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OBJECTIVE: The persistence of HPV infection is a significant etiological factor in the development of cervical cancer. The present study investigated the prevalence and genotype distribution of human papillomavirus (HPV) in a cohort of 164,137 unvaccinated women from Wenzhou, aiming to provide guidance for clinics in the cervical cancer screening and HPV vaccination strategies. METHODS: The present retrospective study included a total of 164,137 women, comprising 118,484 outpatients and 45,653 healthy female subjects recruited from 2015 to 2020. Cervical exfoliated cells were collected from these participants for subsequent DNA extraction. The extracted DNA samples were underwent analysis using a fluorescence in situ hybridization method, encompassing the detection of 27 HPV genotypes. RESULTS: The overall prevalence of HPV was 17.35%; this corresponded to a prevalence of 19.10% in the outpatient group and 12.82% in the healthy female group. Among the outpatient group, the five most prevalent HPV genotypes were identified as HPV 52, 58, 16, 53, and 61. In the healthy female group, the five most common HPV genotypes were found to be HPV 52, 53, 58, 61, and 81. Additionally, it was estimated that the highest rate of HPV infection occurred among individuals aged between 10 and 19 years old (44.65%) and those aged between 60 and 69 years old (27.35%). CONCLUSIONS: The prevalence of HPV in this region is substantial; therefore, it is imperative to implement scientifically sound and rational clinical interventions such as vaccination. Routine cervical screening should be performed to prevent the development of cervical intraepithelial neoplasia resulting from persistent infection with high-risk HPV, particularly in women with gynecological diseases and those over 60 years old.

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Peptide P7 specifically binds with basic fibroblast growth factor (bFGF) to inhibit the proliferation and invasion of numerous types of cancer cell. However, this effect has remained to be demonstrated in ovarian cancer-derived cell lines. In the present study, the protein P7 was used treat bFGF-stimulated SKOV3 epithelial ovarian cancer cells to explore the therapeutic potential of P7. An MTT and a scratch wound assay were used to respectively evaluate the proliferation and migration of bFGF-stimulated SKOV3 cells treated with P7. Reverse transcription-quantitative polymerase chain reaction analysis was used to detect the gene expression of urokinase-type plasminogen activator (uPA), as well as matrix metallopeptidase (MMP)-2 and -9, which have a role in cell migration/invasion. The morphology and proliferation of SKOV3 cells were not significantly affected by different concentrations of P7. However, P7 had an obvious inhibitory effect on the proliferation and migration of bFGF-stimulated SKOV3 cells. Treatment with P7 significantly lowered the gene expression of uPA, MMP-2 and MMP-9 compared with that in the control group. In conclusion, the present results suggested that P7, which, at least in part, acts through inhibition of bFGF, may have a potential therapeutic application in epithelial ovarian cancer.

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BACKGROUND: Endometrial cancer (EC) is common type of gynecologic malignancy affecting a large number of females around the world. While most early stage cases are well managed with a relatively benign prognosis, the late stage cases have poor survival. Among the many biomarkers identified, serum human epididymis protein 4 (HE4) and CA125 are most promising surrogates for EC detection. METHODS: We performed a meta-analysis to estimate the diagnostic accuracy of HE4 and CA125 and compared their performance. A literature research was performed in Medline, Cochrane Literature Library and CNKI. After filtering, twelve studies evaluating the diagnostic value of serum HE4, alone or in comparison with CA125, were included. The total sample size was 1106 patients and 1480 controls. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were calculated and summary receiver operating characteristic (SROC) curves were plotted to assess the diagnostic accuracy. RESULTS: The pooled estimates for HE4 were sensitivity: 0.71 (95%CI 0.56-0.82), specificity: 0.87 (95%CI 0.80-0.92), and area under ROC curve: 0.88 (0.85-0.91), compared to 0.35 (95% CI 0.25-0.46), 0.83 (95% CI 0.71-0.91), and 0.58 (95% CI 0.54-0.63), respectively, of CA125. Subgroup analysis demonstrated a better performance of HE4 in Caucasian population, compared to Chinese population. CONCLUSION: This analysis suggested that when stage and histological type are not specifically considered, serum HE4 is generally a better tool than CA125 in EC diagnosis by its significantly higher sensitivity than CA125.

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BACKGROUND: This study aimed to determine the in vitro and in vivo properties of sixteen frequently used endometrial cancer (EC) cell lines, including the cell proliferation rate, morphology, hormone receptor expression patterns, PTEN, hMLH1 expression, p53 mutation, karyotype, and tumorigenicity in mouse xenograt model. METHODS: Twelve type I (AN3, ECC-1, EN, EN-1, EN-11, HEC-1A, HEC1B, Ishikawa, KLE, MFE-280, MFE-296, MFE-319) and four type II (ARK1, ARK2, HEC-155/180, SPEC-2) endometrial cancer cell lines were studied. Cell proliferation and morphology were determined using cell growth curves and light microscopy, respectively. Real-time PCR was performed to measure the mRNA levels of target genes. Denaturing High Performance Chromatography (DHPLC) screening and PCR/sequencing were performed to identify p53 mutations. G-banding was applied for karyotyping. Tumorigenicity was evaluated using mouse xenograft. RESULTS: The population doubling time of the cell lines ranged between 19 and 41 h. Ishikawa, ECC-1, and MFE-280 have high while AN3 and EN1 have low expression of ER-α and ER-ß. Expression of total PR and PR-B uniformly decreased in all type II cell lines and several type I cell lines (AN3, HEC-1A, HEC1B, KLE, EN-1). Regression analyses revealed significant correlations between PR-B and total PR (p < .001), between isoforms ER-α and ER-ß (p < .001), and between total PR and ER (p < .001), mRNA levels in type I cell lines. p53 mutations were detected in exons 5-8 of seven out of twelve type I and one out of four type II cell lines. PTEN expression was more uniformly suppressed in type II than type I cells, while hMLH1 did not show this pattern. All the five cell lines tested contained severe karyotype abnormalities. Mouse xenograft results indicated that HEC-1A, HEC-1B and EN-1 type I as well as ARK1 and ARK2 type II cell lines had potent tumorigenic activities. Low PR-B and ER-α expression in type I cell lines were associated with high tumorigenic activity. CONCLUSIONS: This study provides resource information on EC cell lines commonly used in laboratories, which could be used for choosing cell lines suitable for specific research purposes. The results of karyotype analysis and p53 mutation together with hormone receptor expression pattern and morphology comparison strongly suggested an independent nature of these cell lines, excluding the possibility of cross-contamination between cell lines. Additionally, this information suggests potential directions for future studies on the pathogenic mechanisms of endometrial cancer.

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In this study, we investigated the differential expression of microRNAs in an ovarian cancer cell line HO-8910PM with increased migration and invasiveness activities. miR-1 was found to be one of the microRNA species most significantly downregulated in HO-8910PM compared with the control cell line HO-8910. We demonstrated that ovarian cancer tissues expressed decreased levels of miR-1 compared to non-neoplastic tissues. In vitro experiments showed that overexpression of miR-1 in HO-8910PM led to an inhibition of cell proliferation, blocking of cell cycle progression by G1 phase arrest, and decreased migration and invasiveness of HO-8910PM cells. Moreover, we confirmed that the expression of c-Met, a potential target of miR-1, was significantly inhibited following overexpression of miR-1 in HO-8910PM cells. Further analyses indicated that expression of factors including p-Akt, p-ERK1/2, CDK4, and p-Rb in HO-8910PM cells were affected by manipulation of c-Met expression. Infection of HO-8910PM cells with lentivirus vector expressing miR-1 led to a significant inhibition of tumor growth in the tumor subcutaneous nude mouse model. Taken together, these results indicated that miR-1 is downregulated in ovarian cancer tissues, and may play a tumor suppressive role by inhibiting c-Met expression and its effects on the regulation of cell proliferation, migration and invasion.

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Specific blocking of interactions between ligands and receptors along the angiogenic pathways represents an effective approach for enhancing the efficacy as well as reducing adverse effects of chemotherapy. Over the past decade, there was a rapid progression in the application of this therapeutic strategy in cancer treatment. Anti-angiogenic therapy is the most promising targeted therapy for ovarian cancer. The addition of bevacizumab to conventional chemotherapy, either in the first-line setting or at disease relapse, may improve overall survival (OS) of ovarian cancer patients, at least in a subset of patients with poor prognosis. In this article, we summarize published data on the major agents used for anti-angiogenic therapy in ovarian cancers. We will review the molecular mechanisms, results of clinical trial of existing agents and describe the development of new agents. The limitations and side effects of angiogenesis inhibitor are also discussed.

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INTRODUCTION: Serum epididymis protein 4 (HE4) level is a useful biomarker for the management of ovarian and endometrial cancer patients. Urine HE4-test, with its easier access than serum test, has emerged as a new method with promising application for the diagnosis of ovarian cancer. Areas covered: This review summarizes data regarding the detection and alteration of HE4 in urine samples collected from ovarian cancer patients and controls. The performance and limitation of the assay and potential direction of future study are also discussed. Expert commentary: Several studies have demonstrated an appreciable efficiency of urine HE4-test in the discrimination of ovarian cancer patients from general population. However, the data is based on small cohorts, and the performance of urine HE4-test need to be validated in larger groups. An algorithm incorporating other important factors may allow a quantitative assessment of cancer possibility. Future studies on the HE4 renal secretion and HE4 degradation dynamics in urine are also required for the establishment of standard protocols for the application of urine HE4-test in clinical settings.

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INTRODUCTION: Serum epididymis protein 4 (HE4) represents a useful biomarker for the management of ovarian cancer and endometrial cancer patients. However, HE4 levels are affected by many physiopathological conditions or disorders that should be taken into consideration for an efficient application of this biomarker. Areas covered: The review provides an up-to-date reference on the multiple physiopathological factors that cause fluctuation of HE4 serum levels, and evaluates their impact on HE4-test in clinical settings. Potential mechanisms underlying the regulation of HE4 expression are also discussed. The review is based on data from literature search of PubMed and the author's opinions. Expert commentary: Studies have shown that physiopathological factors such as age, infection/inflammation, renal function, menopause and hormonal levels impose significant impacts on HE4 serum levels. HE4 amount shed into the circulation is related to HE4 expression and secretion by tumor as well as normal tissues, which is affected by cancer heterogeneity, vascular permeability, renal clearance and HE4 degradation. Investigation on interfering factors builds a basis for the construction of a quantitative logarithm for individualized application of HE4-test in clinical settings.

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An aromatase encoded by the CYP19 gene catalyzes the final step in the biosynthesis of estrogens, which is related to endometriosis development. To assess the association of CYP19 gene polymorphisms with the risks of endometriosis, chocolate cysts and endometriosis-related infertility, a case-control study was conducted in Chinese Han women by recruiting 225 healthy control females, 146 patients with endometriosis, 94 endometriosis women with chocolate cyst and 65 women with infertility resulting from endometriosis, as diagnosed by both pathological and laparoscopic findings. Individual genotypes at rs2236722:T>C, rs700518:A>G, rs10046:T>C and [TTTA]n polymorphisms were identified. Allelic and genotypic frequencies were compared between the control group and case groups by chi-square analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined by logistic regression analysis to predict the association of CYP19 gene polymorphisms with the risk of endometriosis, the related chocolate cysts and infertility. The genotype distributions of the tested CYP19 gene polymorphisms were not significantly different between the healthy control group and the endometriosis/endometriosis with the chocolate cyst group. However, the CYP19 rs700518AA genotype was significantly associated with an increased risk of endometriosis-related infertility (55.4% in the infertility group vs 25.3% in the control group, P<0.001; OR (95% CI): 3.66 (2.06-6.50)) under the recessive form of the A allele. Therefore, we concluded that in Chinese Han females CYP19 gene polymorphisms are not associated with susceptibility to endometriosis or chocolate cysts, whereas CYP19 rs700518AA genotype confers genetic susceptibility to endometriosis-related infertility.

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BACKGROUND: The unfolded protein response, autophagy and endoplasmic reticulum (ER) stress-induced apoptosis regulate tumor cell fate and have become novel signaling targets for the development of cancer therapeutic drugs. Curcumin has been used to treat several different cancers, including ovarian cancer, in clinical trials and research; however, the role of ER stress and autophagy in the therapeutic effects of curcumin and new curcumin analogues remains unclear. METHODS: Cell viability was determined using the MTT assay. Apoptosis was detected using flow cytometry with PI/Annexin V-FITC staining. The expression levels of ER stress- and autophagy-related proteins were analyzed by western blotting. The activation of autophagy was detected using immunofluorescence staining. RESULTS: We demonstrated that B19 induced HO8910 cell apoptosis in a dose-responsive manner. We also determined and that this effect was associated with corresponding increases in a series of key components in the UPR and ER stress-mediated apoptosis pathways, followed by caspase 3 cleavage and activation. We also observed that B19 treatment induced autophagy in HO8910 cells. The inhibition of autophagy using 3-methyladenine (3-MA) increased levels of intracellular misfolded proteins, which enhanced ovarian cancer apoptosis. CONCLUSIONS: Our data indicate that ER stress and autophagy may play a role in the apoptosis that is induced by the curcumin analogue B19 in an epithelial ovarian cancer cell line and that autophagy inhibition can increase curcumin analogue-induced apoptosis by inducing severe ER stress.

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PURPOSE: The sleep disorder in pregnant women remains unfamiliar to perinatal care providers, resulting in lack of appropriate care. This study was designed to investigate the prevalence of sleep disorder-related symptoms in pregnant women and to identify the associated risk factors. METHODS: Married pregnant women were enrolled from their first trimester and followed up until delivery. Nonpregnant married healthy women were selected as controls. A survey questionnaire was administered to each of them. RESULTS: We successfully performed a survey to 1,993 pregnant women and 598 nonpregnant women. The overall prevalence of sleep disorder-related symptoms in pregnant women was significantly higher than the controls (56.1 vs. 29.9 %, P < 0.05). There was higher prevalence of snoring (30.2 %), observed sleep apnea (1.1 %), mouth breathing (23.7 %), nocturnal arousal (46.5 %), insomnia (35.1 %), and daytime sleepiness (52.6 %) in pregnant women. There were no significant differences of the prevalence of bruxism (7.0 vs. 6.7 %), sleep talking (8.1 vs. 7.2 %), and sleep walking (0.4 vs. 0.2 %) between the two groups (P > 0.05). Nocturnal sleep time (8.0 ± 1.3 h) was less in the third trimester compared with the nonpregnant women (8.2 ± 1.1 h) (P < 0.05). Smoking (OR = 3.39), drinking (OR = 2.40), allergic rhinitis/asthma (OR = 1.71), an obvious difference in neck circumference (OR = 1.11), and waistline (OR = 1.07) changes between the first and third trimesters were the risk factors for sleep disorder-related problems. CONCLUSIONS: There is a high prevalence of sleep disorder-related symptoms in pregnant women. Our data may provide a baseline for prevention and treatment of sleep disturbances in pregnant women.

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Premature rupture of membranes (PROM) is a common obstetric complication frequently occurring with concomitant chorioamnionitis. The present study aimed to evaluate levels of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in serum and amniotic fluid in pregnant women with PROM and to compare sTREM-1 with the commonly used laboratory indicators, serum C-reactive protein (CRP) and white blood cell (WBC) count. A total of 55 pregnant women with PROM were enrolled. Their venous blood and amniotic fluid were collected at delivery. sTREM-1 concentrations in the serum and amniotic fluid were determined by enzyme-linked immunosorbent assay. The measured data were compared with the pathological results of the placenta and fetal membrane. Meanwhile, sTREM-1 was compared with the laboratory indicators, serum CRP and WBC count. Serum and amniotic fluid sTREM-1 levels were significantly higher in pregnant women with subclinical chorioamnionitis compared to pregnant women without chorioamnionitis. Serum concentration of sTREM-1 yielded a sensitivity of 81.8% and a specificity of 77.3% for the prediction of subclinical chorioamnionitis. The amniotic fluid concentration of sTREM-1 resulted in a sensitivity of 81.8% and a specificity of 86.4% for the prediction of subclinical chorioamnionitis. In conclusion, serum and amniotic fluid sTREM-1 levels may emerge as early biological indicators for predicting PROM complicated with subclinical chorioamnionitis. sTREM-1 levels are superior to WBC count in predicting subclinical chorioamnionitis.

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