Effect of Nalbuphine Combined with Propofol on Relieving Visceral Pain and Cognitive Function in Patients Undergoing Laparoscopic Ovarian Tumor Resection.

Objective: This study evaluated the effectiveness of nalbuphine combined with propofol in reducing visceral pain and preserving cognitive function during laparoscopic ovarian tumor resection. Methods: A total of 100 patients undergoing laparoscopic ovarian tumor resection from January 2019 to January 2022 were randomly assigned to either the control group or the research group (50 patients each). The control group received fentanyl combined with propofol for anesthesia, while the research group received nalbuphine combined with propofol. Various anesthetic parameters, hemodynamics, visceral pain(Visual analog scale was used to evaluate the degree of pain at rest and during movement at 2h, 6h, and 12h after the operation), cognitive function (Mini-Mental State Examination (MMSE) scale was used to assess the cognitive function before the operation and 1 day, 3 days, and 5 days after the operation, including time and place, language, orientation, calculation, delayed memory and useability), and incidence of adverse reactions were assessed and compared between the two groups. Results: The research group exhibited significantly lower propofol dosage and anesthesia recovery time compared to the control group (P < .05). Hemodynamic stability, as indicated by SBP (Systolic Blood Pressure), DBP (Diastolic Blood Pressure), and SpO2 （Peripheral Capillary Oxygen Saturation）levels, was better maintained in the research group, especially at the beginning of the operation (P < .05). VAS (Visual Analog Scale) scores for pain at rest and during exercise were significantly lower in the research group at 2h and 6h post-operation (P < .05). MMSE (Mini-Mental State Examination) scores were higher in the research group compared to the control group at 1and3 days post-operation (P < .05). Additionally, the incidence of adverse reactions was significantly lower in the research group (8.00%) compared to the control group (20.00%, P < .05).The above results were subjected to t test and χ2 test. Conclusions: Nalbuphine combined with propofol effectively alleviates visceral pain during laparoscopic ovarian tumor resection, stabilizes hemodynamics, and preserves cognitive function. This combination demonstrates promising analgesic and sedative effects with high safety, suggesting its potential for widespread clinical use.

Identification of immune-related biomarkers and construction of regulatory network in patients with atherosclerosis.

BACKGROUND: More and more evidence has established the crucial roles of the innate and adaptive immune systems in driving atherosclerosis-associated chronic inflammation in arterial blood vessels. Thus, the goal of this research was to determine immune-related biomarkers in atherosclerosis. METHODS: In this study, we conducted analysis on the mRNA expression profile of atherosclerosis obtained from Gene Expression Omnibus. Differentially expressed genes (DEGs) between atherosclerosis and control samples and immune-related genes (IRGs) were intersected to obtain differentially expressed immune-related genes (DEIRGs). The protein-protein interaction (PPI) network was created by STRING database and hub genes were identified by the MCODE plug-in. Furthermore, the receiver operating characteristic (ROC) curve was executed to verify the diagnostic value of the hub genes, and microRNA (miRNA)-gene-transcription factor (TF) regulatory networks were used to explain the regulatory mechanism of hub genes in atherosclerosis. Finally, qRT-PCR was performed to identify the mRNA levels of the target genes. RESULTS: A total of 199 overlapping genes were screened out as DEIRGs by intersecting the DEGs and IRGs. Then, 6 hub genes with high diagnostic value (IFIH1, IFIT1, IFIT2, IFIT3, ISG15 and OAS3) were identified via PPI network and ROC curve. Finally, miRNA-gene-TF networks revealed the regulatory mechanism of diagnostic genes.We used the carotid artery of AS patients and normal human carotid artery plaque samples for qRT-PCR verification, and the results showed that the hub gene had the same trend. CONCLUSION: Our study identified IFIH1, IFIT1, IFIT2, IFIT3, ISG15 and OAS3 as immune-related hub genes of atherosclerosis. These genes may serve as potential therapeutic targets for atherosclerosis patients.

Deciphering the expression patterns of homologous recombination-related lncRNAs identifies new molecular subtypes and emerging therapeutic opportunities in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the leading killer among women with gynecologic malignancies. Homologous recombination deficiency (HRD) has attracted increasing attention due to its significant implication in the prediction of prognosis and response to treatments. In addition to the germline and somatic mutations of homologous recombination (HR) repair genes, to widely and deeply understand the molecular characteristics of HRD, we sought to screen the long non-coding RNAs (lncRNAs) with regard to HR repair genes and to establish a prognostic risk model for EOC. Herein, we retrieved the transcriptome data from the Genotype-Tissue Expression Project (GTEx) and The Cancer Genome Atlas (TCGA) databases. HR-related lncRNAs (HRRlncRNAs) associated with prognosis were identified by co-expression and univariate Cox regression analyses. The least absolute shrinkage and selection operator (LASSO) and multivariate stepwise Cox regression were performed to construct an HRRlncRNA risk model containing AC138904.1, AP001001.1, AL603832.1, AC138932.1, and AC040169.1. Next, Kaplan-Meier analysis, time-dependent receiver operating characteristics (ROC), nomogram, calibration, and DCA curves were made to verify and evaluate the model. Gene set enrichment analysis (GSEA), immune analysis, and prediction of the half-maximal inhibitory concentration (IC50) in the risk groups were also analyzed. The calibration plots showed a good concordance with the prognosis prediction. ROCs of 1-, 3-, and 5-year survival confirmed the well-predictive efficacy of this model in EOC. The risk score was used to divide the patients into high-risk and low-risk subgroups. The low-risk group patients tended to exhibit a lower immune infiltration status and a higher HRD score. Furthermore, consensus clustering analysis was employed to divide patients with EOC into three clusters based on the expression of the five HRRlncRNAs, which exhibited a significant difference in checkpoints' expression levels and the tumor microenvironment (TME) status. Taken together, the results of this project supported that the five HRRlncRNA models might function as a biomarker and prognostic indicator with respect to predicting the PARP inhibitor and immune treatment in EOC.

Identification of Key Differentially Methylated/Expressed Genes and Pathways for Ovarian Endometriosis by Bioinformatics Analysis.

The goal of this study was to identify genes that were differentially methylated and differentially expressed and their related signaling pathways in ovarian endometriosis tissue. First, the DNA methylation and gene expression profiles in the endometrial tissue of patients with ovarian endometriosis were studied using Illumina 450K methylation microarray analysis and the GSE141549 gene expression dataset. Second, differentially methylated and differentially expressed genes, herein referred to as differentially methylated/expressed genes, were identified and protein-protein interaction networks and functional analysis of these genes were determined. Third, qPCR and immunohistochemistry of patient samples was used to confirm the differential expression of a subset of differentially methylated/expressed genes. Finally, the GSE7305 dataset was used confirm the expression profile of differentially methylated/expressed genes and to determine the potential usefulness of these genes for diagnosis of endometriosis. A total of 37 hypermethylated low-expression genes and 66 hypomethylated high-expression genes were identified in ovarian endometriosis patients. Protein-protein interaction and functional analysis highlighted 8 hypermethylated low-expression genes (KRT19, KRT8, ESR1, PRL, SFN, IL20RA, IL2RB, and PAX8) and 4 hypomethylated high-expression genes (CYP11A1, NR5A1, ME1, and GSTM1). Significantly, both of these gene sets had a diagnostic value for patients with ovarian endometriosis. Signaling pathways that were identified included JAK-STAT (involving IL20RA and IL2RB), prolactin (involving PRL and ESR1), Staphylococcus aureus infection (involving KRT19), viral protein interaction with cytokine and cytokine receptor (involving IL20RA and IL2RB), cytokine-cytokine receptor interaction (involving IL20RA and IL2RB), and drug metabolism-cytochrome P450 (involving GSTM1). The differentially methylated/expressed genes and enriched signaling pathways identified in this study are likely to be associated with the process of ovarian endometriosis.

Comparison of two laparoscopic vaginoplasties using a single peritoneal flap in patients with Mayer-Rokitansky-Küster-Hauser syndrome.

INTRODUCTION AND HYPOTHESIS: To compare two laparoscopic vaginoplasties using a single peritoneal flap (SPF), namely the Hebei I technique and the Hebei II technique, for creation of a neovagina in patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. METHODS: A comparative retrospective study was conducted at a university-based tertiary care hospital. From September 2008 to September 2019, 72 patients with MRKH syndrome underwent either the Hebei I technique (n = 49) or the Hebei II technique (n = 23). The perioperative results, complications and anatomical outcomes of two groups were recorded and compared. The functional results of patients who became sexually active were assessed through the Female Sexual Function Index (FSFI) questionnaire. RESULTS: Two techniques achieved anatomical and functional success without intraoperative complications. There was no significant difference in perioperative results, anatomical findings and the FSFI scores between the two groups. Patients in the Hebei II group had a relatively shorter operative time than those in the Hebei I group (P = 0.064). What is more, compared with the Hebei I group, the Hebei II group had significantly fewer granulomatous polyps at the top of the neovagina (P = 0.029) and less mucous production of the neovagina (P = 0.025) during the first 3 months after surgery. CONCLUSIONS: Both the Hebei I and Hebei II techniques are feasible approaches for creating a neovagina which can bring satisfactory anatomical and sexual outcomes in patients with MRKH syndrome. However, the Hebei II technique may be a good alternative to the Hebei I technique because of its relatively shorter operative time, fewer neovaginal secretions and fewer granulomatous polyps.

Genetic Variation of Glutathione S-Transferase M1 Is Associated with Patients with Ovarian Endometriosis and Endometriosis-Related Primary Infertility.

BACKGROUND: The aim of the study was to investigate the role of the genetic variation of glutathione S-transferase M1 (GSTM1) in the development of ovarian endometriosis and endometriosis-related primary infertility risk. METHODS: This case-control study included 564 women with ovarian endometriosis and 576 normal women in the control group in northern China. The polymorphism of GSTM1 was genotyped by polymerase chain reaction (PCR)/ligase detection reaction method. To assess the biological significance of polymorphisms, the level of GSTM1 mRNA expression in patients' endometrial tissues with different genotypes was detected by quantitative real-time PCR (qRT-PCR). RESULTS: Compared with the positive genotype, the null genotype of GSTM1 was associated with the risk of developing ovarian endometriosis (OR = 1.29, 95% CI = 1.02-1.62). Further analysis showed that patients with a null genotype also had a significantly higher risk of primary infertility than patients with positive genotypes (OR = 1.59, 95% CI = 1.01-2.49). In addition, we found that GSTM1 mRNA expression was present in the endometrial tissue of all patients, but the expression level of patients with a positive genotype was nearly 10 times higher than that of patients with a negative genotype. CONCLUSION: Our results suggest that the GSTM1 polymorphism is not only related to the genetic susceptibility to ovarian endometriosis but also a potential molecular marker of primary infertility in patients with ovarian endometriosis.

Promoter Methylation of the MGRN1 Gene Predicts Prognosis and Response to Chemotherapy of High-Grade Serous Ovarian Cancer Patients.

Aberrant DNA methylation is considered to play a critical role in the chemoresistance of epithelial ovarian cancer (EOC). In this study, we explored the relationship between hypermethylation of the Mahogunin Ring Finger 1 (MGRN1) gene promoter and primary chemoresistance and clinical outcomes in high-grade serous ovarian cancer (HGSOC) patients. The MALDI-TOF mass spectrometry assays revealed a strong association between hypermethylation of the MGRN1 upstream region and platinum resistance in HGSOC patients. Spearman's correlation analysis revealed a significantly negative connection between the methylation level of MGRN1 and its expression in HGSOC. In vitro analysis demonstrated that knockdown of MGRN1 reduced the sensitivity of cells to cisplatin and that expression of EGR1 was significantly decreased in SKOV3 cells with low levels of MGRN1 expression. Similarly, EGR1 mRNA expression was lower in platinum-resistant HGSOC patients and was positively correlated with MGRN1 mRNA expression. Kaplan-Meier analyses showed that high methylation of the MGRN1 promoter region and low expression of MGRN1 were associated with worse survival of HGSOC patients. In multivariable models, low MGRN1 expression was an independent factor predicting poor outcome. Furthermore, low expression of EGR1 was also been confirmed to be significantly related to the poor prognosis of HGSOC patients by Kaplan-Meier. The hypermethylation of the MGRN1 promoter region and low expression of MGRN1 were associated with platinum resistance and poor outcomes in HGSOC patients, probably by altering EGR1 expression.

The HSP70 gene predicts prognosis and response to chemotherapy in epithelial ovarian cancer.

BACKGROUND: Chemotherapy resistance is an intractable problem in treating patients with epithelial ovarian cancer (EOC). Heat shock proteins (HSPs) act as apoptosis inhibitors and are highly conserved genetically. Most HSPs have strong cytoprotective effects, and their overexpression inhibits apoptosis. This has been demonstrated for HSP70. Heat shock protein 70 (HSP70) expression is abnormally upregulated in malignant cells. Furthermore, HSP70 can inhibit cell death and promote chemotherapeutic resistance. In our study, the relationship between the HSP70 gene and primary chemotherapy resistance and clinical outcome in patients with EOC was explored. METHODS: Quantitative real-time polymerase chain (qRT-PCR) was applied to determine HSP70 messenger RNA (mRNA) levels, and immunohistochemistry assay was conducted to determine HSP70 protein level. HSP70 overexpression was assessed to clarify its role on chemotherapy resistance to cisplatin in SKOV3 cell lines. RESULTS: RT-qPCR assay indicated a strong relationship between HSP70 expression and chemotherapy resistance in patients with EOC. In cultured SKOV3 cells, overexpression of HSP70 inhibited cell sensitivity to cisplatin. Kaplan-Meier analysis demonstrated high HSP70 expression was associated with poor outcome of EOC patients. In multivariate models, high HSP70 expression independently predicted this poor outcome. CONCLUSIONS: HSP70 predicts the prognosis and response to chemotherapy in EOC patients.

Adaptive Linear Span Network for Object Skeleton Detection.

Conventional networks for object skeleton detection are usually hand-crafted. Despite the effectiveness, hand-crafted network architectures lack the theoretical basis and require intensive prior knowledge to implement representation complementarity for objects/parts in different granularity. In this paper, we propose an adaptive linear span network (AdaLSN), driven by neural architecture search (NAS), to automatically configure and integrate scale-aware features for object skeleton detection. AdaLSN is formulated with the theory of linear span, which provides one of the earliest explanations for multi-scale deep feature fusion. AdaLSN is materialized by defining a mixed unit-pyramid search space, which goes beyond many existing search spaces using unit-level or pyramid-level features. Within the mixed space, we apply genetic architecture search to jointly optimize unit-level operations and pyramid-level connections for adaptive feature space expansion. AdaLSN substantiates its versatility by achieving significantly higher accuracy and latency trade-off compared with the state-of-the-arts. It also demonstrates general applicability to image-to-mask tasks such as edge detection and road extraction. Code is available at https://github.com/sunsmarterjie/SDL-Skeletongithub.com/sunsmarterjie/SDL-Skeleton.

FOXP4-AS1 is a favorable prognostic-related enhancer RNA in ovarian cancer.

Ovarian cancer (OV) is the main cause of deaths worldwide in female reproductive system malignancies. Enhancer RNAs (eRNAs) are derived from the transcription of enhancers and has attracted increasing attention in cancers recently. However, the biological functions and clinical significance of eRNAs in OV have not been well described presently. We used an integrated data analysis to identify prognostic-related eRNAs in OV. Tissue-specific enhancer-derived RNAs and their regulating genes were considered as putative eRNA-target pairs using the computational pipeline PreSTIGE. Gene expression profiles and clinical data of OV and 32 other cancer types were obtained from the UCSC Xena platform. Altogether, 71 eRNAs candidates showed significant correlation with overall survival (OS) of OV samples (Kaplan-Meier log-rank test, P<0.05). Among which, 23 were determined to be correlated with their potential target genes (Spearman's r > 0.3, P<0.001). It was found that among the 23 prognostic-related eRNAs, the expression of forkhead box P4 antisense RNA 1 (FOXP4-AS1) had the highest positive correlation with its predicted target gene FOXP4 (Spearman's r = 0.61). Moreover, the results were further validated by RT-qPCR analysis in an independent OV cohort. Our results suggested the eRNA FOXP4-AS1 expression index may be a favorable independent prognostic biomarker candidate in OV.

DNA methylome profiling identifies novel methylated genes in epithelial ovarian cancer patients with platinum resistance.

AIM: Platinum-based chemotherapy is widely used for epithelial ovarian cancer (EOC). As high as 20-25% of EOC patients will not respond to the initial chemotherapy. Accumulated evidences have implied that DNA methylation may serve as a potential bio-marker for chemotherapy-resistant phenotypic screening; however, the pattern underlying primary platinum resistance remains unclear. METHODS: Reduced representation bisulfite sequencing (RRBS) analysis was performed to identify differences in methylation status between primary platinum-resistant patients Progression free survival (PFS) (PFS < 6 months, n = 8) and extreme sensitive patients (PFS ≥ 24 months, n = 8). The Qubit 3.0 Fluorometer was used for the quantification of RRBS library. The RRBS library was sequenced on Illumina HiSeq2500 sequencer as 50 bp paired-end reads. RESULTS: After screening, 94 valid hyper-/hypo-methylated regions were identified to be located within 94 gene promoter and exon regions (adjusted q ≤ 0.5), which were primarily associated with cell-cell adhesion, B cell activation and lymphocyte activation according to GO analysis. The 19 differentially methylated regions (DMR) located in the promoter region including TRC-GCA11-1, LOC105370912, ANO7P1, DHX4,MSH2, CDCP2, CCNL1, ARHGAP42P2, PRDM13, LOC101928344, USP29, ZIC5,IL1RAPL1, EVX2, ABR, MGRN1, UBALD1, LINC00261, and ISL2 were identified according to the order of P-values from low to high, of which MSH2, LINC00261, MGRN1, ZIC5, EVX2, CCNL1, and DHX40 were presented to play a variety of roles in cancers process based on the previous studies. CONCLUSION: DNA methylome profiling based on RRBS assay is an effective method for screening aberrantly methylated genes in primary platinum-resistant patients, which may serve as a potential epigenetic bio-marker for the prediction of primary platinum resistance.