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There is currently no large sample data of cytology, high-risk human papillomavirus (hrHPV), and colposcopy results of vaginal intraepithelial neoplasia (VaIN) in women who underwent hysterectomy and those who did not. We aim to explore the values of cytology, hrHPV, and colposcopy reports in detecting VaIN. A retrospective study of women diagnosed with VaIN by colposcopy-directed biopsy was performed at the Obstetrics and Gynecology Hospital of Fudan University, China, between January 1, 2014, and December 31, 2014. A total of 529 cases of VaIN were diagnosed, including 16.1% VaIN2/3 and 83.9% VaIN1. The ratio of VaIN2/3 in VaIN among patients after hysterectomy and with an intact uterus was 35.1% and 12.0%, respectively. The sensitivity of cytology for VaIN2/3 in only, concomitant, and posthysterectomy VaIN was 42.1%, 80.0%, and 80.8%, respectively. The sensitivity of hrHPV and cytology/hrHPV cotesting for VaIN2/3 in patients with an intact uterus versus those after hysterectomy was 93.5% versus 92.3% and 92.0% versus 100.0%, respectively. Notably, 13.3% of the patients with VaIN and 9.7% of the patients with VaIN2/3 underwent hysterectomy for noncervical diseases. The sensitivity of cytology and hrHPV for VaIN is noninferior to that of CIN2+, and thus these methods can help in the early detection of VaIN effectively.

BackgroundEndometrial carcinoma is one of the most common gynecological malignancies in women. The diagnosis of the disease at early or premalignant stages is crucial for the patient's prognosis. To date, diagnosis and follow-up of endometrial carcinoma and hyperplasia require invasive procedures. Therefore, there is considerable demand for the identification of biomarkers to allow non-invasive detection of these conditions.MethodsIn this study, we performed a quantitative proteomics analysis on serum samples from simple endometrial hyperplasia, complex endometrial hyperplasia, atypical endometrial hyperplasia, and endometrial carcinoma patients, as well as healthy women. Serum samples were first depleted of high-abundance proteins, labeled with isobaric tags (iTRAQ™), and then analyzed via two-dimensional liquid chromatography and tandem mass spectrometry. Protein identification and quantitation information were acquired by comparing the mass spectrometry data against the International Protein Index Database using ProteinPilot software. Bioinformatics annotation of identified proteins was performed by searching against the PANTHER database.ResultsIn total, 74 proteins were identified and quantified in serum samples from endometrial lesion patients and healthy women. Using a 1.6-fold change as the benchmark, 12 proteins showed significantly altered expression levels in at least one disease group compared with healthy women. Among them, 7 proteins were found, for the first time, to be differentially expressed in atypical endometrial hyperplasia. These proteins are orosomucoid 1, haptoglobin, SERPINC 1, alpha-1-antichymotrypsin, apolipoprotein A-IV, inter-alpha-trypsin inhibitor heavy chain H4, and histidine-rich glycoprotein.ConclusionsThe differentially expressed proteins we discovered in this study may serve as biomarkers in the diagnosis and follow-up of endometrial hyperplasia and endometrial carcinoma.

There was a higher incidence of SSI in low-risk patients in Vietnam compared with developed countries. Excessive reliance on antimicrobial therapy as a means to limit SSI places patients at higher risk of adverse effects from treatment and also may contribute to worsening problems with antimicrobial resistance. Establishment of an infection control program with guidelines for antimicrobial use should improve the use of prophylactic antibiotics and attention to proper surgical and wound-care techniques. These interventions also should reduce the incidence of SSI and its associated morbidity and costs.

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Patients with ovarian cancer frequently develop acquired drug resistance after the long-term chemotherapy, leading to disease progression. Enhanced epithelial-mesenchymal transition (EMT) has been implicated in chemoresistance of ovarian cancer cells; however, the molecular mechanisms involved are largely undefined. Pyruvate dehydrogenase kinase 1 (PDK1), a key regulatory enzyme in glucose metabolism, has been recognized as a gatekeeper of the Warburg effect, a hallmark of cancer. In this study, the function of PDK1 in cisplatin resistance of ovarian cancer in terms of growth and EMT was investigated. PDK1 was upregulated in cisplatin-resistant ovarian cancer cells. PDK1 knockdown in resistant cells led to increased sensitivity to cisplatin-induced cell death and apoptosis. PDK1 downregulation also reversed the EMT and cell motility in cisplatin-resistant cells. In a mouse xenograft model, tumors derived from PDK1-silenced ovarian cancer cells exhibited decreased tumor growth and EMT compared with control after the cisplatin treatment. Mechanistically, PDK1 overexpression led to increased phosphorylation of EGFR, and blocking EGFR kinase activity by erlotinib reversed cisplatin resistance induced by PDK1 overexpression. Furthermore, in patients with ovarian cancer, higher PDK1 and p-EGFR levels were associated with chemoresistance. These results supported that PDK1 contributes to chemoresistance of ovarian cancer by activating EGFR. Therefore, PDK1 may serve as a promising target to combat chemoresistance of ovarian cancer.

BACKGROUND: Extended high-risk human papillomavirus (hrHPV) genotype testing (hrHPVGT) has emerged as a new strategy to help optimize the efficiency of hrHPV triage. METHODS: Women with an atypical squamous cells of undetermined significance (ASC-US) cervical Papanicolaou test result who underwent hrHPVGT between October 2017 and May 2021 at the Obstetrics and Gynecology Hospital of Fudan University in Shanghai, China, were studied. For hrHPVGT, a proprietary multiplex real-time polymerase chain reaction assay was used. hrHPVGT and viral load test results in selected patients were correlated with histopathologic follow-up findings available within 6 months. RESULTS: In total, 17,235 women with ASC-US cytology who had hrHPVGT results were identified in the Obstetrics and Gynecology Hospital of Fudan University database. The hrHPV-positive rate was 61.8%, and the most prevalent hrHPV genotypes were type 52 (HPV52) (16%), HPV16 (11.3%), HPV58 (10.2%), and HPV53 (8.4%). Single hrHPV genotypes were detected in 65.9% of women with hrHPV-positive results, and multiple genotypes were detected in 34.1%. Histopathologic cervical findings within 6 months were available in 5627 hrHPV-positive women and 2223 hrHPV-negative women. High-grade cervical intraepithelial lesions or cervical cancer (cervical intraepithelial neoplasia 2 or greater [CIN2+]) were identified in 7.5% of hrHPV-positive women who had ASC-US cytology and in 0.9% of hrHPV-negative women who had ASC-US cytology. The greatest risk for CIN2+ was in single hrHPV genotype infections with HPV16 (21.1%), HPV33 (15.2%), HPV82 (10%), and HPV18 (9.9%). hrHPVGT for genotypes HPV16, HPV33, HPV82, HPV18, HPV31, HPV45, HPV58, and HPV52 identified 95% of CIN2+ cases with 90.8% sensitivity, 53.8% specificity, a positive predictive value of 10.2%, and a negative predictive value of 99%. A significantly increased viral load was associated only with women who had HPV16-related CIN2+. CONCLUSIONS: hrHPVGT for women who have ASC-US cytology allows for risk stratification capable of optimizing the efficiency of triage for hrHPV-positive women.

BackgroundThe tumour microenvironment conferred by mesenchymal stem cells (MSCs) plays a key role in tumour development and progression. We previously determined that platelet-activating factor receptor (PAFR) was overexpressed in ovarian cancer cells (OCCs) and that PAF can promote ovarian cancer progression via PAF/PAFR-mediated inflammatory signalling pathways. Evidence suggests that MSCs can secrete high concentrations of PAF. Here, we investigated the role of PAF/PAFR signalling in the microenvironment mediated by MSCs and OCCs and its effect on cancer progression.MethodsThe PAF concentrations in the culture media of MSCs, OCCs and co-cultured MSCs and OCCs were determined by ELISA. The effects of MSCs on OCCs in vitro were assessed on cells treated with conditioned medium (CM). The expression and phosphorylation of key proteins in the PAF/PAFR signalling pathway were evaluated. In vivo, MSCs/RFP and SKOV3 cells were co-administered at different proportions to nude mice by interscapular injection. Mice in the WEB2086 group were intraperitoneally injected with the PAFR antagonist WEB2086 at a dose of 1 mg/kg.d for the duration of the animal experiments. Tumour progression was observed, and the weight and survival time of mice were measured. The PAF concentration in peripheral and tumour site blood was determined by ELISA.ResultsHigh concentrations of PAF were detected in CM from MSCs and MSCs co-cultured with OCCs. Both types of medium promoted non-mucinous OCC proliferation and migration but had no effect on mucinous-type OCCs. These effects could be blocked by PAFR inhibitors. The expression and phosphorylation of key proteins in the PAF/PAFR pathway significantly increased upon treatment with PAF and MSC-CM. In vivo, the tumour volume was larger following co-injection of SKOV3 cells and MSCs/RFP than following injection of SKOV3 cells alone. The tumour-promoting effect of MSCs/RFP was blocked by the PAFR antagonist WEB2086. Serum PAF concentrations significantly increased in co-injected mice.ConclusionOur results suggest that the tumour-promoting effect of MSCs on OCCs via their cross-talk in the tumour microenvironment was, at least in part, mediated by the PAF/PAFR pathway, suggesting a new target for the treatment of ovarian cancer.