5.875(95 % CI: 3.125, 11.044), respectively. The diagnostic accuracy of every model by dual-energy CT angiography was significantly higher than that by original CT imaging(all P = 0.000). CONCLUSIONS: The dual-energy CT angiography can distinguish malignant pelvic masses from benign masses by providing characteristic images of feeding arteries and mass shape.

The changes of DNA double-strand breaks and DNA repair during ovarian reserve formation in mice.

DNA double-strand break (DSB) repair is crucial to maintain genomic stability for sufficient ovarian reserve. It remains unknown the changes of DSBs formation and DNA repair in germ cells during ovarian reserve formation in FVB/N mice. We demonstrated germ cell numbers increased significantly (all P < 0.05) from E11.5 to E13.5 and decreased significantly (all P> 0.05) until P2. OCT4 and SOX2 analyses indicated pluripotency peaks at E13.5 then decreases significantly (all P 0.05) until P2. γH2AX analyses revealed DSB formation significantly (P < 0.05) increased from E13.5 until P2. RAD51 and DMC1 data revealed homologous recombination (HR) pathway repair of DSBs is persistent active during meiosis (E13.5- P2) (all P> 0.05). 53BP1 and KU70 data indicate the non-homologous end-joining pathway (NHEJ) remains active during meiosis. 53BP1 expression was highest at E13.5 (P < 0.05). KU70 expression was higher in germ cells from E15.5 to P2 (all < P 0.05). PH3 and KI67 analyses revealed germ cell proliferation was not significantly different (all P> 0.05) from E13.5 to P2. Caspase-3 and TUNEL analyses showed germ cells apoptosis was not significantly different (all P > 0.05) from E13.5 to P2. In conclusion, we found both germ cell number and pluripotency peak at E13.5 and decline during meiosis. We demonstrated HR and NHEJ continually repair DSBs during meiosis. RAD51 and DMC1 are continuously expressed during meiosis. 53BP1 is mainly expressed at E13.5. KU70 continually functions from E15.5 to P2. Proliferating and apoptotic cells were rarely detected during meiosis. Results provide a basis for further study of how DSBs and DNA repair affect germ cell development.