Ovarian clear cell carcinoma (OCCC) is the second most common epithelial ovarian carcinoma (EOC). It is refractory to chemotherapy with a worse prognosis after the preliminary optimal debulking operation, such that the treatment of OCCC remains a challenge. OCCC is believed to evolve from endometriosis, a chronic immune/inflammation-related disease, so that immunotherapy may be a potential alternative treatment. Here, gene set-based analysis was used to investigate the immunofunctionomes of OCCC in early and advanced stages. Quantified biological functions defined by 5917 Gene Ontology (GO) terms downloaded from the Gene Expression Omnibus (GEO) database were used. DNA microarray gene expression profiles were used to convert 85 OCCCs and 136 normal controls into to the functionome. Relevant offspring were as extracted and the immunofunctionomes were rebuilt at different stages by machine learning. Several dysregulated pathogenic functions were found to coexist in the immunopathogenesis of early and advanced OCCC, wherein the complement-activation-alternative-pathway may be the headmost dysfunctional immunological pathway in duality for carcinogenesis at all OCCC stages. Several immunological genes involved in the complement system had dual influences on patients’ survival, and immunohistochemistrical analysis implied the higher expression of C3a receptor (C3aR) and C5a receptor (C5aR) levels in OCCC than in controls.

Serous carcinoma (SC) is the most common and lethal subtype of epithelial ovarian carcinoma; immunotherapy is a potential treatment for SC, however, the global immunological functions of SC as well as their change during the progression of SC have not been investigated in detail till now. We conducted a genome-wide integrative analysis to investigate the immunofunctionomes of SC at four tumor stages by quantifying the immunological functions defined by the Gene Ontology gene sets. DNA microarray gene expression profiles of 1100 SCs and 136 normal ovarian tissue controls were downloaded from the Gene Expression Omnibus database and converted to the functionome. Then the immunofunctionomes were reconstructed by extracting the offspring from the functionome for the four SC staging groups. The key immunological functions extracted from immunofunctionomes with a series of filters revealed that the immunopathy of SC consisted of a group of deregulated functions with the core members including B cell activation and differentiation, regulation of leukocyte chemotaxis/cellular extravasation, antigen receptor mediated signaling pathway, T helper mediated immunity and macrophage activation; and the auxiliary elements included leukocyte mediated immunity, regulation of inflammatory response, T cell differentiation, mononuclear cell migration, megakaryocyte differentiation, complement activation and cytokine production. These deregulated immunological functions reveal the candidates to target in the immunotherapy.

During certain clinical situations, some parturients require instruments for operative vaginal delivery, and various designs of vacuum extractors may affect the fetal head. To investigate the biomechanical effects of divergent sizes of silicone rubber vacuum extractors, we employed finite element analysis in this study. First, we constructed computer models for different vacuum extractor sizes (diameters: 40 mm, 50 mm, 60 mm, and 70 mm), flat surface, hemispherical ball, and fetal head shape. A hemispherical ball was the main design for the vacuum extractor model, and the material used for the vacuum extractor was silicone rubber. Next, the settings of 1 mm vacuum extractor displacement and vacuum cap pressure of 60 cmHg were applied. The main observation markers of this study were the respective von Mises stresses on the vacuum extractor and skull by the reaction force on the fixed end. The concluded results revealed that vacuum extractors with larger diameters lead to greater reaction force, stress, and strain on fetal heads. Therefore, this study’s biomechanical analytic consequences suggest that clinicians avoid selecting larger vacuum extractors during operative instrumental delivery so that fetal heads will experience less external force, deformation, and resultant complications. It could also provide a practical reference for obstetricians for instrumental vaginal delivery with the vacuum extractor made of silicone rubber.

Operative delivery requires the use of a vacuum extractor; obstetricians can choose the appropriate vacuum extractor to make the delivery process smoother and safer. However, there is no biomechanical literature focused on the imposed effects of a vacuum extractor prepared with different materials and vacuum pressure on the fetal head during the process of delivery. Therefore, we first established and performed the finite element analytical model to explore the influences of vacuum extractors manufactured from different materials on the fetal head under various extractive pressures. The model of the vacuum extractor was designed as a hemispherical shape, and the material of the vacuum extractor was composed of silicone rubber and stainless steel for comparison. Four different vacuum pressures (500 cm H₂O, 600 cm H₂O, 700 cm H₂O, and 800 cm H₂O) were applied as the factors for investigation. The reaction force on the fetal head, von Mises stress of vacuum extractor, and von Mises stress on the skull of fetal head were measured and analyzed to evaluate the effects. The results revealed that subtle divergent influences of different vacuum pressures were observed, and the stainless-steel vacuum extractor induced a larger reaction force (358.04–361.37 N), accompanied with stress (13.547–13.675 MPa), on the fetal head than non-metallic or relatively softer materials. The results provide a reliable basis for selecting proper vacuum extractor during operative delivery to avoid obstetrical complications, such as scalp scratch, cephalohematoma and even intracerebral hemorrhage.

Epithelial ovarian cancers (EOCs) are fatal and obstinate among gynecological malignancies in advanced stage or relapsed status, with serous carcinomas accounting for the vast majority. Unlike EOCs, borderline ovarian tumors (BOTs), including serous BOTs, maintain a semimalignant appearance. Using gene ontology (GO)-based integrative analysis, we analyzed gene set databases of serous BOTs and serous ovarian carcinomas for dysregulated GO terms and pathways and identified multiple differentially expressed genes (DEGs) in various aspects. The SRC (SRC proto-oncogene, non-receptor tyrosine kinase) gene and dysfunctional aryl hydrocarbon receptor (AHR) binding pathway consistently influenced progression-free survival and overall survival, and immunohistochemical staining revealed elevated expression of related biomarkers (SRC, ARNT, and TBP) in serous BOT and ovarian carcinoma samples. Epithelial–mesenchymal transition (EMT) is important during tumorigenesis, and we confirmed the SNAI2 (Snail family transcriptional repressor 2, SLUG) gene showing significantly high performance by immunohistochemistry. During serous ovarian tumor formation, activated AHR in the cytoplasm could cooperate with SRC, enter cell nuclei, bind to AHR nuclear translocator (ARNT) together with TATA-Box Binding Protein (TBP), and act on DNA to initiate AHR-responsive genes to cause tumor or cancer initiation. Additionally, SNAI2 in the tumor microenvironment can facilitate EMT accompanied by tumorigenesis. Although it has not been possible to classify serous BOTs and serous ovarian carcinomas as the same EOC subtype, the key determinants of relevant DEGs (SRC, ARNT, TBP, and SNAI2) found here had a crucial role in the pathogenetic mechanism of both tumor types, implying gradual evolutionary tendencies from serous BOTs to ovarian carcinomas. In the future, targeted therapy could focus on these revealed targets together with precise detection to improve therapeutic effects and patient survival rates.

Background: Operative delivery is a technique used during vaginal or cesarean birth to facilitate the patient’s labor course through the assistance of a vacuum extractor. This method is increasingly used compared with forceps. This study aimed to investigate the forced effects of vacuum extractors comprising vacuum cups with different thicknesses on the fetal head and the vacuum extractor during vacuum-assisted delivery and to determine the optimal thickness for reducing the failure rate and minimizing neonatal and maternal morbidity. Methods: A biomechanical model was developed to examine the impact of vacuum cups with varying thicknesses. This simulation three-dimensional (3D) geometry model was used to evaluate hemispherical-shaped vacuum extractors made of silicone rubber having a similar cup diameter of 70 mm with varying thicknesses (1-5 mm), which were applied to the three models (flat surfaces, hemispherical balls, and fetal head). Under one boundary condition and two different loading conditions, finite element analysis was utilized to simulate the force of vacuum extractors on the fetal head during the process of operative delivery. The main observation indicators were the reaction forces of the constructed model, and von Mises stress on both the vacuum extractors and fetal head. Results: For the reaction forces on each axis, we found that the sum of the reaction force values on each axis was increased as the thickness of the vacuum extractor was increased, regardless of the surface type. In addition, the reaction force of the fixed-support end was increased with the increased thickness of the vacuum extractor. The von Mises stress distributions of vacuum extractors comprising vacuum cups with different thicknesses, revealed that the thinner the cup, the greater the von Mises stress exerted on the extractor itself regardless of the surface type. The distribution of von Mises stress on the skull structure of the fetal head showed that the thinner the cup, the greater the von Mises stress exerted on the skull structure regardless of the surface type. Conclusion: A thinner vacuum extractor cup may result in greater injury to the fetus; hence, a thicker vacuum extractor cup is preferably utilized during vacuum-assisted operative delivery. Using a thicker vacuum extractor should yield a higher successful delivery rate and reduce fetal injury.