Cervical septum incision adversely impacts clinical outcomes in women with complete uterine septum and duplicated cervix.

STUDY OBJECTIVE: To investigate the reproductive outcomes of women with complete septate uterus and duplicated cervix who either did or did not receive cervical septum incision during hysteroscopic transcervical incision of the uterine septum. DESIGN: Retrospective study approved by the Hospital Ethics Committee. SETTING: Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China. PATIENTS: Women with complete septate uterus and duplicated cervix who underwent hysteroscopic transcervical incision of the uterine septum in Obstetrics and Gynecology Hospital of Fudan University between January 2008 and December 2020 (n=105). INTERVENTIONS: Hysteroscopic incision of the septum. MEASUREMENTS AND MAIN RESULTS: Included patients were grouped according to whether or not cervical septum incision was performed. Reproductive outcomes including gravidity, abortion rate, preterm birth rate, full-term birth rate, premature rupture of membranes (PROM), and cervical incompetence were assessed. In no incision group, the abortion rate (7.4%) was significantly lower than that of incision group (27.6%, p=0.01); the preterm birth rate (4.6%) was significantly lower than that of incision group (36.8%); and the full-term birth rate (95.5%) exceeded that of incision group (63.2%, p<0.01). Incidence of PROM and cervical incompetence during pregnancy was higher in incision group (15.8% and 10.5%, p<0.01 and p=0.03). CONCLUSION: Significantly improved reproductive outcomes were observed among patients with complete septate uterus and duplicated cervix whose cervical septum was preserved during the hysteroscopic transcervical incision of the uterine septum procedure.

Lineage Replacement and Genetic Changes of Four HR-HPV Types during the Period of Vaccine Coverage: A Six-Year Retrospective Study in Eastern China.

OBJECTIVE: This study aimed to provide clinical evidence for lineage replacement and genetic changes of High-Risk Human Papillomavirus (HR-HPV) during the period of vaccine coverage and characterize those changes in eastern China. METHODS: This study consisted of two stages. A total of 90,583 patients visiting the Obstetrics and Gynecology Hospital of Fudan University from March 2018 to March 2022 were included in the HPV typing analysis. Another 1076 patients who tested positive for HPV31, 33, 52, or 58 from November 2020 to August 2023 were further included for HPV sequencing. Vaccination records, especially vaccine types and the third dose administration time, medical history, and cervical cytology samples were collected. Viral DNA sequencing was then conducted, followed by phylogenetic analysis and sequence alignment. RESULTS: The overall proportion of HPV31 and 58 infections increased by 1.23% and 0.51%, respectively, while infection by HPV33 and 52 decreased by 0.42% and 1.43%, respectively, within the four-year vaccination coverage period. The proportion of HPV31 C lineage infections showed a 22.17% increase in the vaccinated group, while that of the HPV58 A2 sublineage showed a 12.96% increase. T267A and T274N in the F-G loop of HPV31 L1 protein, L150F in the D-E loop, and T375N in the H-I loop of HPV58 L1 protein were identified as high-frequency escape-related mutations. CONCLUSIONS: Differences in epidemic lineage changes and dominant mutation accumulation may result in a proportional difference in trends of HPV infection. New epidemic lineages and high-frequency escape-related mutations should be noted during the vaccine coverage period, and regional epidemic variants should be considered during the development of next-generation vaccines.

3D reconstruction of the uterus and automatic segmentation of the uterine cavity on 3D magnetic resonance imaging: A preliminary study.

Purpose: To determine the differences in 3D shape features between septate uterus (SU) and normal uterus and to train a network to automatically delineate uterine cavity on 3D magnetic resonance imaging (MRI). Methods: A total of 43 patients (22 cases of partial septate uterus and 21 cases of complete septate uterus) were included in the experimental group. Nine volunteers were recruited as a control group. The uterine cavity (UC), myometrium (UM), and cervical canal of the uterus were segmented manually using ITK-SNAP software. The three-dimensional shape features of the UC and UM were extracted by using PyRadiomics. The recurrent saliency transformation network (RSTN) method was used to segment the UC. Results: The values of four 3D shape features were significantly lower in the control group than in the partial septate group and the complete septate group, while the values of two features were significantly higher (p < 0.05). The UCs of the three groups were significantly different in terms of flatness and sphericity. The values of six features were significantly lower in the UMs of the control group than in those of the partial septate group and the complete septate group (p < 0.05). After the deep learning networks were trained, the Dice similarity coefficient (DSC) scores of the four folds for different thresholds were all over 80 %. The average volume ratio between predictions and manual segmentation was 101.2 %. Conclusions: Based on 3D reconstruction, 3D shape features can be used to comprehensively evaluate septate uterus and provide a reference for subsequent research. The UC can be automatically segmented on 3D MRI using the RSTN method.

Associations of Single Versus Multiple Human Papillomavirus Infections With the Prevalence of Cervical Intraepithelial Neoplasia 2/3 and Squamous Cell Carcinoma Lesions: Human Papillomavirus Type-Specific Attribution.

The risk of developing cervical squamous lesions in women with multiple high-risk human papillomavirus (hrHPV) infections is uncertain. The aim of this retrospective study was to investigate the type-specific attribution and phylogenetic effects of single and multiple hrHPV subtypes in cervical squamous lesions. All cases with cervical histopathologic diagnosis and human papillomavirus (HPV) genotyping results in the 6 months preceding biopsy from October 2018 to December 2022 were studied and analyzed. Over the study period, 70,361 cases with histopathologic follow-up and prior HPV genotyping were identified. The hrHPV-positive rate was 55.6% (39,104/70,361), including single hrHPV detected in 27,182 (38.6%), 2 types of hrHPV detected in 8158 (11.6%), and 3 types of hrHPV detected in 2486 (3.5%). Among 16,457 cases with a histologically diagnosed squamous lesion (cervical intraepithelial neoplasia 1: 11411; cervical intraepithelial neoplasia 2/3: 4192; squamous cell carcinoma: 854 cases), the prevalence of single hrHPV infection increased, but the rate of multiple concomitant hrHPV infections showed negative association as the degree of squamous lesions increased. Among women with a single HPV16 infection, cervical intraepithelial neoplasia 2/3 and squamous cell carcinoma (CIN2+) diagnostic rate was 30.6%, and it increased to 47.6% when coinfected with HPV33 (P < .001) but significantly decreased when coinfected with all other hrHPV types (P < .05). By comparing CIN2+ diagnostic rates in 40 most common 2 types of hrHPV infections with related single hrHPV infection, CIN2+ rates were decreased in 12 combinations (30.0%), equivalent in 26 combinations (65.0%), and increased in 2 combinations (5.0%). The cases with 3 types of HPV infections reduced the risk for CIN2+ compared with related single HPV infections. HPV16+52+53, HPV16+52+68, HPV16+52+51, HPV16+39+52, and HPV16+58+53 significantly decreased the risk of CIN2+ compared with HPV16 single infection (P < .05). This study demonstrates that multiple hrHPV infections are not associated with cumulatively higher risk for CIN2+ development, suggesting that oncogenic progression of multiple hrHPV-associated cervical squamous lesions is neither synergistic nor a cumulative effect at the phylogenetic level, possibly a way of competitive interference.

Application of a diagnosis flow draft based on appearance impression for detection of vulvar disease.

OBJECTIVES: The aims of this retrospective study were to evaluate the clinical applicability of the latest International Society for the Study of Vulvovaginal Disease (ISSVD) and International Federation for Cervical Pathology and Colposcopy (IFCPC) terminology for vulvar diseases, and to explore a new evaluation flow to optimize decision-making on diagnosis. METHODS: A total of 1,068 patients with 5,340 qualified vulvar images were evaluated by observers using 2011 ISSVD and 2011 IFCPC terminology systems. The sensitivity, specificity, positive predictive value, negative predictive value, Youden Index and Overall Diagnostic Value (ODV) were calculated for each finding in the two systems. Then the disease diagnosis order and a diagnosis flow draft (DFD) were obtained. RESULTS: A total of 15 kinds of vulvar diseases were diagnosed. The proportion of patients accompanied with cervical or vaginal intraepithelial neoplasia was highest (83.3 %) in vulvar Paget's disease group (p<0.001). Total area of lesions was larger in vulvar Paget's disease, lichen simplex chronicus and lichen sclerosus group (p<0.001). Among the top five findings of ODV, some findings inferred several (≥6) kinds of diseases, while some findings only exist in a certain disease. When the DFD was used, the agreement between the initial impression and histopathology diagnosis was 68.8 %, higher than those when ISSVD an IFCPC terminology systems used (p=0.028), and it didn't change with the experience of the observer (p=0.178). CONCLUSIONS: Based on the findings in ISSVD and IFCPC terminology systems, we explored a DFD for observers with different experience on the detection of vulvar disease.

Vaccine escape challenges virus prevention: The example of two vaccine-preventable oncogenic viruses.

Over the years, the pace of developing vaccines for HBV and HPV has never stopped. After more than 30 years of application, the HBV vaccine has reduced 80% of hepatocellular carcinoma (HCC). However, vaccine escape variants occur under selective pressure induced by widespread vaccination and antiviral therapy, which results in fulminant infection and horizontal transmission. Several mechanisms have been studied to explain HBV vaccine escape, including vaccine escape mutations (VEMs) in the major hydrophilic region, which leads to a decrease in the binding ability to neutralize antibodies and is the primary escape mechanism, protein conformational and N-linked glycosylation sites changes caused by VEMs, differences in genotype distribution, gene recombination, and some temporarily unknown reasons. However, effective solutions are still being explored. The HPV vaccine has also been proven to prevent 70%-90% of cervical cancer worldwide. Cases of HPV infection after being vaccinated have been observed in clinical practice. However, few researchers have paid attention to the mechanism of HPV vaccine escape. Thus, we reviewed the literature on vaccine escape of both HBV and HPV to discuss the mechanism of the virus escaping from vaccine protection and possible solutions to this problem. We analyzed the gap between studies of HPV and HBV and made prospects for further research in HPV vaccine escape.

Assessment of key parameters of normal uterus in women of reproductive age.

Currently, the precise and detailed anatomical data of the normal uterus, especially the myometrium thickness in various parts of the uterus, are lacking. This study aims to provide normal references for uterine size in healthy reproductive-aged Chinese women to facilitate the application of hysteroscopic surgery. A total of 298 women of reproductive age with normal uterine were included. Parity was significantly correlated with uterine measurements (P < 0.05), and age impacted several measurements (P < 0.05). At each uterine site examined, the myometrium was thinner in nulliparous women than in parous or primiparous women (P < 0.001). Similarly, the extrauterine measurements for parous or primiparous women were larger than those for nulliparous women. Weight affected some external measurements but not myometrial thicknesses, while height did not affect uterine measurements (P > 0.05). There was a positive correlation between body mass index (BMI) and extrauterine measurements as well as myometrial thickness (P < 0.05). The mathematical model of the uterine size for women of reproductive age was constructed stratified by parity. The study is the first to provide a detailed statistical description of the accurate anatomical parameters of the uterus in Chinese reproductive-aged women and has great significance for improving the safety and effectiveness of hysteroscopic surgery for patients.

Vulvar squamous intraepithelial neoplasia epithelial thickness in hairy and non-hairy sites: a single center experience from China.

Introduction: A large-sample study focusing on VIN lesions of a more precise thickness is needed to help guide clinical treatment. This study aimed to investigate the depth of vulvar intraepithelial neoplasia (VIN) and involved skin appendages to provide evidence for laser surgery. Methods: The study retrospectively enrolled and analyzed the clinical characteristics of VIN patients in the obstetrics and gynecology department of a university hospital between January 1, 2019 and December 30, 2021. The study further explored the thickness of epithelium and skin appendages of 285 women with low-grade VIN (VIN1) and 285 women with high-grade VIN (VIN2/3). Results: The study included 1,139 (80%) VIN1 and 335 (20%) VIN2/3 cases. The VIN1 and VIN2/3 groups showed a significant difference in human papillomavirus infection (P<0.01) but not in cytology (P = 0.499). Most (89.90%, 1,325) cases occurred in one area of the vulva, whereas 10.11% were multifocal. VIN commonly occurred on the posterior fourchette (76.85%), labia majora (11.61%), and labia minora (9.92%). The VIN2/3 group reported a significantly higher positive rate for concurrent cervical and vaginal intraepithelial neoplasia (160 of 285) than the VIN1 group (321 of 953) (P=0.000). The involved epithelial thicknesses in VIN2/3 and VIN1 were 0.69 ± 0.44 and 0.49 ± 0.23 mm, respectively, both of which were greater than the corresponding noninvolved epithelial thickness (0.31 ± 0.19 and 0.32 ± 0.10 mm, P<0.001 and P<0.001, respectively). In cases of appendage involvement, the VIN thickness was 1.98 ± 0.64 mm. Conclusions: VIN thickness was generally ≤1 mm for the superficial lesions in non-hairy areas. However, for lesions extending onto hairy areas, the thickness was approximately 3 mm, leading to the destruction of involved skin appendages.

Analysis of publications on HPV genotype co-infection: a bibliometric study on existing research.

Purpose: To identify the bibliometric information of Human papillomavirus (HPV) genotype co-infection in certain literature database over the past two decades. Methods: Web of Science was used as the main database to identify all eligible articles focusing on HPV genotype co-infection at the date of October 16, 2022. From this journal database, we identified 463 articles on HPV genotype co-infection, conducted statistical analysis according to the author, journal, publication year and month, country or region, keyword and impact factor. Results: The articles included in our analysis were published between 1994 and 2022. The index of citations per year ranged from 170.4 to 13.1. These articles were from 78 countries or regions, with most publications from the United States (n = 73), followed by China (n = 65) and Italy (n = 50). The journal that contributed the most publications on HPV heterotypic gene co-infection was PLOS ONE with a total of 29 articles, followed by JOURNAL OF MEDICAL VIROLOGY (n = 28), INFECTIOUS AGENTS AND CANCER (n = 14) and JOURNAL OF CLINICAL VIROLOGY (n = 12). Among existing research in the field of HPV co-infection, we found that epidemiological distribution and infection mechanism has been the two major topics for scholars, and studies on detection methods for HPV multiple genotypes were also included. Conclusion: Over decades, epidemiological studies and mechanism investigationhas been the central topics when it comes to HPV genotypes co-infection. Studies on HPV co-infection remained relatively insufficient, mainly stays in qualitative level while detailed infection data and high quality literature publications were still lack of valuable discussion.

Risk factors of LEEP margin positivity and optimal length of cervical conization in cervical intraepithelial neoplasia.

Background: The conization length for cervical precancerous lesions is essential for treatment but is left undetermined. This study aims to explore the reasonable and optimal conization length in patients with different types of cervical transformation zones (TZs) to reach the treatment outcome of margin negative in the surgery. Methods: From July 2016 to September 2019, a multi-center prospective case-control study with or suspicion of cervical precancer was enrolled from five medical centers in Shanghai, China. The clinical characteristics, cytology, human papillomavirus (HPV), histopathology, and details of cervical conization were recorded. Results: A total of 618 women were enrolled in this study; 6.8% (42/618) had positive internal (endocervical and stromal) margins and 6.8% (42/618) had positive external (ectocervical) margins of loop electrosurgical excision procedure (LEEP) specimen. Comparing the positive internal margin group with the negative group, age (p = 0.006) and cytology (p = 0.021) were significantly different. Multivariate logistic regression analysis showed that the risk factors for positive internal margin were cytology ≥ high-grade squamous intraepithelial lesion (HSIL) (odds ratio (OR) 3.82, p = 0.002) and age (OR 1.11, p < 0.001). The positive internal margin rate was 2.7%, 5.1%, and 6.9% in TZ1, TZ2, and TZ3, respectively, while the positive external margin was 6.7%, 3.4%, and 1.4%, respectively. In the TZ3 group, the HSIL positive internal margin of the 15-16-mm group (10.0%, 19/191) was significantly greater than in TZ1 (2.7%, 4/150) (p = 0.010) and TZ2 (5.0%, 9/179) (p = 0.092); when excision length increases to 17-25 mm, the positive internal margin rate dramatically decreased to 1.0% (1/98). Conclusion: A cervical excision length of 10-15 mm is reasonable for TZ1 and TZ2 patients, while 17-25 mm is optimal for TZ3 excision with more negative internal margins.

Value of loop electrosurgical excision procedure conization and imaging for the diagnosis of papillary squamous cell carcinoma of the cervix.

Background: Loop electrosurgical excision procedure (LEEP) conization and hysterectomy are performed for some patients with papillary squamous cell carcinoma (PSCC), whereas only hysterectomy is performed for others. We aimed to determine the optimal management for PSCC. Methods: Patients diagnosed with PSCC by colposcopy-directed biopsy between June 2008 and January 2020 who underwent LEEP conization and hysterectomy or only hysterectomy at our hospital were enrolled. Results of cervical cytology, high-risk human papillomavirus testing, transvaginal sonography, pelvic magnetic resonance imaging, LEEP, hysterectomy, and pathology testing of colposcopy-directed biopsy samples were analyzed. Results: A total of 379 women were diagnosed with PSCC by colposcopy-directed biopsy; 174 underwent LEEP before hysterectomy and 205 underwent only hysterectomy. Patients underwent and did not undergo LEEP were aged 47 ± 11 years and 52 ± 11 years, respectively. Among women who underwent LEEP, the agreement between LEEP and hysterectomy pathology was 85.1%. For women who underwent only hysterectomy, the agreement between preoperative clinical staging and pathological staging after hysterectomy was 82.4%. For patients with preoperative imaging indicative of malignancy, the accuracy of LEEP for diagnosing and staging PSCC was 88.5%, whereas for the hysterectomy-only group, it was 86.2%. For patients without malignancy detected with imaging, the accuracy of LEEP for diagnosing and staging PSCC was 81.6%; however, for those who did not undergo LEEP, it was 70.0%. Conclusion: For women diagnosed with PSCC by colposcopy-directed biopsy, LEEP conization is necessary for an accurate diagnosis when imaging does not indicate cancer; however, LEEP is not necessary when imaging indicates cancer.

25-hydroxycholesterol inhibits human papillomavirus infection in cervical epithelial cells by perturbing cytoskeletal remodeling.

Persistent high-risk human papilloma virus (HR-HPV) infection is the main risk factor for cervical cancer, threatening women's health. Despite growing prophylactic vaccination, annual cervical cancer cases are still increasing and show a trend of younger onset age. However, therapeutic approaches towards HPV infection are still limited. 25-hydrocholesterol (25HC) has a wide-spectrum inhibitory effect on a variety of viruses. To explore efficient interventions to restrict HPV infection at an early time, we applied different pseudoviruses (PsV) to evaluate anti-HPV efficacy of 25HC. We tested PsV inhibition by 25HC in cervical epithelial-derived HeLa and C-33A cells, using high-risk (HPV16, HPV18, HPV59), possibly carcinogenic (HPV73), and low-risk (HPV6) HPV PsVs. Then we established murine genital HPV PsV infection models and applied IVIS to evaluate anti-HPV efficacy of 25HC in vivo. Next, with the help of confocal imaging, we targeted 25HC activity at filopodia upon HPV exposure. After that, we used RNA-seq and Western blot analysis to investigate (1) how 25HC disturbs actin cytoskeleton remodeling during HPV infection and (2) how prenylation regulates the cytoskeletal remodeling signaling pathway. Our findings suggest that 25HC perturbs F-actin rearrangement by reducing small GTPase prenylation. In this way, the phenomenon of HPV virion surfing was restricted, leading to failed infection.

Construction and evaluation of intrauterine adhesion model in rats by different methods of mechanical injury.

PURPOSE: The study aimed to establish a stable and effective animal model for the experimental study of intrauterine adhesion (IUA) by evaluating various mechanical injury methods. METHODS: A total of 140 female rats were divided into four groups according to the extent and area of endometrial injury: group A (excision area: 2.0 × 0.5 cm2), group B (excision area: 2.0 × 0.25 cm2), group C (endometrial curettage) and group D (sham operation). On the 3rd, 7th, 15th and 30th day after the operation, the tissue samples of each group were collected, and the uterine cavity stenosis and histological changes were recorded by HE and Masson staining. Immunohistochemistry of CD31 was applied to visualize microvessel density (MVD). The pregnancy rate and the number of gestational sacs were used to evaluate the reproductive outcome. RESULTS: The results showed that endometrium injured by small-area endometrial excision or simple curettage could be repaired. The ratio of fibrosis in groups A and B was higher than that in groups C and group D 30 days after modeling (P < 0.001). The number of endometrial glands and MVD in group A was significantly lower than those in groups B, C and D (P < 0.05). The pregnancy rate in group A was 20%, which was lower than that in groups B (33.3%), C (89%) and D (100%) (P < 0.05). CONCLUSION: Full-thickness endometrial excision has a high rate of success in constructing stable and effective IUA models in rats.

HPV genotyping of cervical histologic specimens of 61, 422 patients from the largest women hospital in China.

Objectives: We investigated HPV genotypes in a large cohort of patients with definitive cervical histologic diagnosis. Methods: HPV testing was performed by real-time PCR assay, including 18 high-risk HPV (hrHPV) and 3 low-risk HPV (lrHPV). Totally 61,422 patients with documented HPV genotyping results within 6 months before cervical histologic diagnoses were included. Results: HrHPV positive rate was 55.1% among all tested cases with the highest in adenosquamous carcinoma (94.1%), followed by squamous cell carcinoma (SCC) (93.7%), cervical intraepithelial neoplasia 2/3 (CIN2/3) (92.8%). HrHPV positive rates were significantly higher in high-grade squamous lesions than in those in glandular lesions. HPV16 was the most common genotype followed by HPV52 and HPV58 in CIN2/3. The most frequent hrHPV genotype in adenocarcinoma in situ (AIS) was HPV18, followed by HPV16, HPV45 and HPV52. In SCC cases, HPV16 was the most common type followed by HPV58, HPV52, HPV18 and HPV33. However, HPV18 showed significantly higher prevalence in adenocarcinoma and adenosquamous carcinoma than in that in SCC. Theoretically, the protective rates of 2/4-valent and 9-valent vaccine were 69.1% and 85.8% for cervical cancers. Conclusions: The prevalence of HPV genotypes in Chinese population was different from that in Western population. Some hrHPV types were identified in cervical precancerous lesions and cancers, which are not included in current HPV vaccines. These data provide baseline knowledge for future HPV vaccine development.

The possible impact of novel mutations in human papillomavirus 52 on the infection characteristics.

Human papillomavirus 52 (HPV52) infection is prevalent in the Chinese population, and variations in HPV52 show correlations with oncogenicity. However, no specific variation in HPV52 was reported to show relevancy to infection characteristics. In this study, we retrieved 222 isolates of E6 and L1 full-length genes from 197 Chinese women with HPV52 infection. After sequence alignment and phylogenetic tree construction, we found that 98.39 % of the collected variants belonged to the sublineage B2 and two variants displayed incongruence between the phylogenetic tree of E6 and L1. The analysis of the infection pattern showed that the presence of C6480A/T mutation in the L1 gene was associated with single infection (P=0.01) and persistent infection (P=0.047) of HPV52, while the A6516G nucleotide change was relevant to transient infection (P=0.018). Our data also indicated that variations T309C in the E6 gene and C6480T, C6600A in L1 were more commonly presented in patients with high-grade cytology (P<0.05). One HPV52 breakthrough infection after vaccination was identified, which hinted at the immune escape post-vaccination. Young coitarche age and non-condom usage were correlated to multiple infections. This study provided insight into the polymorphism of HPV52 and revealed the impact of variations in HPV52 on its infection characteristics.

Clinical Diagnostic Value of Atypical Glandular Cells in Cervical Cytology: A Single Center Experience From China.

OBJECTIVE: This study aimed to investigate the diagnostic value of atypical glandular cells (AGCs) by analyzing the prevalence and histopathology of AGCs according to cervical cytology. METHODS: The authors retrospectively reviewed and analyzed the demographic characteristics and histopathological outcomes including pathological diagnosis, pathological site, and epithelial distribution of the AGC cases that were diagnosed by cervical cytology. RESULTS: A total of 387 AGC patients with follow-up records were included. Among them, the prevalence of AGC-not otherwise specified (NOS) and AGC-favor neoplastic (FN) was 73.39% (284/387) and 26.62% (103/387), respectively. The high-risk human papillomavirus (hr-HPV)-positive rate was higher in AGC-FN than in AGC-NOS ( p = .002). The difference in pathological severity was statistically significant between hr-HPV-positive and negative AGC patients ( p = .010). Hr-HPV-positive AGC mainly occurs in cervical diseases, whereas hr-HPV-negative AGC is mainly related to endometrial lesions. Precancerous or malignant lesions were found in 36.43% (141/387) of AGC cases and were more commonly seen in AGC-FN than AGC-NOS ( p < .001). The histopathological severity and the incidence of uterine disease were higher among AGC women aged 40 years and older than those younger than 40 years ( p < .05). The possibility of the abnormal origin of glandular epithelial was higher than that of squamous epithelial in AGC patients aged 40 years and older ( p = .0003). CONCLUSIONS: The management of AGC women by age triage is reasonable because the incidence of the glandular epithelial lesion and uterine disease increases in AGC patients 40 years or older. Standardized clinical diagnosis and regular follow-up are recommended for all AGC patients.

Human papillomavirus integration perspective in small cell cervical carcinoma.

Small cell cervical carcinoma (SCCC) is a rare but aggressive malignancy. Here, we report human papillomavirus features and genomic landscape in SCCC via high-throughput HPV captured sequencing, whole-genome sequencing, whole-transcriptome sequencing, and OncoScan microarrays. HPV18 infections and integrations are commonly detected. Besides MYC family genes (37.9%), we identify SOX (8.4%), NR4A (6.3%), ANKRD (7.4%), and CEA (3.2%) family genes as HPV-integrated hotspots. We construct the genomic local haplotype around HPV-integrated sites, and find tandem duplications and amplified HPV long control regions (LCR). We propose three prominent HPV integration patterns: duplicating oncogenes (MYCN, MYC, and NR4A2), forming fusions (FGFR3-TACC3 and ANKRD12-NDUFV2), and activating genes (MYC) via the cis-regulations of viral LCRs. Moreover, focal CNA amplification peaks harbor canonical cancer genes including the HPV-integrated hotspots within MYC family, SOX2, and others. Our findings may provide potential molecular criteria for the accurate diagnosis and efficacious therapies for this lethal disease.

Transplantation of bFGF-transfected bone mesenchymal stem cells on collagen scaffolds promotes the regeneration of injured rat endometrium.

OBJECTIVE: This study aimed to verify the role of basic fibroblast growth factor (bFGF)-bone mesenchymal stem cells (BMSCs) loaded on collagen scaffolds for the repair of injured endometrium. METHODS: We established an intrauterine adhesion (IUA) model in rats by endometrial resection and implanted BMSCs and bFGF-BMSCs loaded on collagen scaffolds into uteri. A total of 100 IUA model rats were divided into five groups: the control group, scaffold group, BMSC+scaffold group, vector-BMSC group, and bFGF-BMSC+scaffold group. The rats were sacrificed on the 3rd, 7th, 15th, and 45th days. The endometrium thickness, number of glands, and microvascular density were measured by hematoxylin and eosin staining, Masson staining, and immunohistochemistry staining of CD31. The expression of bFGF, vascular endothelial growth factor (VEGF), vimentin, and Ki67 was assayed by immunohistochemistry staining. RESULTS: The bFGF-BMSCs loaded on the collagen scaffold significantly increased the endometrial thickness, gland number, and microvascular density, which greatly promoted the regeneration of the injured endometrium (P<0.0001). In addition, the expression levels of bFGF, VEGF, vimentin, and Ki67 were significantly higher in the bFGF-BMSC+scaffold group than in the BMSC+scaffold group (P<0.05). CONCLUSIONS: Our findings indicated that bFGF-BMSCs loaded on collagen scaffolds have the ability to prompt the regeneration of the endometrium after injury, contributing to a better understanding of stem cell treatment for intrauterine adhesion.

Evaluation of pharmacokinetics and safety of a long-term estradiol-releasing stent in rat uterine.

Purpose: Intrauterine adhesion (IUA), often leading to gynecological complications including amenorrhea, abdominal pain and infertility, is frequently induced by injuries to the endometrium. Hence it would be of great benefit to take efforts to prevent adhesion after intrauterine operations. Orally administration of 17ß-estradiol (E2) is commonly used to promote endometrium regeneration, but is limited by low concentrations at the injured sites. We aim at preparing an E2-releasing uterine stent, which could improve the efficiency of E2 therapy and be utilized for IUA prevention. Methods: We designed a silicone rubber stent, which could be implanted in the uterine cavity and continuously release E2 in long term. Stents were placed in rodent uterine, and removed at different time points. Remaining E2 in stent was measured by high performance liquid chromatography (HPLC), and organ E2 concentrations were detected by enzyme-linked immuno sorbent assay (ELISA). Endometrium morphology was examined by histological staining of paraffin sections. Results: Our stent showed a controlled release of E2 in rodent uterine for over 60 days, and significantly increased E2 concentration in serum and in situ uterine. After the stent was removed from uterine, E2 rapidly reverted to a normal level. Also, the stent did not induce pathological changes in endometrium. Conclusions: The uterine stent provided abundant local E2 in uterine cavity with satisfactory safety. The silicone rubber based E2-releasing uterine stent could be further advanced by adjusting its shape and E2 load for its clinical application, and might promisingly help lowering the incidence of IUA.

A novel cuproptosis-related gene signature for predicting prognosis in cervical cancer.

Purpose: Cuproptosis, a form of copper-induced cell death, can be a promising therapeutic target for refractory cancers. Hence, we conducted this research to explore the association between cuproptosis and prognosis in cervical cancer (CC). Methods: For constructing a prognostic signature based on cuproptosis-related genes from TCGA database, the least absolute shrinkage and selection operator Cox regression was utilized. The GSE44001 cohort was utilized for validation. Results: A total of nine cuproptosis-related genes showed distinct expression in CC and normal samples in TCGA-GTEx cohort. Two risk groups were identified based on a seven-gene signature. A significant decrease in overall survival was observed in the high-risk group (p < 0.001). The risk score (HR = 2.77, 95% CI = 1.58-4.86) was an autocephalous predictor with a better predictive ability than the clinical stage. Functional analysis indicated that immune activities were suppressed more in the high-risk group than in the low-risk group. A total of 11 candidate compounds targeting the signature were identified. Conclusion: A total of seven cuproptosis-related gene signatures were constructed to predict prognosis and propose a new therapeutic target for patients with CC.