Objective: Persistent high-risk human papillomavirus (HPV) infection causes precancerous cervical lesions with subsequent progression to cervical cancer. HPV infection is very common in women of childbearing age, particularly with early onset of sexual activity. Treatments such as cold knife conization are usually used for women of childbearing age with cervical intraepithelial neoplasia 2+, which may cause delayed fertility, cervical insufficiency, and other adverse pregnancy outcomes during subsequent pregnancies. Methods: Focused ultrasound (FUS) is a non-ionizing, non-invasive treatment method used to treat gynecological conditions such as cervicitis and vulvovaginal disease. Results: A protocol has been developed to evaluate the value of FUS in the treatment of women of childbearing age with cervical lesions with fertility preservation. Conclusion: This study aimed to evaluate the therapeutic effect of FUS treatment and fertility protection in women of childbearing age with cervical lesions who require family planning. Trial registration number Chinese Clinical Trial Registry (ChiCTR2300076739).

Birth defects impose a significant global health burden, driving an urgent need for improved prenatal diagnostic and therapeutic strategies. Amniotic fluid stem cells (AFSCs) have emerged as a uniquely advantageous cell source in this context. This review provides a comprehensive synthesis of the multifaceted roles of AFSCs in advancing fetal medicine. We begin by detailing their biological characteristics, including origin, heterogeneity, and markers, while highlighting how their properties are influenced by gestational and pathological factors. We then elaborate on their dual mechanisms of tissue repair, focusing on direct homing/engraftment and, predominantly, their potent paracrine and extracellular vesicle (EV)-mediated actions. The core of the review systematically examines the integrated applications of AFSCs across a clinical continuum: (1) in disease modeling, where they serve as a foundation for generating patient-specific induced pluripotent stem cells (iPSCs) and complex organoids to study genetic disorders; (2) in prenatal diagnosis, exploring their potential contribution to fetal microchimerism and cell-free fetal DNA to refine non-invasive testing; and (3) in therapeutic interventions, reviewing preclinical progress in treating conditions such as pulmonary hypoplasia, myelomeningocele, and hematopoietic diseases via transamniotic stem cell therapy (TRASCET) or EV administration. Finally, we discuss the current limitations, including standardization hurdles and mechanistic knowledge gaps and the promising future of AFSCs, underpinned by their ethical sourcing, ease of access, and strong regenerative potential. This work consolidates the evidence positioning AFSCs as a transformative, unified platform for innovating the prevention, diagnosis, and treatment of birth defects.

To identify factors associated with tubal obstruction following laparoscopic tubal fenestration and embryo removal in patients with tubal pregnancy, and to develop a preliminary prediction model based on these factors. Clinical data of 310 patients who underwent laparoscopic tubal fenestration and embryo removal for tubal pregnancy at the Third Affiliated Hospital of Zhengzhou University between June 2020 and June 2025, and subsequently received hysterosalpingography, were retrospectively collected. Patients were randomly divided into a training set (n = 217) and a validation set (n = 93) using a 7:3 ratio. Based on hysterosalpingography results, the training set was further divided into a patent group (n = 135) and an obstruction group (n = 82). Multivariate logistic regression analysis was used to identify influencing factors for postoperative tubal obstruction. A nomogram prediction model for postoperative tubal obstruction was constructed using the R language, and its performance was evaluated through internal split-sample validation. The preoperative β-hCG level (100 IU/L), maximum diameter of pelvic fluid (mm), and the proportion of pregnancies located in the interstitial and isthmic portions of the fallopian tube were significantly higher in the obstruction group compared to the patent group, while the diameter of the tubal mass was smaller. These differences were statistically significant (all P < 0.05). Logistic regression analysis indicated that preoperative β-hCG level (100 IU/L), site of tubal pregnancy, maximum diameter of pelvic fluid (mm), and diameter of the tubal mass (mm) were independently associated with postoperative tubal obstruction (P < 0.05). A nomogram was established using these factors. The area under the receiver operating characteristic curve (AUC) for the training set was 0.824 (95

The tumorigenesis and progression of conventional cervical squamous cell carcinoma generally follow a well-defined cascade: from normal cervix uteri to high-grade cervical intraepithelial neoplasia (precancer), cervical carcinoma in situ, and ultimately invasive cervical carcinoma. However, biomarkers and targets that reflect tumor evolution during CSCC progression at different time points within the same patient remain lacking. We integrated single-cell RNA sequencing with spatial transcriptomics from a series of human cervix uteri tissues spanning the cascade of cervical premalignant lesions and malignant progression obtained from the same patients. We found that fibroblasts and endothelial cells decreased, whereas immune cells (mainly T cells and B cells) increased during CSCC development. Moreover, the immune response-related GNLY-fibroblasts and GNLY-endothelial cells were significantly enriched during the PCT of CSCC. Additionally, a panel of gene signatures (CLDN1, ISG15, PTGDS) with clinical significance for the precise diagnosis and personalized treatment strategies of PCT was identified. This gene panel may serve as an auxiliary diagnostic indicator in cervical biopsy specimens and help identify lesions associated with malignant progression. CLDN1 and ISG15 promote CSCC progression, whereas PTGDS suppresses it. Moreover, ISG15, synthesized by inflammatory cancer-associated fibroblasts (CAFs), enhances the stability of FGF1, thereby activating the FGF1/FGFR1/PI3K/AKT/mTOR signaling pathway. FGFR1 and PI3K/AKT/mTOR inhibitors were found to suppress CSCC cell proliferation in vitro and tumor growth in vivo. High ISG15 and CLDN1 expression correlated with poor survival in cervical cancer tissue microarrays and with reduced immunotherapy response in exploratory public datasets, pending validation in CSCC cohorts. Our study defines the ecosystem of PCT from cell subpopulations, the communicating gene networks, and key signal transductions involved in PCT of CSCC. These findings offer new insights into the spatiotemporal evolution of the human cervix in premalignant and malignant lesions, paving the way for improved CSCC diagnosis and therapy.

Lysine-specific demethylase 1 (LSD1) is a promising target in cancer therapy and plays an important role in the occurrence and development of tumors. However, research on LSD1 in endometrial cancer (EC) is indeed limited, and the related research on LSD1 inhibitors targeting EC is even rarer. In this study, our group developed a novel Tertiary Amine LSD1 inhibitor-596. 596 could specifically target LSD1 and inhibit the demethylation levels of H3K4me1/2 in a dose-dependent manner, thereby inhibited the proliferation of EC cells in vitro and in vivo. Moreover, in-depth studies have shown that 596 induces cell death in EC cells through the autophagy pathway, increasing the formation of autophagosomes and the expression of autophagy-related proteins. Transcriptomic sequencing revealed that 596-induced gene enrichment was related to the PI3K/AKT/mTOR pathway. The treatment group of 596 was able to attenuate the activation of the mTOR signaling cascade, and the combination treatment of 596 and the mTOR inhibitor rapamycin (RAPA) effectively reduced the survival rate, migration ability, and invasion ability of EC cells. Further studies in vitro and in vivo indicated that 596 could reduce the feedback activation of AKT mediated by the mTOR inhibitor rapamycin. In summary, our findings demonstrate that the LSD1 inhibitor 596 enhances the activity of the mTOR inhibitor by attenuating the feedback activation of AKT. LSD1 may be as a potential therapeutic target in EC, and LSD1 inhibitors represent an important therapeutic strategy in EC treatment.

Early miscarriage, a common pregnancy complication predominantly occurring before 12 weeks, is conclusively linked to embryonic chromosomal abnormalities. Given the rising proportion of pregnancies at advanced maternal age, a contemporary re-examination of the relationships among early miscarriage, sex chromosomal anomalies, and maternal age is imperative to optimize clinical counseling strategies. This retrospective study analyzed cases from the Medical Genetics and Prenatal Diagnosis Center at the Third Affiliated Hospital of Zhengzhou University (July 2022–December 2024). Inclusion criteria required fetal samples with < 10

Cervical cancer continues to require more precise and clinically adaptable local treatment strategies, particularly in the face of insufficient drug accumulation at the lesion site, systemic toxicity of conventional chemotherapy, limited development of postoperative tissue-interfacing platforms, and the anatomical constraints of standard radiotherapy devices. In this mini-review, we summarize the current landscape of polymer-based biomaterials for local therapy in cervical cancer from both materials and clinical perspectives. Specifically, we discuss three interconnected application domains: local drug delivery systems, polymeric scaffolds and tissue-interfacing platforms, and 3D-printed radiotherapy devices. Recent studies indicate that polymer-based local delivery systems, including nanofiber- and hydrogel-based formulations, can improve cervicovaginal retention, controlled release, and local therapeutic exposure. Scaffold-based systems further extend the role of biomaterials by combining sustained local delivery with defect-specific support and tissue interaction, whereas 3D-printed radiotherapy devices contribute primarily through precision enablement, individualized implantation guidance, and improved conformity in anatomically challenging cases. Despite these advances, most available studies remain preclinical or early translational, and important barriers persist in long-term safety, standardization, clinically relevant validation, and workflow integration. Future progress will depend on application-specific design, stronger translational rigor, and closer integration of biomaterials, imaging, and personalized clinical practice.

Pelvic organ prolapse (POP) is a common benign gynecological disorder that substantially affects quality of life, particularly in aging female populations. Current management strategies, including standardized vaginal pessaries and synthetic surgical meshes, are often limited by poor anatomical adaptability, mechanical mismatch with native pelvic tissues, and long-term safety concerns. These limitations have driven increasing interest in personalized and biomechanically compatible therapeutic solutions. Three-dimensional (3D) printing, also known as additive manufacturing, has emerged as a promising bioengineering technology to address these unmet clinical needs. By enabling layer-by-layer fabrication directly from digital models, 3D printing allows for precise control over device geometry, mechanical properties, and material composition, facilitating patient-specific design. This narrative review summarizes recent progress in 3D printing for POP management across three major application domains: (i) next-generation meshes based on biodegradable polymers, elastomeric materials, natural biomaterials, and hydrogel systems; (ii) customized vaginal pessaries tailored to individual pelvic anatomy using imaging-assisted workflows; and (iii) imaging-based pelvic models and prototype devices for surgical planning, education, and exploratory assessment. Overall, existing studies demonstrate that 3D printing enables improved biomechanical compatibility, enhanced tissue integration, and multifunctional device design, including drug delivery capability. Although current evidence is largely pre-clinical or based on pilot studies, additive manufacturing holds strong potential to advance POP management toward safer, personalized, and functionally optimized clinical solutions.

Endometrial carcinoma (EC) is a heterogeneous gynecological malignancy. Epigenetic dysregulation promotes the initiation, progression, immune evasion, and therapeutic resistance of EC. Aberrant DNA methylation, histone methylation, histone acetylation, and chromatin remodeling affect key EC-associated pathways and help shape distinct molecular subtypes, including POLE-mutated and mismatch repair-deficient tumours. In this review, we summarize the major epigenetic alterations implicated in EC, with emphasis on DNA methylation regulators, histone-modifying enzymes, and emerging epigenetic targets such as DNMTs, HDACs, LSD1, EZH2, PRMTs, and BET proteins. We further highlight the rapidly evolving immunotherapy landscape in EC, including clinically established or practice-changing regimens such as pembrolizumab-, dostarlimab-, durvalumab-, and lenvatinib-based strategies, particularly in advanced or recurrent disease. In parallel, we discuss investigational epigenetic therapies, including DNMT inhibitors, HDAC inhibitors, LSD1 inhibitors, EZH2-targeted agents, PRMT inhibitors, and BRD4-directed approaches, which are being explored to restore tumour suppressor pathways, enhance tumour immunogenicity, and improve sensitivity to immune checkpoint blockade. By integrating EC-specific epigenetic mechanisms with current immunotherapy advances and ongoing combination strategies, this review provides a clinically oriented perspective on biomarker-guided precision treatment for EC.

Aberrant expression of lysine-specific demethylase 1 (LSD1) has been consistently implicated in a broad spectrum of malignancies, underscoring its relevance as a therapeutic target. Despite growing interest, the development of LSD1 inhibitors continues to face significant challenges, in part due to the enzyme’s dual role in catalysis and as a scaffolding protein within chromatin-remodeling complexes. Recent insights into the non-enzymatic functions of LSD1 have shifted the focus toward disrupting its protein–protein interactions, particularly with chromatin-modifying enzymes, as a complementary or alternative therapeutic strategy. In light of the limited systematic evaluation of available technologies, this work provides a critical overview and comparative analysis of current screening platforms and binding affinity assays, with particular attention to approaches capable of identifying LSD1 scaffold inhibitors. These efforts aim to accelerate the discovery of next-generation LSD1-targeted therapies with improved translational potential in oncology.

Palmitoylation plays a crucial role in the pathophysiology of diabetes, and an increase in palmitoylation may inhibit the function of insulin receptors, thereby affecting the progression of gestational diabetes mellitus (GDM). However, its involvement in gestational diabetes mellitus (GDM) remains underexplored. This study analyzed GDM-related datasets and 30 palmitoylation-related genes (PRGs), identifying MNDA, FCGR3B, and AQP9 as significantly upregulated biomarkers in GDM samples. Consistent with the dataset analysis, reverse transcription-polymerase chain reaction (RT-qPCR) confirmed elevated AQP9 expression. Comprehensive analyses, including nomogram construction, enrichment analysis, immune infiltration assessment, molecular regulatory network generation, drug prediction, and molecular docking, were conducted. The biomarker-based nomogram demonstrated excellent predictive performance for GDM risk. MNDA, FCGR3B, and AQP9 were significantly enriched in pathways such as “Myc-targets-v1” and “TNFA signaling via NFkB.” Additionally, eosinophil infiltration showed a strong positive correlation with these biomarkers. Regulatory networks involving SH3BP5-AS1-hsa-miR-182-5p-AQP9 and hsa-miR-182-5p-AQP9-ELF5 were identified, and stable binding energies were observed between the biomarkers and corresponding drugs. These findings provide promising avenues for early GDM screening and diagnosis.

Breast cancer is one of the most common malignancies in women. This study aimed to explore the association between healthy lifestyle, biological aging and breast cancer risk in pre- and postmenopausal women. This study included 125,579 participants. Biological aging was calculated using the PhenoAge algorithm. Cox regression models and counterfactual mediation analysis was utilized. During an average follow-up of 13.65 years, 5418 breast cancers occurred. In the overall women participants, compared to the healthy lifestyle group, the HR (95% CI) for unhealthy lifestyle regarding incident breast cancer was 1.28 (1.13, 1.33). Compared to the lowest tertile of accelerated aging (AA), the HR (95% CI) for the highest tertile regarding breast cancer risk was 1.22 (1.14, 1.30). Consistent results observed only in postmenopausal participants. The joint effect of a healthy lifestyle and AA on breast cancer risk was statistically significant (P < 0.001). The AA-mediated breast cancer risk ratio was 17.69 (95% CI 8.19, 27.19) when comparing healthy to unhealthy lifestyles. In the study, healthy lifestyle and lower levels of AA were significantly associated with a reduced risk of breast cancer, particularly among postmenopausal women. In addition, AA mediated 17.02-17.69% of the link between lifestyle and breast cancer risk.

Background: Polycystic ovary syndrome (PCOS) is the most prevalent reproductive endocrine illness in women of reproductive age and is one of the most important causes of female infertility. The pathogenesis of PCOS is complex. Although mesenchymal stem cell therapy is anticipated to be a successful treatment for PCOS, its long-term safety, including tumorigenesis in patients, remains unknown. Objective: This study aimed to confirm the efficacy and safety of human umbilical cord mesenchymal stem cells in improving fertility in PCOS mice. Methods: In this study, dehydroepiandrosterone (DHEA) was used to construct a C56BL/6 mouse PCOS model, human umbilical cord mesenchymal stem cells (hUC-MSCs) were used as a treatment, and the reproductive phenotype was observed in parallel breeding experiments to confirm the efficacy of the treatment. A 4-month follow-up period, final blood tests, and organ histology were carried out to confirm the long-term safety of the treatment. Results: After hUC-MSCs treatment, the sex hormone disorder of mice was corrected, the morphology and function of the ovary were improved, the number of offspring was significantly increased compared to the control group, and no adverse reactions related to stem cell transplantation such as tumor formation were found within 4 months. Conclusion: The treatment of hUC-MSCs is safe and effective in treating PCOS over the long term.

Persistent HPV infection is the primary cause of cervical carcinogenesis. While HPV testing as a screening modality has reduced cervical cancer incidence, standalone HPV screening cannot distinguish persistent infections, necessitating novel molecular markers to identify effective HPV infection in cervical epithelial cells. Genes associated with HPV-positive cervical lesions were screened using GEO databases, with SYCP2’s diagnostic potential evaluated by ROC curve analysis. TCGA data were analyzed for SYCP2-clinicopathological correlations and prognostic significance. RNA-seq following SYCP2 silencing identified differentially expressed genes, with functional characterization via GO/KEGG enrichment. Downstream effector IL13RA2 was validated at RNA/protein levels. SYCP2-immunological parameter correlations were investigated using the TISIDB repository. Integrated analysis of four GEO datasets identified SYCP2 as a key upregulated gene in HPV16-positive cervical cancer compared to HPV-negative tissues. Clinical analyses revealed SYCP2 overexpression correlated with lymph node metastasis and worse disease-free survival (HR (high) = 2.1, P = 0.0096). ROC curves demonstrated diagnostic efficacy for cervical lesions (CIN2+: AUC = 0.846(95

目的:探讨子宫颈癌发病率变化和预后影响因素,构建用于预测患者预后的列线图.方法:收集并整理SEER数据库2000～2018 年子宫颈癌数据.评估子宫颈癌的发病率变化;采用Kap-lan-Meier法计算患者总体生存率(OS);使用单因素和多因素Cox回归筛选预后影响因素.构建预测模型并使用列线图可视化,使用受试者工作特征(ROC)曲线、校准曲线和决策曲线分析评估其预测效能.结果:子宫颈癌发病率总体呈下降趋势,中青年和黑种人发病率最高,亚洲和太平洋岛国人发病率逐渐下降.本研究共纳入 20194 例子宫颈癌患者,其 1 年、3 年、5 年和 10 年 OS 分别为90.1%、75.5%、69.4%和61.9%.单因素和多因素Cox回归分析结果提示年龄、婚姻状态、种族、肿瘤最大径、病理分级、病理类型、FIGO 分期和区域淋巴结转移情况是患者预后的影响因素(P＜0.05).自身验证和内部验证结果显示,构建的列线图具有良好的预测准确性和临床适用性.结论:子宫颈癌发病率总体呈下降趋势,基于独立影响因素构建的列线图可在治疗前良好地预测患者预后.

Objective: The objective of this study is to assess the clinical performance of a urine-based high-risk human papillomavirus (hrHPV) test for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+).Methods: Between September and December 2021, women aged 20 to 65 years referred to colposcopy clinic were prospectively recruited at three clinical centers in China. Paired urine and cervical specimens from all enrolled women were obtained for hrHPV DNA fluorescence quantitative PCR test. The results of liquid-based cytology (LBC), colposcopy and diagnostic biopsies were collected. We evaluated the sensitivity and specificity for CIN and assessed the agreement/kappa value.Results: A total of 732 women (median age, 40 years) with valid results were included in the study, and 130 (17.8%) women were histologically confirmed as CIN2+. The sensitivity of urine and cervical test for CIN2+ and CIN3+ were 87.69% and 85.45%, respectively. The specificity of urine test performed better than cervical test in women with 2. The overall agreement of hrHPV detection between urine and cervical specimens was 80.74%, with higher agreement for types 16 and 18 (91.67% and 96.58%).Conclusion: The data suggested that the urine-based hrHPV test may be an alternative approach for cervical cancer screening.

In brief Inflammation and abnormal immune response are the key processes in the development of endometriosis (EMs), and m6A modification can regulate the inflammatory response. This study reveals that METTL3-mediated N6-methyladenosine (m6A) modification plays an important role in EMs. Abstract m6A modification is largely involved in the development of different diseases. This study intended to investigate the implication of m6A methylation transferase methyltransferase like 3 (METTL3) in EMs. EMs- and m6A-related mRNAs and long non-coding RNAs were identified through bioinformatics analysis. Next, EM mouse models established by endometrial autotransplantation and mouse endometrial stromal cell (mESC) were prepared and treated with oe-METTL3 or sh-MIR17HG for pinpointing the in vitro and in vivo effects of METTL3 on EMs in relation to MIR17HG through the determination of mESC biological processes as well as estradiol (E2) and related lipoprotein levels. We demonstrated that METTL3 and MIR17HG were downregulated in the EMs mouse model. Overexpression of METTL3 suppressed the proliferation, migration, and invasion of mESCs. In addition, METTL3 enhanced the expression of MIR17HG through m6A modification. Moreover, METTL3 could inhibit the E2 level and alter related lipoprotein levels in EMs mice through the upregulation of MIR17HG. The present study highlighted that the m6A methylation transferase METTL3 prevents EMs progression by upregulating MIR17HG expression.

Abstract The aim of this study was to clarify the distribution of SCN1A variants in each condition of SCN1A seizure disorders and the proportion of the SCN1A variant types in different conditions of SCN1A seizure disorders.This study consisted of querying SCN1A variants in ClinVar, reclassificating ClinVar P/LP SCN1A missense variants provided by a singgle submitter, validating conditions of SCN1A Seisure Disorders by reclassification of P/LP variants and screening variant types of conditions of SCN1A Seisure Disorders by validation.The result showed that most of the P/LP SCN1A missense variants provided by a single submitter in ClinVar remained at the P/LP level (247/383), and a few variants were converted from P/LP to VUS (136/383). The condition "Early infantile epileptic encephalopathy with suppression bursts" shown in ClinVar was actually all other conditons, such as Dravet syndrome/Severe myoclonic epilepsy of infancy(DS/SMEI)(69/89) and Generalized epilepsy with febrile seizures plus/Borderline severe myoclonic epilepsy of infancy(GEFS+/SMEB) (3/89). Both in missense and trunction, DS/SMEI-related SCN1A variants had the highest proportion (291/371, 78.4%),and there were still quite a few some SCN1A variants are associated with other conditions such as GEFS+, FMH, DEE, Lennox-Gastaut Syndrome and Intractable childhood epilepsy with generlaized tonic-clonic seizures (80/371, 21.6%).This provided data support for clinicians to grasp the severity of epilepsy caused by these SCN1A variants.

目的 赖氨酸特异性去甲基化酶1(LSD1)已被报道在多种恶性肿瘤中发挥作用,但其在子宫内膜癌中的作用少有报道.本研究旨在探讨LSD1在子宫内膜癌中的作用及其可能的机制.方法 在子宫内膜癌细胞系Ishikawa和HEC1 A中分别使用慢病毒和质粒对LSD1进行敲除和过表达.通过定量逆转录聚合酶链反应(RT-qPCR)和蛋白质印迹法(WB)验证转染结果.采用CCK-8实验、集落形成实验、伤口愈合实验和transwell侵袭实验分别检测LSD1对子宫内膜癌细胞体外增殖、克隆、迁移和侵袭的影响.通过肿瘤异种移植实验验证LSD1对子宫内膜癌细胞增殖的影响.结果 与正常子宫内膜组织相比,LSD1在子宫内膜癌中表达水平升高,与肿瘤的分期及分级有关,并影响患者的预后.下调LSD1后,CCK-8实验和集落形成实验显示子宫内膜癌细胞的增殖能力明显下降,伤口愈合实验显示细胞的迁移能力减弱,transwell侵袭实验则证实了细胞的侵袭能力随之降低,而上调LSD1后结果则相反.通过WB和免疫组化法发现CD9的表达水平随着LSD1的降低而升高.此外,下调LSD1可抑制Ishikawa和HEC1 A细胞在体内的肿瘤发生.结论 LSD1是一种致癌因子,能显著促进子宫内膜癌细胞的增殖、迁移和侵袭,并反向调控下游因子CD9,为其作为子宫内膜癌的治疗靶点提供了更多依据.