Tranexamic acid, an antifibrinolytic agent with a well-established safety profile, promotes hemostasis by inhibiting fibrin degradation. In recent years, intravenous tranexamic acid has gained wide acceptance as a prophylactic antihemorrhagic agent in surgical settings. However, data on its local administration remain limited. This study was designed to evaluate whether prophylactic local infiltration of tranexamic acid into cervical and vaginal tissues before surgery could reduce intraoperative blood loss. A double-blind, randomized, placebo-controlled trial was conducted at a tertiary medical center between April 2022 and December 2024. Sixty women undergoing benign vaginal hysterectomy were randomized (1:1) to receive either 1 g TXA (in 10 ml saline) or placebo via local cervical/vaginal infiltration 5 min pre-incision. The primary outcome was delta hemoglobin (ΔHb; pre- to postoperative hemoglobin change). Outcomes were compared using appropriate tests (t test or Mann-Whitney U, as indicated) with α = 0.05. Ethical approval was obtained from our institutional review board. Sixty patients were enrolled. Baseline characteristics of the two groups were comparable. The mean hemoglobin reduction was 1.48 ± 0.73 g/dl in the tranexamic acid group versus 1.27 ± 1.02 g/dl in controls (p = 0.36). Estimated blood loss, transfusion rates, and operative parameters did not differ significantly. Mucosal dissection was significantly easier in the tranexamic acid group (86.7% vs 40.0%, p < 0.01). No thromboembolic events occurred. Local prophylactic tranexamic acid did not reduce total blood loss. Vaginal hysterectomy remains a safe procedure with minimal bleeding.

Cervical insufficiency (CI) affects 0.1-2% of pregnancies and represents a significant cause of second-trimester pregnancy loss and preterm birth, yet its pathophysiology remains incompletely understood. This study investigated whether aquaporin-3 (AQP3) facilitates hydrogen peroxide (H₂O₂) transport into cervical macrophages, driving their polarization toward a pro-inflammatory phenotype and subsequent cervical matrix degradation. Cervical tissues from women with CI demonstrated 1.45-fold higher AQP3 expression compared to gestational age-matched controls, with increased colocalization with macrophages. Tissue H₂O₂ levels were elevated 2.43-fold in CI, accompanied by increased oxidative damage markers and reduced collagen content. In vitro studies using THP-1 macrophages revealed that AQP3 knockdown prevented intracellular H₂O₂ accumulation despite pro-inflammatory stimulation, blocking M1 polarization and NF-κB activation. Co-culture experiments demonstrated that AQP3-dependent M1 macrophages increased matrix metalloproteinase (MMP)-9 activity 3.8-fold and reduced fibroblast collagen content by 59%. Both H₂O₂ scavenging with PEG-catalase and NF-κB inhibition with Bay 11-7082 prevented macrophage-mediated matrix degradation. These findings suggest that AQP3 may serve as an important mediator linking oxidative stress to inflammatory cervical remodeling through facilitation of H₂O₂ influx, NF-κB activation, and M1 macrophage polarization. Targeting AQP3 or its downstream signaling may represent a potential therapeutic approach that requires preclinical validation to prevent CI-associated pregnancy complications.

This study examines hypoxia’s role in regulating ATXN3 (ATXN3) across cervical cancer subtypes and its impact on tumor progression. We analyzed ATXN3 expression in clinical samples and cell lines (C33A, HeLa, SiHa), assessing proliferation/migration/invasion after ATXN3 modulation. The study investigated whether ATXN3 is regulated by hypoxia through hypoxia-inducible factor 1α (HIF-1α). Downstream mechanisms were explored using clinical samples and cell lines, comparing P53 and signal transducer and activator of transcription 5 (STAT5)/p-STAT5 levels between cancer tissues and adjacent non-cancerous tissues, and assessing changes following ATXN3 manipulation. ATXN3 was downregulated in human papillomavirus(HPV18+) cervical adenocarcinoma but upregulated in HPV16+ cervical squamous cell carcinoma. ATXN3 suppressed malignant behaviors in C33A and HeLa but promoted them in SiHa. HIF-1α expression was elevated in cancer tissues versus non-cancerous tissues, with hypoxic conditions differentially regulating ATXN3 via HIF-1α across cell lines. Cervical cancer tissues showed lower P53 and higher p-STAT5 (in HPV16+ squamous cell carcinoma). ATXN3 overexpression stabilized P53 in C33A/HeLa and increased p-STAT5 in SiHa, with inverse effects upon silencing. The findings suggest that hypoxia promotes the progression of subtypes of cervical cancer by regulating ATXN3-enhanced P53/p-STAT5 levels, which may provide a novel therapeutic strategy for clinical applications.

As an acknowledged inflammatory cytokine, CXCL17 is also participated in various malignancies, including pancreatic ductal adenocarcinoma, lung cancer, colon cancer, and thyroid carcinoma. Nevertheless, it is still unclear whether CXCL17 is correlated with tumorigenesis and advancement of cervical cancer. The aim of this study was to study the clinical significance of CXCL17 in cervical cancer patients and its associations with epithelial-to-mesenchymal transition (EMT) markers. The present study analyzed the CXCL17 expression pattern in cervical cancer and investigated its correlation with clinicopathological parameters in 80 cervical cancer cases. Furthermore, the correlation between CXCL17 and EMT markers were evaluated. The results showed CXCL17 expression was positive in 67.50% (54/80) cases. Our results revealed CXCL17 expression was significantly correlated with lymph node metastasis and clinical stage (P < .05). GPR35 expression was significantly enhanced in cervical cancer tissues. More importantly, CXCL17 expression was correlated with snail or vimentin expression. Simultaneously, CXCL17 expression had a negative correlation with E-cadherin expression. These results demonstrated the close correlation between CXCL17 expression and EMT markers. Our findings revealed that CXCL17 promotes advancement of cervical cancer via influence of some critical EMT markers.

Validated LC-MS/MS method for cisplatin quantification in plasma, whole blood, and cervical cancer tissue via diethyldithiocarbamate derivatization: Clinical application in cervical cancer.

We report the case of a 51‐year‐old male who experienced transient unilateral hypoglossal nerve palsy (HNP) after undergoing elective shoulder surgery under general anesthesia. Tracheal intubation was performed using a C‐MAC D‐Blade video laryngoscope (Karl Storz). Intubation was uneventful, with clear visualization of the vocal cords corresponding to a Cormack–Lehane Grade I view, no airway trauma was visible. Shortly after extubation, the patient complained of tongue swelling, dysarthria, and dysphagia. Clinical examination confirmed an isolated ipsilateral HNP. A brain and neck MRI conducted 4 h postoperatively showed no structural abnormalities along the hypoglossal nerve pathway, and an otolaryngological assessment identified no additional lesions. The patient was managed conservatively, including supportive speech therapy, and made a complete recovery within 14 weeks. This case report highlights a rare incidence of isolated HNP, which occurred in a patient with prior cervical spine fusion and obesity during video laryngoscopy. Possible contributing factors include compression or stretching of the hypoglossal nerve due to airway manipulation, patient positioning, or instrumentation in proximity of cicatrized cervical soft tissue. It is the first case report of HNP following video laryngoscopy with complete recording of the video laryngoscopy. Although video laryngoscopy enhances visual access during intubation, clinicians should remain cautious about potential localized tissue and nerve stress, particularly when using hyperangulated blades. This case highlights that video laryngoscopy does not inherently guarantee reduced soft tissue trauma when compared with traditional direct laryngoscopy.

Performance of an artificial intelligence-based tool for cervical precancer screening in five countries in Africa: a prospective, observational, diagnostic accuracy study.

ABSTRACT The tumor microenvironment (TME) has a central role in many cancers, particularly by fostering an immunosuppressive milieu. Chimeric antigen receptor (CAR)-based immunotherapy displays a promising strategy to re-direct immune cells toward specific antigens, thereby inducing targeted cytotoxicity. The fibroblast activation protein (FAP) is overexpressed in various cancer types and has shown promise in CAR-based therapies. However, its application in gynecological cancers remains unexplored. This study evaluates the efficacy of anti-FAP CAR-NK cells as a targeted immunotherapy for cervical cancer and cancer-associated fibroblasts (CAFs). FAP expression was quantified on cervical cancer cell lines, primary cervical cancer tissues, and cells isolated from these tissues. Alpharetroviral SIN vectors were used to transduce NK-92 cells and primary cord blood-derived NK cells with 3rd-generation anti-FAP CARs. Immunohistochemistry and flow cytometry revealed high FAP expression on CaSki cells, cervical cancer tissues, and primary cervical CAFs. In 2D co-cultures with FAP-positive target cells, anti-FAP CAR-NK cells exhibited significantly enhanced cytotoxicity and elevated degranulation compared to control NK cells, with no observed effects against FAP-negative target cells. Primary NK cells revealed high cytotoxicity against cervical cancer cells with a high release of cytolytic enzymes. Anti-FAP CAR-NK cells also showed efficient elimination of cervical cancer cells and CAFs in 3D tumor spheroid models. These findings underscore the potential of anti-FAP CAR-NK cells as a potent therapeutic approach for cervical cancer and suggest broader applicability in diseases characterized by high FAP expression.

Background and Objectives: We aim to examine the histopathological results following hysterectomy performed due to insufficient cervical tissue in patients diagnosed with high-grade squamous intraepithelial lesions (HSILs) who underwent the loop electrosurgical excision procedure (LEEP) and cold-knife conisation (CKC) and exhibited continuity at the surgical margin and residual disease. Materials and Methods: Thirty-four patients who underwent hysterectomy due to insufficient cervical tissue and had HSILs at the surgical margin were included in this study. The following information was analysed: age, body mass index (BMI), parity, menopausal status (premenopausal/postmenopausal), smoking history, smear result, HPV result, colposcopic cervical biopsy result, transformation zone information, LEEP+Endocervical Curettage (ECC) histopathological result, CKC+ECC histopathological result, hysterectomy material histopathological result, presence or absence of cervical glandular involvement, and presence or absence of residual lesions in the hysterectomy material. Results: The mean (±SD) age of the study cohort was 46.7 ± 8.3 years, the mean BMI was 27.4 ± 2.3 kg/m2, and the mean parity was 2.5 ± 0.7. According to the results of the hysterectomy performed on these 34 patients, in whom Cervical Intraepithelial Neoplasia 3 (CIN3) continuity at the surgical margin and the inability to perform re-excision were determined, 8 patients (23.5%) had CIN2, 19 patients (55.9%) had CIN3, 3 patients (8.8%) had adenocarcinoma in situ, and 4 patients (11.8%) had squamous cell carcinoma (SCC). Histopathological examinations of the hysterectomy specimens revealed negative surgical margins in all patients, while glandular involvement was present in 13 patients (34.2%). Conclusions: It should be borne in mind that patients with HSILs showing continuity at the surgical margin may have an underlying squamous cell carcinoma. These patients should be carefully evaluated for hysterectomy if they do not have sufficient cervical tissue for repeat excisional procedures.

Cervical cancer remains a major global health burden, necessitating the identification of novel therapeutic targets to overcome the limitations of current treatments. Here, we comprehensively investigated the role of integrator complex subunit 13 (INTS13) in cervical cancer progression. Our analysis of publicly available The Cancer Genome Atlas (TCGA) datasets revealed that INTS13 is significantly overexpressed in cervical cancer tissues across various histological subtypes, correlating with advanced tumor T-stage and predicting poorer overall survival. Single-cell RNA sequencing further localized INTS13 expression predominantly to malignant epithelial cells within the tumor microenvironment, where its expression correlated with genes involved in critical cellular processes. Furthermore, elevated expression has been observed in cervical cancer tissues from surgically-treated patients and in various primary human cervical cancer cells. In vitro functional studies demonstrated that genetic silencing or CRISPR/Cas9-mediated knockout of INTS13 significantly inhibited the proliferation, migration, and invasion of primary cervical cancer cells, while selectively inducing apoptosis. Conversely, ectopic INTS13 overexpression markedly enhanced these malignant phenotypes. Mechanistically, we identified heterogeneous nuclear ribonucleoprotein C (hnRNPC) as a critical downstream effector, with INTS13 regulating hnRNPC expression, and the restoration of hnRNPC effectively reversing the anti-cervical cancer effects observed upon INTS13 silencing. Furthermore, the transcription factor ZNF384 (zinc finger protein 384) was identified as an upstream regulator that directly binds to and positively governs INTS13 expression. Finally, in vivo animal models confirmed that targeted silencing of INTS13 significantly impeded cervical cancer xenograft growth in nude mice, reduced cellular proliferation, and augmented apoptosis, consistently accompanied by a reduction in hnRNPC expression. These findings collectively establish INTS13 as a crucial precancerous gene in cervical cancer, promoting malignant phenotypes primarily through the ZNF384-INTS13-hnRNPC signaling axis.

Background: Cervical cancer (CC) is the fourth most common malignancy in women around the world, with more than 600,000 new cases registered in 2022 and around 350,000 deaths. It is a growing social problem, especially in developing countries. Almost all cases of cervical cancer are caused by persistent infection with oncogenic high-risk human papillomavirus (HPV). This malignancy usually exhibits a gradual development through well-defined precursor stages, known as cervical intraepithelial neoplasia (CIN) grades 1, 2, and 3, before evolving into invasive carcinoma. In diagnostic practice, several biomarkers have been implemented to improve the detection of high-risk cervical lesions. p16 and Ki-67 greatly aid in identifying HPV-driven dysplasia, but they cannot always reliably distinguish progressive lesions from regressive or transient HPV infections. These limitations highlight the need for novel biomarkers with better predictive accuracy to complement current screening and diagnostic algorithms. ROMO1 has become a possible marker of a high-ROS, high-risk tumor phenotype in a number of cancers. Although oxidative stress, HPV, and cervical carcinogenesis have been linked, nothing is known about ROMO1’s involvement in cervical neoplasia. There is currently a lack of thorough information regarding the expression of ROMO1 in normal vs. precancerous lesions and in cervical cancer, as well as on whether or not its expression is correlated with the severity of the disease. In order to define ROMO1 expression throughout the course of cervical squamous neoplastic development, the current study was created. Methods: We performed immunohistochemical analysis of ROMO1 expression on cervical tissue samples from three groups: healthy cervix (n = 30), cervical intraepithelial neoplasia (CIN) (n = 41), and invasive cervical carcinoma (n = 205). ROMO1 expression in invasive carcinoma was evaluated using an H-score scale. Results: ROMO1 expression was basal in all normal cervix samples (0/30 cases). In contrast, CIN lesions showed 100% ROMO1 expression in the suprabasal layers of abnormal cells in all CIN cases. In invasive cervical carcinomas, ROMO1 expression was heterogeneous. In our cancer cohort (n = 205), ROMO1 H-score showed no significant association with the following: FIGO stage I vs. II vs. III (p = 0.25); histologic grade G1 vs. G2 vs. G3 (p = 0.46); lymphovascular invasion (no vs. yes; p = 0.80); nodal status N0 vs. N1 (p = 0.67); patient age (≤50 y vs. >50 y; p = 0.38). However, ROMO1 expression did vary by histologic subtype (AC vs. ASC vs. SCC; p = 0.02), with SCC enriched for strong staining compared to AC/ASC. With regard to tumor stage (pT stage), pT2a tumors exhibited significantly lower ROMO1 (pT1b1–pT2b; p = 0.035) than pT1b1 (p = 0.04). No other clinicopathologic variable remained significant. Notably, ROMO1 expression was highest in stage I tumors and declined in more advanced stages of cervical carcinoma. Conclusions: These results show a clear pattern of ROMO1 expression across the cervical neoplasia spectrum: it is attenuated in invasive tumors (with a peak in early-stage illness), significantly raised in pre-cancerous CIN lesions, and negligible in normal epithelium. The idea that oxidative stress may be the primary cause of early malignant transformation in the cervix is supported by the noticeable overexpression of ROMO1 in early lesions. For the detection of early-stage cervical carcinoma and high-grade precancerous lesions, ROMO1 may be a useful auxiliary biomarker.

Intracervical injections directly deliver therapies into the cervix. We previously explored ethyl cellulose (EC)-ethanol intracervical injections as a treatment for cervical dysplasia in low- and middle-income countries. Here we: (1) compared swine and human cervices to assess swine as a model for intracervical injections, and (2) evaluated two speculum-compatible injectors: a custom single needle injector and an extender injector, assembled from off-the-shelf components, to determine what parameters produced optimal distribution. Mechanical properties of swine and human cervices were compared. Swine cervices were injected with EC-ethanol iohexol using both injectors. Distribution and leakage volumes in tissue were visualized with microCT and quantified with 3D Slicer. Mechanical testing showed swine and human cervical tissue yielded comparable storage and loss moduli (p > 0.05). Ex vivo studies showed injections ≥ 10mm deep and < 2 mL significantly reduced backflow and crack formation for both injectors. Additionally, the extender injector produced significantly less crack formation than the single needle injector. These findings indicate swine cervices are a clinically relevant model for intracervical injection studies. The extender device when inserted ≥ 10mm and delivering < 2 mL of EC-ethanol achieved the most consistent results across intracervical delivery protocols.

Mitochondrial hyperfunction is important for cervical cancer progression. Solute carrier family 30 member 9 (SLC30A9) is a member of the solute carrier family 30, specifically a zinc transporter that plays a critical role in mitochondrial zinc homeostasis and maintaining mitochondrial function. We investigated the expression, function, and underlying mechanisms of SLC30A9 in the context of cervical cancer. Single-cell RNA sequencing analysis revealed a marked overexpression of SLC30A9 within the malignant epithelial cell population of cervical squamous cell carcinoma. This elevated SLC30A9 expression was further corroborated in clinical specimens from local patients and across various established and primary cervical cancer cells. SLC30A9 shRNA or knockout (via CRISPR/Cas9 method) significantly impeded the viability, proliferation, cell cycle progression and migration, and triggered apoptosis in cervical cancer cells. SLC30A9 depletion disrupted mitochondrial function, inhibiting mitochondrial respiration, mitochondrial membrane potential, mitochondrial complex I activity, and ATP production, also caused mitochondrial Zn2+ accumulation, reactive oxygen species (ROS) production and oxidative injury. Conversely, overexpression of SLC30A9 in cervical cancer cells demonstrated enhanced mitochondrial complex I activity, increased ATP production, and augmented cellular proliferation and migration. Bioinformatic analysis, coupled with functional validation, identified PRDM1 (PR Domain Containing 1) as a key transcription factor regulating SLC30A9 expression. Silencing or knockout of PRDM1 resulted in a significant reduction in SLC30A9 promoter activity, as well as decreased SLC30A9 mRNA and protein levels in primary cervical cancer cells. Chromatin immunoprecipitation (ChIP) assays confirmed increased PRDM1 binding to the SLC30A9 promoter region in cervical cancer tissues. In vivo studies showed that SLC30A9 knockdown led to a remarkable decrease in the growth of xenografts formed by primary cervical cancer cells. These SLC30A9-silenced xenografts exhibited mitochondrial dysfunction, proliferation inhibition and apoptosis induction. These findings collectively suggest that PRDM1-driven SLC30A9 overexpression significantly contributes to the malignant phenotype of cervical cancer, possibly through promoting mitochondrial hyperfunction.

The uterine cervix is a soft biological tissue with critical biomechanical functions in pregnancy. It is a mechanical barrier that supports the growing fetus. As pregnancy progresses, the cervix becomes more compliant and eventually opens in late pregnancy to facilitate childbirth. This dual function is facilitated by extensive remodeling of the cervical extracellular matrix (ECM), giving rise to its complex time-dependent material properties. Premature cervical remodeling is known to result in preterm birth, defined as birth before 37 weeks of gestation. While previous work has studied cervical remodeling using various biomechanical methods, it remains unclear how the intrinsic or flow-independent viscoelastic behavior of the cervix is influenced by cervical remodeling. In this study, an anisotropic reactive viscoelastic material model was formulated and investigated under tensile deformation to understand material behavior in cervical remodeling. To calibrate the model, experimental force relaxation data was used from uniaxial tension tests on Rhesus macaque cervical specimens from four gestational time points. The results showed that cervical tissue equilibrium and instantaneous stiffness significantly decreased from the nonpregnant (NP) to the late pregnancy status. In addition, cervical tissue in the late third trimester relaxed faster to equilibrium than the other gestational groups, particularly at prescribed grip-to-grip strains greater than 30%. This fast relaxation to equilibrium helps the cervix dissipate tensile hoop stresses induced by the fetus during labor, preventing its rupture. This work provides insights into time-dependent cervical remodeling features, which are crucial for developing diagnostic methods and treatments for preterm birth.

Cell division cycle 20 homologue (Cdc20), a key regulator of the anaphase-promoting complex/cyclosome (APC/C), is frequently overexpressed in human cancers and represents a promising therapeutic target. However, monotherapy targeting Cdc20 has shown limited efficacy, partly due to compensatory activation of cyclin-dependent kinase 1 (Cdk1). In this study, we investigated the combinatorial potential of the pan-Cdk inhibitor ZK304709 with the Cdc20 inhibitor apcin in HeLa cervical cancer cells. Transcriptomic analysis revealed that both CDC20 and CDK1 are upregulated in cervical cancer tissues. Mechanistically, apcin treatment induced cyclin B1 accumulation and enhanced Cdk1 phosphorylation at Thr161, suggesting feedback activation. In contrast, ZK304709 reduced p-Cdk1(T161) levels and suppressed Cdc20 expression at both protein and mRNA levels. Functionally, the combination of apcin and ZK304709 synergistically inhibited cell proliferation and induced G2/M phase arrest in HeLa cells. These findings demonstrate that dual inhibition of Cdk1 and Cdc20 disrupts compensatory signalling pathways and enhances antitumour efficacy in HeLa cells, providing a rational strategy for combination therapy in cervical cancer.

Objective: Cervical cancer (CC) is a leading factor in cancer-associated mortality among women worldwide. Protein arginine methyltransferase 1 (PRMT1) is involved in tumor growth, metastasis, and immune regulation in various types of cancer. However, the specific role of PRMT1 in CC remains unclear. This study aims to assess the expression pattern of PRMT1 in CC and its effects on tumor growth, angiogenesis, immune response, and metastasis. Material and Methods: We used quantitative reverse-transcription polymerase chain reaction and Western blot to detect the expression of PRMT1 in mouse tumor tissues and normal cervical tissues and the differential expression of PRMT1 in human cervical epithelial cells (HCerEpiC) and CC cell lines (HeLa). An ectopic CC mouse model was established and treated with anti-PRMT1 antibody or PRMT1 recombinant protein to evaluate PRMT1 expression in tumor tissues, tumor volume, weight, and histological changes. Transwell and tube formation assays were performed to assess the effects of PRMT1 on CC cell migration, invasion, and endothelial cell tube formation. The regulation of the cGAS-STING (cyclic GMP–AMP synthase–stimulator of interferon genes) signaling pathway in HeLa cells by PRMT1 was also investigated using PicoGreen staining and Western blot analysis. Results: The expression of PRMT1 was noticeably higher in tumor tissues than in normal tissues ( P &lt; 0.001) as well as in HeLa than in HCerEpiC ( P &lt; 0.001). In the mouse model, anti-PRMT1 treatment significantly inhibited tumor growth and reduced PRMT1 expression ( P &lt; 0.001). Treatment with PRMT1 recombinant protein promoted tumor growth and increased PRMT1 expression ( P &lt; 0.001). Histological analysis revealed that anti-PRMT1 treatment led to tumor cell shrinkage, nuclear condensation, and tissue necrosis, whereas PRMT1 recombinant protein treatment promoted cell proliferation and nuclear enlargement. Moreover, anti-PRMT1 treatment suppressed the expression of angiogenesis-related markers (a-smooth muscle actin, Cluster of differentiation 31, and glucose transporter 1) and significantly increased CD8+ immune cell infiltration, while PRMT1 recombinant protein enhanced angiogenesis and inhibited CD8 expression ( P &lt; 0.001). Knockdown of PRMT1 (Sh-PRMT1) significantly inhibited HeLa cell migration and invasion, while overexpression of PRMT1 (Ov-PRMT1) significantly promoted these processes ( P &lt; 0.001). Tube formation assays showed that Sh-PRMT1 treatment suppressed tube formation in human umbilical vein endothelial cells, whereas Ov-PRMT1 increased the number of formed tubes ( P &lt; 0.001). Finally, Sh-PRMT1 treatment significantly increased the activation of the cGAS-STING signaling pathway, while Ov-PRMT1 suppressed its activity ( P &lt; 0.001). Conclusion: PRMT1 promotes CC progression by enhancing tumor growth, angiogenesis, and immune evasion, partly by regulating the cGAS-STING pathway. Hence, it may serve as a potential therapeutic target.

The cervix undergoes morphological and structural changes during pregnancy in preparation for delivery. Assessing the progression of these changes using transvaginal ultrasound (TVUS) is crucial for preterm birth prediction. However, existing methods such as cervical length have limitations in capturing subtle tissue changes. Although tissue analysis using TVUS has been explored to address these limitations, achieving consistent and reproducible results in quantitative analysis remains challenging due to high inter-observer variability and a lack of standardized region of interest (ROI) definitions. This study proposes an oriented cervical canal region (O-CCR) framework that identifies regions containing ultrasound features while preserving anatomical spatial information. We utilized 1436 TVUS images for training, validation, and testing, with 189 additional images from a different hospital for external validation. CCR was defined to include the cervical canal and its surrounding region after aligning the IO and EO parallel to ensure anatomical consistency in the cervix. To validate the effectiveness of O-CCR in handling various orientations, we applied five oriented object detection models (Oriented R-CNN, ReDet, S2A-Net, R3Det, and Oriented RepPoints) and evaluated their CCR localization performance. We compared the performance of five models implemented within O-CCR framework. Among them, Oriented RepPoints achieved the highest average precision (AP) of 0.981 at the intersection over union (IoU) threshold of 0.5, compared to Oriented R-CNN (0.968), S2A-Net (0.962), ReDet (0.964), and R3Det (0.980) on the test dataset. Notably, Oriented RepPoints demonstrated superior performance even at higher thresholds of 0.6 (0.931) and 0.7 (0.743) and the lowest average orientation error (AOE) of 9.1980 in CCR localization. The proposed O-CCR framework exhibited reliable performance in CCR localization regardless of varying orientations and morphological configurations, while providing standardized regions that preserve the anatomical spatial information of the cervix. The consistent CCR could be applied to quantitative analysis of cervical tissue properties in future research. Ultimately, this approach could support the development of automated cervical change assessment for prenatal care.

Cervical cancer is a common malignancy which is very harmful to women’s health worldwide. Copper metabolism has become research highlight and is expected to be new therapeutic target of cancers, but the copper metabolism related genes connect with cervical cancer remain unclear. This study identified and experimentally verified the copper metabolism-related genes in cervical cancer. First, the gene expression profile of cervical cancer was downloaded from the Gene Expression Omnibus database to identify significantly differentially expressed genes of cervical cancer, and these genes were intersected to copper metabolism data set to screened out copper metabolism related genes in cervical cancer. Then gene ontology and Kyoto Encyclopedia of Gene and Genomes enrichment analysis were conducted, the protein-protein interactions were analyzed using the online database STRING11.0. The Cancer Genome Atlas database was used to validate the screening genes and analyze their diagnostic value. Cervical tissue samples from 8 patients with cervical cancer as the experimental group and 10 patients with benign uterine fibroids as the control group were collected, mRNAs was extracted and quantitative real time polymerase chain reaction was used to verify the selected genes. The Human Protein Atlas database was used to verify the expression of the selected genes, and their immune infiltration was studied based on the The Cancer Genome Atlas database. MiRNA-hub gene network, transcription factor-hub gene network and chemical-hub gene network were constructed by us to accurately investigate the molecular mechanism and potential drugs underlying copper metabolism related genes we screened out in cervical cancer. Aquaporin1 and cyclin-dependent kinases1 were the copper metabolism-related genes in cervical cancer we screened out by bioinformatics methods and then validated by clinical samples. Aquaporin1 and cyclin-dependent kinases1 could play an important role in the mechanism of cervical cancer and could be targets of cervical cancer concerning copper metabolism.

Cervical cancer (CC) can be prevented through continuous screening and the timely detection of cervical intraepithelial neoplasia (CIN) using immunohistochemistry techniques to identify biomarker expressions. In a previous study, we proposed nuclear REST loss as a biomarker in precancerous lesions and CC; however, no validated antibodies are available for detecting REST in cytology or cervical tissues. Although we have developed an IgM-type anti-REST monoclonal antibody capable of detecting REST in liquid-based cytology cells, it was not useful for the detection of REST in cervical tissues by immunohistochemistry. The main objective of this study is to generate single-chain variable fragments (scFvs) for the clinical evaluation of REST in cervical tissues from women with CIN and CC. Using RNA from an IgM-producing hybridoma anti-REST, we conducted RT-PCR and PCR to obtain the coding sequences for the variable regions of the heavy and light chains. These sequences were joined with a linker to create a single-chain antibody. The scFv was then cloned into the pSyn1 vector, expressed in E. coli TG1, and purified through chromatography. Subsequently, it was characterized using immunological methods to assess its biological activity and employed to evaluate REST expression in cytological samples and cervical tissues. The anti-REST scFv represents an innovative detection tool that retains the antigen recognition of the parental IgM while overcoming its size limitation, enabling tissue penetration and detection of REST in cervical samples. Its application facilitates the identification of REST in cervical samples, reinforcing REST’s potential as a diagnostic biomarker for CC and CIN.

PRMT5, a type II methyltransferase catalyzing symmetric dimethylation of arginine residues, has emerged as a promising therapeutic target in various cancers. However, the precise mechanism by which PRMT5 mediated the tumor immune microenvironment, particularly CD8+ T cell recruitment in cervical cancer remains elusive. Analysis of data from The Cancer Genome Atlas (TCGA) revealed elevated PRMT5 mRNA levels in cervical cancer tissues, which correlated with reduced immune cell infiltration and poorer patient prognosis. To further investigate the role of PRMT5 in tumor development, a CD8 knockout (KO) mouse tumor model was utilized. Significant inhibition of tumor growth was observed in cervical cancer using a mouse model lacking PRMT5. Notably, this antitumor effect was attenuated in CD8 KO mice lacking functional CD8+ T cells. Mechanistically, RNA sequencing (RNA-seq) analysis was conducted to explore how PRMT5 regulates immune cell recruitment. Disruption of PRMT5 was found to increase the secretion of chemokine CXCL10 by tumor cells. CXCL10 binds to its receptor CXCR3, thereby recruiting T cells to the tumor. Furthermore, in CXCR3 KO mice, PRMT5 knockdown failed to enhance T cell infiltration into tumors. These findings indicate that PRMT5 knockdown promotes CD8+ T cell recruitment to the tumor microenvironment via CXCL10 signaling. Furthermore, the therapeutic efficacy of the selective PRMT5 inhibitor EPZ015666 was evaluated in a cervical cancer xenograft mouse model. Treatment with EPZ015666 effectively suppressed tumor growth. In summary, these findings elucidate a novel mechanism whereby PRMT5 depletion in cervical cancer cells triggers a CXCL10-mediated chemotactic response, enhancing CD8+ T cell infiltration and restricting tumor progression. Thus, our study provides compelling evidence supporting the potential targeting of PRMT5 as a viable immunotherapeutic strategy for cervical cancer.