Simultaneous occurrence of two distinct histotypes of ovarian endometriosis-associated cancer in bilateral ovaries: implications for monoclonal histogenesis from a case report.

Background: Transformation of endometriosis to malignancy is a rare occurrence. Clear cell ovarian cancer and endometrioid ovarian cancer are the two histotypes most consistently linked to endometriosis. The exact pathways leading to malignant transformation of endometriosis remain elusive. Case presentation: A 41-year-old woman presented to our hospital with a ten days history of abdominal pain which was not responsive to medication. Pathological examination revealed an unexpected finding of bilateral endometriosis associated with distinct malignancies: a clear cell carcinoma in the right ovary and a well-differentiated endometrioid carcinoma in the left ovary. Molecular analysis indicated a shared somatic driver mutation in ING1 in the eutopic endometrium and the bilateral ovaries while simultaneously exhibiting specific genetic alterations unique to each carcinoma. Notably, several common mutation sites were also identified, including previously reported common oncogenes (KRAS, PIK3CA, ARID1A). This finding prompts the hypothesis of a possible monoclonal origin of the two tumours. Conclusion: This case represents an exceedingly rare occurrence of two different histotypes of ovarian endometriosis-associated cancer manifesting simultaneously in bilateral ovaries. Based on genetic analysis, we hypothesize that these malignancies may have a monoclonal origin, providing insights into understanding the different biological mechanisms underlying carcinogenesis.

Characteristics of high-risk HPV infection in women with vaginal intraepithelial neoplasia in Beijing, China.

We evaluated the characteristics of high-risk human papillomavirus (Hr-HPV) infection in different grades of vaginal intraepithelial neoplasia (VaIN). 7469 participants were involved in this study, of which 601 were diagnosed with VaIN, including single vaginal intraepithelial neoplasia (s-VaIN, n = 369) and VaIN+CIN (n = 232), 3414 with single cervical intraepithelial neoplasia (s-CIN), 3446 with cervicitis or vaginitis and 8 with vaginal cancer. We got those results. First, the most popular HPV genotypes in VaIN were HPV16, 52, 58, 51, and 56. Second, our study showed that higher parity and older age were risk factors for VaIN3 (p < 0.005). Third, the median Hr-HPV load of VaIN+CIN (725) was higher than that of s-CIN (258) (p = 0.027), and the median Hr-HPV load increased with the grade of VaIN. In addition, the risk of VaIN3 was higher in women with single HPV16 infections (p = 0.01), but those with multiple HPV16 infections faced a higher risk of s-VaIN (p = 0.003) or VaIN+CIN (p = 0.01). Our results suggested that women with higher gravidity and parity, higher Hr-HPV load, multiple HPV16 infections, and perimenopause or menopause status faced a higher risk for VaIN, while those with higher parity, single HPV16 infections, and menopause status are more prone to VaIN3.

OBIA: An Open Biomedical Imaging Archive.

With the development of artificial intelligence (AI) technologies, biomedical imaging data play an important role in scientific research and clinical application, but the available resources are limited. Here we present Open Biomedical Imaging Archive (OBIA), a repository for archiving biomedical imaging and related clinical data. OBIA adopts five data objects (Collection, Individual, Study, Series, and Image) for data organization, and accepts the submission of biomedical images of multiple modalities, organs, and diseases. In order to protect personal privacy, OBIA has formulated a unified de-identification and quality control process. In addition, OBIA provides friendly and intuitive web interfaces for data submission, browsing, and retrieval, as well as image retrieval. As of September 2023, OBIA has housed data for a total of 937 individuals, 4136 studies, 24,701 series, and 1,938,309 images covering 9 modalities and 30 anatomical sites. Collectively, OBIA provides a reliable platform for biomedical imaging data management and offers free open access to all publicly available data to support research activities throughout the world. OBIA can be accessed at https://ngdc.cncb.ac.cn/obia.

Honokiol alleviates radiation-induced premature ovarian failure via enhancing Nrf2.

BACKGROUND: The ovary is highly sensitive to radiation, and patients receiving radiotherapy are at significant risk of premature ovarian failure (POF). This study aimed to explore the radioprotective effect of honokiol (HKL) on ionizing radiation (IR)-induced POF. METHODS: Female C57BL/6 mice were administered intraperitoneally with vehicle or HKL once daily for 7 days. On day 7, the mice in the IR and HKL+IR groups were exposed to 3.2 Gy whole-body radiation for one hour after the intraperitoneal injection and sacrificed 12 or 72 h after radiation exposure. The gonadosomatic index (GSI) was calculated. Blood samples were collected for enzyme-linked immunosorbent assay (ELISA). Ovaries were harvested for histological examination, immunohistochemistry, immunofluorescence, TUNEL, western blot, and qPCR. The fertility assessment was evaluated by calculating live offspring number. RESULTS: The optimum dose of HKL against radiation was 10 mg/kg via intraperitoneal injection. POF was induced 72 h after irradiation with significantly downregulated proliferating cell nuclear antigen (PCNA). The numbers of primordial and preantral follicles decreased significantly after irradiation (p < .001), whereas the number of atretic follicles increased (p < .001). The serum levels of estradiol (E2 ) and anti-Müllerian hormone (AMH) decreased to 50% of the control group after irradiation (p < .05). Moreover, the GSI after irradiation was 27% lower than in the control group (p < .05). The number of offspring in the IR group dropped by 50% compared with the control group (p < .05). HKL pretreatment protected the animals' fertility, GSI, PCNA, serum levels of E2 and AMH, and the number of primordial and preantral follicles. Significant upregulation of apoptosis-related proteins such as Pho-P53, Bax, Cyto C, C-caspase-3, C-PARP, and pyroptosis-related proteins such as Pho-NF-κB p65, NLRP3, caspase-1, IL-1ß, and IL-18 was observed after irradiation, while the expression of Bcl-2 decreased. HKL pretreatment prevented these changes. After irradiation, malondialdehyde (MDA), Nrf2, and HO-1 were upregulated. HKL treatment activated the expression of Nrf2 and HO-1 and promoted the nucleus translocation of Nrf2. Furthermore, HKL did not affect ovarian reserves under physiological conditions. CONCLUSIONS: HKL ameliorated IR-induced POF by inhibiting apoptosis and pyroptosis by enhancing Nrf2 expression and translocation.

Survival outcomes of abdominal radical hysterectomy, laparoscopic radical hysterectomy, robot-assisted radical hysterectomy and vaginal radical hysterectomy approaches for early-stage cervical cancer: a retrospective study.

BACKGROUND: This study compared the survival outcomes of abdominal radical hysterectomy (ARH) (N = 32), laparoscopic radical hysterectomy (LRH) (N = 61), robot-assisted radical hysterectomy (RRH) (N = 100) and vaginal radical hysterectomy (VRH) (N = 45) approaches for early-stage cervical cancer to identify the surgical approach that provides the best survival. METHODS: Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method, and survival curves were compared using the log-rank test. RESULTS: The volume of intraoperative blood loss was greater in the ARH group than in the LRH group, the RRH group or the VRH group [(712.50 ± 407.59) vs. (224.43 ± 191.89), (109.80 ± 92.98) and (216.67 ± 176.78) ml, respectively; P < 0.001]. Total 5-year OS was significantly different among the four groups (ARH, 96.88%; LRH, 82.45%; RRH, 94.18%; VRH, 91.49%; P = 0.015). However, no significant difference in 5-year DFS was observed among the four groups (ARH, 96.88%; LRH, 81.99%; RRH, 91.38%; VRH, 87.27%; P = 0.061). CONCLUSION: This retrospective study demonstrated that ARH and RRH achieved higher 5-year OS rates than LRH for early-stage cervical cancer.

Carbon dot decorated Co3O4 nanozymes responsive to the NIR-II window for mild photothermal-enhanced nanocatalytic therapy.

Although NIR-II laser-mediated photothermal therapy (PTT) is considered as an emerging strategy for tumor therapy, its therapeutic effects are still seriously hampered by low photothermal conversion efficacy, limited tissue penetration depth, and inevitable damage to adjoining healthy tissues. Herein, we report a mild second-near-infrared (NIR-II) photothermal-augmented nanocatalytic therapy (NCT) nanoplatform based on CD@Co3O4 heterojunctions by depositing NIR-II-responsive carbon dots (CDs) onto the surface of Co3O4 nanozymes. The as-prepared Co3O4 nanozymes possess multi-enzyme-mimicking catalytic activity including peroxidase, catalase, and glutathione-peroxidase to realize the cascade amplification of ROS levels owing to the presence of multivalent Co2+ and Co3+. CDs with a high NIR-II photothermal conversion efficiency (PCE) (51.1%) enable the realization of mild PTT (∼43 °C), which could not only avoid damage to adjoining healthy tissues but also enhance the multi-enzyme-mimic catalytic activity of Co3O4 nanozymes. More importantly, the NIR-II photothermal properties of CDs and the multi-enzyme-mimicking catalytic activity of Co3O4 nanozymes are greatly augmented by the fabrication of heterojunctions due to the induced localized surface plasmonic resonance (LSPR) and accelerated carrier transfer. On the basis of these advantages, satisfactory mild PTT-amplified NCT is accomplished. Our work presents a promising approach for mild NIR-II photothermal-amplified NCT based on semiconductor heterojunctions.

Assessing the clinical utility of multi-omics data for predicting serous ovarian cancer prognosis.

Ovarian cancer (OC) is characterised by heterogeneity that complicates the prediction of patient survival and treatment outcomes. Here, we conducted analyses to predict the prognosis of patients from the Genomic Data Commons database and validated the predictions by fivefold cross-validation and by using an independent dataset in the International Cancer Genome Consortium database. We analysed the somatic DNA mutation, mRNA expression, DNA methylation, and microRNA expression data of 1203 samples from 599 serous ovarian cancer (SOC) patients. We found that principal component transformation (PCT) improved the predictive performance of the survival and therapeutic models. Deep learning algorithms also showed better predictive power than the decision tree (DT) and random forest (RF). Furthermore, we identified a series of molecular features and pathways that are associated with patient survival and treatment outcomes. Our study provides perspective on building reliable prognostic and therapeutic strategies and further illuminates the molecular mechanisms of SOC.Impact statementWhat is already known on this subject? Recent studies have focussed on predicting cancer outcomes based on omics data. But the limitation is the performance of single-platform genomic analyses or the small numbers of genomic analyses.What do the results of this study add? We analysed multi-omics data, found that principal component transformation (PCT) significantly improved the predictive performance of the survival and therapeutic models. Deep learning algorithms also showed better predictive power than did decision tree (DT) and random forest (RF). Furthermore, we identified a series of molecular features and pathways that are associated with patient survival and treatment outcomes.What are the implications of these findings for clinical practice and/or further research? Our study provides perspective on how to build reliable prognostic and therapeutic strategies and further illuminates the molecular mechanisms of SOC for future studies.

Robotic-assisted laparoscopic and thoracoscopic approach: a challenging multidisciplinary minimally invasive surgery of intravascular leiomyomatosis with intracardiac extension.

OBJECTIVE: To show a case of severe intravascular leiomyomatosis with intracardiac extension treated by a multidisciplinary minimally invasive surgery. DESIGN: Stepwise demonstration of the technique with a video. SETTING: General Hospital. PATIENT(S): A 40-year-old woman with palpitation and dyspnea. INTERVENTION(S): The patient was diagnosed with intravascular leiomyomatosis by computed tomography scan. She underwent a successful single-stage minimally invasive surgery with complete excision. MAIN OUTCOME MEASURE(S): The feasibility and safety of using this technique for intravascular leiomyomatosis with intracardiac extension. RESULT(S): A combined thoracoabdominal surgery was successfully performed. During the procedure, cardiopulmonary bypass was maintained for 72 minutes. The patient soon recovered and was discharged. CONCLUSION(S): Minimally invasive surgery is a possible choice for intravascular leiomyomatosis with intracardiac extension.

4SC-202 exerts an anti-tumor effect in cervical cancer by targeting PRLR signaling pathway.

The aim of the present study is to investigate whether 4SC-202, a selective class I histone deacetylase inhibitor (HDACi), plays an anti-tumor role in cervical cancer (CC) by targeting prolactin receptor (PRLR). CCK-8 and colony formation assays were used to evaluate the effects of 4SC-202 on the proliferation of CC cells in vitro. Effects of 4SC-202 on the cell cycle distribution and apoptosis in SiHa cells were determined by flow cytometry and western blotting, respectively. Immunofluorescence, western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to detect the activities of PRLR-related pathways and PRLR expression in CC cells. A xenograft tumor model in nude mice was established to examine effects of 4SC-202 on the tumor growth, apoptosis and PRLR-related pathways in vivo. The biochemical analyzer and H&E staining were used to detect the serum biochemical indexes and organ toxicity. 4SC-202 inhibited the proliferation of CC cells (SiHa, HeLa, and CaSki) in vitro in a time- and dose-dependent manner. SiHa cells were treated with 1 or 5 µM 4SC-202 for 72 h and then subjected to various functional assays. The assays showed that 4SC-202 significantly induced G2/M phase arrest and apoptosis, while inhibiting the activities of PRLR-related pathways and PRLR expression. In addition, 4SC-202 reduced tumor growth and induced apoptosis in vivo. 4SC-202 down-regulated the expression of PRLR and activities of PRLR-related pathways in the mouse model, displayed no effects on serum biochemical indicators and caused no toxicity to mouse organs. This finding suggests that 4SC-202 may serve as a novel therapeutic agent for CC.

Case Report and Review of Literature: Camrelizumab Combined with Fuzuloparib and Apatinib for Platinum-Resistant Recurrent Ovarian Cancer.

Background: The mortality rate of ovarian cancer (OC) ranks first among female genital tract malignant tumors, which seriously threatens women's life and health. Because of its insidious onset and poor prognosis, it has become a thorny problem in the clinic, especially for patients with platinum-resistant recurrent ovarian cancer (PROC). In recent years, the medical treatment of OC has made gratifying results, bringing hope to the patients. Case Description: A 54-year-old OC patient who has failed previous neoadjuvant chemotherapy, cytoreductive surgery, and postoperative chemotherapy was diagnosed with PROC. Then she received combination treatment of fuzuloparib (100mg PO BID), apatinib (250mg PO QD), and camrelizumab (200mg IV Q3W) for every 3-week cycle in a Phase II study for PROC patients. In the phase II study, her condition stabilized, responded well to treatment with a sharp decrease by 91.14% of target lesions and disappearances of non-target lesions, and continued to receive regular treatment with progression-free survival exceeding 15 months and no serious adverse events. Conclusion: The present case proves PROC patients might have a sustained response to triplet combination with camrelizumab, combined with fuzuloparib and apatinib.

Diagnosis and Prediction of Endometrial Carcinoma Using Machine Learning and Artificial Neural Networks Based on Public Databases.

Endometrial carcinoma (EC), a common female reproductive system malignant tumor, affects thousands of people with high morbidity and mortality worldwide. This study was aimed at developing a prediction model for the diagnosis of EC in the general population. First, we obtained datasets GSE63678, GSE106191, and GSE115810 from the Gene Expression Omnibus (GEO) database, dataset GSE17025 from the GEO database, and the RNA sequence of EC from The Cancer Genome Atlas (TCGA) database to constitute the training, test, and validation groups, respectively. Subsequently, the 96 most significantly differentially expressed genes (DEGs) were identified and analyzed for function and pathway enrichment in the training group. Next, we acquired the disease-specific genes by random forest and established an artificial neural network for the diagnosis. Receiver operating characteristic (ROC) curves were utilized to identify the signature across the three groups. Finally, immune infiltration was analyzed to reveal tumor-immune microenvironment (TIME) alterations in EC. The top 96 DEGs (77 down-regulated and 19 up-regulated genes) were primarily enriched in the interleukin-17 signaling pathway, protein digestion and absorption, and transcriptional misregulation in cancer. Subsequently, 14 characterizing genes of EC were identified by random forest. In the training, test, and validation groups, the artificial neural network was constructed with high diagnostic accuracies of 0.882, 0.864, and 0.839, respectively, and areas under the ROC curve (AUCs) of 0.928, 0.921, and 0.782, respectively. Finally, resting and activated mast cells were found to have increased in TIME. We constructed an artificial diagnostic model with excellent reliability for EC and uncovered variations in the immunological ecosystem of EC through integrated bioinformatics approaches, which might be potential diagnostic targets for EC.

Fuzuloparib Maintenance Therapy in Patients With Platinum-Sensitive, Recurrent Ovarian Carcinoma (FZOCUS-2): A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Trial.

PURPOSE: This phase III trial aimed to explore the efficacy and safety of fuzuloparib (formerly fluzoparib) versus placebo as a maintenance treatment after response to second- or later-line platinum-based chemotherapy in patients with high-grade, platinum-sensitive, recurrent ovarian cancer. PATIENTS AND METHODS: Patients with platinum-sensitive, recurrent ovarian cancer previously treated with at least two platinum-based regimens were assigned (2:1) to receive fuzuloparib (150 mg, twice daily) or matching placebo for 28-day cycles. The primary end points were progression-free survival (PFS) assessed by blinded independent review committee (BIRC) in the overall population and PFS by BIRC in the subpopulation with germline BRCA 1/2 mutation. RESULTS: Between April 30, 2019, and January 10, 2020, 252 patients were randomly assigned to the fuzuloparib (n = 167) or placebo (n = 85). As of July 1, 2020, the median PFS per BIRC assessment in the overall population was significantly improved with fuzuloparib treatment (hazard ratio [HR], 0.25; 95% CI, 0.17 to 0.36; one-sided P < .0001) compared with that with placebo. The HR derived from a prespecified subgroup analysis showed a consistent trend of benefit in patients with germline BRCA 1/2 mutations (HR, 0.14; 95% CI, 0.07 to 0.28) or in those without mutations (HR, 0.46; 95% CI, 0.29 to 0.74). The most common grade ≥ 3 treatment-emergent adverse events reported in the fuzuloparib group were anemia (25.1%), decreased platelet count (16.8%), and decreased neutrophil count (12.6%). Only one patient (0.6%) discontinued fuzuloparib because of treatment-related toxicity (concurrent decreased white blood cell count and neutrophil count). CONCLUSION: Fuzuloparib as maintenance therapy achieved a statistically significant and clinically meaningful improvement in PFS for patients with platinum-sensitive, recurrent ovarian cancer versus placebo, regardless of germline BRCA 1/2 mutation, and showed a manageable safety profile.

Robotic-Assisted Laparoscopic Sacrocolpopexy for Pelvic Organ Prolapse: A Single Center Experience in China.

OBJECTIVE: The aim is to investigate the efficiency and outcome of robotic-assisted sacrocolpopexy (RASC) in a cohort of patients with pelvic organ prolapse (POP) in our Gynecology Department. METHODS: We performed a retrospective study of female patients who underwent RASC in Chinese PLA General Hospital from January 2013 to December 2020. Their clinical features included age, degree of prolapse, menopause time, body mass index, pregnancy, delivery, operation time, and bleeding volume. All patients were followed up for more than 6 months. POP-Q was recorded to evaluate the position of prolapsed organs. PFDI-20, PFIQ-7, and PGI-I were used to evaluate the life quality after surgery. RESULTS: Twenty-four patients with POP received RASC in our center. The intraoperative bleeding was 86.9 ± 98.3 ml (20-300 ml). The operation time was 143.5 ± 47.3 min (60-240 minutes). The hospitalization time was 10.4 ± 2.1 days (8-16 days). And the follow-up time was 40.8 ± 22.0 months (6-72 months). In the POP-Q follow-up, postoperative Aa, Ba, Ap, Bp, and C were significantly improved than those before surgery (P < 0.05). The objective and subjective cure rate was 100%. PGI-I score was very good in 9 (9/24), very good in 10 (10/24), and good in 3 (3/24). Postoperative PFDI-20 and PFIQ-7 were 2.78 ± 3.82 and 1.57 ± 3.86, which decreased dramatically after surgery (P < 0.05). Mesh exposure occurred in 4 cases (16.7%) at 2-12 months. The exposed diameters were less than 1 cm in 3 cases (2 A/T3/S1) and 1-2 cm in 1 case (3 B/T3/S1). These mesh exposures healed after conservative observation or mesh excision. CONCLUSION: RASC for POP has the advantage of less bleeding and hospitalization time. It is a minimally invasive option for pelvic organ prolapse.

Application of expanded noninvasive prenatal test in prenatal diagnosis of fetuses with increased nuchal translucency.

OBJECTIVES: To investigate the efficiency of the upgraded noninvasive prenatal test (NIPT-Plus) in fetuses with increased nuchal translucency (NT). METHODS: Fetuses with an increased NT at or above 2.5 mm were selected for prenatal diagnosis. Amniotic fluid was collected from all cases for karyotype analysis and copy number variation sequencing (CNV-seq), and cell-free fetal DNA (cfDNA) in maternal blood was tested using Noninvasive Prenatal Test (NIPT-Plus) before amniocentesis in some cases. The results of amniocentesis with different NT thicknesses were analyzed and compared with those of NIPT-Plus. RESULTS: A total of 125 eligible patients were divided into group A (2.5 mm ≤ NT < 3.0 mm) and group B (NT ≥ 3.0 mm). In group A, the detection rate of chromosomal aneuploidy and pathogenic copy number variation (CNV) was 10.6% and 6.4%, respectively. The total chromosome abnormality rate in group B (34.7%) was significantly higher than that in group A (17%). In 72 patients who underwent NIPT-Plus and amniocentesis, chromosomal aneuploidy accounted for 80.8% of the total chromosomal abnormalities. Among 21 cases of chromosomal aneuploidy, NIPT-Plus detected 20 cases. The sensitivity and specificity of NIPT-Plus toward aneuploidy detection were 95.2% and 100%, respectively. Among the five cases of pathogenic CNV, only two were detected using NIPT-Plus. CONCLUSION: NIPT-plus is recommended as the first choice for fetal diagnosis in pregnant women with 2.5 mm ≤ NT < 3.0 mm who do not accept invasive prenatal diagnosis. When NT ≥ 3.0 mm and NIPT-Plus detects chromosomal aneuploidy, a rapid prenatal diagnosis can be performed through amniocentesis. In cases where NIPT-Plus yields negative results, amniocentesis still needs to be performed to detect chromosome microdeletions/duplications in order to avoid a missed diagnosis.

Characteristics of the Cervicovaginal Microenvironment in Childbearing-Age Women with Different Degrees of Cervical Lesions and HR-HPV Positivity.

Persistent infection with high-risk human papillomavirus (HR-HPV) is the most important determinate in the development of cervical cancer, and cervical microecology can modulate cervical viral infection. However, few studies have been conducted on the microecological analysis of cervical diseases using strict physiological factors. This study investigated the characteristics and dynamics of cervical microecology in childbearing-age Chinese women with different degrees of HR-HPV-positive cervical lesions. A total of 168 subjects were selected according to the selection criteria, including healthy HPV-negative individuals (n = 29), HR-HPV-infected individuals (n = 29), low-grade squamous intraepithelial lesion individuals (LSIL, n = 32), high-grade squamous intraepithelial lesion individuals (HSIL, n = 40), and cervical cancer individuals (n = 38). We sampled cervical secretions from each subject and performed comparative analysis using the 16S rRNA sequencing method. Comparison analysis showed that Lactobacillus and Ignatzschineria were the dominant genera in the healthy group, while Gardnerella and Prevotella were more enriched in the disease groups. Based on the taxa composition, we roughly divided the development of cervical cancer into two phases: phase I was from healthy status to HR-HPV infection and LSIL; phase II was from LSIL to HSIL and cervical cancer. Different interactions among different genera were observed in different groups. Prevotella inhibited the abundance of Lactobacillus in the healthy group, while Prevotella inhabited the abundance of Gardnerella in the other groups. In the HR-HPV infection group, Ignatzschineria and Enterococcus showed a positive interaction but dissociated with the increase in cervical lesions, which might eventually lead to a continuous decrease in the abundances of Lactobacillus and Ignatzschineria.

Exploring the Potential Key IncRNAs with Endometriosis by Construction of a ceRNA Network.

PURPOSE: The etiology and pathophysiology of endometriosis remain unclear. Current research indicates long noncoding RNA (lncRNA) may play an important role in the pathogenesis and development of endometriosis. However, the molecular mechanism of lncRNA in endometriosis is far from clear. PATIENTS AND METHODS: The lncRNA and mRNA expression of 8 patients with ovarian endometriosis were determined by high-throughput RNA sequencing (8 ectopic endometria samples vs 8 eutopic endometria samples), and miRNA expression profiles were obtained from our previous study. Then a lncRNA-associated competing endogenous RNA (ceRNA) network was constructed by combining the regulatory interaction and negative co-expression interaction between the differentially expressed lncRNAs/mRNAs and miRNAs by different rules. RESULTS: The constructed lncRNA-related ceRNA network was composed of two separate networks, network 1 including 14,137 dysregulated lncRNA-mRNA interactions, referring to 242 lncRNAs, 55 miRNAs and 1600 mRNAs, network 2 including 4459 dysregulated lncRNA-mRNA interactions, referring to 111 lncRNAs, 39 miRNAs and 1151 mRNAs. The top six hub lncRNAs (LINC01140, MSC-AS1, HAGLR, CKMT2-AS1, JAKMIP2-AS1, AL365361.1) in the significant ternary relationship of mRNA-miRNA-lncRNA in network 1, and the top six hub lncRNAs (PAX8-AS1, MIR17HC, PART1, HOXA-AS3, PLAC4, LINC00511) in the significant ternary relationship of mRNA-miRNA-lncRNA in network 2 were selected. Functional enrichment analysis of these lncRNA-related mRNAs indicated that the lncRNAs in network 1 mainly take part in positive regulation of phagocytosis, myeloid leukocyte activation, and tissue remodeling, while the lncRNAs in network 2 mainly take part in negative regulation of cell proliferation, blood vessel development and regulation of epithelial cell differentiation, which is consistent with the results obtained from the different rules to construct the networks. CONCLUSION: lncRNA-related ceRNA network analysis recognized key lncRNAs related to the development of endometriosis.

Relative clinical utility of simultaneous 18F-fluorodeoxyglucose PET/MRI and PET/CT for preoperative cervical cancer diagnosis.

OBJECTIVE: To investigate the utility of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/magnetic resonance imaging (PET/MRI) for the preoperative diagnosis of cervical cancer. METHODS: We retrospectively analyzed 114 patients who were diagnosed with cervical cancer and underwent PET/MRI (n = 59) or PET/computed tomography (PET/CT) (n = 65) before surgery. The maximal standardized uptake value (SUVmax) and mean SUV (SUVmean) were determined for regions of interest in the resultant radiographic images. RESULTS: Relative to PET/CT, 18F-FDG PET/MRI exhibited higher specificity and sensitivity in defining the primary tumor bounds and higher sensitivity for detection of bladder involvement. The SUVmax and SUVmean of PET/MRI were remarkably higher than those of PET/CT as a means of detecting primary tumors, bladder involvement, and the lymph node status. However, no significant differences in these values were detected when comparing the two imaging approaches as a means of detecting vaginal involvement or para-aortic lymph node metastasis. CONCLUSIONS: These outcomes may demonstrate the capability of 18F-FDG PET/MRI to clarify preoperative cervical cancer diagnoses in the context of unclear PET/CT findings. However, studies directly comparing SUVs in different lesion types from patients who have undergone both PET/MRI and PET/CT scans are essential to validate and expand upon these findings.

Combined exome sequencing and deep phenotyping in highly selected fetuses with skeletal dysplasia during the first and second trimesters improves diagnostic yield.

OBJECTIVE: To investigate the genetic etiology of skeletal dysplasia in highly selected fetuses during the first and second trimesters using deep phenotyping and exome sequencing (ES). METHOD: Fetuses with short femurs were identified using the established prenatal diagnostic approach. A multidisciplinary team reviewed fetal phenotypic information (prenatal ultrasound findings, fetal postmortem, and radiographs) in a cohort of highly selected fetuses with skeletal dysplasia during the first and second trimesters. The affected families underwent multiplatform genetic tests. RESULTS: Of the 27 affected fetuses, 21 (77.8%) had pathogenic or potential pathogenic variations in the following genes: COL1A1, FGFR3, COL2A1, COL1A2, FLNB, DYNC2LI1, and TRIP11. Two fetuses had compound heterozygous mutations in DYNC2LI1 and TRIP11, respectively, and the other 19 carried de novo autosomal dominant variants. Novel variants were identified in COL1A1, COL2A1, COL1A2, DYNC2LI1, and TRIP11 in 11 fetuses. We also included the first description of the phenotype of odontochondrodysplasia in a prenatal setting. CONCLUSIONS: ES or panel sequencing offers a high diagnostic yield for fetal skeletal dysplasia during the first and second trimesters. Comprehensive and complete phenotypic information is indispensable for genetic analysis and the expansion of genotype-phenotype correlations in fetal skeletal abnormalities.

A Successful Pregnancy after Laparoscopic Surgery: Severe Recurrent Pelvic Arteriovenous Malformation Managed by Laparoscopic Internal Iliac Artery Ligation.

STUDY OBJECTIVE: To show a case of severe pelvic arteriovenous malformation (AVM) treated by laparoscopic internal iliac artery ligation after 2 uterine artery embolization (UAE) procedures, where successful pregnancy was achieved after surgery. DESIGN: Stepwise demonstration of the technique with a video. SETTING: Chinese PLA General Hospital. INTERVENTIONS: A 36-year-old woman with heavy menstrual bleeding was diagnosed with pelvic AVM by computed tomography scan. Before surgical intervention, she underwent 2 UAE procedures that temporarily reduced menstrual blood loss. Finally, we performed a laparoscopic internal iliac artery ligation on her. After the surgery, she conceived naturally. During the cesarean section, no AVMs were found. CONCLUSION: Laparoscopic internal iliac artery ligation can be a choice for patients who still have severe symptoms of AVM after UAE.

An Open-label, Multicenter, Single-arm, Phase II Study of Fluzoparib in Patients with Germline BRCA1/2 Mutation and Platinum-sensitive Recurrent Ovarian Cancer.

PURPOSE: Fluzoparib (PARP inhibitor) showed promising antitumor activity for advanced ovarian cancer in a phase I study. This study aimed to assess the efficacy and safety of fluzoparib in patients with germline BRCA1/2-mutated recurrent ovarian cancer. PATIENTS AND METHODS: This open-label, multicenter, single-arm, phase II study enrolled patients with platinum-sensitive recurrent ovarian cancer and germline BRCA1/2 mutation who had previously received two to four lines of platinum-based chemotherapy. Fluzoparib 150 mg was administered orally twice daily. The primary endpoint was independent review committee (IRC)-assessed objective response rate per RECIST v1.1. RESULTS: A total of 113 patients were enrolled and received at least one dose of fluzoparib. As of data cutoff on March 21, 2020, the median follow-up period was 15.9 months (interquartile range, 13.5-18.5). The IRC- and investigator-assessed objective response rates were 69.9% [95% confidence interval (CI), 60.6-78.2] and 70.8% (95% CI, 61.5-79.0), respectively. The objective response rates were similar across all prespecified subgroups. The median IRC- and investigator-assessed progression-free survival was 12.0 months (95% CI, 9.3-13.9) and 10.3 months (95% CI, 9.2-12.0), respectively. The 12-month survival rate was 93.7% (95% CI, 87.2-96.9). Grade ≥3 adverse events occurred in 63.7% (72/113) of the patients, with the most common one being anemia/decreased hemoglobin. Adverse events that led to treatment interruption, dose reduction, and discontinuation occurred in 39.8%, 34.5%, and 0.9% of patients, respectively. One treatment-related death occurred. CONCLUSIONS: Fluzoparib demonstrated promising antitumor activity and acceptable safety profile in germline BRCA1/2-mutated, platinum-sensitive relapsed ovarian cancer. Thus, fluzoparib might be a novel treatment option for this population.