Ovarian clear cell carcinoma (OCCC) is a highly aggressive gynecological malignancy characterized by distinct clinicopathological features and resistance to chemotherapy. Despite advances in multi-omics characterization, the translational regulatory landscape of OCCC remains unexplored. Here, we performed ribosome profiling to systematically investigate translation control mechanisms in OCCC. We conducted an integrated analysis of transcriptomic and translatomic data from 22 clinical specimens. This study is the first to analyze translational dysregulation in OCCC at sub-codon resolution using translational group data resources. Integrated analysis identified novel unannotated open reading frames (ORFs) encoding functional micropeptides. Furthermore, we uncovered widespread translational dysregulation in OCCC, with experimental validation confirming the pro-tumorigenic role of translationally upregulated RBM4. This study bridges a critical gap between genomic, transcriptomic, and proteomic landscapes in OCCC, offering valuable mechanistic insights into its pathogenesis.

Pelvic organ prolapse (POP) complicating pregnancy is rare, and evidence for its management remains limited. We report a case of advanced POP during pregnancy that was successfully managed with a ring pessary. A 40-year-old woman with longstanding prolapse presented with worsening symptoms during pregnancy. Conservative management with a vaginal pessary provided effective antepartum support and allowed continuation of pregnancy until spontaneous labor. After vaginal delivery, prolapse recurred and was successfully managed with pessary reinsertion during the puerperium after lochia had decreased. At short-term follow-up, the prolapse remained well controlled and no pessary-related complications were observed. This case supports the feasibility of conservative pessary management in selected pregnant women with POP and suggests that reinsertion during the puerperium may be useful for ongoing symptom control.

Purpose:To evaluate the outcome and safety of transanal drainage tube (TDT) placement following surgical repair of chronic third- and fourth-degree perineal tears. Patients and Methods:A retrospective cohort study was conducted at Peking Union Medical College Hospital (2016-2024), including 31 patients with chronic perineal tears who underwent surgical repair. Patients were stratified into success (n=23) and failure (n=8) groups. Surgical failure was defined as persistence of fecal incontinence at six months postoperatively. Data included demographics, surgical details, TDT use, Wexner, and SF-12 scores. Results:The procedure demonstrated an overall success rate of 74.2% (23/31). Postoperative SF-12 and Wexner scores improved significantly in both the success and failure groups (p < 0.05). The success group had longer tube retention (9[7-11.5] vs 7[6-7] days, p=0.03). Further analysis revealed that prolonged drainage duration beyond 8 days was associated with improved success rates. Patients in the TDT group showed significantly greater improvement in Wexner scores (11.42 ± 3.13 vs 7.67 ± 3.37, p = 0.004). No major TDT-related complications occurred. Conclusion:Transanal drainage tube placement may enhance anal sphincter function when used at the time of anal sphincteroplasty. Maintaining TDT for more than 8 days is associated with higher success rate. Both successful and unsuccessful repairs lead to significant improvements in quality of life and fecal incontinence symptoms.

This study aimed to investigate the influence of cancer type on radiotherapy-induced otitis media with effusion (RTOME) occurrence and to assess the impact of anatomical region-specific radiation exposure on both RTOME incidence rates and associated pathogenic processes. A retrospective analysis was conducted on 1046 head and neck cancer (HNC) patients who underwent radiotherapy at Peking Union Medical College Hospital between 2016 and 2023. The incidence of RTOME was assessed across various cancer types, and the radiation exposure probabilities of different head and neck regions were compared between patients with and without RTOME using the chi-squared test (χ2) test and the Mann-Whitney U test. The overall incidence of RTOME in patients with HNC was 5.83%. The incidence varied significantly by cancer type, with nasopharyngeal carcinoma showing the highest rate (17.40%), followed by ocular and orbital cancers (6.25%), nasal cavity and paranasal sinus cancer (4.35%), oral cavity and oropharyngeal cancers (4.32%), laryngeal and hypopharyngeal cancers (0.32%), and thyroid cancers (0%). Furthermore, patients with RTOME exhibited significantly-higher radiation exposure frequencies in five specific anatomical regions: the skull base and intracranial, parotid and periauricular, nasal cavity and paranasal sinuses, nasopharynx, and parapharyngeal space, than those without RTOME. The incidence of RTOME is strongly associated with both cancer type and radiation exposure to specific anatomical regions. Radiation targeting certain areas may increase the risk of developing RTOME.

Hearing loss poses a significant global public health challenge, seriously jeopardizing both physical and mental health. As an emerging omics technique, metabolomics reflects the metabolic state influenced by both genetic and environmental factors and has been increasingly applied to hearing loss research. This review summarizes the latest advances in metabolomics applied to several types of acquired hearing loss, including age-related hearing loss, noise-induced hearing loss, and sudden sensorineural hearing loss. Through the identification and functional enrichment of differentially expressed metabolites in samples such as inner ear tissues, perilymph, and plasma, metabolomics aims to explore the pathogenesis and identify diagnostic and prognostic biomarkers of acquired hearing loss, providing promising prospects for novel treatments. Evidence we gather from existing studies suggests potential correlations of metabolomic pathways-such as amino acid metabolism, lipid metabolism, purine and pyrimidine metabolism, and autophagy- with acquired hearing loss. Biomarkers like sphingosine also show their potential to predict its diagnosis and prognosis. Finally, we highlight the importance of standardizing the experimental design and expanding the sample size to enhance the accuracy and comparability of metabolomics results. Integration of metabolomics with multiple techniques and multidimensional information, as well as promotion of clinical transformation may be the future developmental direction in this field.

Objectives Acquired cholesteatoma is an abnormal and invasive growth of keratinized squamous epithelial cells in the middle ear. The study aims to explore the role of exosomal miRNAs in the pathogenesis of acquired cholesteatoma and their potential in clinical application.Methods Cholesteatoma and matched retroauricular skin samples were collected from 14 patients and exosomes were directly isolated from tissues. The specific exosomal miRNA expression pattern in cholesteatoma was determined through miRNA sequencing. The potential roles of differentially expressed miRNAs (DE-miRNAs) were investigated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The enriched pathways of the top nine DE-miRNAs were further explored. Furthermore, the expression levels of these DE-miRNAs were validated in plasma-derived exosomes from 12 cholesteatoma patients, 6 chronic otitis media patients, and 4 healthy individuals to identify the candidate biomarkers for cholesteatoma.Results Tissue-derived exosomes were successfully extracted from cholesteatoma and normal skin tissues. We found 14 upregulated miRNAs and 25 downregulated miRNAs in the cholesteatoma-derived exosomes. Bioinformatics analysis indicated that the DE-miRNAs participated in multiple biological processes, cell components, and molecular functions. The differential expression of hsa-miR-223-3p and hsa-miR-142-5p was verified in plasma-derived exosomes from cholesteatoma patients, and they showed a modest ability to distinguish between cholesteatoma and normal samples (AUC = 0.81 and AUC = 0.84, respectively). We further identified the potential functions of these two miRNAs in cholesteatoma pathogenesis.Conclusion Our study is the first to explore the specific exosomal miRNA profile of acquired cholesteatoma tissue. Exosomal miR-223-3p and miR-142-5p can be considered as promising biomarkers for acquired middle ear cholesteatoma.

Objective:To investigate the impact of different radiation fields on the risk of otitis media with effusion (OME) in nasopharyngeal carcinoma (NPC) patients and to develop a nomogram to identify high-risk patients after radiotherapy. Methods:Clinical data were collected from 170 NPC patients who underwent radiotherapy at Peking Union Medical College Hospital (January 2016-December 2021, development group) and 73 patients (January 2022-June 2024, validation group). Multivariate logistic regression analyses were used to identify risk factors for OME, and a nomogram was constructed based on these findings. Results:Multivariate analysis revealed that gender, invaded eustachian tube, and radiation to the parotid and periauricular field and parapharyngeal space were independent risk factors for OME. The nomogram demonstrated good discrimination, with AUC values of 0.813 (development group) and 0.798 (validation group). Calibration was confirmed with Hosmer-Lemeshow test results (p > 0.33), and decision curve analysis indicated significant clinical utility within a threshold probability range of 0.09-0.94. When the risk threshold exceeded 0.38, the predicted high-risk population matched well with actual OME cases, highlighting high clinical predictive efficiency. Conclusion:In conclusion, radiation fields are significant risk factors for OME in NPC patients. The developed nomogram enables early identification of high-risk patients, supporting timely intervention.

Facial nerve (FN) injury seriously affects human social viability and causes a heavy economic and social burden. Although mesenchymal stem cell-derived exosomes (MSC-Exos) promise therapeutic benefits for injury repair, there has been no evaluation of the impact of MSC-Exos administration on FN repair. Herein, we explore the function of MSC-Exos in the immunomodulation of macrophages and their effects in repairing FN injury. An ultracentrifugation technique was used to separate exosomes from the MSC supernatant. Administrating MSC-Exos to SD rats via local injection after FN injury promoted axon regeneration and myelination and alleviated local and systemic inflammation. MSC-Exos facilitated M2 polarization and reduced the M1-M2 polarization ratio. miRNA sequencing of MSC-Exos and previous literature showed that the MAPK/NF-κb pathway was a downstream target of macrophage polarization. We confirmed this hypothesis both in vivo and in vitro. Our findings show that MSC-Exos are a potential candidate for treating FN injury because they may have superior benefits for FN injury recovery and can decrease inflammation by controlling the heterogeneity of macrophages, which is regulated by the p38 MAPK/NF-κb pathway.

Background The present study aims to identify the differential miRNA expression profile in middle ear cholesteatoma and explore their potential roles in its pathogenesis.Methods Cholesteatoma and matched normal retroauricular skin tissue samples were collected from patients diagnosed with acquired middle ear cholesteatoma. The miRNA expression profiling was performed using small RNA sequencing, which further validated by quantitative real-time PCR (qRT-PCR). Target genes of differentially expressed miRNAs in cholesteatoma were predicted. The interaction network of 5 most significantly differentially expressed miRNAs was visualized using Cytoscape. Further Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses were processed to investigate the biological functions of miRNAs in cholesteatoma.Results The miRNA expression profile revealed 121 significantly differentially expressed miRNAs in cholesteatoma compared to normal skin tissues, with 56 upregulated and 65 downregulated. GO and KEGG pathway enrichment analyses suggested their significant roles in the pathogenesis of cholesteatoma. The interaction network of the the 2 most upregulated (hsa-miR-21-5p and hsa-miR-142-5p) and 3 most downregulated (hsa-miR-508-3p, hsa-miR-509-3p and hsa-miR-211-5p) miRNAs identified TGFBR2, MBNL1, and NFAT5 as potential key target genes in middle ear cholesteatoma.Conclusions This study provides a comprehensive miRNA expression profile in middle ear cholesteatoma, which may aid in identifying therapeutic targets for its management.

Abstract Background Hearing loss (HL) is a worldwide public health issue for which the role of dyslipidemia has not been fully elucidated. This study aimed to use the atherogenic index of plasma (AIP), a well-established serum lipid marker, to investigate the association of dyslipidemia with HL among the general population. Methods Participants (n = 3267) from the National Health and Nutrition Examination Survey database (2005–2012, 2015–2018) were included in the present study. The AIP was calculated based on the following formula: log10 (triglycerides/high-density lipoprotein cholesterol). HL was defined as a pure-tone average of at least 20 dBHL in the better ear. Weighted multivariable logistic regression, subgroup analysis, generalized additive model, and threshold analysis were adopted to reveal the association between the AIP and HL. Results In this study of US adults, a positive association was found between the AIP and high-frequency HL. However, the association between the AIP and low-frequency HL was not as strong. In addition, a reverse L-shaped curve with an inflection point located at -0.27 was detected between the AIP and high-frequency HL, followed by a significant positive association after the inflection point. Conclusions The potential of the AIP as a bioindicator for high-frequency HL is noteworthy, and maintaining an AIP value below a certain threshold might provide beneficial outcomes in the management of high-frequency HL.

Abstract Background Ovarian clear cell carcinoma (OCCC), well known for its chemoresistance to platinum-based chemotherapy, exhibited a good response in clinical trials of anti–PD-1/PD-L1 inhibitors. By assessing PD-L1 expression, we sought to determine the potential therapeutic benefit of PD-1/PD-L1 inhibitors in OCCC. Methods and results The retrospective study included 152 individuals with OCCC between 2019 and 2022 at Peking Union Medical College Hospital. Paired tumors of primary versus recurrent lesions (17 pairs from 15 patients) or primary versus metastatic lesions (11 pairs from 9 patients) were also included. The 22C3 pharmDx assay and whole sections were used for PD-L1 immunohistochemical staining. Pathologists with experience in premarket clinical trials evaluated PD-L1 expression based on various diagnostic criteria (TPS 1%, CPS 1, or CPS 10). The number and percentage of positive PD-L1 cases were 34 (22.4%, TPS ≥ 1%) and 59 (38.8%, CPS ≥ 1), respectively. Thirty-three (21.7%) of the cases had high PD-L1 expression (CPS ≥ 10). Half of the platinum-resistant patients (11/22) were PD-L1 positive (CPS ≥ 1). In addition, positive PD-L1 expression (CPS ≥ 1) was related to clinicopathological characteristics that represented a worse prognosis, such as advanced stages, lymph node metastasis, and distant metastasis (p = 0.032, p < 0.001 and p = 0.003, separately). PD-L1 was expressed equally or more in the recurrent lesion compared with its matched primary lesion. Conclusions In conclusion, anti–PD-1/PD-L1 inhibitors are a promising therapeutic choice for OCCC. For evaluation of PD-L1 expression, CPS is more recommended than TPS. Evaluation of recurrent lesion was still suitable and predictive when the primary tumor tissue was not available. Distant metastatic lesions can serve as alternative samples for PD-L1 evaluation, while usage of lymphatic metastatic lesions is not recommended.

Abstract BACKGROUND We aimed to analyze the survival benefit of adjuvant chemotherapy in patients with T1N0M0 triple-negative breast cancer (TNBC) (age-stratified and tumor size-stratified) to guide more precise treatment. METHODS This study recruited 6482 pT1N0M0 TNBC patients from 2010–2015 in the SEER database (*Stat 8.3.6 software). The χ[2] test was used to compare categorical variables between different tumor sizes. OS and BCSS of patients with T1mic, T1a, T1b and T1cN0M0 TNBC were studied and Kaplan-Meier survival curves were plotted for the prognosis of patients receiving versus not receiving chemotherapy stratified by age and tumor size. RESULTS A total of 6482 T1N0M0 TNBC patients were included in this study, with a total of 4244 (65.47%) patients receiving adjuvant chemotherapy and 2238 (34.53%) not receiving adjuvant chemotherapy, whose 5-year OS was 92.4% and 85.4% (p < 0.001) and 5-year BCSS was 95.1% and 94.9% (p = 0.46), respectively. Among them, 15.2% (16/105), 24.5% (159/650), 58.7% (1046/1781), and 76.6% (3023/3946) received chemotherapy for T1mic, T1a, T1b, and T1c, respectively. The 5-year OS with and without chemotherapy was 93.3% vs. 94.7% (p = 0.95), 98.7% vs. 94.4% (p = 0.004), 94.8% vs. 87.7% (p < 0.001), and 91.2% vs. 77.0% (p < 0.001), respectively, and the 5-year BCSS was 100% vs. 93.3% (p = 0.026),99.3% vs 98.1% (p = 0.22), 96.9% vs 96.3% (p = 0.36), and 94.3% vs 91.4% (p < 0.001), respectively. Among the T1mic patients, receiving chemotherapy did not improve OS (p = 0.95), but instead decreased BCSS (p = 0.026). When patients were stratified by age, it was found that for age > 65 years, T1a patients receiving chemotherapy did not improve OS and BCSS (p = 0.07, p = 0.45). For T1b patients, receiving chemotherapy at age > 75 years did not improve OS and BCSS (p = 0.065, p = 0.13). For T1c patients, receiving chemotherapy did not improve OS and BCSS at age > 80 years (p = 0.19, p = 0.15). CONCLUSION This study found that adjuvant chemotherapy improved OS but not BCSS in T1N0TNBC patients. T1mic patients receiving chemotherapy did not improve OS but decreased BCSS, T1a and T1b patients adjuvant chemotherapy improved OS but not BCSS. >65 years old T1a, > 75 years old T1b and > 80 years old Tc patients receiving chemotherapy did not improve survival and could be used as a clinical reference for patients exempted from chemotherapy.

The two most prevalent subtypes of epithelial ovarian carcinoma (EOC) are ovarian clear cell carcinoma (OCCC) and high-grade serous ovarian carcinoma (HGSC). Patients with OCCC have a poor prognosis than those with HGSC due to chemoresistance, implying the need for novel treatment target. In this study, we applied single-cell RNA sequencing (scRNA-seq) together with bulk RNA-seq data from the GEO (Gene Expression Omnibus) database (the GSE189553 dataset) to characterize and compare tumor heterogeneity and cell-level evolution between OCCC and HGSC samples. To begin, we found that the smaller proportion of an epithelial OCCC cell subset in the G2/M phase might explain OCCC chemoresistance. Second, we identified a possible pathogenic OCCC epithelial cell subcluster that overexpresses LEFTY1. Third, novel biomarkers separating OCCC from HGSC were discovered and subsequently validated on a wide scale using immunohistochemistry. Amine oxidase copper containing 1 (AOC1) was preferentially expressed in OCCC over HGSC, while S100 calcium-binding protein A2 (S100A2) was detected less frequently in OCCC than in HGSC. In addition, we discovered that metabolic pathways were enriched in the epithelial compartment of the OCCC samples. In vitro experiments verified that inhibition of oxidative phosphorylation or glycolysis pathways exerted direct antitumor effects on both OCCC and HGSC cells, while targeting glutamine metabolism or ferroptosis greatly attenuated chemosensitivity only in OCCC cells. Finally, to determine whether there were any variations in immune cell subsets between OCCC and HGSC, data from scRNA-seq and mass cytometry were pooled for analysis. In summary, our work provides the first holistic insights into the cellular and molecular distinctions between OCCC and HGSC and is a valuable source for discovering new targets to leverage in clinical treatments to improve the poor prognosis of patients with OCCC.

Objectives: To conduct a systematic review and meta-analysis of clinical studies describing the possible prognostic factors affecting hearing outcomes in Otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) patients. To provide guidance for clinical work, avoiding profound irreversible hearing loss affecting patients' lives. Methods: A literature search was performed in PubMed, MEDLINE, EMBASE, Cochrane, Scopus, and Web of Science to identify English articles published before December 1, 2022. After screening the articles, the Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias of the extracted literature, and studies with high quality (score > 6) were included. Results: Four studies were included: 1 was a retrospective cohort study, and 3 were case-control studies. We performed a meta-analysis of 4 factors: facial palsy, hypertrophic pachymeningitis, ANCA-negative status, and the period from onset to diagnosis. The results showed that there was a significant association between facial palsy [odds ratio (OR) 1.51; 95% confidence interval (CI) 1.07-2.15; I2 = 0%; P = .02], hypertrophic pachymeningitis (OR 1.73; 95% CI 1.18-2.53; I2 = 24%; P = .005), ANCA negativity (OR 1.75; 95% CI 1.11-2.77; I2 = 33; P = .02), and poor hearing prognosis in OMAAV patients. However, the period from onset to diagnosis (SEM ± SD 2.54; 95% CI -1.56 to 6.64; I2 = 98%; P = .22) of OMAAV was not significantly associated with poor hearing outcomes. Conclusion: We found that OMAAV patients with facial palsy, hypertrophic pachymeningitis, and ANCA negativity have a significant association with poor hearing prognosis, which provides diagnosis and treatment guidance in protecting patients' hearing.

AIM:As the second most prevalent subtype of epithelial ovarian cancers, ovarian clear cell carcinoma (OCCC) is known for its chemoresistance to conventional platinum-based therapy. In this work, we examined the tryptophan (Trp) metabolism enzymes' differential expression in patients with OCCC to assess the potential for personalised treatment.METHODS:A total of 127 OCCC tissues were used to construct tissue microarrays, and immunohistochemistry (IHC) staining of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 was performed. The correlations between Trp enzyme expression and clinical characteristics were analysed.RESULTS:Positive IDO1, IDO2, TDO2 and IL4I1 staining was identified in 26.8%, 94.5%, 75.6% and 82.7% of OCCC respectively. IDO1-positive samples were more common in the chemoresistant group than in the platinum-sensitive group (46.7% vs. 19.8%). Moreover, positive expression of IDO1, TDO2 and IL4I1 was related to advanced stage, metastasis, bilateral tumours, endometriosis and tumour rupture (p < 0.05) respectively. Univariate analysis revealed a significant association between bilateral tumours, lymph node metastasis, advanced stage, distant metastasis and aberrant cytology with a poor prognosis for OCCC, while the absence of residual tumour was correlated with a favourable outcome (p < 0.05). However, only bilateral tumours and lymph node metastases were related to a poor prognosis after multivariate analysis.CONCLUSION:This is the first study to investigate the expression of the Trp enzymes IDO1, IDO2, TDO2 and IL4I1 in OCCC tissues. IDO2, TDO2 and IL4I1 were detected in the majority of OCCC. Clinical traits were correlated with IDO1, IDO2, TDO2 and IL4I1 expression. IDO1 may be used as a therapeutic target given the large percentage of chemoresistant cases with IDO1 expression. These results will aid the development of personalised therapies for OCCC.

AbstractBackground:Cholesteatoma is a chronic disease that is caused by the abnormal proliferation of keratinized squamous epithelial cells in the middle ear. This study aims to explore the role of exosomal miRNAs in the pathogenesis of cholesteatoma and their potential in clinical diagnosis.Methods:We collected samples of cholesteatoma and normal retroauricular skin from 14 patients and isolated exosomes from these tissues. Exosomes were identified by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting. Further miRNA sequencing was conducted to identify the unique exosomal miRNA expression pattern in cholesteatoma. The potential roles of differentially expressed miRNAs (DE-miRNAs) were investigated via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Then, we filtered the top 9 DE-miRNAs to perform KEGG pathway enrichment analysis, and we validated the levels of these DE-miRNAs in peripheral blood plasma-derived exosomes from 12 cholesteatoma patients, 6 chronic otitis media patients and 4 healthy individuals.Results:Tissue-derived exosomes were successfully extracted from cholesteatoma and normal skin tissues. MiRNA sequencing revealed 14 upregulated miRNAs and 25 downregulated miRNAs in the cholesteatoma-derived exosomes. Bioinformatics analysis indicated that the DE-miRNAs participated in a variety of biological processes, cell components and molecular functions. The differential expression of hsa-miR-223-3p and hsa-miR-142-5p was verified in plasma-derived exosomes from cholesteatoma patients, and these molecules showed a modest ability to distinguish between cholesteatoma and normal samples (AUC=0.81 and AUC=0.84, respectively). We further identified the potential functions of these molecules in cholesteatoma pathogenesis through a KEGG pathway network.Conclusions:Our study is the first to explore the specific exosomal miRNA profile of cholesteatoma. Exosomal miR-223-3p and miR-142-5p can be considered promising biomarkers for the diagnosis of cholesteatoma.

Introduction There is currently no satisfactory model for predicting malignant transformation of endometriosis. The aim of this study was to construct and evaluate a risk model incorporating noninvasive clinical parameters to predict endometriosis-associated ovarian cancer (EAOC) in patients with endometriosis. Material and Methods We enrolled 6809 patients with endometriosis confirmed by pathology, and randomly allocated them to training (n = 4766) and testing cohorts (n = 2043). The proportion of patients with EAOC in each cohort was similar. We extracted a total of 94 demographic and clinicopathologic features from the medical records using natural language processing. We used a machine learning method - gradient-boosting decision tree - to construct a predictive model for EAOC and to evaluate the accuracy of the model. We also constructed a multivariate logistic regression model inclusive of the EAOC-associated risk factors using a back stepwise procedure. Then we compared the performance of the two risk-predicting models using DeLong's test. Results The occurrence of EAOC was 1.84% in this study. The logistic regression model comprised 10 selected features and demonstrated good discrimination in the testing cohort, with an area under the curve (AUC) of 0.891 (95% confidence interval [CI] 0.821-0.960), sensitivity of 88.9%, and specificity of 76.7%. The risk model based on machine learning had an AUC of 0.942 (95% CI 0.914-0.969), sensitivity of 86.8%, and specificity of 86.7%. The machine learning-based risk model performed better than the logistic regression model in DeLong's test (p = 0.036). Furthermore, in a prospective dataset, the machine learning-based risk model had an AUC of 0.8758, a sensitivity of 94.4%, and a specificity of 73.8%. Conclusions The machine learning-based risk model was constructed to predict EAOC and had high sensitivity and specificity. This model could be of considerable use in helping reduce medical costs and designing follow-up schedules.

There is currently no satisfactory model for predicting malignant transformation of endometriosis. The aim of this study was to construct and evaluate a risk model incorporating noninvasive clinical parameters to predict endometriosis-associated ovarian cancer (EAOC) in patients with endometriosis. We enrolled 6809 patients with endometriosis confirmed by pathology, and randomly allocated them to training ( n  = 4766) and testing cohorts ( n  = 2043). The proportion of patients with EAOC in each cohort was similar. We extracted a total of 94 demographic and clinicopathologic features from the medical records using natural language processing. We used a machine learning method – gradient-boosting decision tree – to construct a predictive model for EAOC and to evaluate the accuracy of the model. We also constructed a multivariate logistic regression model inclusive of the EAOC-associated risk factors using a back stepwise procedure. Then we compared the performance of the two risk-predicting models using DeLong's test. The occurrence of EAOC was 1.84% in this study. The logistic regression model comprised 10 selected features and demonstrated good discrimination in the testing cohort, with an area under the curve (AUC) of 0.891 (95% confidence interval [CI] 0.821–0.960), sensitivity of 88.9%, and specificity of 76.7%. The risk model based on machine learning had an AUC of 0.942 (95% CI 0.914–0.969), sensitivity of 86.8%, and specificity of 86.7%. The machine learning-based risk model performed better than the logistic regression model in DeLong's test ( p  = 0.036). Furthermore, in a prospective dataset, the machine learning-based risk model had an AUC of 0.8758, a sensitivity of 94.4%, and a specificity of 73.8%. The machine learning-based risk model was constructed to predict EAOC and had high sensitivity and specificity. This model could be of considerable use in helping reduce medical costs and designing follow-up schedules.

Background: Loss or partial loss of one X chromosome induces Turner syndrome (TS) in females, causing major medical concerns, including otologic disorders. However, the underlying genetic pathophysiology of otologic disorders in TS is mostly unclear. Methods: Ear-related genes of TS (TSEs) were identified by analyzing differentially expressed genes (DEGs) in two Gene Expression Omnibus (GEO)-derived expression profiles and ear-genes in the Comparative Toxicogenomic Database (CTD). Subsequently, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Disease Ontology (DO) analyses; Gene Set Enrichment Analysis (GSEA); and Gene Set Variation Analysis (GSVA) were adopted to study biological functions. Moreover, hub genes within the TSEs were identified by assessing protein-protein interaction (PPI), gene-microRNA, and gene-transcription factor (TF) networks. Drug-Gene Interaction Database (DGIdb) analysis was performed to predict molecular drugs for TS. Furthermore, three machine-learning analysis outcomes were comprehensively compared to explore optimal biomarkers of otologic disorders in TS. Finally, immune cell infiltration was analyzed. Results: The TSEs included 30 significantly upregulated genes and 14 significantly downregulated genes. Enrichment analyses suggested that TSEs play crucial roles in inflammatory responses, phospholipid and glycerolipid metabolism, transcriptional processes, and epigenetic processes, such as histone acetylation, and their importance for inner ear development. Subsequently, we described three hub genes in the PPI network and confirmed their involvement in Wnt/β-catenin signaling pathway and immune cell regulation and roles in maintaining normal auditory function. We also constructed gene-microRNA and gene-TF networks. A novel biomarker (SLC25A6) of the pathogenesis of otologic disorders in TS was identified by comprehensive comparisons of three machine-learning analyses with the best predictive performance. Potential therapeutic agents in TS were predicted using the DGIdb. Immune cell infiltration analysis showed that TSEs are related to immune-infiltrating cells. Conclusion: Overall, our findings have deepened the understanding of the pathophysiology of otologic disorders in TS and made contributions to present a promising biomarker and treatment targets for in-depth research.