Impact of high-performance human papillomavirus testing to improve cervical cancer screening in China: a prospective population-based multicentre cohort study.

OBJECTIVES: The aim of the study was to evaluate the clinical performance of HBRT-H14, a real-time PCR-based assay that separates human papillomavirus (HPV) 16 and HPV18 from 12 other high-risk (HR) HPV types, in population according to Chinese guideline. METHODS: A total of 9829 eligible women aged 21-64 years from Henan, Shanxi, and Guangdong provinces were performed by HBRT-H14 testing and liquid-based cytology (LBC) screening at baseline and followed up for 3-year. The sensitivity, specificity, positive predictive value (absolute risk), and negative predictive value of LBC diagnosis and HPV testing were calculated for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) Lesions. RESULTS: At baseline, 80 (0.81%) participants were diagnosed with CIN2+. HR-HPV with reflex LBC had a significantly higher sensitivity (78/80, 97.50% [95% CI, 91.34-99.31%] vs. 62/80, 77.50% [67.21-85.27%], McNemar's test p < 0.001), and a slightly lower specificity (8528/9749, 87.48% [86.80-88.12%] vs. 8900/9749, 91.29% [90.72-91.83%], McNemar's test p < 0.001) than LBC with reflex HR-HPV for CIN2+. 7832 (79.6%) participants completed 3-year follow-up and 172 (2.20%) participants were cumulatively diagnosed with CIN2+. Compared with LBC with reflex HR-HPV, HR-HPV with reflex LBC significantly increased the sensitivity (161/172, 93.60% [88.91-96.39%] vs. 87/172, 50.58% [43.18-57.96%], McNemar's test p < 0.001), but marginally decreased the specificity (6776/7660, 88.46% [87.72-89.16%] vs. 6933/7660, 90.51% [89.83-91.15], McNemar's test p < 0.001). In addition, the absolute 3-year risk of CIN2+ in HPV16/18-positive individuals was as high as 33% (80/238), whereas the risk in the HPV-negative population was only 0.16% (11/6787), much lower than those in the negative for intraepithelial lesion or malignancy population (1.21%, 85/7018). Moreover, similar results were found in women ≥30 years old. DISCUSSION: The study has indicated that HBRT-14 has a reliable clinical performance for use in cervical screening. The validated HPV test would improve the quality of population screening.

Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus.

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert-amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity.

RNA modifications in gynecological cancer: current status and future directions.

Currently, more than 170 modifications have been identified on RNA. RNA modification mainly regulates RNA splicing, intracellular transport, degradation, translation, and stability. Gynecologic cancer (GC) mainly includes cervical cancer (CCA), ovarian cancer (OC), Endometrial cancer (EMC), among others, is the leading cause of cancer-related death. At present, there is still a lack of effective means to eradicate such diseases, so it is important to conduct more in-depth research on gynecological cancers. Numerous studies have shown that a series of epigenetic changes occur during the development of gynecologic cancer. This article reviews the latest findings on the functional significance of RNA modification in gynecologic cancer and discusses the therapeutic potential of RNA modification-related inhibitors in the treatment of gynecologic cancer.

Development of a green, concise synthesis of nicotinamide derivatives catalysed by Novozym® 435 from Candida antarctica in sustainable continuous-flow microreactors.

An increasing number of studies have shown that many nicotinamide derivatives exhibited extensive biological activities, such as anti-inflammatory and antitumor activity. In this paper, a green, concise synthesis of nicotinamide derivatives in sustainable continuous-flow microreactors catalysed by Novozym® 435 from Candida antarctica has been developed. Application of an easily obtainable and reusable lipase in the synthesis of nicotinamide derivatives from methyl nicotinate and amines/benzylamines reacted for 35 min at 50 °C led to high product yields (81.6-88.5%). Environmentally friendly tert-amyl alcohol was applied as a reaction medium. Substantially shorter reaction times as well as a significant increase in the product yield were obtained as compared to the batch process. This innovative approach provides a promising green, efficient and rapid synthesis strategy for pharmaceutical synthesis and further activity research of novel nicotinamide derivatives.

A Morpholine Derivative N-(4-Morpholinomethylene)ethanesulfonamide Induces Ferroptosis in Tumor Cells by Targeting NRF2.

Small molecule drugs containing morpholine-based moieties have become crucial candidates in the tumor targeted therapy strategies, but the specific molecular mechanisms of these drugs causing tumor cell death require further investigation. The morpholine derivative N-(4-morpholinomethylene)ethanesulfonamide (MESA) was used to stimulate prostate and ovarian cancer cells and we focused on the ferroptosis effects, including the target molecule and signal pathways mediated by MESA. The results showed that MESA could induce ferroptosis to cause the proliferation inhibition and apoptosis effects of tumor cells according to the identification of ferroptosis inhibitor fer-1 and other cell death inhibitors. Further MESA could significantly increase the intracellular malondialdehyde (MDA), reactive oxygen species (ROS) and Fe2+ levels in tumor cells and mediate the dynamic changes of ferroptosis-relative molecules GPX4, nuclear factor erythroid2-related factor 2 (NRF2), ACSL4, SLC7A11 and P62-Kelch-like ECH-associated protein 1 (KEAP1)-NRF2-antioxidant response element (ARE) signal pathways. Further, NRF2 overexpression could reduce the tumor cell death and ROS levels exposure to MESA. Most importantly, it was confirmed that MESA could bind to NRF2 protein through molecular docking and thermal stability assays and NRF2 was a target molecule of MESA for inducing ferroptosis effects in tumor cells. Collectively, our findings indicated the ferroptosis effects of the morpholine derivative MESA in prostate and ovarian cancer cells and its function mechanism including targeted molecule and signal pathways, which would be helpful for developing MESA as a prospective small molecule drug for cancer therapy based on cell ferroptosis.

High-throughput virtual screening to identify potential small molecule inhibitors of the Zα domain of the adenosine deaminases acting on RNA 1(ADAR1).

Changes in RNA editing are closely associated with diseases such as cancer, viral infections, and autoimmune disorders. Adenosine deaminase (ADAR1), which acts on RNA 1, plays a key role in adenosine to inosine editing and is a potential therapeutic target for these various diseases. The p150 subtype of ADAR1 is the only one that contains a Zα domain that binds to both Z-DNA and Z-RNA. The Zα domain modulates immune responses and may be suitable targets for antiviral therapy and cancer immunotherapy. In this study, we attempted to utilize molecular docking to identify potential inhibitors that bind to the ADAR1 Zα domain. The virtual docking method screened the potential activity of more than 100,000 compounds on the Zα domain of ADAR1 and filtered to obtain the highest scoring results.We identified 71 compounds promising to bind to ADAR1 and confirmed that two of them, lithospermic acid and Regaloside B, interacts with the ADAR1 Zα domain by surface plasmonic resonance technique. The molecular dynamics calculation of the complex of lithospermic acid and ADAR1 also showed that the binding effect of lithospermic acid to ADAR1 was stable.This study provides a new perspective for the search of ADAR1 inhibitors, and further studies on the anti-ADAR11 activity of these compounds have broad prospects.

Zinc Oxide-Loaded Cellulose-Based Carbon Gas Sensor for Selective Detection of Ammonia.

Cellulose-based carbon (CBC) is widely known for its porous structure and high specific surface area and is liable to adsorb gas molecules and macromolecular pollutants. However, the application of CBC in gas sensing has been little studied. In this paper, a ZnO/CBC heterojunction was formed by means of simple co-precipitation and high-temperature carbonization. As a new ammonia sensor, the prepared ZnO/CBC sensor can detect ammonia that the previous pure ZnO ammonia sensor cannot at room temperature. It has a great gas sensing response, stability, and selectivity to an ammonia concentration of 200 ppm. This study provides a new idea for the design and synthesis of biomass carbon-metal oxide composites.

MYL9 promotes squamous cervical cancer migration and invasion by enhancing aerobic glycolysis.

OBJECTIVE: This study explored the mechanism of squamous cervical cancer (SCC) progression. METHODS: Reverse transcription-quantitative polymerase chain reaction and western blotting were used to evaluate the expression of myosin light chain 9 (MYL9) in SCC tissues and cell lines. Furthermore, Transwell and Boyden assays were used to assess the function of MYL9 in SCC progression. In addition, the levels of lactate and aerobic glycolysis were used to explore the detailed mechanism of MYL9 in SCC. RESULTS: The mRNA and protein levels of MYL9 were elevated in SCC tissues, and MYL9 knockdown inhibited the migration and invasion of SCC cell lines. A mechanistic study demonstrated that MYL9 promotes SCC migration and invasion by enhancing aerobic glycolysis and increasing the activity of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway. CONCLUSIONS: MYL9 was upregulated in SCC, and it enhanced JAK2/STAT3 pathway activity and promoted metastasis and glycolysis in SCC.

The construction and analysis of tricarboxylic acid cycle related prognostic model for cervical cancer.

Introduction: Cervical cancer (CC) is the fourth most common malignant tumor in term of in incidence and mortality among women worldwide. The tricarboxylic acid (TCA) cycle is an important hub of energy metabolism, networking one-carbon metabolism, fatty acyl metabolism and glycolysis. It can be seen that the reprogramming of cell metabolism including TCA cycle plays an indispensable role in tumorigenesis and development. We aimed to identify genes related to the TCA cycle as prognostic markers in CC. Methods: Firstly, we performed the differential expressed analysis the gene expression profiles associated with TCA cycle obtained from The Cancer Genome Atlas (TCGA) database. Differential gene list was generated and cluster analysis was performed using genes with detected fold changes >1.5. Based on the subclusters of CC, we analysed the relationship between different clusters and clinical information. Next, Cox univariate and multivariate regression analysis were used to screen genes with prognostic characteristics, and risk scores were calculated according to the genes with prognostic characteristics. Additionally, we analyzed the correlation between the predictive signature and the treatment response of CC patients. Finally, we detected the expression of ench prognostic gene in clinical CC samples by quantitative polymerase chain reaction (RT-qPCR). Results: We constructed a prognostic model consist of seven TCA cycle associated gene (ACSL1, ALDOA, FOXK2, GPI, MDH1B, MDH2, and MTHFD1). Patients with CC were separated into two groups according to median risk score, and high-risk group had a worse prognosis compared to the low-risk group. High risk group had lower level of sensitivity to the conventional chemotherapy drugs including cisplatin, paclitaxel, sunitinib and docetaxel. The expression of ench prognostic signature in clinical CC samples was verified by qRT-PCR. Conclusion: There are several differentially expressed genes (DEGs) related to TCA cycle in CC. The risk score model based on these genes can effectively predict the prognosis of patients and provide tumor markers for predicting the prognosis of CC.

Cervical HPV infection in Guangzhou, China: an epidemiological study of 198,111 women from 2015 to 2021.

Persistent high-risk human papillomavirus (HPV) infection is the pivotal cause of cervical carcinogenesis. HPV types distribution varies greatly by region, and its long-term changes of prevalence remain to be fully characterized in China. Here, the largest population of 198,111 consecutive women who underwent routine cervical screening were investigated from 2015 to 2021 in Guangzhou, south China. The results showed that the overall HPV prevalence was 21.66% (42,911/198,111), and the annual prevalence increased significantly from 2015 to 2021 (p < 0.001). HPV52, 16, 58, CP8304, 51, 53, 39, and 68 were the most prevalent HPV types. The relative HPV-positive rate correlated positively with the progression of cervical intraepithelial neoplasia (p < 0.001); HPV16 was the predominant carcinogenic type, followed by HPV52 and HPV18. HPV infections were significantly age-specific, and 26.51% (11,375/42,911) of cases were caused by multiple HPV types. In addition, HPV infections typically cleared over a median time of 16 (interquartile range 9-31) months, and the clearance of HPV16 was significantly faster than that of other types (p < 0.001). These findings may serve as a guide for local governments to evaluate HPV vaccination and cervical cancer prevention strategies in south China.

PAX1 and SEPT9 methylation analyses in cervical exfoliated cells are highly efficient for detecting cervical (pre)cancer in hrHPV-positive women.

Studies have investigated PAX1 and SEPT methylation were closely associated with cervical cancer. For this study, we verified the expressions of PAX1 and SEPT9 methylation in 236 hrHPV women cervical exfoliated cells by using quantitative methylation-specific PCR and we further explored their diagnostic value in cervical (pre)cancer detection. Our results identified that the methylation rates and levels of PAX1 and SEPT9 increased with cervical lesion severity. For a diagnosis of cervical (pre)cancer, the area under the curve (AUC) of PAX1 methylation was 0.77 (95% CI 0.71-0.83) and the AUC of SEPT9 methylation was 0.86 (95% CI 0.81∼0.90). Analyses of the PAX1 and SEPT9 methylation statuses alone or combined with commonly used tests can efficiently identify cervical (pre)cancer. In particular, SEPT9 methylation might serve as an effective and powerful biomarker for the diagnosis of cervical (pre)cancer and as an alternative triage test in HPV-based cervical (pre)cancer screening programs.Impact StatementWhat is already known on this subject? This subject showed that PAX1 and SEPT9 methylation were closely associated with cervical cancer. The methylation rates and levels of PAX1 and SEPT9 increased with cervical lesion severity and reached a peak in cervical cancer exfoliated cells. We further assessed the diagnostic performances of PAX1 and SEPT9 methylation in cervical cancer screening. In detecting cervical (pre)cancer, the sensitivity values of PAX1 and SEPT9 methylation were up to 61.18% and 82.35%, respectively, and the specificity values of PAX1 and SEPT9 methylation were up to 95.36% and 86.75%, respectively. Moreover, the ROC curve analysis showed AUC values of 0.77 for PAX1 methylation and 0.86 for SEPT9 methylation tests, which were significantly superior to other commonly used tests. These findings suggest that PAX1 and SEPT9 methylation detection may have great clinical potential in cervical cancer screening.What the results of this study add? The rates and levels of PAX1 and SEPT9 methylation increased with the severity of the cervical lesions. For a diagnosis of cervical (pre)cancer, the area under the curve (AUC) of PAX1 methylation was 0.77 (95% CI 0.71-0.83), and the sensitivity and specificity values were 61.18% and 95.36%, respectively. The AUC value of the SEPT9 methylation was 0.86 (95% CI 0.81 ∼ 0.90), and the sensitivity and specificity values were 82.35% and 86.75%, respectively. Compared with the various tests we conducted, the PAX1 methylation showed the highest specificity (95.36%), and the SEPT9 methylation demonstrated the highest accuracy(86.00%).What the implications are of these findings for clinical practice and/or further research? The methylation levels of PAX1 and SEPT9 had a certain predictive effect on the severity of cervical lesions in hrHPV-positive women. In addition, SEPT9 methylation analysis performs better than PAX1 methylation analysis and commonly used tests in cervical exfoliated cells for detecting cervical (pre)cancer in hrHPV-positive women. SEPT9 methylation analysis merits consideration as an effective and objective, alternative triage test in HPV-based cervical (pre)cancer screening programs.

Septin9 DNA methylation as a promising biomarker for cervical cancer.

Aberrant Septin9 methylation in cervical cancer has been rarely studied. We aimed to identify its diagnostic value in cervical cancer using cervical scrapings, and its predictive potential in plasma for pelvic nodal metastasis of cervical cancer. The statuses of methylated Septin9 in fresh cervical lesions and cervical scrapings were first evaluated by using quantitative methylation-specific PCR. Subsequently, the relationship between Septin9 methylation in 113 plasma samples and pelvic nodal metastasis of cervical cancer was evaluated. Methylated Septin9 was detected in all cancerous tissues, but not in cervicitis. The degrees of Septin9 methylation increased with growing severity of cervical lesions in cervical scrapings. The sensitivity of methylated Septin9 was lower than that of cytology, while it yielded a high specificity and area under the curve in detecting high-grade squamous intraepithelial lesion or cervical cancer; and when Septin9 methylation combined with HPV16/18 genotyping, the sensitivity would increase from 70.42% to 82.39%. Plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%. In conclusion, we demonstrated methylated Septin9 to be an innovative diagnostic biomarker for cervical cancer and its non-invasive predictive potential in plasma for pelvic nodal metastasis of cervical cancer.Impact statementWhat is already known on this subject? The occurrence of cervical cancer is related to Septin9 methylation. In fresh specimens and cervical scrapings, we found the degrees of methylated Septin9 increased with growing severity of cervical lesions. Compared with HPV16/18 genotyping and cytological detection, Septin9 methylation had a better specificity and AUC in detecting ≥ HSIL. Furthermore, plasma-based Septin9 methylation also had a high specificity for pelvic lymphatic metastasis prediction.What the results of this study add? Methylation analysis of Septin9 indicated a similar sensitivity, specificity and AUC in detecting ≥ HSIL, relative to HPV16/18 genotyping. Compared with cytological method, Septin9 methylation also yielded a higher specificity and AUC in detecting ≥ HSIL. And we also found plasma-based Septin9 methylation had a high discriminatory power in predicting pelvic nodal metastasis of cervical cancer, with an optimal specificity of 81.48%; additionally an increasing sensitivity from 50% to nearly 80% was found when combined with SCCAg.What the implications are of these findings for clinical practice and/or further research? This study aimed to evaluate the relationship between Septin9 methylation and cervical cancer, and to explore the value of methylated Septin9 in the detection of cervical (pre)cancerous lesions. Moreover, we would explore plasma-based ctDNA biomarkers for pelvic lymphatic metastasis prediction of cervical cancer, to improve non-invasive predictive accuracy of pelvic nodal metastasis and reduce the complications caused by pelvic lymphadenectomy.

Single-Cell RNA-Sequencing Atlas Reveals the Tumor Microenvironment of Metastatic High-Grade Serous Ovarian Carcinoma.

Ovarian cancer is the most common and lethal gynecological tumor in women worldwide. High-grade serous ovarian carcinoma (HGSOC) is one of the histological subtypes of epithelial ovarian cancer, accounting for 70%. It often occurs at later stages associated with a more fatal prognosis than endometrioid carcinomas (EC), another subtype of epithelial ovarian cancer. However, the molecular mechanism and biology underlying the metastatic HGSOC (HG_M) immunophenotype remain poorly elusive. Here, we performed single-cell RNA sequencing analyses of primary HGSOC (HG_P) samples, metastatic HGSOC (HG_M) samples, and endometrioid carcinomas (EC) samples. We found that ERBB2 and HOXB-AS3 genes were more amplified in metastasis tumors than in primary tumors. Notably, high-grade serous ovarian cancer metastases are accompanied by dysregulation of multiple pathways. Malignant cells with features of epithelial-mesenchymal transition (EMT) affiliated with poor overall survival were identified. In addition, cancer-associated fibroblasts with EMT-program were enriched in HG_M, participating in angiogenesis and immune regulation, such as IL6/STAT3 pathway activity. Compared with ECs, HGSOCs exhibited higher T cell infiltration. PRDM1 regulators may be involved in T cell exhaustion in ovarian cancer. The CX3CR1_macro subpopulation may play a role in promoting tumor progression in ovarian cancer with high expression of BAG3, IL1B, and VEGFA. The new targets we discovered in this study will be useful in the future, providing guidance on the treatment of ovarian cancer.

Human Umbilical Cord Mesenchymal Stem Cells Improve Premature Ovarian Failure through Cell Apoptosis of miR-100-5p/NOX4/NLRP3.

Premature ovarian failure refers to a series of symptoms of perimenopausal hot flashes, night sweats, decreased libido, vaginal dryness, insomnia, reduced menstruation, sparse hair, even amenorrhea, and even infertility before the age of 40 due to the decline of ovarian function. Premature ovarian failure is a common and difficult disease in gynecology. Its prevalence is increasing gradually, and the trend is younger. The aim of this experiment was to elucidate the role of human umbilical cord mesenchymal stem cells (HUCMSCs) in premature ovarian failure and its mechanism. HUCMSCs, KGN cells, and HEK293T cells were used in this experiment. Quantitative PCR and microarray analysis, ELISA inflammation and oxidative stress kits, RNA pull-down assay, luciferase reporter assay, proliferation assay, EDU staining, and Western blot analysis were used. In an in vitro model of premature ovarian failure, HUCMSCs attenuated inflammatory response, oxidative stress, and apoptosis. HUCMSCs ameliorated the premature ovarian failure model. The miR-100-5p expression was induced by HUCMSCs through methylation. miR-100-5p regulation influenced the role of HUCMSCs in an in vitro model of premature ovarian failure. HUCMSCs inhibited the in vitro expression of NOX4, NLRP3, and GSDMD proteins in the model. NOX4/NLRP3 signaling pathway affects the role of HUCMSCs in an in vitro model of premature ovarian failure through miR-100-5p. This experiment elucidated the role of HUCMSCs in premature ovarian failure and its mechanism, with a view to providing a clinical reference.

Circ_0025033 deficiency suppresses paclitaxel resistance and malignant development of paclitaxel-resistant ovarian cancer cells by modulating the miR-532-3p/FOXM1 network.

BACKGROUND: Ovarian cancer (OC) is the main cause of cancer-related death in women, and drug resistance is a leading cause of treatment failure. Recently, the involvement of circular RNAs (circRNAs) in cancer progression has become an area of increased investigation. The objective of this study is to uncover the function and regulatory mechanism of circ_0025033 in paclitaxel (PTX)-resistant OC cells. METHODS: The expression of circ_0025033, FOXM1 and miR-532-3p was investigated using quantitative real-time polymerase chain reaction (qRT-PCR), and the protein expression of FOXM1 was quantified by western blot. Cell biological functions, including cell viability, migration/invasion and apoptosis, were explored using 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays, transwell assays and flow cytometry assays. The interaction between miR-532-3p and circ_0025033 or FOXM1 predicted by bioinformatics analysis was validated by pull-down assay and dual-luciferase reporter assay. Exosomes were isolated to determine the further function of circ_0025033. RESULT: Circ_0025033 and FOXM1 were highly expressed, while miR-532-3p was poorly expressed in OC tissues and cells, and the expression pattern was greater in PTX-resistant OC cells. Circ_0025033 knockdown lessened PTX resistance, suppressed migration/invasion and promoted apoptosis of PTX-resistant cells. With respect to mechanism, circ_0025033 upregulated the expression of FOXM1 by targeting miR-532-3p, and circ_0025033 knockdown blocked the malignant activities of PTX-resistant OC cells by enriching miR-532-3p and suppressing FOXM1. Exosomes derived from PTX-resistant cells with circ_0025033 knockdown also could repress the malignant actions of PTX-resistant OC cells. CONCLUSION: Circ_0025033 downregulation impaired PTX resistance and malignant activities of PTX-resistant OC cells by regulating the miR-532-3p/FOXM1 network.

Clinical characteristics of 1,055 Chinese patients with Mayer-Rokitansky-Küster-Hauser syndrome: a nationwide multicentric study.

OBJECTIVE: To reveal the proportion of concomitant extragenital malformations in a large cohort of Chinese patients with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. STUDY DESIGN: Retrospective study. SETTING: Tertiary teaching hospitals in China. PATIENT(S): A total of 1,055 Chinese Han women with MRKH syndrome diagnosed and treated at 11 Chinese tertiary teaching hospitals from January 2015 to January 2020. INTERVENTION(S): Karyotype analysis, hormone profiling, pelvic ultrasonography, spinal roentgenograms, urologic ultrasonography, and Chinese female reproductive tract malformation registry platform (https://ecrf.linklab.com/). MAIN OUTCOME MEASURE(S): Patients' demographic and clinical characteristics, concurrent malformations, and family histories. RESULT(S): Of the 1,055 Chinese Han patients with MRKH, 69.6% had type I MRKH syndrome and the remaining 30.4% had type II MRKH syndrome. Among the type II patients, 12.6% had müllerian duct aplasia, unilateral renal aplasia/ectopic kidney, and cervicothoracic somite dysplasia association. Skeletal malformations were the most common associated extragenital malformations in the study (22.0%, 232/1,055), of which idiopathic scoliosis and congenital vertebral malformations were the 2 main skeletal malformations (80.6% and 14.2%, respectively). Renal malformations were the second-highest associated extragenital malformations (9.7%, 102/1,055), with unilateral renal agenesis and ectopic kidney being the most common renal malformations (48.0% and 22.5%, respectively). CONCLUSION(S): Type II disease was less common among Chinese patients with MRKH syndrome compared with European patients. Skeletal malformations were more common extragenital malformations than renal malformations in our cohort.

Biological effects of NODAL on endometrial cancer cells and its underlying mechanisms.

Activin A receptor type 1C (ALK7) and its ligand nodal growth differentiation factor (NODAL) serve numerous roles in cancer cells, including regulating cancer invasion, migration and apoptosis. NODAL promotes breast cancer cell apoptosis by activating ALK7; however, ALK7 and NODAL expression in endometrial cancer (EC), as well as their effects and underlying mechanisms in EC cells, are not completely understood. The present study aimed to characterize the expression of NODAL and ALK7 in EC, as well as the underlying mechanisms. The expression levels of ALK7 and NODAL were detected via reverse transcription-quantitative PCR and western blotting. Cell transfection was performed to overexpress NODAL or interfere ALK7. Cell proliferation, invasion and migration were detected via Cell Counting Kit-8, Transwell and wound healing assays, respectively. Flow cytometry was performed to detect cell apoptosis and western blotting was conducted to detect the expression levels of apoptosis-related proteins. NODAL and ALK7 expression levels were significantly decreased in EC cell lines compared with normal endometrial cells. NODAL overexpression inhibited EC cell proliferation, invasion and migration, and promoted EC cell apoptosis compared with the overexpression-negative control (Ov-NC) group. Moreover, NODAL overexpression significantly increased ALK7 expression levels in EC cells compared with the Ov-NC group. ALK7 reversed NODAL overexpression-mediated inhibition of EC cell proliferation, invasion and migration, and promotion of EC cell apoptosis. The present study indicated that NODAL inhibited EC cell proliferation, invasion and migration, and promoted EC cell apoptosis by activating ALK7.

Incidence, persistence and clearance of cervical human papillomavirus among women in Guangdong, China 2007-2018: A retrospective cohort study.

BACKGROUND: Previous studies showed the incidence, persistence and clearance of cervical human papillomavirus (HPV) among women varies from regions. There is no study on dynamic changes of HPV infection among women in Guangdong. METHODS: It is a retrospective cohort study that included gynecological outpatients aged ≥15 years and retested for HPV within 24 months in Guangdong Women and Children Hospital to estimate HPV incidence, persistence and clearance. Outcomes were estimated through the proportion of HPV incidence, persistence and clearance in HPV-negative or HPV-positive women. Moreover, we examined HPV incidence, persistence and clearance among women who retested in four calendar periods: 0-6, 6-12, 12-18, 18-24 months after the first test. RESULTS: 33,328 gynecological outpatients were included in our study. Incidence rates of any HPV, high-risk (HR) HPV and low-risk (LR) HPV were 10.58%, 8.68% and 4.83%. The most common incident HR HPV were HPV52 (2.69%), HPV16 (1.23%) and HPV58 (1.23%). Persistence rates of any HPV, HR HPV and LR HPV were 47.55%, 42.77% and 33.88%. HPV52 (42.33%), HPV58 (40.74%) and HPV68 (32.36%) were commonly found persistent types. And clearance rates of any HPV, HR HPV and LR HPV were 52.44%, 57.23% and 66.12%.The lowest clearance rates were observed for HPV52 (57.67%), HPV68 (67.64%) and HPV39 (68.56%). HPV incidence and persistence were higher among women aged 15-19 years and ≥55 years. HPV incidence and persistence were found higher among women who retested within 6 months than others in other periods. CONCLUSIONS: HPV52, 58, 68, and 39 were the more likely to cause incident and persistent infection, and less likely to be cleared among women in Guangdong. HPV incidence and persistent infection were higher among women aged both younger and older women compared to middle aged women. HPV retesting period may impact the detection of HPV incidence, persistence and clearance.

Artificial intelligence-assisted cytology for detection of cervical intraepithelial neoplasia or invasive cancer: A multicenter, clinical-based, observational study.

OBJECTIVE: Artificial intelligence (AI) could automatedly detect abnormalities in digital cytological images, however, the effect in cervical cancer screening is inconclusive. We aim to evaluate the performance of AI-assisted cytology for the detection of histologically cervical intraepithelial lesions (CIN) or cancer. METHODS: We trained a supervised deep learning algorithm based on 188,542 digital cytological images. Between Mar 13, 2017, and Oct 20, 2018, 2145 referral women from organized screening were enrolled in a multicenter, clinical-based, observational study. Cervical specimen was sampled to generate two liquid-based slides: one random slide was allocated to AI-assisted reading, and the other to manual reading conducted by skilled cytologists from senior hospital and cytology doctors from primary hospitals. HPV testing and colposcopy-directed biopsy was performed, and histological result was regarded as reference. We calculated the relative sensitivity and relative specificity of AI-assisted reading compared to manual reading for CIN2+. This trial was registered, number ChiCTR2000034131. RESULTS: In the referral population, AI-assisted reading detected 92.6% of CIN 2 and 96.1% of CIN 3+, significantly higher than or similar to manual reading. AI-assisted reading had equivalent sensitivity (relative sensitivity 1.01, 95%CI, 0.97-1.05) and higher specificity (relative specificity 1.26, 1.20-1.32) compared to skilled cytologists; whereas higher sensitivity (1.12, 1.05-1.20) and specificity (1.36, 1.25-1.48) compared to cytology doctors. In HPV-positive women, AI-assisted reading improved specificity for CIN1 or less at no expense of reduction of sensitivity compared to manual reading. CONCLUSIONS: AI-assisted cytology may contribute to the primary cytology screening or triage. Further studies are needed in general population.