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Lu Zhang, Qing Wang, Hongwei Zhang, Yu Xie, Long Sui, Qing Cong Medical Center of Diagnosis and Treatment for Cervical Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Qing Cong; Long SuiMedical Center of Diagnosis and Treatment for Cervical Diseases, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of ChinaTel +86 15900798278; +86 13801788118Fax +86 21 33189900Email 151468770@qq.com; suilong@fudan.edu.cnPurpose: To examine the screening history of vaginal intraepithelial neoplasia (VaIN) and vaginal cancer.Patients and Methods: We included women with histologically confirmed VaIN or vaginal cancer by colposcopy-directed biopsy between 1 January 2019 and 31 December 2019. The results of cytology, hrHPV, colposcopic examination and history of hysterectomy were retrospectively analysed.Results: A total of 26,432 colposcopies were performed during the study period, among which 2131 women (1835 [86.1%] with VaIN 1; 268 [12.6%] with VaIN 2/3; and 28 [1.3%] with vaginal cancer) were retrospectively studied. hrHPV test positivity was significantly higher than that of cytology for VaIN 1 (84.4% vs 67.3%; P < 0.001) and VaIN 2/3 (92.0% vs 79.9%; P < 0.001) but not for vaginal cancer (84.6% vs 78.6%; P = 0.73). Additionally, the concordance rates for colposcopic impression were 79.5%, 54.5%, and 92.8% for VaIN1, VaIN2/3, and vaginal cancer, respectively. All 372 patients had a history of hysterectomy, and 81.0% (282/348) of indications were related to cervical precancer and cancer. Although cytology test positivity was significantly higher in patients with hysterectomy than in patients without hysterectomy (76.2% vs 67.5%; P < 0.001), cytology combined with hrHPV can help to detect more than 95% of VaIN and vaginal cancer cases in both groups (96.2% for patients with hysterectomy and 96.5% for patients without hysterectomy).Conclusion: VaIN and vaginal cancer are not rare diseases. Although cytology was sensitive (67.5%– 76.2%) for detecting vaginal lesions regardless of hysterectomy, cytology combined with hrHPV improves detection accuracy up to 95% in both groups.Keywords: cytology, human papilloma virus, colposcopy, vaginal intraepithelial neoplasia, vaginal cancer

Yanyun Li,1,&ast; Ying-Xin Gong,1,&ast; Qing Wang,1 Shujun Gao,1 Hongwei Zhang,1 Feng Xie,1 Qing Cong,1 Limei Chen,1 Qi Zhou,1 Zubei Hong,2 Lihua Qiu,2 Fang Li,3 Yu Xie,1 Long Sui1 1Department of Gynecology and Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Gynecology and Obstetrics, Renji Hospital of Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Gynecology and Obstetrics, Shanghai Dongfang Hospital of Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Long Sui; Yu XieObstetrics and Gynecology Hospital of Fudan University, 419 Fangxie Road, Shanghai, 200011, People’s Republic of ChinaTel +86-21-33189900Fax +86-21-63450900Email suilong@fudan.edu.cn; yuxie18@fudan.edu.cnPurpose: Early-stage cervical cancer is usually diagnosed by colposcopy-directed biopsy (CDB) and/or endocervical curettage (ECC), but some neglected lesions must be detected by conization because they are occult. This study aimed to explore the optimal method for detecting these “occult” cervical cancers.Patients and Methods: A total of 1299 patients who were high-risk for early-stage cervical cancer from five centres in China were prospectively included. We evaluated the diagnostic performance of cytology, HPV testing, colposcopy and CDB&ECC for detecting “occult” cervical cancer and discussed the diagnostic importance of transformation zone (TZ) type, conization length and the proportion of cervical cone excision.Results: The diagnostic agreement between colposcopy impression and conization was 64.5% and 72.4% between CDB&ECC and conization. Forty-two patients were finally diagnosed with pathologic cancer, and the sensitivities of cytology, colposcopy, CDB&ECC were 4.8%, 7.1%, and 47.4%, respectively. Twenty cases were neglected by CDB&ECC but further diagnosed as cancer by conization, considered to be occult cervical cancer, accounting for 1.6%. Cytologic high-grade squamous intraepithelial lesion (HSIL)+, positive HPV, biopsy HSIL+ and cervical TZ type 3 were considered risk factors for developing HSIL+, while colposcopy impression HSIL+ was not. There was a significant difference between cancerous and HSIL patients in the proportion of cervical cone excision (P< 0.001), which was recognized as a risk factor (P< 0.001) for detecting cancer, while the length of cervical cone excision was not. The average proportion was 0.62, and the minimal effective proportion was 0.56.Conclusion: Since the incidence of occult cervical cancer neglected by CDB&ECC, colposcopy and cytology was far beyond expectations, conization is necessary, especially in patients with TZ type 3, high-grade cytology and biopsy results. As the cervical length varies in patients, the proportion of cervical cone excision might be a better indicator for detecting occult cervical cancer.Keywords: cervical conization, colposcopy-directed biopsy, high-grade intraepithelial lesion, length proportion, occult cervical cancer, transformation zone

AIM To assess the performance of the apparent diffusion coefficient (ADC) and relative ADC (rADC) to differentiate benign from malignant breast lesions using the plateau pattern of the time–intensity curve (Type II TIC), including the impact of lesions-enhancement subtypes and menopausal status of patients. MATERIALS AND METHODS Between September 2016 and December 2019, 408 patients with 169 benign and 239 malignant lesions with Type II TIC underwent magnetic resonance imaging (MRI), including diffusion-weighted imaging, with b-values of 50 and 800 s/mm2. ADC and rADC values were calculated by placing regions of interest (ROIs) on the lesion, the parenchyma of the normal breast, and the pectoralis major muscle. A receiver operating characteristic (ROC) curve was generated to compare the diagnostic performance of each parameter in distinguishing between benign and malignant breast lesions. Further classification was undertaken to study the discriminatory performance of each parameter in the different lesions enhancement subtypes (mass-like enhancement [MLE] and non-MLE [NMLE]) and menopausal status of patients (pre-menopausal and post-menopausal). RESULTS There was a significant difference in the ADC and rADC values between benign and malignant lesions. The sensitivities of lesion ADC, gland rADC, and muscle rADC were 79.29%, 77.51%, and 79.29%, respectively, with specificities of 94.56%, 82.01%, and 94.98%, respectively. The area under the ROC curve (AUC) of muscle rADC was the highest (AUC=0.92), especially in the MLE subtype (AUC=0.96), and was not affected by the menopausal status. CONCLUSION Muscle rADC and lesion ADC assessment improved the diagnostic performance of breast MRI in distinguishing between benign and malignant breast lesions with Type II TIC, especially muscle rADC in the MLE subtype.

To systematically investigate the effect of imaging features at different DCE-MRI phases to optimise a radiomics model based on DCE-MRI for the prediction of tumour-infiltrating lymphocyte (TIL) levels in breast cancer. This study retrospectively collected 133 patients with pathologically proven breast cancer, including 73 patients with low TIL levels and 60 patients with high TIL levels. The volumes of breast cancer lesions were manually delineated on T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and each phase of DCE-MRI, followed by 6250 quantitative feature extractions. The least absolute shrinkage and selection operator (LASSO) method was used to select predictive feature sets for the classifiers. Four models were developed for predicting TILs: (1) single enhanced phase radiomics models; (2) fusion enhanced multi-phase radiomics models; (3) fusion multi-sequence radiomics models; and (4) a combined radiomics-based clinical model. Image features extracted from the delayed phase MRI, especially DCE_Phase 6 (DCE_P6), demonstrated dominant predictive performances over features from other phases. The fusion multi-sequence radiomics model and combined radiomics-based clinical model achieved the highest predictive performances with areas under the curve (AUCs) of 0.934 and 0.950, respectively; however, the differences were not statistically significant. The DCE-MRI radiomics model, especially image features extracted from the delayed phases, can help improve the performance in predicting TILs. The radiomics nomogram is effective in predicting TILs in breast cancer. • Radiomics features extracted from DCE-MRI, especially delayed phase images, help predict TIL levels in breast cancer. • We developed a nomogram based on MRI to predict TILs in breast cancer that achieved the highest AUC of 0.950.

Objectives. To evaluate the value of the whole volume apparent diffusion coefficient (ADC) histogram in distinguishing between benign and malignant breast lesions and differentiating different molecular subtypes of breast cancers and to assess the correlation between ADC histogram parameters and Ki-67 expression in breast cancers. Methods. The institutional review board approved this retrospective study. Between September 2016 and February 2019, 189 patients with 84 benign lesions and 105 breast cancers underwent magnetic resonance imaging (MRI). Volumetric ADC histograms were created by placing regions of interest (ROIs) on the whole lesion. The relationships between the ADC parameters and Ki-67 were analysed using Spearman’s correlation analysis. Results. Of the 189 breast lesions included, there were significant differences in patient age ( P < 0.001 ) and lesion size ( P = 0.006 ) between the benign and malignant lesions. The results also demonstrated significant differences in all ADC histogram parameters between benign and malignant lesions (all P < 0.001 ). The median and mean ADC histogram parameters performed better than the other ADC histogram parameters (AUCs were 0.943 and 0.930, respectively). The receiver operating characteristic (ROC) analysis revealed that the 10th percentile ADC value and entropy could determine the human epidermal growth factor receptor 2 (HER-2) status (both P = 0.001 ) and estrogen receptor (ER)/progesterone receptor (PR) status ( P = 0.020 and P = 0.041 , respectively). Among all breast cancer lesions, 35 tumours in the low-proliferation group ( Ki − 67 < 14 % ) and 70 tumours in the high-proliferation group ( Ki − 67 ≥ 14 ) were analysed with ROC curves and correlation analyses. The ROC analysis revealed that entropy and skewness could determine the Ki-67 status ( P = 0.007 and P < 0.001 , respectively), and there were weak correlations between ADC entropy ( r = 0.383 ) and skewness ( r = 0.209 ) and the Ki-67 index. Conclusion. The volumetric ADC histogram could serve as an imaging marker to determine breast lesion characteristics and may be a supplemental method in predicting tumour proliferation in breast cancer.

Background: Emerging evidences have indicated that the aberrant expression of long noncoding RNAs (lncRNAs) was responsible for drug resistance, which represents a major obstacle for chemotherapy failure. Our previous study has showed that small nuclear RNA host gene 12 (SNHG12) was increased and contributed to cell growth and invasion in cervical cancer. In the present study, we aimed to investigate the role of the lncRNA SNHG12 in cisplatin (DDP) resistance and elucidate its underlying mechanisms in cervical cancer.Methods: The expression and prognosis of SNHG12 in cervical cancer tissues were evaluated based on bioinformatics. MTT, colony formation assay and flow cytometer were performed to detect cell viability. Further, Molecular relationships among CTD-3252C9.4, IRF1 and IFI6 were investigated via luciferase reporter assay, western blot, and qRT-PCR. Finally, subcutaneous xenograft model was established to verify our findings.Results: In the present study, we evaluated the cell apoptosis and half maximal inhibitory concentration (IC50) of cervical cancer upon DDP treatment. Mechanically, we found that SNHG12 upregulated WEE1 expression to regulate cell and DDP resistance via sponging miR-503-5p. Moreover, SNHG12 silencing inhibited the growth of DDP-resistant cervical cancer tumors in vivo. Conclusions: Taken together, our findings suggested that a SNHG12/miR-503-5p/ WEE1 axis which modulated the chemoresistance of cervical cancer cell to DDP, and provided promising targets for dealing with the chemoresistance of cervical cancer.

The aim of the study was to investigate the value of cytology, high-risk human papillomavirus (hrHPV) status and colposcopy in the early diagnosis of vaginal cancer after hysterectomy.A retrospective study was performed in the Obstetrics and Gynecology Hospital of Fudan University. Posthysterectomy patients who were diagnosed with vaginal high-grade intraepithelial lesion (HSIL) by colposcopy-directed biopsy with colposcopy impression of extensive HSIL or suspicion of cancer and underwent upper or total vaginectomy from January 2009 to December 2017 were included.Eighty-six posthysterectomy vaginal HSIL patients were included. Available abnormal cytology and positive hrHPV were observed in 90.7% (49/54) and 96.2% (51/53) of the patients, respectively. A total of 18.6% (16/86) of the patients were diagnosed with squamous cell cancer by vaginectomy, and the average interval between hysterectomy and vaginectomy was 3.5 years. Among them, 62.5% (10/16) cancers occurred after hysterectomy for cervical cancer, 31.2% (5/16) after hysterectomy for cervical precancer, and 6.3% (1/16) after hysterectomy for myoma. An indication for hysterectomy (cervical cancer vs HSIL, odds ratio = 7.2, 95% CI = 1.9-28.0, p = .004) and colposcopy impression of vaginal cancer (vaginal cancer vs HSIL, odds ratio = 5.9, 95% CI = 1.3-26.8, p = .021) were high-risk factors of cancer confirmed by vaginectomy in colposcopy-directed biopsy vaginal intraepithelial neoplasia 2/3 posthysterectomy in multiple logistic regression analysis.Colposcopy is pivotal in the evaluation of abnormal cytology/hrHPV tests in follow-up of cervical cancer patients after hysterectomy and decision-making for vaginectomy in detecting early cancer.

Introduction We investigated the prevalence and carcinogenic risks of individual high-risk human papillomavirus (HR-HPV) in all types of cervical cytology specimens in the Shanghai population. Methods A total of 124,251 cases with cotesting of cytology and HPV genotyping between October 2017 and February 2020 were included. Results The overall HPV positive rate was 24.3%, with 22.9% for HR-HPV and 6.1% for low-risk HPV. The top five most common HR-HPV subtypes were HPV 52/16/58/53/39 in the entire studied population, and HPV 16/53/56/51/39 in women with abnormal cytology. The most prevalent subtypes in negative/LSIL, HSIL, and glandular lesions were HPV 52, 16, and 18, respectively. HPV 16, 33, 26, 18, 58, and 82 were the most common subtypes significantly associated with an increased risk for HSIL + cytology. HPV 16/18 were present in 53.6% and 66.7%, and HPV 16/18/31/33/45/52/58 were identified in 90.3% and 80.1% of HSIL and squamous cell carcinoma cytology, respectively. HPV 16/18 and HPV 16/18/31/33/45/52/58 were detected in 37.0% and 44.4% of women with cytologic interpretation of in situ and invasive adenocarcinoma. Conclusions This large-scale study identified the most common HPV subtypes in each cytology category, and the carcinogenic risks of individual HR-HPV in the studied Shanghai population. The results would provide valuable information for the development of next-generation HPV vaccines and cervical cancer screening programs for the Chinese population, and, more specifically, the Shanghai metropolitan population.

Objective The effect of lumbar traction on low back pain (LBP) patients is controversial. Our study aims to assess changes in the intervertebral disc water content after lumbar traction using T2 mapping and explore the correlation between changes in the T2 value and Oswestry Disability Index (ODI)/visual analogue scale (VAS) score. Design Lumbar spine magnetic resonance imaging was performed, and the ODI/VAS scores were recorded in all 48 patients. Midsagittal T2-weighted imaging and T2 mapping were performed to determine the Pfirrmann grade and T2 value. Then, the T2 values were compared between pre- and posttraction, and the correlation between changes in the T2 value and ODI/VAS scores were examined. Results In the traction group, the changes in the nucleus pulposus (NP) T2 values for Pfirrmann grades II-IV and the annulus fibrosus (AF) T2 values for Pfirrmann grade II were statistically significant after traction ( P < 0.05). Changes in the mean NP T2 value of 5 discs in each patient and in the ODI/VAS score showed a strong correlation ( r = 0.822, r = 0.793). Conclusion T2 mapping can be used to evaluate changes in the intervertebral disc water content. Ten sessions of traction resulted in a significant increase in quantitative T2 measurements of the NP in discs for Pfirrmann grade II-IV degeneration and remission of the patients’ clinical symptoms in the following 6 months. Changes in the mean NP T2 value of 5 discs in each patient were strongly correlated with changes in the ODI/VAS score.

Qing Cong,1,2,* Ling Lin,1,3,* Biao Qi,4 Congjian Xu,1,2 Xiaoyan Zhang1,2 1Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, People’s Republic of China; 3Institutes of Biomedical Sciences of Shanghai Medical School, Fudan University, Shanghai, People’s Republic of China; 4Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Congjian Xu; Xiaoyan ZhangDepartment of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, 200011, People’s Republic of ChinaEmail xucj@hotmail.com; zhxy@fudan.edu.cnPurpose: To alleviate the sufferings of the chemotherapy patients, we developed a novel active targeted therapeutic system and showed its potential as a promising drug delivery strategy.Methods: We utilized the human chorionic gonadotropin (HCG) ligand-receptor mediation to make an actively targeted drug delivery system with optimal HCG polypeptide fragment as target head base, polyethylene glycol–polylactic acid copolymers as nanometer materials to load chemotherapy drug methotrexate (MTX), to highly selectively deliver MTX into choriocarcinoma lesions, and to investigate the efficacy, targeting and tolerability of the complex in vitro experiments.Results: Our data show that choriocarcinoma cell lines JEG-3 and JAR exhibited high expression levels of HCG receptor, peptide HCGβ 81-95 specifically bonded to HCG receptor-positive cells and HCG81-NP efficiently delivered MTX to choriocarcinoma cells. HCG81-NP-MTX inhibited cell proliferation and reduced G0/G1 to S phase transition in JEG-3 and JAR cells.Conclusion: We designed an active targeting therapy system of choriocarcinoma, significantly improved chemotherapy efficacy in vitro, and provided a theoretical basis for the treatment of malignant trophoblastic tumors.Keywords: choriocarcinoma, human chorionic gonadotropin, nanoparticle, methotrexate, cell proliferation

PurposeTo assess whether apparent diffusion coefficient (ADC) metrics can be used to assess tumor-infiltrating lymphocyte (TIL) levels in breast cancer, particularly in the molecular subtypes of breast cancer.MethodsIn total, 114 patients with breast cancer met the inclusion criteria (mean age: 52 years; range: 29–85 years) and underwent multi-parametric breast magnetic resonance imaging (MRI). The patients were imaged by diffusion-weighted (DW)-MRI (1.5 T) using a single-shot spin-echo echo-planar imaging sequence. Two readers independently drew a region of interest (ROI) on the ADC maps of the whole tumor. The mean ADC and histogram parameters (10th, 25th, 50th, 75th, and 90th percentiles of ADC, skewness, entropy, and kurtosis) were used as features to analyze associations with the TIL levels in breast cancer. Additionally, the correlation between the ADC values and Ki-67 expression were analyzed. Continuous variables were compared with Student’s t-test or Mann-Whitney U test if the variables were not normally distributed. Categorical variables were compared using Pearson’s chi-square test or Fisher’s exact test. Associations between TIL levels and imaging features were evaluated by the Mann-Whitney U and Kruskal-Wallis tests.ResultsA statistically significant difference existed in the 10th and 25th percentile ADC values between the low and high TIL groups in breast cancer (P=0.012 and 0.027). For the luminal subtype of breast cancer, the 10th percentile ADC value was significantly lower in the low TIL group (P=0.041); for the non-luminal subtype of breast cancer, the kurtosis was significantly lower in the low TIL group (P=0.023). The Ki-67 index showed statistical significance for evaluating the TIL levels in breast cancer (P=0.007). Additionally, the skewness was significantly higher for samples with high Ki-67 levels in breast cancer (P=0.029).ConclusionsOur findings suggest that whole-lesion ADC histogram parameters can be used as surrogate biomarkers to evaluate TIL levels in molecular subtypes of breast cancer.

Lichen sclerosus (LS) is a chronic inflammatory disease with a potential for atrophy, destructive scarring, functional impairment, and increased risk of malignant evolution. 1 , 2 Notably, a significant number of LS patients are asymptomatic. It is most frequently seen in the anogenital area. 3 Women with vulvar LS often present with severe pruritus and soreness of the vulvar and perianal areas. 4 In advanced stages, there is destruction of the vulvar anatomy. 2 If untreated, it is associated with a 2% to 6% lifetime risk of malignant squamous neoplasia of the vulva. 5 , 6 , 7 Otherwise, potent topical corticosteroid is the gold standard for obtaining remission and reducing malignancy in vulvar LS. 7 , 8 Despite the possibility for treatment, the true etiology of LS remains unknown. 7 In long‐standing and classic LS, the lymphocytic infiltrate is located under a band of homogenized collagen below the dermo‐epidermal junction. 9 One study showed a significantly increase of pro‐inflammatory cytokines in LS patients. 10 We hypothesize that the elevated inflammation of LS leads to alteration of smooth muscle, subcutaneous adipose tissue, extracellular matrix (ECM), and innervation of the vulva and aim to evaluate the changes of tissues by testing the expression of marker genes. To avoid the disturbance of various treatments, only untreated patients were included for this study.

OBJECTIVE The aim of the study was to estimate risks of cervical intraepithelial neoplasia 2+ (CIN 2+) on loop electrosurgical excisional procedure (LEEP) specimens with the diagnosis of endocervical curettage (ECC) CIN 1 compared with biopsy CIN 1. MATERIALS AND METHODS We performed a retrospective computer-based search for subjects enrolled in the Obstetrics and Gynecology Hospital of Fudan University. The case group comprised women with an ECC CIN 1 (ECC results of CIN 1 with colposcopy-directed biopsy results ≤CIN 1), and the control group comprised women with a biopsy CIN 1 (colposcopy-directed biopsy results of CIN 1 with negative ECC findings) diagnosis. Variables, including age, cytology, high-risk human papillomavirus, and ECC results, were included in univariate and multivariate logistic regression analyses. p < .05 was defined statistically significant. RESULTS Overall, 1,195 women with ECC CIN 1 and/or biopsy CIN 1 diagnosis who underwent LEEP participated in the study. ECC CIN 1 comprised 400 women, with LEEP histopathology results revealing 104 (26.00%) CIN 2+. Biopsy CIN 1 comprised 795 women, with LEEP histopathology results showing 150 (18.87%) CIN 2+. Univariate logistic regression showed that cytology (p < .001) and ECC (p = .005) results differ significantly between less than CIN 2+ and CIN 2+. Multivariate logistic regression revealed that the cytology of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions (OR = 4.73, 95% CI = 2.78-8.05, p < .001) and high-grade squamous intraepithelial lesions or worse (HSIL+, OR = 4.88, 95% CI = 3.00-7.94, p < .001), and ECC CIN 1 (OR = 1.80, 95% CI = 1.33-2.44, p < .001) were risk factors for CIN 2 + . CONCLUSIONS Endocervical curettage CIN 1 has a greater risk of CIN 2+ diagnosis than biopsy CIN 1, but high-grade cytology has a higher risk than ECC CIN 1.

To save more lives, critically ill patients need to make timely decisions or predictive diagnosis and treatment in emergency and harsh conditions, such as earthquakes, medical emergencies, and hurricanes. However, in such circumstances, medical resources such as medical staff and medical facilities are short supply abnormally. So, we propose a method for decompensation prediction in emergency and harsh conditions. The method includes components such as patient information collection, data selection, data processing, and decompensation prediction. Based on this, this paper demonstrates the method using MIMIC-III data. Firstly, we tried a series of machine learning models to predict physiological decompensation. Secondly, to detect patients whose condition deteriorates rapidly under severe and limited circumstances, we try to reduce the essential physiological variables as much as possible for prediction. The experimental results show that the Bi-LSTM-attention method, combined with eleven essential physiological variables, can be used to predict the decompensation of severe ICUs patients. The AUC-ROC can reach 0.8509. Furthermore, these eleven physiological variables can be easily monitored without the need for complicated manual and massive, costly instruments, which meets the real requirements under emergency and harsh conditions. In summary, our decompensation prediction method can provide intelligent decision support for saving more lives in emergency and harsh conditions.

The high mortality rate of ovarian cancer is connected with the development of acquired resistance to multiple cancer drugs, especially cisplatin. Activation of cytoprotective autophagy has been implicated as a contributing mechanism for acquired cisplatin resistance in ovarian cancer cells. Hexokinase 2 (HK2) phosphorylates glucose to generate glucose-6-phosphate, the rate-limiting step in glycolysis. Higher HK2 expression has been associated with chemoresistance in ovarian cancer. However, whether HK2 functionally contributes to cisplatin resistance in ovarian cancer is unclear. In this study, we investigated the role of HK2 in regulating ovarian cancer cisplatin resistance. Increased HK2 levels were detected in drug-resistant human ovarian cancer cells and tissues. Cisplatin downregulated HK2 in cisplatin-sensitive but not in resistant ovarian cancer cells. HK2 knockdown sensitized resistant ovarian cancer cells to cisplatin-induced cell death and apoptosis. Conversely, HK2 overexpression in cisplatin-sensitive cells induced cisplatin resistance. Mechanistically, cisplatin increased ERK1/2 phosphorylation as well as autophagic activity. Blocking autophagy with the autophagy inhibitor 3-MA sensitized resistant ovarian cancer cells to cisplatin. HK2 overexpression enhanced cisplatin-induced ERK1/2 phosphorylation and autophagy while HK2 knockdown showed the opposite effects. Blocking the MEK/ERK pathway using the MEK inhibitor U0126 prevented cisplatin-induced autophagy enhanced by HK2 overexpression. Furthermore, HK2 knockdown sensitized resistance ovarian tumor xenografts to cisplatin in vivo. In conclusion, our data supported that HK2 promotes cisplatin resistance in ovarian cancer by enhancing drug-induced, ERK-mediated autophagy. Therefore, targeting HK2 may be a new therapeutic strategy to combat chemoresistance in ovarian cancer.

Purpose To assess the diagnostic accuracy of magnetic resonance (MR) imaging for differentiating stage T1 or lower tumors from stage T2 or higher tumors and to analyze the influence of different imaging protocols in patients with bladder cancer. Materials and Methods A systematic literature search for original diagnostic studies was performed in PubMed, Medline, the Cochrane Library, and Web of Science. The methodologic quality of each study was evaluated by two independent reviewers who used the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Data necessary to complete 2 × 2 tables were obtained, and patient, study, and imaging characteristics were extracted. Statistical analysis included data pooling, heterogeneity testing, sensitivity analyses, and forest plot construction. Results Seventeen studies (1449 patients with bladder cancer) could be analyzed. The pooled sensitivity and specificity of MR imaging were 0.90 (95% confidence interval [CI]: 0.83, 0.94) and 0.88 (95% CI: 0.77, 0.94), respectively, for differentiating tumors staged T1 or lower from those staged T2 or higher. Diffusion-weighted imaging and use of higher field strengths (3 T) improved sensitivity (0.92; 95% CI: 0.86, 0.96) and specificity (0.96; 95% CI: 0.93, 0.98). Conclusion This meta-analysis demonstrated high diagnostic performance of MR imaging for differentiating T1 or lower tumors from T2 or higher tumors in patients with bladder cancer. Higher field strength (3 T) and the use of diffusion-weighted imaging can slightly help improve sensitivity and specificity.

Endocervical curettage (ECC) is an optional practice during colposcopy, and the indication for endocervical curettage (ECC) is controversial between Europe and the USA. Here, we explored the value of ECC in a specific situation. An elderly post-loop electrosurgical excision procedure woman, who had undergone a colposcopy 4 months before, went for her follow-up and abnormal cytology was found, and both the ECC and punch biopsy showed negative results. Then, a second ECC was performed, which led to the diagnosis of a high-grade squamous intraepithelial lesion. This case report shows that ECC is useful for diagnosing elderly women with Type 3 squamocolumnar junction.

Purpose To evaluate the utility of the whole-lesion histogram apparent diffusion coefficient (ADC) for characterizing the heterogeneity of mucinous breast carcinoma (MBC) and to determine which ADC metrics may help to best differentiate subtypes of MBC. Materials and Methods This retrospective study involved 52 MBC patients, including 37 pure MBC (PMBC) and 15 mixed MBC (MMBC). The PMBC patients were subtyped into PMBC-A (20 cases) and PMBC-B (17 cases) groups. All patients underwent preoperative diffusion-weighted imaging (DWI) at 1.5T and the whole-lesion ADC assessments were generated. Histogram-derived ADC parameters were compared between PMBC vs. MMBC and PMBC-A vs. PMBC-B, and receiver operating characteristic (ROC) curve analysis was used to determine optimal histogram parameters for differentiating these groups. Results The PMBC group exhibited significantly higher ADC values for the mean (P = 0.004), 25th (P = 0.004), 50th (P = 0.004), 75th (P = 0.006), and 90th percentiles (P = 0.013) and skewness (P = 0.021) than did the MMBC group. The 25th percentile of ADC values achieved the highest area under the curve (AUC) (0.792), with a cutoff value of 1.345 × 10−3mm2/s, in distinguishing PMBC and MMBC. The PMBC-A group showed significantly higher ADC values for the mean (P = 0.049), 25th (P = 0.015), and 50th (P = 0.026) percentiles and skewness (P = 0.004) than did the PMBC-B group. The 25th percentile of the ADC cutoff value (1.476 × 10−3mm2/s) demonstrated the best AUC (0.837) among the ADC values for distinguishing PMBC-A and PMBC-B. Conclusion Whole-lesion ADC histogram analysis enables comprehensive evaluation of an MBC in its entirety and differentiating subtypes of MBC. Thus, it may be a helpful and supportive tool for conventional MRI. Level of Evidence: 4 Technical Efficacy Stage 2 J. Magn. Reson. Imaging 2017.

To investigate whether whole-tumor apparent diffusion coefficient (ADC) histogram analysis could be helpful to evaluate breast phyllode tumor (PT) grades.This institutional review board-approved retrospective study included 56 PTs (23 benign lesions, 22 borderline lesions, and 11 malignant lesions) from August 2011 to November 2017. MRI was performed using a 1.5 T MR system equipped with a 4-channel SENSE breast coil. All cases were divided into two groups, benign PT (BPT) and borderline or malignant PT (BMPT). The conventional MR parameters included age, longest diameter, shape, margin, internal enhancement characteristics, cystic component of the tumor, wall of the cystic component, peritumoral edema on T2-weighted imaging (T2WI), T1-weighted imaging (T1WI) and T2WI signal intensity, time-signal intensity curve (TIC) patterns and early-stage enhancement ratio (EER). The ADC values were determined in three different types of regions of interest (ROIs), including a circular ROI (ROI-c), single-slice ROI (ROI-s), and whole-tumor ROI (ROI-w). All ADC values were measured twice by Observer A and B (with a 2-week interval). The Ki-67 index was determined, and cases were classified into a "negative group" (Ki-6714%) and a "positive group" (Ki-67≥14%). SPSS Statistics V21.0 was used for the statistical analyses.Our study included 23 cases of BPT and 33 cases of BMPT (including 22 borderline PTs and 11 malignant PTs). Only 23 patients in BMPT group had Ki-67 results, and 17 of these were positive. Regarding conventional MR features, significant differences were observed in the margin (P = 0.011), cystic component (P0.001), peritumoral edema on T2WI (P0.001), and cystic wall (P = 0.011) of the PT between the BPT and BMPT groups. Regarding the ADC value, good intraobserver agreement for ROI-c, ROI-s and ROI-w measurements was obtained. For the three different ROIs, the intraclass correlation coefficient (ICC) values were 0.905 for ROI-c (P 0.05), 0.965 (P 0.05) for ROI-s and 0.994 (P 0.05) for ROI-w. ADC parameter indicated that the figure of ROI-s tended to be higher than the ROI-c and ROI-w, while the ROI-c and ROI-w values were similar. However, no significant difference was found in ADC values between the BPT and BMPT groups for ROI-c, ROI-s and mean ROI-w values and the 10th, 25th, 50th and 75th ROI-w. The areas under the ROC curves for the mean ROI-w and the 10th, 25th, 50th and 75th ROI-w were 0.568, 0.613, 0.567, 0.544, and 0.540, respectively.Based on the results obtained in our study, the whole-tumor ADC histogram could not improve differentiation of the breast PT grade, while conventional MR images could provide more meaningful information, so morphological characteristics may be valuable than ADC value, and ADC could be used as a supplemental method to differentiate PT grades.

In this study, we established a long-term three-dimensional (3D) culture system by using integrin ligand modified alginate hydrogels to encapsulate and differentiate neural progenitor cells (NPCs) toward oligodendrocyte (OL) lineage cells. The porosity of the hydrogel was optimized by varying the alginate concentrations and then characterized by scanning electronic microscopy (SEM). The surface plasmon resonance (SPR) test was used to confirm the ligand-integrin interactions indicating adherence between the NPC surfaces and the hydrogels. Following encapsulation in the hydrogels, both mouse and human NPC sphere cultures could be maintained up to 90 days. Mouse NPC spheres were differentiated into viable neurons, astrocytes and mature OLs by day 60 in all groups whereas human NPC spheres were differentiated into neurons and later into GFAP positive astrocytes and O4 positive pre-OL within 90 days. The species difference in the timeline of OL development between mouse and human was reflected in this system. The ligand LXY30 interacting with the α3β1 integrin receptor was more effective in promoting the differentiation of hNPCs to OL lineage cells compared with the ligand LXW64 interacting with the αvβ3 integrin receptor, hyaluronic acid interacting with CD44 receptor or without any ligand. This study is the first to differentiate O4+ pre-OLs from hNPCs in a LXY30-α3β1 (integrin-ligand) modified alginate 3D hydrogel culture. This 3D platform could serve as a valuable tool in disease modeling, drug discovery, and NPC transplantation.

Background The 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. Methods The 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. Results High 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. Conclusion Our 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.

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.

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.

Punch biopsy is important in the diagnosis of cervical cancer. However, it may fail to detect early cervical cancers. A retrospective study was performed in the largest academic women’s hospital in China to demonstrate cervical cancer that colposcopy-directed biopsy failed to detect. Methods. Patients who were diagnosed with high-grade squamous intraepithelial lesion (HSIL), adenocarcinoma in situ (AIS), and persistent low-grade squamous intraepithelial lesion (LSIL) via colposcopy-directed biopsy and had further undergone loop electrosurgical excision procedure (LEEP) conization were included. These procedures were performed at Obstetrics and Gynecology Hospital of Fudan University from July 1, 2013, to December 31, 2016. In total, 5.98% (760/12714) of patients who underwent conization were diagnosed with invasive cervical cancer. Persistent LSIL (0.24%), HSIL (6.37%), and AIS (24.31%) were detected cancer by conization. Histological subtypes included squamous cell carcinoma (92.0%), adenocarcinoma (5.1%), adenosquamous carcinoma (1.8%), adenoid basal type carcinoma (0.9%), and small cell neuroendocrine carcinoma (0.1%). Cytology reports consisted of HSIL (45.4%), atypical squamous cells of undetermined significance (ASC-US) (16.1%), and LSIL (11.6%), and atypical squamous cells cannot exclude HSIL (ASC-H) (9.3%), squamous cell carcinoma (0.9%), AGC (atypical glandular cells, 0.9%), AIS (0.4%), and NILM (negative for intraepithelial lesion or malignancy, 15.4%). The sensitivity of high-risk human papillomavirus (hrHPV) screening (96.4%) was significantly higher than that of cytology (84.6%) (P<0.01), with sensitivity of cotesting at 99.8% and a ratio of double-negative results at 0.2%. The sensitivity of cytology and hrHPV screening of different cervical cancer histologic subtypes was also demonstrated. In this large retrospective study, we systematically reported the cytology, hrHPV, pathology, and stages of cervical cancer that colposcopy-directed biopsy failed to detect.

Ginkgolide B (GB), the primary active component of Ginkgo biloba extracts, may have antitumor properties. The objective of this study was to determine the effects and possible mechanisms of GB in ovarian cancer cells. In this study, human ovarian cancer cell lines (SKOV3 and CAOV3) were treated with different concentrations of GB alone or in combination with Cis-diaminodichloroplatinum (CDDP). An MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was performed to determine cell viability. The apoptosis rates of cells were measured by flow cytometric analysis. The expression of apoptosis-associated and proliferation-associated proteins was detected by Western blot. The cytotoxicity of GB was analyzed using a lactate dehydrogenase assay. Treatment with 100 µM GB for 3 days significantly inhibited SKOV3 and CAOV3 cell proliferation by 57.3% and 63.1% compared with control cells, respectively, as determined by MTT assay. Similarly, the apoptotic cell population was increased when treated with GB in a dose-dependent manner both in SKOV3 and CAOV3 cells. These effects were characterized by the upregulation of p21, p27, cleaved capase-3, and cleaved caspase-8 and downregulation of cyclin D1. In addition, a combined treatment of low concentrations of GB and CDDP showed an additive effect on the inhibition of SKOV3 cell proliferation. Furthermore, GB had significantly less cytotoxicity than CDDP in normal human ovarian surface epithelial cells. This study suggests that GB can be proposed as an effective antiproliferative and apoptosis-inducing agent with interesting translational application in ovarian cancers, used in addition to conventional chemotherapy.

To observe the therapeutic efficacy of Danggui Buxue Decoction No.1 (当归补血汤1号, DB1) in treating patients of non-small cell lung cancer (NSCLC) at the peri-operational stage and its impact on the patients’ immune function. Eighty-two NSCLC patients were randomly assigned to two groups equally, the control group and the test group, they were given conventional treatment, while to the test group, DB1 were given additionally. The observation was conducted by testing the changes of T-lymphocyte subsets, natural killer (NK) cell activity, serum levels of immunoglobulin (IgA, IgM, IgG), interleukin-2 (IL-2), tumor necrosis factor α (TNF-α), cytokeratin fragment 19 (CYFRA21-1) and carcinoembryonic antigen (CEA) in NSCLC patients before and after administration of DB1, and analyzing the patients’ general condition. The level of CD3+, CD4+, the ratio of CD4 and CD8+, IgA, IgM, IgG and IL-2 decreased in patients with NSCLC on day 1 after operation, and the level of CD8 and TNF-α increased compared to pre-operation. While the levels of CD3+, CD4+, CD4 /CD8+, NK cell activity, serum IgA, IgM, IgG, IL-2 began to elevate, CD8 and TNF-α levels began to decline in patients administered with DB1 on day 3 after the operation, earlier than patients who did not use the decoction. The level of CYFRA21-1 and CEA, was immediately decreased after operation in both groups. Applying DB1 to NSCLC patients at an early post-operational stage could alleviate the impairment and accelerate the recovery of immune function of patients to enhance their immunity. DB1 also shows an anti-tumor action to a certain degree.

Catalyst regeneration and the retention of high catalytic activity are still the critical issues in environmental application. A novel fluidized gas–liquid–solid electrochemical reactor was developed to simultaneously remove chlorinated pollutants and in situ regenerate the spent catalyst. Activated carbon modified with palladium catalyst (AC–Pd) was prepared for electrochemical dechlorination. For the 4-chlorophenol wastewater of initial concentration 200 mg L −1 , the removal efficiency could nearly reach 100% in less than 30 min. Catalytic activity of AC–Pd catalyst was preserved effectively even in consecutive cycling run without special regeneration. OH radicals, generated by electrochemical reaction, played a critical role in self-regeneration of AC–Pd. High catalytic activity of spent AC–Pd catalyst provided an attractive alternative in wastewater treatment.

Gestational diabetes mellitus (GDM) presents with moderate inflammation, insulin resistance and impaired glucose uptake, which may result from increased maternal fat mass and increased circulation of placental hormones and adipokines. In this study, we set out to test whether the surge in chorionic gonadotrophin (CG) secretion is a cause of inflammation and impaired insulin sensitivity in GDM. We first found that LH/chorionic gonadotrophin receptors (CG/LHR) were expressed at low levels in insulin-sensitive murine 3T3-L1 adipocytes and murine C2C12 myocytes. CG treatment not only directly reduced insulin-responsive gene expression, including that of glucose transporter 4 (GLUT4), but also impaired insulin-stimulated glucose uptake in 3T3-L1 cells. Moreover, CG treatment increased the expression of the proinflammatory cytokine monocyte chemotactic protein 1 (MCP1) and upregulated nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activity in 3T3-L1 cells. Clinically, pregnant women who had higher CG levels and elevated MCP1 developed GDM. Above all, apart from prepregnancy BMI and MCP1 level, CG level was associated with abnormal glucose tolerance. In summary, our findings confirmed that higher CG levels in pregnancy possibly played a role in GDM development partly by impairing the functions of insulin, such those involved in as glucose uptake, while promoting inflammation in adipocyte.

Autophagy is a dynamic and highly regulated process of self-digestion responsible for cell survival and reaction to oxidative stress. As oxidative stress is increased in uremia and is associated with vascular calcification, we studied the role of autophagy in vascular calcification induced by phosphate. In an in vitro phosphate-induced calcification model of vascular smooth muscle cells (VSMCs) and in an in vivo model of chronic renal failure, autophagy was inhibited by the superoxide dismutase mimic MnTMPyP, superoxide dismutase-2 overexpression, and by knockdown of the sodium-dependent phosphate cotransporter Pit1. Although phosphate-induced VSMC apoptosis was reduced by an inhibitor of autophagy (3-methyladenine) and knockdown of autophagy protein 5, calcium deposition in VSMCs was increased during inhibition of autophagy, even with the apoptosis inhibitor Z-VAD-FMK. An inducer of autophagy, valproic acid, decreased calcification. Furthermore, 3-methyladenine significantly promoted phosphate-induced matrix vesicle release with increased alkaline phosphatase activity. Thus, autophagy may be an endogenous protective mechanism counteracting phosphate-induced vascular calcification by reducing matrix vesicle release. Therapeutic agents influencing the autophagic response may be of benefit to treat aging or disease-related vascular calcification and osteoporosis.

Background Ovarian cancer is predominant of epithelial cell origin and often present at an advanced stage with poor prognosis. Most animal models of ovarian carcinoma yield thecal/granulose cell tumors, rather than adenocarcinomas. The best reported induction rate of adenocarcinoma in rats is 10-45% by an ovarian implantation of 7, 12-dimethylbenz[a]anthracene (DMBA) coated silk suture. We provided an improved procedure to construct the model by the ovarian implantation of DMBA-coated cloth strip. Methods A sterile suture (as S group) or a piece of cloth strip (as CS group) was soaked in DMBA before ovarian implantation in Wistar rats. Tumor size, incidence rate and pathological type were analyzed. Results Ovarian tumors in rats of CS group were first noted at 16 wk post implantation and reached a cumulative incidence of 75% (96/128) at 32 wk, while the tumor incidence rate in S group at 32 wk was only 46.25% (37/80). The tumor size in CS group (3.63 ± 0.89 cm) was larger than that of S group (2.44 ± 1.89 cm) (P Conclusion The model in our study yields much higher incidence and specificity of epithelial derived tumors and showed histological similarities to human ovarian cancers, which would be more suitable for therapeutic research.

PURPOSE We performed an observational study over 5 years on patients with postoperative ascites who had undergone laparoscopic surgery in our hospital. METHODS Patients with postoperative ascites of unknown origin were monitored in the hospital from July 2006 to June 2010. Clinical manifestations, biochemical analysis, and treatment are discussed in the study. RESULTS Of 21,380 laparoscopic surgeries, 8 cases of postoperative ascites of unknown origin were identified in otherwise healthy women. None of the patients revealed any definitive causes even after an extensive diagnostic work-up and recovered uneventfully with general supportive treatments. CONCLUSIONS Postoperative ascites of unknown origin are a rare complication of laparoscopic gynecologic surgery. We surmised that the most likely cause of the ascites is a diffuse peritoneal injury by some substances used during the operation, and supportive therapy is very important.

Women carrying BRCA1 mutations have a higher risk of developing ovarian cancers. Options to reduce this risk are largely limited to prophylactic surgery, which leads to a decrease in the quality of life and permanently damages fertility. There is a obvious and an urgent need to identify a noninvasive approach to effectively prevent the ovarian cancer risk, specifically for those women of reproductive age. Our previous studies showed that the use of the herbal remedy Ginkgo biloba may reduce the risk for nonmucinous ovarian cancer. Here, we explored whether Ginkgo biloba might also be an effective agent to reduce BRCA1-associated ovarian cancer (always serous-type) risk. A human ovarian surface epithelial cell line-636 was developed from a BRCA1-mutant carrier. Cells were treated with ginkgolide B (GB) or dimethyl sulfoxide, and protein lysates from the cells were applied to antibody microarrays to determine upregulated or downregulated protein expression patterns. Anticancer activities and the associated networking pathways with the altered proteins were analyzed by using the Pathway Studio software. After GB treatment, 28 proteins were shown to be consistently upregulated (1.5-15.5-fold), and 22 proteins were downregulated (1.5-28.3-fold). Bioinformatics software analysis indicated that multiple mechanisms and signal pathways are involved in anticancer activities in BRCA1-mutant cells induced by GB treatment. These pathways include cell proliferation, tumor suppression, and DNA damage repair. Our study suggested that GB found in the herbal Ginkgo biloba may have cancer-preventive activities in BRCA1-mutant ovarian epithelial cells.

Background Endometrial 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. Methods In 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. Results In 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. Conclusions The differentially expressed proteins we discovered in this study may serve as biomarkers in the diagnosis and follow-up of endometrial hyperplasia and endometrial carcinoma.