Metabolism pathway-based subtyping in endometrial cancer: An integrated study by multi-omics analysis and machine learning algorithms.

Endometrial cancer (EC), the second most common malignancy in the female reproductive system, has garnered increasing attention for its genomic heterogeneity, but understanding of its metabolic characteristics is still poor. We explored metabolic dysfunctions in EC through a comprehensive multi-omics analysis (RNA-seq datasets from The Cancer Genome Atlas [TCGA], Cancer Cell Line Encyclopedia [CCLE], and GEO datasets; the Clinical Proteomic Tumor Analysis Consortium [CPTAC] proteomics; CCLE metabolomics) to develop useful molecular targets for precision therapy. Unsupervised consensus clustering was performed to categorize EC patients into three metabolism-pathway-based subgroups (MPSs). These MPS subgroups had distinct clinical prognoses, transcriptomic and genomic alterations, immune microenvironment landscape, and unique patterns of chemotherapy sensitivity. Moreover, the MPS2 subgroup had a better response to immunotherapy. Finally, three machine learning algorithms (LASSO, random forest, and stepwise multivariate Cox regression) were used for developing a prognostic metagene signature based on metabolic molecules. Thus, a 13-hub gene-based classifier was constructed to predict patients' MPS subtypes, offering a more accessible and practical approach. This metabolism-based classification system can enhance prognostic predictions and guide clinical strategies for immunotherapy and metabolism-targeted therapy in EC.

Transcriptome and metabolome analyses reveal anthocyanins pathways associated with fruit color changes in plum (Prunus salicina Lindl.).

Plum (Prunus salicina Lindl.) is one of the most widely cultivated and important fruit trees in temperate and cold regions. Fruit color is a significant trait relating to fruit quality in plum. However, its development mechanism has not been studied from the aspects of transcriptional regulation and metabolomic progress. To reveal the mechanism of fruit color developments in plums, we selected the fruits of two plum cultivars, 'Changli84' (Ch84, red fruit) and 'Dahuangganhe' (D, yellow fruit) as plant materials for transcriptome sequencing and metabolomic analysis were performed. Based on the data of transcriptome and metabolome at three fruit developmental stages, young fruit stage, color-change stage, and maturation stage, we identified 2,492 differentially expressed genes (DEGs) and 54 differential metabolites (DMs). The KEGG analysis indicated that "Flavonoid biosynthesis" was significantly enriched during three fruit development stages. Some DEGs in the "Flavonoid biosynthesis" pathway, had opposite trends between Ch84 and D, including chalcone synthase (CHS), dihydroflavonol 4-reductase (DFR) and flavonol synthase (FLS). Also, the genes encoding MYB-bHLH-WD (MBW) protein complexes, especially MYBs and bHLHs, showed a close relationship with plum fruit color. In the current study, DMs like procyanidin B1, cyanidin 3-glucoside, and cyanidin-3-O-alpha-arabinopyranoside were key pigments (or precursors), while the carotene and carotenoids did not show key relationships with fruit color. In conclusion, the anthocyanins dominate the color change of plum fruit. Carotenes and carotenoids might be related to the color of plum fruit, but do not play a dominate role.

Risk factors of perioperative complications and management with enhanced recovery after primary surgery in women with epithelial ovarian carcinoma in a single center.

The present study aimed to evaluate the postoperative complications and the impact of an enhanced recovery programme in patients who underwent primary surgery (including extensive upper abdominal surgery) for epithelial ovarian carcinoma (EOC). All patients with stage I-IV ovarian carcinoma who underwent primary surgery were identified, and postoperative complications were evaluated and graded according to the Clavien-Dindo classification. Of 161 patients, 46 (28.57%) underwent surgical staging, 27 (16.77%) standard cytoreduction, 12 (7.45%) en bloc debulking and 76 (47.20%) extraradical debulking. A total of 157 patients (97.52%) achieved optimal tumor reduction (<1 cm). The mean postoperative hospitalization time was 17.33±11.29 days after completion of the initial postoperative chemotherapy (IPC), and the IPC interval was 16.22±10.09 days. A total of 13 patients (8.07%) had grade 3 complications (9 with wound dehiscence, 3 with digestive tract leakage and 1 with a bladder fistula). A total of 2 patients (1.24%) had grade 4-5 complications [1 patient with severe pneumonia returned to the intensive care unit (ICU) for tracheotomy and respiration rehabilitation; the other patient died of septicemia on day 19]. The multivariate analysis of the preoperative factors revealed that a human epididymis protein 4 (HE4) level of ≥717 pM (P=0.015) and Federation International of Gynecology and Obstetrics (FIGO) stage IV (P=0.004; compared with stage IIIC) were associated with grade 3-5 complications. The bootstrap analysis revealed that a cancer antigen 125 (CA125) level of ≥1,012 U/ml (P=0.034), a HE4 level of ≥717 pM (P=0.007) and FIGO stage IV (P=0.002; compared with stage IIIC) were significantly associated with grade 3-5 complications. Meanwhile, the multivariate analysis of the postoperative factors did not reveal any risk factors associated with grade 3-5 complications; the bootstrap analysis revealed that only transfer to the ICU after surgery (P=0.026) was significantly associated with grade 3-5 complications. In conclusion, the study found that application of enhanced recovery after surgery protocols is feasible in patients with EOC, especially in those undergoing advanced extensive upper abdominal surgery, and CA125, HE4 and FIGO stage IV were related with the occurrence of adverse perioperative outcomes.

A Review of the Clinical Characteristics and Novel Molecular Subtypes of Endometrioid Ovarian Cancer.

Ovarian cancer is one of the most common gynecologic cancers that has the highest mortality rate. Endometrioid ovarian cancer, a distinct subtype of epithelial ovarian cancer, is associated with endometriosis and Lynch syndrome, and is often accompanied by synchronous endometrial carcinoma. In recent years, dysbiosis of the microbiota within the female reproductive tract has been suggested to be involved in the pathogenesis of endometrial cancer and ovarian cancer, with some specific pathogens exhibiting oncogenic having been found to contribute to cancer development. It has been shown that dysregulation of the microenvironment and accumulation of mutations are stimulatory factors in the progression of endometrioid ovarian carcinoma. This would be a potential therapeutic target in the future. Simultaneously, multiple studies have demonstrated the role of four molecular subtypes of endometrioid ovarian cancer, which are of particular importance in the prediction of prognosis. This literature review aims to compile the potential mechanisms of endometrioid ovarian cancer, molecular characteristics, and molecular pathological types that could potentially play a role in the prediction of prognosis, and the novel therapeutic strategies, providing some guidance for the stratified management of ovarian cancer.

Emergency craniotomy in patient with intracranial metastatic choriocarcinoma: a case report.

Choriocarcinoma is a highly malignant gynaecological tumour. This disease becomes life-threatening once brain haemorrhage or brain herniation occurs. Timely and accurate brain surgery can gain treatment time for patients that have a large number of cerebral haemorrhages and/or brain herniation. This current report describes a case of choriocarcinoma secondary to a hydatidiform mole in a 55-year-old woman that presented with neurological symptoms. Following admission to hospital, computed tomography examination found that lung and brain metastases were accompanied by cerebral haemorrhage. Cerebral hernia occurred during induction chemotherapy treatment and emergency surgery was performed. The patient recovered after individual chemotherapy and rehabilitation treatment. Patients with a very high risk of choriocarcinoma with brain metastasis should be referred to a comprehensive medical centre. Necessary surgical treatment and individualized chemotherapy can reduce the mortality of patients with choriocarcinoma brain metastasis.

Effect of claudin 1 on cell proliferation, migration and apoptosis in human cervical squamous cell carcinoma.

Claudin 1 is a member of the claudin protein family that serves an important role in tight junctions. Increased or decreased expression levels of claudin 1 are found in several diseases, including breast cancer and viral infections. However, the function of claudin 1 in cervical cancer remains controversial. The aim of the present study was to investigate the biological functions of claudin 1 in different human cervical cancer cell lines. First, SiHa and ME­180 cells with stable claudin 1 overexpression or knockdown were established using lentiviral transduction, and the mRNA and protein levels were measured via reverse transcription­quantitative PCR and western blot analysis. Subsequently, cell proliferation, colony formation and migration experiments were performed in vitro using standard protocols, demonstrating that claudin 1 was able to inhibit cell proliferation and migration in both SiHa and ME­180 cells. Furthermore, cell cycle and apoptosis were detected via flow cytometry and western blotting, and the results revealed that claudin 1 inhibited cell cycle progression and promoted apoptosis. To further verify whether claudin 1 was involved in tumor growth in vivo, xenograft tumors were established in athymic mice via injecting SiHa cells overexpressing claudin 1, which was found to decrease tumor growth in vivo. Furthermore, the association between claudin 1 expression and prognosis was analyzed in different types of cancer in The Cancer Genome Atlas. Overall, the findings of the present study revealed that claudin 1 may serve an antitumor role in cervical squamous cell carcinoma and may be of value as a potential therapeutic target.

Transcriptional regulation of bark freezing tolerance in apple (Malus domestica Borkh.).

Freezing tolerance is a significant trait in plants that grow in cold environments and survive through the winter. Apple (Malus domestica Borkh.) is a cold-tolerant fruit tree, and the cold tolerance of its bark is important for its survival at low temperatures. However, little is known about the gene activity related to its freezing tolerance. To better understand the gene expression and regulation properties of freezing tolerance in dormant apple trees, we analyzed the transcriptomic divergences in the bark from 1-year-old branches of two apple cultivars, "Golden Delicious" (G) and "Jinhong" (H), which have different levels of cold resistance, under chilling and freezing treatments. "H" can safely overwinter below -30 °C in extremely low-temperature regions, whereas "G" experiences severe freezing damage and death in similar environments. Based on 28 bark transcriptomes (from the epidermis, phloem, and cambium) from 1-year-old branches under seven temperature treatments (from 4 to -29 °C), we identified 4173 and 7734 differentially expressed genes (DEGs) in "G" and "H", respectively, between the chilling and freezing treatments. A gene coexpression network was constructed according to this expression information using weighted gene correlation network analysis (WGCNA), and seven biologically meaningful coexpression modules were identified from the network. The expression profiles of the genes from these modules suggested the gene regulatory pathways that are responsible for the chilling and freezing stress responses of "G" and/or "H." Module 7 was probably related to freezing acclimation and freezing damage in "H" at the lower temperatures. This module contained more interconnected hub transcription factors (TFs) and cold-responsive genes (CORs). Modules 6 and 7 contained C-repeat binding factor (CBF) TFs, and many CBF-dependent homologs were identified as hub genes. We also found that some hub TFs had higher intramodular connectivity (KME) and gene significance (GS) than CBFs. Specifically, most hub TFs in modules 6 and 7 were activated at the beginning of the early freezing stress phase and maintained upregulated expression during the whole freezing stress period in "G" and "H". The upregulation of DEGs related to methionine and carbohydrate biosynthetic processes in "H" under more severe freezing stress supported the maintenance of homeostasis in the cellular membrane. This study improves our understanding of the transcriptional regulation patterns underlying freezing tolerance in the bark of apple branches.

Sequential metastasis to the liver and pancreas 4 years after gestational trophoblastic neoplasia: a case report.

This case report describes a 43-year-old female initially diagnosed with gestational trophoblastic neoplasia that then experienced metastasis to the liver and then subsequently to the pancreas nearly 4 years after the primary diagnosis. After resection of the body and tail of the pancreas, the postoperative histopathological examination confirmed a placental site trophoblastic tumour that had developed after several cycles of chemotherapy for the original primary tumour and the liver metastases. This type of sequential recurrence of gestational trophoblastic neoplasia in the primary site or metastatic sites, such as the liver or pancreas, can be cured by a comprehensive treatment strategy involving surgery and/or salvage chemotherapy and continuous follow-up over a long period, especially for patients with a high-risk status.

NUMERICAL ANALYSIS OF SAFETY ZONE OF A LARGE FLAT-PLATE BOUNDED-WAVE EMP SIMULATOR.

The safety zone of a large flat-plate bounded-wave electromagnetic pulse simulator was analyzed using the 3D electromagnetic simulation software Computer Simulation Technology. First, the double-limit requirement cited from the GB 8702 for an instantaneous pulse was clarified compared with the International Commission on Non-Ionizing Radiation Protection guidelines. This means that both the amplitude of the time-domain waveforms and all frequency components should be satisfied with the respective exposure limits. Then, the leakage field of a large flat-plate bounded-wave simulator was simulated. After analyzing the peak amplitude of an instantaneous electric field in a certain area, the observation points along six directions were specified, and the corresponding amplitudes were given. Furthermore, it was verified that the time-domain electric field of the critical points was satisfied with the frequency-domain exposure limits. Finally, the safety distances lower than the reference levels were given, and the safety zones corresponding to the three common exposure limits were obtained.