Small cell carcinoma of the uterine cervix (UCSCC) is a rare and aggressive HPV-linked neuroendocrine malignancy with limited therapeutic options and poor prognosis. Through integrative analysis of whole-exome sequencing (WES), single-cell RNA-seq (scRNA-seq), PinpoRNA-HPV, bulk RNA-sequencing, and immunohistochemistry (IHC), we delineated its molecular architecture. Genomic profiling unveiled the dysregulation of 10 core oncogenic pathways and an exceptionally high tumor mutational burden (TMB), along with frequent alterations in DNA repair genes. ScRNA-seq analysis identified nine distinct malignant subclusters characterized by lineage plasticity (ASCL1/NEUROD1/UCHL1) alongside active HPV18 transcription. The tumor microenvironment exhibited a paradoxical immune landscape: dense infiltration of CD8+ T cells and CD163+ tumor-associated macrophages (TAMs) in the complete absence of tumoral PD1/PD-L1 expression. Cell–cell communication analysis revealed that malignant subclusters specifically overexpress CD47, engaging SIRB1 on TAMs and SIRPG on T cells. IHC validation confirmed a CD8+/CD163+/PD-L1-phenotype and demonstrated that transcriptional CD47 enrichment in malignant clones implicated the CD47-SIRB1 axis as the primary immune checkpoint. These findings indicated UCSCC as an HPV-driven, heterogeneous tumor that might employ CD47 as an alternative immune evasion pathway in the absence of PD-L1, providing a strong rationale for exploring CD47 blockade as a novel potentially therapeutic strategy.

Platinum resistance is the main cause of treatment failure in ovarian cancer. BRCA1/2-mediated DNA damage repairment is an important factor contributing to platinum resistance in ovarian cancer. Altering the expression levels of BRCA1/2 will affect the platinum sensitivity of ovarian cancer. We used proteomics to screen out SFPQ, which bound to BRCA1 with a high abundance. However, the role and potential mechanism of SFPQ in the progression of ovarian cancer remain unclear. Through immunohistochemical staining, we found that SFPQ was overexpressed in ovarian cancer tissues and associated with poor prognosis of patients. Functional analysis showed that SFPQ binds to BRCA1 and inhibits its ubiquitination and degradation, increases the expression level of BRCA1, and promotes platinum resistance of ovarian cancer. Exploration of the upstream mechanism revealed that hsa_circSFPQ_008, which was derived from the SFPQ parental gene, recruits HDAC1 to modify H3K27Ac of the SFPQ promoter and regulates its expression. This study reveals a novel regulatory mechanism by which SFPQ is involved in platinum resistance of ovarian cancer, providing a new theoretical basis for the individualized and precise treatment of ovarian cancer.

This multicenter, randomized, open-label, exploratory Phase 2 trial assessed SHR-2004, an anti-FXI antibody, for venous thromboembolism (VTE) prevention in patients undergoing ovarian cancer surgery-a population at particularly high thrombotic risk conducted at 25 sites in China. Patients with newly diagnosed Stage III-IV or recurrent ovarian cancer scheduled for surgery were randomly assigned (1:1) to receive subcutaneous SHR-2004 (180 mg on Day 1 and 120 mg on Day 15) or enoxaparin-rivaroxaban (subcutaneous enoxaparin 40 mg once daily during hospitalization, followed by oral rivaroxaban 10 mg once daily after discharge until Day 28). The primary efficacy outcome was the composite of VTE events within 28 days. The primary safety outcome was major bleeding (MB) or clinically relevant nonmajor bleeding (CRNMB) from first dose to 28 days. Between February 19, 2024 and September 17, 2024, 198 patients received assigned treatment (90 with SHR-2004, 108 with enoxaparin-rivaroxaban) and were included in the safety analysis. Among 181 patients who completed protocol-mandated ultrasonography, VTE occurred in 11 (12.6%) patients in the SHR-2004 group and 19 (20.2%) in the enoxaparin-rivaroxaban group (difference -8.4%, 95% CI -19.9 to 3.1) by Day 28. MB/CRNMB rates were similar between groups (SHR-2004: 2/90 [2.2%]; enoxaparin-rivaroxaban: 2/108 [1.9%]). In this study, SHR-2004 showed comparable efficacy to enoxaparin-rivaroxaban for preventing postoperative VTE in patients undergoing ovarian cancer surgery, with a similar low risk of MB or CRNMB. The twice-monthly dosing schedule offers a potential advantage over daily anticoagulation, supporting further investigation in adequately powered Phase 3 trials. Trial Registration: ClinicalTrials.gov identifier: NCT06220123.

Thin endometrium (TE), affecting 1.5 %-9.1 % of reproductive-aged women, emerges as a disturbed decidua microenvironment underpinning implantation failure and recurrent pregnancy loss. Through integrated single-cell transcriptomics with histopathology and multiplex immunofluorescence (TSA) validation, we delineated TE as a disease of coordinated repairment impairment and pro-fibrotic remodeling across stromal and immune compartments. Key findings revealed a pathological imbalance in stromal subsets, including the decrease of regenerative IGFBP3 + Stromal_1 cells and expansion of fibrogenic Stromal_2 populations, driving collagen-dominant extracellular matrix remodeling. Concurrently, immune dysfunction was unmasked. NK cells decreased and shifted from immune surveillance to a pro-inflammatory phenotype, T cells transitioned from immune regulation to extracellular matrix remodeling effectors and macrophages adopted a pro-fibrotic phenotype with lipid metabolic collapse. CellChat analysis pinpointed suppression of GZMA-PARD3 and APOE-TREM2 axes as drivers of stromal dysfunction, while the hyperactivated adhesion (LAMA3) and collagen pathways served as central mediators of the fibro-inflammatory cascade. These findings, based on single-cell RNA-seq and spatial verification, suggest therapeutic targets for restoring endometrial homeostasis in TE. These findings suggested that TE as a disease of progressive stromal-immune fibrosis dysregulation, offering novel therapeutic targets to restore endometrial repairment and microenvironmental homeostasis.

Charged multivesicular body protein 4C (CHMP4C), as a subunit of endosomal sorting complex required for transport-III, is important for the abscission checkpoint in cell division, preventing premature cell division and genetic damage. The present study aimed to assess the role of CHMP4C in cervical cancer and the associated mechanisms. The levels of CHMP4C in normal and cervical cancer tissues were detected by immunohistochemistry. The MTT assay, apoptosis, wound-healing assay, and cell invasion assay were performed. Western blotting was performed to analyze the level of cancer-related proteins following CHMP4C downregulation and the CHMP4C expression following E6 downregulation and miR-543 upregulation. The transfection effectiveness of siRNA, plasmid, and miRNA mimic as well as the expression of miR-543 after silencing E6 were assessed by RT-PCR. The dual-luciferase reporter assay was used to demonstrate a connection site between CHMP4C and miR-543. The results demonstrated that CHMP4C expression in cervical cancer tissues was significantly higher than that in normal tissues. Furthermore, downregulation of CHMP4C expression significantly reduced the proliferation, migration and invasion of cervical cancer cells and significantly increased the rate of apoptosis compared to the si-scramble group. Comparison with the si-scramble group, silencing CHMP4C expression also significantly reduced the expression of Bcl2, Bcl-xL and Survivin, and was associated with a significant increase in Caspase-7 expression. After the knockdown of human papillomavirus (HPV)-encoded E6, in comparison to the si-scramble group, microRNA (miR)-543 expression was significantly elevated and CHMP4C expression significantly decreased. Moreover, a connection site was detected between miR-543 and CHMP4C. These findings indicate that CHMP4C accelerates the tumorigenesis and progression of cervical cancer through the HPV E6/miR-543 axis.

Introduction: N-acetyltransferase 10 (NAT10) mediates N4-acetylcytidine (ac4C) mRNA modification and promotes malignant tumor progression. However, there has been limited research on its role in cervical cancer. This study aimed to decipher the role of NAT10 in cervical cancer. Methods: The prognostic value of NAT10 was explored using the cancer genome atlas (TCGA) database and immunohistochemistry of cervical cancer tissue. The biological actions of NAT10 in cervical cancer were investigated by cell proliferation, transwell, wound healing, and chicken chorioallantoic membrane assays. The therapeutic action of remodelin (a NAT10 inhibitor) was verified in a nude mouse model. Mechanistic analyses were conducted by RNA sequencing, ac4C dot blotting, acetylated RNA immunoprecipitation, quantitative PCR, and RNA stability experiments. Results: NAT10 was overexpressed in cervical carcinoma and its overexpression was associated with poor prognosis. NAT10 knockout impaired proliferative and metastatic potentials of cervical cancer cells, while its overexpression had the opposite effects. Remodelin impaired cervical cancer proliferation in vivo and in vitro. NAT10 acetylated solute carrier family 7 member 5 (SLC7A5) enhanced mRNA stability to regulate SLC7A5 expression. Conclusions: NAT10 exerts a critical role in cervical cancer progression via acetylating SLC7A5 mRNA and could represent a key prognostic and therapeutic target in cervical cancer.

BACKGROUND:Spontaneous abortion (SA) is a complex reproductive disease that poses significant clinical challenge. Circular RNAs (circRNAs), a specific class of endogenous non-coding RNAs, hold significant potential for preclinical diagnosis and therapeutic interventions in various diseases. However, the precise roles of circRNAs in SA have yet to be fully elucidated. METHODS:In this study, we employed RNA sequencing and quantitative real-time polymerase chain reaction (qRT-PCR) to identify an upregulated circRNA, circFTO (hsa_circ_0005941), in the placental villi of SA patients. We conducted in vitro and in vivo experiments to ascertainthe functional significance of circFTO in trophoblast cell lines. The molecular mechanisms associated with circFTO were predicted using online databases and confirmed through RNA immunoprecipitation (RIP) assays, Western blotting, and rescue experiments.Additionally, Actinomycin D was employed to assess changes in the stability of target messenger RNA (mRNA) under different treatments. Furthermore, colorimetric examinations were used to evaluate the m6A methylation levels of trophoblast cells, and meRIP-qPCR assays confirmed the m6A modification of CCAR1 mRNA. RESULTS:Our findings revealed that circFTO was upregulated in the placenta of SA patients. Functionally, downregulating circFTO expression enhanced trophoblast cell proliferation, migration, and invasion. Conversely, overexpression of circFTO inhibited these functions in trophoblast cells. Trophoblast organoids derived from normal pregnancies exhibited reduced proliferation upon overexpression of circFTO. Bioinformatics prediction and subsequent experiments demonstrated that circFTO directly bound to and negatively regulated IGF2BP2. Reducing the level of IGF2BP2 partially restored the alterations in trophoblast function caused by circFTO knockdown. Colorimetric assay, RNA decay experiments, and meRIP-qRT-PCR analysis revealed that circFTO knockdown increased m6A methylation levels in CCAR1 mRNA, while circFTO overexpression decreased m6A methylation levels. This modification is known to play a crucial role in Zygotic gene activation. CONCLUSIONS:Our study unveils the pivotal functions of circFTO within trophoblasts and elucidates a unique circFTO-IGF2BP2-CCAR1 axis, which may hold significant potential as diagnostic and therapeutic targets for the treatment of SA. CLINICAL TRIAL NUMBER:Not applicable.

Conventional targeted therapies primarily rely on small molecules and proteins. However, they often struggle to enter specific protein conformations, which limits their therapeutic effectiveness. In contrast, RNA therapy is emerging as a more precise and effective targeting strategy. Through differential analysis comparing Pandora-Seq data with clinical samples, we discovered that the small RNA piR-28846 naturally, occurring in human body, exhibited low expression levels in ovarian cancer tissues. Experimental results indicate that piR-28846 inhibits the growth of ovarian cancer cells. Additionally, piR-28846 demonstrated significant therapeutic effects in xenograft models and ovarian cancer-like organoids. Further studies revealed that piR-28846 binds to NSUN2 and down-regulates it, which in turn affects the stability of KPNA2 mRNA. Notably, KPNA2 negatively regulates NSUN2 expression and localization. Given its inhibitory effects observed in vivo, in vitro, and in the ovarian cancer organoid model, we believe piR-28846 has strong potential as a small nucleic acid therapy of ovarian cancer.

5602 Background: HB0025, developed by Huaota, is a novel anti-PD-L1/VEGF bispecific antibody, with VEGFR1D2 linked at the N-terminal of anti- PD-L1 antibody. Carboplatin and paclitaxel (CP) alone or in combination with PD-(L)1 is a recommended regimen for first-line treatment of advanced endometrial carcinoma (EC) that the ORRs were 40%-68% regardless MMR status. This study assesses the efficacy and safety of HB0025 in combination with chemotherapy in EC patients. Methods: This open-label, multi-center phase II study of HB0025 with CP in primary advanced (stage III or IV) or first recurrent EC. Patients received 20mg/kg HB0025 every 3 weeks with CP for 4-6 cycles, followed by maintenance therapy with HB0025. The primary endpoint was objective response rate (ORR), assessed by RECIST v1.1. Results: As of Dec 25, 2024, 39 patients were enrolled. The median age was 59.0 years (range, 32.0-71.0). The median follow-up time was 3.3 months (range: 0.6-6.9). 31 patients had at least one post-baseline tumor assessment. The ORR and disease control rate (DCR) were 83.9% (26/31) and 100.0% (31/31), respectively. The ORR were 84.0% (21/25) in pMMR patients and 100.0% (4/4) in dMMR patients. Median duration of response (DOR) and progression-free survival (PFS) were not reached. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 18 patients (46.2%), The most common grade ≥3 TRAEs (≥10%) included neutropenia (30.8%), leukopenia (15.4%), thrombocytopenia (10.3%). Any-grade immune-related adverse events (irAEs) only occurred in 2 patients (5.1%). Treatment-related serious adverse events (SAEs) were observed in 5.1% (2/39) of patients. No TRAE led to treatment discontinuation or death. Any-grade hemorrhage events occurred in 7 (17.9%) patients which were all grade 1 in severity. Conclusions: HB0025 in combination with chemotherapy demonstrated promising anti-tumor efficacy with good safety profile. Regardless MMR status, ORR with HB0025 plus CP improved significantly over histologically reported data. A multicentre, randomized, double-blind, controlled phase III trial will commence in 2025. Clinical trial information: NCT06758557 .

Cuproptosis, a recently discovered form of cell death, has emerged as a crucial player in tumor development, although its role in uterine corpus endometrial carcinoma (UCEC) remains inadequately explored. This study aims to identify prognostically relevant cuproptosis-related genes in endometrial cancer. Cuproptosis-related genes were sourced from previously published studies and the FerrDb database. UCEC gene expression profiles and clinical data were obtained from the TCGA database. Differential gene expression was determined using LIMMA analysis, and functional enrichment analysis was conducted on identified cuproptosis-related genes. A prognostic model for UCEC was developed using LASSO Cox regression analysis and a Nomogram, integrating survival data, status, and gene signatures. TIMER analysis assessed the impact of crucial cuproptosis-related genes on immune cell infiltration in UCEC. Validation of the selected genes, CDKN2A, GLS, and PPAT, was performed at both mRNA and protein levels. A total of 27 cuproptosis-related genes were identified, with 19 upregulated and 6 downregulated in UCEC. These genes were associated with key signaling pathways, including the TCA cycle, Pyruvate metabolism, Glycolysis/Gluconeogenesis, and Platinum drug resistance. The LASSO regression and Nomogram models demonstrated robust predictive performance for UCEC prognosis, identifying CDKN2A, GLS, and PPAT as critical prognostic genes. Furthermore, these genes played essential roles in immune cell infiltration in UCEC, confirming their significance. Validation at both mRNA and protein levels solidified the role of CDKN2A, GLS, and PPAT. The identified signature of CDKN2A, GLS, and PPAT demonstrates significant predictive value for UCEC prognosis, suggesting their potential as therapeutic targets, including their application in immunotherapy strategies.

BACKGROUND:Ablative/excisional surgery is the recommended therapy for cervical high-grade squamous intraepithelial lesions (HSILs) but is associated with cervical damage and elevated risk of complications upon subsequent pregnancies. METHODS:This multicenter, randomized, controlled trial compared APL-1702 (2-g ointment containing 5% hexaminolevulinate; photoactivated at 125 J/cm2) versus placebo in adult women with cervical HSILs (randomization ratio: 2:1). Upon completion of 6-month treatment, patients in the APL-1702 group entered into a 6-month extension phase with observation only. The primary efficacy endpoint was treatment response, as defined by normal histology or low-grade squamous intraepithelial lesion (LSIL) histology plus human papillomavirus (HPV) clearance, at 6 months in a modified intent-to-treat (mITT) population. FINDINGS:A total of 402 women were enrolled. The 6-month response rate was 41.1% (104/253) in the APL-1702 group versus 21.7% (28/129) in the placebo group (p < 0.001). The HPV16/18 clearance rates were 31.4% (49/156) and 15.4% (12/78) in the APL-1702 and placebo groups, respectively (p = 0.011). The rates of treatment-emergent adverse events were 56.8% (151/266) and 56.0% (75/134) in the APL-1702 and placebo groups, respectively. At the end of the 6-month extension period, 54.9% (56/102) of the patients who responded at the end of the 6-month treatment period maintained a response. CONCLUSIONS:APL-1702 significantly increased the 6-month response rate in patients with cervical HSILs versus placebo control, with a favorable safety profile. FUNDING:This trial was sponsored by Asieris Pharmaceuticals (Shanghai, China).

BACKGROUND:Stage IB-IIA Cervical Squamous Cell Carcinoma (CSCC) presents diverse clinical outcomes, the mechanisms that cause recurrence in CC patients remain unclear. The goal of this study was to identify predictive biomarkers leading to tumor recurrence in IB-IIA CSCC after surgical treatment by comparing the transcriptional and immune landscape between the recurrence and non-recurrence group. METHODS:We performed mRNA sequencing and multiplexed immunohistochemistry (mIHC) analysis among stage IB-IIA patients with or without recurrence after surgical resection and were followed-up for a median of three years. RESULTS:Integrated analysis indicates that the upregulated gene expression in zinc finger proteins, the activation of the PI3K/Akt pathway, and the low infiltration level of T follicular helper cells and B-cells may serve as potential recurrent biomarkers for CSCC. We also observed significant differences in the immune and genomic landscape between two groups. CONCLUSIONS:These findings provide new insights into the relapse mechanisms of CSCC, which could potentially guide clinical exploration of drug targets.

Studies have shown that circRNAs play an important regulatory role in trophoblast function and embryonic development. Based on sequencing and functional experiments, we found that hsa_circ_0069443 can regulate the function of trophoblast cells, and its presence is found in the exosomes secreted by trophoblast cells. It is known that exosomes mediate the interaction between the uterus and embryo, which is crucial for successful pregnancy. We found that trophoblast cell-derived exosomes overexpressing hsa_circ_0069443 promoted the migration and invasion of endometrial stromal cells as well as the EMT process of endometrial glandular epithelial cells, and this process promotes embryo implantation and adhesion, thus proving that a decrease in hsa_circ_0069443 may be the key factor leading to early pregnancy loss. This study also found that hsa_circ_0069443 can bind to the RNA-binding protein demethylase ALKBH5, affecting the overall m6A level of trophoblast cells, and hsa_circ_0069443 and ALKBH5 can regulate the expression level of FN1, verifying the role of the 0069443/ALKBH5/FN1 axis in trophoblast cells and endometrial stromal cells. In summary, this study demonstrates that hsa_circ_0069443 may be a key factor leading to early pregnancy loss, and the regulation of the hsa_circ_0069443/ALKBH5/FN1 axis may provide new insights into early diagnostic markers for early pregnancy loss.

Endometrial cancer(EC)is one of the most common gynecological malignant tumors.Further investigation of the potential molecular mechanism of EC is important.Small nucleolar RNA(snoRNA)is a type of non-coding RNA,with an unclear biological function in EC.We found that Box C/D snoRNA SNORD3B-2 participated in EC oncogenesis and development via the PI3K-AKT signaling pathway.RNA immunoprecipitation(RIP)revealed that SNORD3B-2 bound to polo-like kinase 1(PLK1)through fibrillin(FBL).RTL-P(reverse transcription at low dNTPs-PCR)and actinomycin D assays confirmed that SNORD3B-2 directed 2'-O-methyl-ation modification of PLK1 mRNA,and the modification could promote the stability of PLK1 mRNA which could mediate tumor growth and metastasis in EC.Moreover,SNORD3B-2 overexpression was associated with retained Exon 3 of RAB17 thus activating the PI3K-AKT signaling pathway.This alternative splicing was achieved by SNORD3B-2 regulating the protein level of splice factor SF3B1(Splicing factor 3b subunit 1).

Objective: This study aims to explore the role of SH2D3A in cervical cancer, as well as its potential interaction with human papillomavirus (HPV) E7 and microRNA (miRNA). Methods: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were used to compare the expressions of SH2D3A in tissues. To assess the effects of SH2D3A on cervical cancer cell phenotypes, SH2D3A was knocked down in SiHa and HeLa cells, followed by cell proliferation (Cell Counting Kit-8 assay), apoptosis (flow cytometry), and invasion (Transwell assay) analyses. A transplantation tumor model was established to compare the tumorigenic ability of cervical cancer cells before and after SH2D3A silencing. Bioinformatics analysis predicted and dual-luciferase reporter assays verified the sponge adsorption effect of SH2D3A on miRNA. Western blot and qRT-PCR analyses were conducted to examine the impact on target genes following the downregulation of HPV E7 and SH2D3A. Results: SH2D3A expression was significantly elevated in cervical cancer tissues. SH2D3A silencing inhibited cell proliferation and invasion, induced apoptosis, and reduced tumorigenesis in nude mice. Bioinformatics tools identified a binding relationship between SH2D3A and miR-143-3p, confirmed by the luciferase reporter assays. Western blot analysis revealed that SH2D3A knockdown led to decreased levels of Janus kinase 1 (JAK1) and signal transducer and activator of transcription 3 (STAT3) proteins. Additionally, qRT-PCR showed that SH2D3A mRNA levels decreased after HPV E7 silencing, whereas miR-143-3p levels significantly increased. Conclusion: HPV E7 influences SH2D3A expression through miR-143-3p, thereby regulating the JAK1/STAT3 pathway. This mechanism promotes the occurrence and development of cervical cancer.

ObjectiveThis study aims to investigate the current status of multiple HPV infection and its association with cervical lesions in the western region of Guangzhou.MethodsA retrospective analysis of clinical data from cervical cancer screening patients was conducted. The patients were grouped based on HPV genotypes and cervical pathology results to explore the prevalence of high-risk HPV infection and its relationship with cervical lesions in the western region of Guangzhou. The study also analyzed the relationship between high-risk HPV infection and cervical lesions among different age groups.ResultsA total of 13,060 patients were included in the study, with an overall infection rate of 18.46% (2,411/13,060). Among them, the infection rate of HPV genotype 16 was 14.14% (341/2,411), HPV genotype 18 was 5.23% (126/2,411), and other 12 high-risk HPV genotypes accounted for 71.96% (1,735/2,411). When comparing the incidence of HSIL+ (high-grade squamous intraepithelial lesion or worse) among different HPV genotypes, the results showed that the HPV 16 infection group (47.50%) had a higher incidence than the HPV 18 infection group (25.40%) and the other 12 high-risk HPV genotypes group (15.97%; P < 0.05). In the multiple infection groups, the pathogenicity rates were 63.64% (7/11) for the 16+18 HPV infection group, 42.97% (55/128) for the 16+other 12 high-risk HPV genotypes infection group, 26.79% (15/56) for the 18+other 12 high-risk HPV genotypes infection group, and 57.14% (8/14) for the 16+18+other 12 high-risk HPV genotypes infection group. These rates were significantly different compared to the single infection group (P <0.01). Although there was no statistically significant difference in the incidence of cervical cancer between the HPV 16 infection group and the HPV 18 infection group, both groups had a higher incidence compared to the group with other 12 high-risk HPV genotypes infection (P < 0.05). Further analysis suggests that the severity of cervical lesions is not associated with the number of high-risk HPV infections, i.e., the severity of cervical lesions is unrelated to multiple HPV infections but is instead related to the pathogenicity of the HPV genotypes. The infection rate and multiple HPV infection rate of women under 35 years old were higher than those of women aged 35 and above (20% vs. 17.1%; 2% vs. 1.3%; P < 0.05). Moreover, the pathogenicity rate of HSIL+ among high-risk HPV infection increased with age.ConclusionsIn the western region of Guangzhou, the overall infection rate of high-risk HPV is 18.46%. The severity of cervical lesions is unrelated to multiple HPV infections. The fundamental reason is the distinct pathogenicity of different HPV genotypes. The HSIL+ pathogenicity rates, from high to low, are in sequence for HPV 16, HPV 18, and the other 12 HPV types.

Eukaryotic cells possess multiple mechanisms of self-destruction, including pyroptosis and necroptosis. Pyroptosis is a type of programmed cell death characterized by cellular rupture and linked to inflammation. SnoRNA, a small non-coding RNA in the nucleolus, can dysregulate specific RNAs through 2'-O-methylation, contributing to tumorigenesis. Our StarBase and qRT-PCR analysis revealed SNORD99 upregulation in endometrial cancer (EC) tissue compared to normal tissue, suggesting its role in pathogenesis. SNORD99 overexpression enhanced migration and proliferation of EC cells, while ASO-mediated suppression reduced malignant cell spread and division. RNA-seq and base-comparing analysis identified GSDMD's differential expression upon SNORD99 overexpression, forming the SNORD99-FBL RNP complex. RTL-P experiments showed SNORD99 increased GSDMD's 2'-O-methylation. SNORD99 reduced GSDMD, caspase-1, and NLRP3 protein levels, implicating its role in pyroptosis. Optical and electron microscopy confirmed enhanced pyroptosis features. In summary, SNORD99 modifies GSDMD via 2'-O-methylation, suppressing pyroptosis and promoting EC progression. Developing pyroptosis-inducing drugs may offer new cancer treatment avenues.

Objective To investigate the application value of uterine artery temporary blocking in cesarean scar pregnancy（CSP）.Methods Sixty patients admitted to Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine from May 2019 to May 2021 diagnosed as type Ⅱand type III CSP by transvaginal ultrasonography and concurrent MRI three-dimensional reconstruction were selected.Random number table method was used to divide them into experimental group and control group, 30 cases each.The treatment success rate, operation time, intraoperative blood loss, length of hospital stay, side effects, endometrial thickness and endometrial blood flow 3 months after operation were compared between the two groups.Results The hospital stay of the experimental group and the control group were（7.3±3.3）d and（8.9±4.2）d, respectively.The hospitalization expenses were（13 566.3±1 967.2） yuan and（14 250.3±1 639.1） yuan.The incidence of side effects were 16.7% and 33.3%,respectively.The treatment success rates of the two groups were 97.6% and 73.3%,respectively.The intraoperative blood loss was（125.3±35.2） mL and（423.3±67.2） mL,respectively.The differences were statistically significant（P＜0.05）,the endometrial thickness was（8.3±1.4） mm and（8.5±1.2） mm, respectively.The operation time was（94.7±15.2） min and（91.3±16.4） min, respectively.There was no statistically significant difference between the two comparisons（P＞0.05）.Compared with the control group, the experimental group had higher success rate, less side effects and less intraoperative blood loss, and the experimental group was significantly better than the control group（P＜0.05）.Moreover, the operation time had no effect, and the endometrial thickness and endometrial blood flow measured by vaginal overmeasurement during ovulation 3 months after the operation had no effect.Conclusion Laparoscopic temporary blockage of uterine artery in the treatment of caesarean section scar pregnancy safety is high, postoperative complications and short-and long-term side effects are less, worthy of recommendation.

Small nucleolar RNAs (snoRNAs) are a class of non-coding RNAs widely distributed in eukaryotic nucleoli. In recent years, studies have revealed that snoRNAs can also participate in the occurrence and development of malignant tumors through different pathways. Cervical cancer is one of the most common malignant tumors of the female reproductive system, and the high-risk HPV virus infection is its main pathogenic mechanism. However, the outcomes in different patients with malignant tumors vary, indicating that other factors might affect the pathogenic process of cervical cancer. In this study, we screened the poor prognosis indicator SNORD6 from the TCGA database to find the snoRNA that affects the disease outcome during the pathogenesis of cervical cancer. We discovered that SNORD6 expression in cervical cancer tissues was higher than that in normal cervical tissues. Cell phenotype experiments revealed that the knockdown of SNORD6 retarded cell proliferation and plate clone formation. Furthermore, G1-S phase cell cycle arrest was induced, DNA synthesis was decreased, cell migration and invasion were reduced, while the level of apoptosis increased, whereas the opposite results were obtained after SNORD6 overexpression. Moreover, after intratumoral injection of ASO-SNORD6, the tumor growth rate slowed down, and the tumor volume decreased compared with the control group. In the mechanism study, we found that SNORD6 concurrently acted as a binding "hub" to promote the formation of the tumor suppressor protein p53 degradation complex E6-E6AP-p53. This reaction enhanced the ubiquitination and degradation of p53, thus influenced the regulation of p53 activities in the cell cycle and apoptosis. This study preliminarily clarified the biological role and specific mechanism of SNORD6 in the occurrence of cervical cancer, broadening the basic theoretical research of ovarian cancer and may provide a new perspective on the diagnosis and treatment of cervical cancer.