Analysis of the diagnostic performance of PAX1/SOX1 gene methylation in cervical precancerous lesions and its role in triage diagnosis.

Methylation panels, tools for investigating epigenetic changes associated with diseases like cancer, can identify DNA methylation patterns indicative of disease, providing diagnostic or prognostic insights. However, the application of methylation panels focusing on the sex-determining region Y-box 1 (SOX1) and paired box gene 1 (PAX1) genes for diagnosing cervical lesions is under-researched. This study aims to examine the diagnostic performance of PAX1/SOX1 gene methylation as a marker for cervical precancerous lesions and its potential application in triage diagnosis. From September 2022 to April 2023, 181 patients with abnormal HPV-DNA tests or cytological exam results requiring colposcopy were studied at Hubei Maternal and Child Health Hospital, China. Data were collected from colposcopy, cytology, HPV-DNA tests, and PAX1/SOX1 methylation detection. Patients were categorized as control, cervical intraepithelial neoplasia Grade 1 (CIN1), Grade 2 (CIN2), Grade 3 (CIN3), and cervical cancer (CC) groups based on histopathology. We performed HPV testing, liquid-based cytology, and PAX1/SOX1 gene methylation testing. We evaluated the diagnostic value of methylation detection in cervical cancer using DNA methylation positivity rate, sensitivity, specificity, and area under the curve (AUC), and explored its potential for triage diagnosis. PAX1/SOX1 methylation positivity rates were: control 17.1%, CIN1 22.5%, CIN2 100.0%, CIN3 90.0%, and CC 100.0%. The AUC values for PAX1 gene methylation detection in diagnosing CIN1+, CIN2+, and CIN3+ were 0.52 (95% confidence interval [CI]: 0.43-0.62), 0.88 (95% CI: 0.80-0.97), and 0.88 (95% CI: 0.75-1.00), respectively. Corresponding AUC values for SOX1 gene methylation detection were 0.47 (95% CI: 0.40-0.58), 0.80 (95% CI: 0.68-0.93), and 0.92 (95% CI: 0.811-1.00), respectively. In HPV16/18-negative patients, methylation detection showed sensitivity of 32.4% and specificity of 83.7% for CIN1+. For CIN2+ and CIN3+, sensitivity was all 100%, with specificities of 83.0% and 81.1%. Among the patients who underwent colposcopy examination, 166 cases had cytological examination results ≤ASCUS, of which 37 cases were positive for methylation, and the colposcopy referral rate was 22.29%. PAX1/SOX1 gene methylation detection exhibits strong diagnostic efficacy for cervical precancerous lesions and holds significant value in triage diagnosis.

HPV positivity status in males is related to the acquisition of HPV infection in females in heterosexual couples.

PURPOSE: Few studies have focused on the impact of human papillomavirus (HPV) positivity in male partners on female HPV infection and cervical lesions. The purpose of this study was to evaluate the impact of the HPV infection status of husbands on wives' cervical HPV infection and lesions. METHODS: We surveyed 251 monogamous couples who attended the outpatient department of Fujian Maternity and Child Health Hospital from 2013 to 2021. HPV type analysis was performed on exfoliated cells of the females' cervix and males' urethra by the PCR-reverse dot blot method. We analyzed the prevalence and consistency of HPV types in 251 couples. Subsequently, the risk of HPV infection in females with HPV-positive male partners was analyzed. SPSS version 26 (IBM, Chicago, USA) was used for statistical analysis. RESULTS: In 251 couples, the most commonly detected high-risk HPV (HR-HPV) genotypes were 52, 51, 16, and 58 for males and 16, 52, 18, and 58 for females. Wives with HPV-positive husbands had higher infection rates for most HR-HPV genotypes. HR-HPV positivity in husbands was a risk factor for the development of cervical lesions in wives (OR = 2.250, P = 0.014). Both single-type (OR = 2.085, P = 0.040) and multiple-type (OR = 2.751, P = 0.036) infection in husbands will contributed to an increased risk of non-HR-HPV infection and cervical lesions in wives. CONCLUSION: Husbands' HPV positivity increases the burden of non-HR-HPV infection and increases the risk of cervical lesions developing in wives. It is hoped to provide a reference value for cervical cancer prevention in females and HPV vaccination in males.

Peripheral blood lymphocytes influence human papillomavirus infection and clearance: a retrospective cohort study.

BACKGROUND: There is a close correlation between HPV infection and systemic immune status. The purpose of this study was to determine which lymphocytes in peripheral blood influence human papillomavirus (HPV) infection and to identify whether peripheral blood lymphocyte (PBL) subsets could be used as biomarkers to predict HPV clearance in the short term. METHODS: This study involved 716 women undergoing colposcopy from 2019 to 2021. Logistic and Cox regression were used to analyze the association of PBLs with HPV infection and clearance. Using Cox regression, bidirectional stepwise regression and the Akaike information criterion (AIC), lymphocyte prediction models were developed, with the C-index assessing performance. ROC analysis determined optimal cutoff values, and their accuracy for HPV clearance risk stratification was evaluated via Kaplan‒Meier and time-dependent ROC. Bootstrap resampling validated the model and cutoff values. RESULTS: Lower CD4 + T cells were associated with a higher risk of HPV, high-risk HPV, HPV18 and HPV52 infections, with corresponding ORs (95% CI) of 1.58 (1.16-2.15), 1.71 (1.23-2.36), 2.37 (1.12-5.02), and 3.67 (1.78-7.54), respectively. PBL subsets mainly affect the natural clearance of HPV, but their impact on postoperative HPV outcomes is not significant (P > 0.05). Lower T-cell and CD8 + T-cell counts, as well as a higher NK cell count, are unfavorable factors for natural HPV clearance (P < 0.05). The optimal cutoff values determined by the PBL prognostic model (T-cell percentage: 67.39%, NK cell percentage: 22.65%, CD8 + T-cell model risk score: 0.95) can effectively divide the population into high-risk and low-risk groups, accurately predicting the natural clearance of HPV. After internal validation with bootstrap resampling, the above conclusions still hold. CONCLUSIONS: CD4 + T cells were important determinants of HPV infection. T cells, NK cells, and CD8 + T cells can serve as potential biomarkers for predicting natural HPV clearance, which can aid in patient risk stratification, individualized treatment, and follow-up management.

Colorimetric and visual determination of uric acid based on decolorization of manganese dioxide nanosheet dispersions.

Serum levels of uric acid (UA) play an important role in the prevention of diseases. Developing a rapid and accurate way to detect UA is still a meaningful task. Hence, positively charged manganese dioxide nanosheets (MnO2NSs) with an average latter size of 100 nm and an ultra-thin thickness of below 1 nm have been prepared. They can be well dispersed in water and form stable yellow-brown solutions. The MnO2NSs can be decomposed by UA via redox reaction, leading to a decline of a characteristic absorption peak (374 nm) and a color fading of MnO2NSs solution. On this basis, an enzyme-free colorimetric sensing system for the detection of UA has been developed. The sensing system shows many advantages, including a wide linear range of 0.10-50.0 µmol/L, a limit of quantitation (LOQ) of 0.10 µmol/L, a low limit of detection (LOD) of 0.047 µmol/L (3σ/m), and rapid response without need of strict time control. Moreover, a simple and convenient visual sensor for UA detection has also been developed by adding an appropriate amount of phthalocyanine to provide a blue background color, which helps to increase visual discrimination. Finally, the strategy has been successfully applied to detect UA in human serum and urine samples.

Prevotella as the hub of the cervicovaginal microbiota affects the occurrence of persistent human papillomavirus infection and cervical lesions in women of childbearing age via host NF-κB/C-myc.

There is evidence that coinfection of cervicovaginal high-risk human papillomavirus (HR-HPV) and bacteria is common in women of childbearing age. However, the relationship between bacterial vaginosis (BV) and persistent HR-HPV infection in women of childbearing age and the underlying mechanisms remain unclear. In this study, we determined whether BV affects persistent HR-HPV infection in women aged 20-45 years and explored the possible mechanisms of their interactions. From January 1 to April 30, 2020, we recruited women aged 20-45 years with and without BV at a ratio of 1:2 from Fujian Maternity and Child Health Hospital. All women were followed up at 0, 12, and 24 months. A BV assay, HR-HPV genotyping and cervical cytology were performed at each follow-up. At 0 months, additional vaginal secretions and cervical exfoliated cells were collected for 16S ribosomal RNA sequencing, bacterial metabolite determination, and POU5F1B, C-myc, TLR4, NF-κB, and hTERT quantification. A total of 920 women were included. The abundance of Prevotella (p = 0.016) and Gardnerella (p = 0.027) were higher, whereas the abundance of Lactobacillus was lower (p = 0.001) in women with persistent HR-HPV infection and high-grade squamous intraepithelial lesions (HSIL). The abundance of Prevotella (p = 0.025) and Gardnerella (p = 0.018) increased in the vaginas of women with persistent HPV16 infection, whereas only the abundance of Prevotella (p = 0.026) was increased in women with persistent HPV18 infection. The abundance of Prevotella in the vagina was significantly positively correlated with the expression levels of TLR4, NF-κB, C-myc, and hTERT in host cervical cells (p < 0.05). Our findings suggest that overgrowth of Prevotella in the vagina may influence the occurrence of persistent HR-HPV infection-related cervical lesions through host NF-κB and C-myc signaling.

The prevalence of human papillomavirus and bacterial vaginosis among young women in China: a cross-sectional study.

BACKGROUND: The natural history of human papillomavirus (HPV) is influenced by vaginal microenvironment disorders, such as bacterial vaginosis (BV). The objective of this study was to assess the epidemiology of HPV combined with BV prevalence among Chinese women aged 20-35 years. METHODS: A total of 2000 sexually active women aged 20-35 years voluntarily enrolled in this study and underwent a ThinPrep cytologic test and PCR-reverse dot blot human papillomavirus genotyping (PCR-RDB HPV test). BV was diagnosed if clue cells were observed (20% more than epithelial cells). RESULTS: The overall HPV infection rate in this population was 16.2% (324/2000). Compared with HPV-negative individuals, BV prevalence was higher in the High-risk human papillomavirus (HR-HPV) (5.9% vs. 3.1%, P < 0.001). BV and HPV-51, -52 infection were more commonly associated with each other. In patients with cervical lesions (≥ CIN 1), the BV prevalence rate was higher than in patients with negative for intraepithelial lesion or malignancy (NILM) (11.9% vs. 3.8%, P = 0.002). CONCLUSION: BV was found to be related to HPV-51, -52 infections and cervical lesions. To better manage HPV infected population, more attention should be paid to the prevention and proper treatment of BV.

Cost-effectiveness and accuracy of cervical cancer screening with a high-risk HPV genotyping assay vs a nongenotyping assay in China: an observational cohort study.

BACKGROUND: New screening techniques may affect the optimal approaches for the prevention of cervical cancer. We evaluated the cost-effectiveness and accuracy of alternative screening strategies to provide evidence for cervical cancer screening guidelines in China. METHODS: In total, 32,306 women were enrolled. The current screening with Cervista® high-risk human papillomavirus (HR-HPV) nongenotyping and cytology cotesting (Cervista® cotesting) was compared with PCR-reverse dot blot HR-HPV genotyping and cytology cotesting (PCR-RDB cotesting). All eligible participants were divided into Arm 1, in which both HR-HPV assays were performed, and Arms 2 and 3, in which the PCR-RDB HPV or Cervista® HR-HPV assay, respectively, was performed. Outcome indicators included the cases, sensitivity, negative predictive value (NPV), colposcopy referral rate and cost of identifying cervical intraepithelial neoplasia of grade 2/3 or worse (CIN2+/CIN3+). RESULTS: Among the eligible participants, 18.4% were PCR-RDB HR-HPV-positive, while 16.9% were Cervista® HR-HPV-positive, which reflects good agreement (k = 0.73). PCR-RDB cotesting identified more CIN3+ cases than Cervista® cotesting in the first round of screening in Arm 1 (37 vs 32) and Arms 2/3 (252 vs 165). The sensitivity and NPV of PCR-RDB cotesting for identifying CIN3+ in Arm 1 (sensitivity: 94.9% vs 86.5%; NPV: 99.9% vs 99.7%) and Arms 2/3 (sensitivity: 95.1% vs 80.9%; NPV: 99.9% vs 99.6%) were higher than those of Cervista® cotesting, but the cost was similar. CONCLUSIONS: The PCR-RDB HR-HPV genotyping and Cervista® HR-HPV assay results were consistent. PCR-RDB cotesting possesses optimal cost-effectiveness for cervical cancer screening in China, which has the highest number of cases globally but low screening coverage.

A novel non-invasive molecular biomarker in ovarian endometriosis: estrogen-related receptor α.

PURPOSE: This study aimed to explore whether estrogen-related receptors α (ERRα) can prognosticate the occurrence and development of ovarian endometriosis (EMs) as a non-invasive biomarker. METHODS: The ectopic and its' correspond eutopic endometria from 47 patients with ovarian EMs and the control normal endometria from 32 cases were collected and detected the mRNA expression of ERRα by RT-qPCR. The serum protein of ERRα were tested by ELISA. The menstrual cycle, ovarian cyst sizes, relative clinical tumour markers, such as CA125, CA19-9 and HE-4, and other demographic data were also involved into analysis in these patients by SPSS 22.0 (IBM, Chicago, IL, USA). RESULTS: The ERRα mRNA expression in ectopic endometria were significantly lower than it in eutopic endometria (P < 0.05) and the normal endometria (P < 0.05). Similarly, the serum ERRα levels in patients with EMs were significantly lower than it in control group (P < 0.01). Moreover, the serum ERRα levels were decreasing with the increasing of the pathological stages and ovarian cyst sizes. While, the serum CA125, CA19-9, CA125/ERRα ratio and CA19-9/ERRα ratio in the study group were significantly higher than those in the control group (all P < 0.01). CONCLUSION: The expression of ERRα is correlated with the development of ovarian EMs pathological stages and ovarian cyst sizes and can be used as a novel and non-invasive biomarker for evaluating the progression of ovarian EMs.

Coinfection of High-Risk Human Papillomavirus and Lower Genital Tract Pathogens in the Development of High-Grade Cervical Lesions.

PURPOSE: This study investigated the infection status and relationship between other common lower genital tract infectious pathogens and high-risk human papillomavirus (HR-HPV) in the high-grade cervical lesions. METHODS: Overall, 882 patients were enrolled in this retrospective study, of which 339 patients (≥HSIL group) were confirmed with high-grade squamous intraepithelial lesions (HSIL) or cervical squamous cell carcinoma (SCC), while 543 patients (≤LSIL group) were diagnosed with low-grade squamous intraepithelial lesions (LSIL) or normal cervical pathology diagnosis. Cervical swab specimens were tested for HPV, pathogenic bacteria (PB), U. urealyticum (UU), M. hominis (MH), and C. trachomatis (CT) in both groups. RESULTS: The infection rates of HR-HPV, PB, UU (at high density), and CT were higher in the ≥HSIL group than in the ≤LSIL group (P < 0.001); however, higher infection rates with MH were not observed (P > 0.05). PB, UU, and CT were associated with HR-HPV infection (P < 0.001). The PB and UU infection rates in the ≥HSIL group were significantly different from those in the ≤LSIL group, regardless of whether there was an HR-HPV infection at the same time (P < 0.05). However, this was not the case for the CT (P > 0.05). Furthermore, 259 pathogenic bacterial strains were detected in 882 cases. The difference in the distribution of pathogenic bacterial flora in the different grades of cervical lesions had no statistical significance, which was prioritized over Escherichia coli (P > 0.05). CONCLUSION: PB, UU, and CT infection is associated with susceptibility to HR-HPV, HR-HPV coinfection with these pathogens might increase the risk of high-grade cervical lesions, and PB and UU might be independent risk factors for cervical lesions.

Knowledge and Attitudes Regarding HPV and Vaccination Among Chinese Women Aged 20 to 35 Years in Fujian Province: A Cross-Sectional Study.

The use of the human papillomavirus (HPV) vaccine was recently approved in Mainland China. This study determined the knowledge and attitudes of young women aged 20 to 35 years in Fujian Province, China, with regard to HPV and vaccination and explored the potential factors influencing their attitudes toward HPV vaccination. This was a cross-sectional study that collected data regarding the knowledge on and attitudes toward HPV and vaccination using questionnaires. Furthermore, the prevalence of HPV was determined from the sampled participants. A total of 1001 young women were included in the survey. This study demonstrated that the HPV prevalence rate was 15.7% (157/1001). Among all patients, 44.9% (n = 449) had heard of HPV; however, detailed knowledge about HPV was lacking. The majority (83.7%) expressed a willingness to be vaccinated. Specifically, knowledge of the dangers of HPV infection was significantly associated with the willingness to be vaccinated. In this study, women cited some concerns and expressed high expectations for the HPV vaccine, but the costs of vaccination reduced their willingness to be vaccinated. This study found that most patients did not have a detailed knowledge of HPV. Thus, there is a need for continued HPV promotion and education efforts, especially on the dangers of HPV infection, among young women aged 20 to 35 years in Fujian Province, China. Furthermore, it is important to subsidize the costs of vaccination for promoting vaccination campaigns in China.

Safety Assessment of Concurrent Vaccination with the HPV Vaccine and the COVID-19 Vaccine in Fujian Province, China: A Retrospective Study.

During acute respiratory infections, women may concurrently receive human papillomavirus (HPV) and respiratory vaccines, as observed during the coronavirus disease 2019 (COVID-19) pandemic in China. However, few studies have assessed the safety of such concurrent administration, which could impact HPV vaccination schedules. This study analyzes the safety and optimal sequence of concurrent HPV and COVID-19 vaccinations. For this purpose, we surveyed women with both vaccines from January to October 2023 in Fujian Province, China. During this process, we collected vaccination history and adverse event (AE) data via telephone or interviews. Participants were grouped as Before, Concurrent, or After based on their vaccination sequence. A Chi-squared test, exact Fisher tests, and logistic regression were used to analyze the incidence of AEs and factors influencing vaccine safety. Overall, 1416 eligible participants were included. Although overall AE risk with the HPV vaccine was unaffected by vaccination sequence, individual AEs varied statistically between groups, including pain at the vaccination site (p < 0.001) and prolonged menstruation duration (p = 0.003). Based on the results, the optimal sequence would be to receive the HPV vaccine after the COVID-19 vaccine (After group). This insight may guide future emergency vaccination sequences for HPV and other respiratory infectious diseases.

ADCY7 mRNA Is a Novel Biomarker in HPV Infection and Cervical High-Grade Squamous Lesions or Higher.

The effect of cervical cancer immunotherapy is limited. Combination therapy will be a new direction for cervical cancer. Thus, it is essential to discover a novel and available predictive biomarker to stratify patients who may benefit from immunotherapy for cervical cancer. In this study, 563 participants were enrolled. Adenylate cyclase 7 (ADCY7) mRNA was detected by real-time quantitative PCR (qPCR) with cervical cytology specimens. The relationship between ADCY7 and cervical intraepithelial neoplasia in grade 2 and higher (CIN2+) was analyzed, and the optimal cut-off values of the relative expression of ADCY7 mRNA to predict CIN2+ were calculated. In addition, the clinical significance of ADCY7 in cervical cancer was determined by the Kaplan-Meier Cox regression based on the TCGA database. The mean ADCY7 mRNA expression increased significantly with cervical lesion development, especially compared with CIN2+ (p < 0.05). Moreover, the expression of ADCY7 increased significantly in high-risk human papillomavirus (HR-HPV) infection but not in HPV-A5/6 species. The area under the receiver operating characteristic curve (AUC) of ADCY7 was 0.897, and an optimal cut-off was 0.435. Furthermore, ADCY7 had the highest OR (OR= 8.589; 95% CI (2.281-22.339)) for detecting CIN 2+, followed by HPV genotyping, TCT, and age (OR = 4.487, OR = 2.071, and OR = 1.345; 95% CI (1.156-10.518), (0.370-8.137), and (0.171-4.694), respectively). Moreover, this study indicated that higher ADCY7 levels could be a suitable predictor for poor prognosis in cervical cancer due to immune cell infiltration. A new auxiliary predictor of CIN2+ in cervical cytology specimens is ADCY7 ≥ 0.435. Furthermore, it may be a promising prognosis predictor and potential immunotherapy target for the combined treatment of cervical cancer and possibly further block HR-HPV persistent infection.

Platelet-to-Lymphocyte Ratio (PLR) as the Prognostic Factor for Recurrence/Residual Disease in HSIL Patients After LEEP.

Purpose: The platelet-to-lymphocyte ratio (PLR) is considered correlated with cancer prognosis including cervical cancer, in addition to high-risk papillomavirus (HR-HPV) infection, of which the predictive value in prognosis of high-grade squamous intraepithelial lesions (HSILs) remains unknown. Here, the prognostic predictive value of PLR in HSIL after loop electrosurgical excision procedure (LEEP) was evaluated. Patients and Methods: This study included 335 nonpregnant participants with histopathologically confirmed HSIL and 3- and 5-year follow-ups from the Fujian Cervical Lesions Screening Cohorts (FCLSCs) between September 2016 and September 2018. PLR and other variables were evaluated to identify the factors related to the recurrence/residual cervical intraepithelial neoplasia (CIN)-free survival (RFS), namely, the time from LEEP at baseline to first detection of recurrence/residual CIN or end of follow-up, by logistic and Cox regression. Results: In the Kaplan‒Meier analysis, HR-HPV infection (p=0.049/0.012), higher PLR (p=0.031/0.038), and gland invasion (p=0.047) had a higher risk for recurrence/residual CIN at the 3-/5-year follow-up. The univariate logistic and Cox regression analyses showed significant differences and a higher cumulative risk in patients with HR-HPV infection (OR=3.917, p=0.026; HR=3.996, p=0.020) and higher PLR (OR=2.295, p=0.041; HR=2.161, p=0.030) at the 5-year follow-up. The findings by multivariate Cox regression analysis were similar, indicating a poor prognosis for patients with HR-HPV infection (HR=3.901, p=0.023) and higher PLR (HR=2.082, p=0.038) at the 5-year follow-up. The calibration plot showed a better model fit for RFS at the 3-year follow-up. Conclusion: Preoperative PLR level and HR-HPV infection could be available markers for predicting recurrence/residual disease of HSIL after LEEP. Clinically, combining PLR with HR-HPV tests may provide novel evaluation method and reference for management in post-treatment patients with cervical precancerous lesions.

Cervical Lesion Classification Method Based on Cross-Validation Decision Fusion Method of Vision Transformer and DenseNet.

Objective: In order to better adapt to clinical applications, this paper proposes a cross-validation decision-making fusion method of Vision Transformer and DenseNet161. Methods: The dataset is the most critical acetic acid image for clinical diagnosis, and the SR areas are processed by a specific method. Then, the Vision Transformer and DenseNet161 models are trained by the fivefold cross-validation method, and the fivefold prediction results corresponding to the two models are fused by different weights. Finally, the five fused results are averaged to obtain the category with the highest probability. Results: The results show that the fusion method in this paper reaches an accuracy rate of 68% for the four classifications of cervical lesions. Conclusions: It is more suitable for clinical environments, effectively reducing the missed detection rate and ensuring the life and health of patients.

Low Level FLT3LG is a Novel Poor Prognostic Biomarker for Cervical Cancer with Immune Infiltration.

Introduction: The FMS-related tyrosine kinase 3 (FLT3) ligand (FLT3LG), a growth factor, binds to FLT3 on dendritic cell (DCs) to enhance their differentiation and expansion. It has shown great potential as an immunotherapy target for cancers. However, the expression and function of FLT3LG in cervical cancer remain largely unknown. Materials and Methods: In this study, we obtained the expression of FLT3LG, the clinical prognosis in cervical cancer, via multiple databases, including The Cancer Genome Atlas (TCGA), the TISIDB database, and Tumor Immune Estimate Resource (TIMER). The results were further investigated using real-time quantitative PCR (qPCR) cytology specimens in 489 patients. Furthermore, Kaplan-Meier Cox regression and prognostic nomogram analyses were used to assess FLT3LG's clinical significance in cervical cancer patients. All calculations used the R package. Results: As a result, FLT3LG expression decreased in cervical cancer compared with standard samples. And the low expression of FLT3LG was associated with a poor prognosis. Furthermore, Receiver Operating Characteristics (ROC) analysis indicated that FLT3LG might serve as a valuable diagnostic biomarker for cervical cancer. Additionally, it indicated that the FLT3LG had the highest odds ratio (OR=10.519; (7.371-27.071)) for detecting CIN 2+. In addition, our result also demonstrated that expression of FLT3LG was closely related to immune cells, immune inhibitors, immunostimulators, receptors, and chemokines in CESC. Conclusion: Research on FLT3LG provided insight into its critical function. Hence, the low expression of FLT3LG may be a valuable biomarker in CESC patients linked with immune infiltration.

Lipid reprogramming induced by the TFEB-ERRα axis enhanced membrane fluidity to promote EC progression.

BACKGROUND: Estrogen-related receptor α (ERRα) has been reported to play a critical role in endometrial cancer (EC) progression. However, the underlying mechanism of ERRα-mediated lipid reprogramming in EC remains elusive. The transcription factor EB (TFEB)-ERRα axis induces lipid reprogramming to promote progression of EC was explored in this study. METHODS: TFEB and ERRα were analyzed and validated by RNA-sequencing data from the Cancer Genome Atlas (TCGA). The TFEB-ERRα axis was assessed by dual-luciferase reporter and chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR). The mechanism was investigated using loss-of-function and gain-of-function assays in vitro. Lipidomics and proteomics were performed to identify the TFEB-ERRα-related lipid metabolism pathway. Pseudopods were observed by scanning electron microscope. Furthermore, immunohistochemistry and lipidomics were performed in clinical tissue samples to validate the ERRα-related lipids. RESULTS: TFEB and ERRα were highly expressed in EC patients and correlated to EC progression. ERRα is the direct target of TFEB to mediate EC lipid metabolism. TFEB-ERRα axis mainly affected glycerophospholipids (GPs) and significantly elevated the ratio of phosphatidylcholine (PC)/sphingomyelin (SM), which indicated the enhanced membrane fluidity. TFEB-ERRα axis induced the mitochondria specific phosphatidylglycerol (PG) (18:1/22:6) + H increasing. The lipid reprogramming was mainly related to mitochondrial function though combining lipidomics and proteomics. The maximum oxygen consumption rate (OCR), ATP and lipid-related genes acc, fasn, and acadm were found to be positively correlated with TFEB/ERRα. TFEB-ERRα axis enhanced generation of pseudopodia to increase the invasiveness. Mechanistically, our functional assays indicated that TFEB promoted EC cell migration in an ERRα-dependent manner via EMT signaling. Consistent with the in vitro, higher PC (18:1/18:2) + HCOO was found in EC patients, and those with higher TFEB/ERRα had deeper myometrial invasion and lower serum HDL levels. Importantly, PC (18:1/18:2) + HCOO was an independent risk factor positively related to ERRα for lymph node metastasis. CONCLUSION: Lipid reprogramming induced by the TFEB-ERRα axis increases unsaturated fatty acid (UFA)-containing PCs, PG, PC/SM and pseudopodia, which enhance membrane fluidity via EMT signaling to promote EC progression. PG (18:1/22:6) + H induced by TFEB-ERRα axis was involved in tumorigenesis and PC (18:1/18:2) + HCOO was the ERRα-dependent lipid to mediate EC metastasis.

Changes of the vaginal microbiota in HPV infection and cervical intraepithelial neoplasia: a cross-sectional analysis.

This study aimed to explore the changes of the vaginal microbiota and enzymes in the women with high-risk human papillomavirus (HR-HPV) infection and cervical lesions. A total of 448 participants were carried out HPV genotyping, cytology tests, and microecology tests, and 28 participants were treated as sub-samples, in which vaginal samples were characterized by sequencing the bacterial 16S V4 ribosomal RNA (rRNA) gene region. The study found the prevalence of HR-HPV was higher in patients with BV (P = 0.036). The HR-HPV infection rate was 72.73% in G. vaginalis women, which was significantly higher than that of women with lactobacillus as the dominant microbiota (44.72%) (P = 0.04). The positive rate of sialidase (SNA) was higher in women with HR-HPV infection (P = 0.004) and women diagnosed with cervical intraepithelial neoplasia (CIN) (P = 0.041). In HPV (+) women, the α-diversity was significantly higher than that in HPV (-) women. The 16S rRNA gene-based amplicon sequencing results showed that Lactobacillus was the dominant bacteria in the normal vaginal microbiota. However, the proportion of Gardnerella and Prevotella were markedly increased in HPV (+) patients. Gardnerella and Prevotella are the most high-risk combination for the development of HPV (+) women. The SNA secreted by Gardnerella and Prevotella may play a significant role in HPV infection progress to cervical lesions.

The Impact of Malignancy on Assisted Reproductive Outcomes for Cancer Survivors: A Retrospective Case-Control Study.

Background: Related studies have shown that it is safe for cancer patients to undergo assisted reproduction. However, studies on whether a history of cancer affects long-term reproductive outcomes in women who undergo assisted reproductive technology (ART) are scarce. In this study, we evaluated the long-term reproductive outcomes of patients with malignant tumors undergoing ART treatment and explored the impact of malignancy history on ART outcomes. Methods: This retrospective study analyzed the clinical outcomes of patients with malignant tumors undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles compared with those of age-matched healthy infertile women at Fujian Maternity and Child Health Hospital between January 2003 and October 2020. We evaluated ovarian stimulation outcome, the pregnancy rate, the live birth rate, the risk of adverse obstetric outcomes and birth outcomes. Results: This study included 59 patients in the cancer group for data analysis who had a history of malignancy. By matching, a total of 118 healthy infertile women were included in the control group. No statistically significant association was found in terms of age, duration of infertility, BMI, or insemination type between the two groups of patients. Thyroid cancer(45.8%) and gynecologic malignancies (44.07%) were the major cancer types in this study. There were statistically significant differences in the antral follicle count (AFC) (12.00 ± 7.86 vs. 14.90 ± 8.71, P=0.033), length of ovarian stimulation (9.98 ± 2.68 vs. 11.42 ± 2.43, P=0.033) and endometrial thickness on the trigger day (10.16 ± 3.11 vs. 10.84 ± 2.17, P<0.001) between the two groups. The total gonadotropin dose, number of oocytes retrieved, fertilization rate, cleavage rate, high-quality embryo rate, blastocyst rate and first-time embryo-transfer (ET) implantation rate were nonsignificantly lower in the cancer group than in the control group (P>0.05). There were no significant differences in the clinical pregnancy rate per ET cycle (32% vs. 40.39%, P=0.156), live birth rate per ET cycle (27% vs. 35.96%, P=0.119), miscarriage rate per ET cycle (5% vs. 4.43%, P=0.779), or preterm delivery rate per ET cycle (11.11% vs. 17.80%, P=0.547) between the two groups. Additionally, regression analysis showed that a history of malignancy was not a risk factor for reproductive outcomes. Conclusions: Overall, it is feasible for women with a history of cancer to conceive using ART is feasible and their long-term reproductive outcomes are similar to these of healthy infertile women. A history of cancer does not decrease the number of retrieved oocytes, increase the risk of adverse obstetric outcomes or affect birth outcomes.

Prevalence of Human Papillomavirus and Genotype Distribution in Pregnant and Non-Pregnant Women in China.

PURPOSE: The status of human papillomavirus (HPV) infection in pregnant and non-pregnant women in China remains unclear. This study aimed to compare the prevalence and genotype distributions of HPV between pregnant and non-pregnant women in China. PATIENTS AND METHODS: A case-control study was conducted of pregnant women during the second trimester and age-matched non-pregnant women attending the Fujian Maternity and Child Health Hospital between January 1, 2017 and December 31, 2018. Participants underwent cervical cytology testing and HPV genotyping. The genotyping test was able to identify 14 high-risk HPV (HR-HPV), four possible HR-HPV, and five low-risk HPV (LR-HPV) types. Further colposcopy and a cervical biopsy were performed if indicated. The primary outcomes were HPV prevalence and genotype distribution. RESULTS: In total, 1077 pregnant and 1077 non-pregnant women were enrolled. Compared with non-pregnant women, pregnant women had a higher prevalence of HPV (24.2% vs 14.8%), HR-HPV (20.2% vs 11.7%), and LR-HPV (8% vs 4.5%) infection. In pregnant women, the most prevalent HPV genotypes were HPV-52 (6.0%), -16 (3.5%), -58 (2.6%), -53 (2.5%), and -51 (2.5%), while in non-pregnant women the most prevalent genotypes were HPV-52 (3.6%), -81 (1.9%), -51 (1.8%), -68 (1.4%), and -16 (1.3%). In women aged ≥35 years, HR-HPV (P=0.002) and LR-HPV (P=0.001) prevalence were significantly higher in pregnant women. However, in women aged <35 years, only HR-HPV prevalence was higher in pregnant women. Pregnant and non-pregnant women with HPV-16 and HPV-58 infection had a high prevalence of high-grade squamous intra-epithelial lesions (HSIL) (HPV-16: P<0.001 and P=0.005, HPV-58: P=0.043 and P=0.005); but with other HR-HPV genotypes, only non-pregnant women had an increased HSIL prevalence. CONCLUSION: In China, the HPV prevalence is higher in pregnant women than that in non-pregnant women and is also age- and genotype-dependent. HPV-infected pregnant women aged ≥35 years and those with HPV-16 should be closely monitored to enable rapid clinical intervention.

Free Fatty Acid is a Promising Biomarker in Triage Screening for Patients with Colorectal Cancer: A Case-Control Study.

PURPOSE: The aim of our study was to identify the diagnostic ability of free fatty acids (FFAs) in younger colorectal cancer (CRC) patients by comparing carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9). METHODS: Patients screened for CRC at Fujian Medical University Union Hospital from January 2011 to December 2014 were recruited. Patients pathologically diagnosed with CRC or colorectal adenoma (CA) and healthy control participants were included. The enzyme endpoint method was applied to measure FFA levels. Receiver operating characteristic (ROC) curve analysis was performed to further evaluate the diagnostic ability of FFAs. RESULTS: FFA levels in late-stage patients (tumour-node-metastasis (TNM) stages III-IV) were higher than those in early-stage patients (TNM stages I-II) (P=0.02). The FFA levels in CRC patients were higher than those in controls of all ages, those younger than 50 years, males and females (P<0.001), and this difference was larger for patients younger than 50 years and females than for the all ages group. There was no significant difference in the FFA level between CA patients and healthy participants (P=0.53). The area under the curve (AUC) values of FFA, CEA, CA19-9, FFA+CEA, FFA+CA19-9 and FFA+CEA+CA19-9 distinguished CRC patients from controls at all ages, with values of 0.604, 0.731, 0.640, 0.754, 0.678 and 0.758, respectively; however, in the younger CRC patients (age≤50), the AUC values were 0.701, 0.735, 0.669, 0.798, 0.749, and 0.801. The AUC in female patients younger than 50 years was larger than that in males (0.769 vs 0.660), and this value was greater than the value for CEA in males (0.739) and females (0.729). CONCLUSION: The FFA level not only can complement the predictive ability of the CEA and CA19-9 levels but also has a superior predictive ability in female and younger patients with CRC. FFA levels may have a potential role in triage screening of early CRC.