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Circulating tumor cells (CTCs) have considered to be promising liquid biopsy in cancer due to the intact information of whole cells and the potential to reflect micrometastasis. However, CTCs research are extremely limited in ovarian cancer, probably due to their rarity. The predictive value of CTCs and circulating tumor microemboli (CTM) in metastasis remains to be elucidated in ovarian cancer. This study tried to identify CTCs/CTM in ovarian cancer with considerably positive rate. To preliminarily identify the invasive capacity of CTCs/CTM, the epithelial-mesenchymal transition (EMT) patterns of CTCs/CTM was evaluated. Moreover, for comprehensive understanding of invasiveness of disseminated cells in ovarian cancer, EMT pattern of exfoliated tumor cells in ascites were also confirmed in this study.Peripheral blood samples and ascites samples were collected from 22 ovarian cancer patients. The Microfiltration combined with morphological analysis was used to detect CTC single cells or cell clusters. Microfiltration combined with morphological analysis was applied in the CTC isolation and identification. EMT was evaluated by immunofluorescence via markers including vimentin and cytokeratin.Microfiltration combined with morphological analysis was introduced to detect CTCs/CTM with a positivity rate of 40.9% in ovarian cancer patients. The number of CTC varied from 1 to 8, with CTM number from 4 to 30. CTCs/CTM of all samples have experienced EMT process. Vimentin was expressed in all CTC samples and all tumor cells in ascites, while cytokeratin was expressed in 44.4% (4/9) of CTC samples. There were no significant differences of the clinical parameters between the CTC-positive and CTC-negative patients.This study showed that both CTCs/CTM and detached tumor cells in ascites might have undergone complete or partial EMT in ovarian cancer. Moreover, microfiltration combined with cytomorphological analysis showed a considerable CTC detection rate.

Objective: This study aimed to investigate the optimal depth of vulvar intraepithelial neoplasia (VIN) and involved skin appendages to provide evidence for treatment. Methods: The study retrospectively enrolled and analyzed the clinical characteristics of all VINs in the obstetrics and gynecology department of a university hospital from January 1, 2019, to December 30, 2021. The study further explored the thickness of epithelium and skin appendages of 285 women with low-grade VIN (VIN 1) and 285 women with high-grade VIN (VIN 2/3). Results: The study included 1,474 VINs: 1,139 (80%) VIN 1 and 335 (20%) VIN 2/3 cases. The VIN 1 and VIN 2/3 groups showed a significant difference in HPV infection (PConclusions: VIN thickness was generally ≤1 mm for the superficial lesions in non-hairy areas. Lesions extending onto hairy areas were about 3 mm, destroying involved skin appendages.

The value of extended high-risk human papillomavirus (hrHPV) genotyping for cervical cancer screening in women with low-grade squamous intraepithelial lesion (L-SIL) cytology has been recognized, but few studies have investigated this.Women with L-SIL Papanicolaou results who underwent human papillomavirus (HPV) genotyping between October 2017 and October 2021 at the Obstetrics and Gynecology Hospital of Fudan University were identified. Their HPV results were correlated with immediate histopathologic follow-up findings.In total, 8726 women who had L-SIL cytology and extended HPV genotyping results were analyzed. The overall hrHPV-positive rate was 84% in women with L-SIL, and the most prevalent hrHPV genotypes were type 52 (HPV52) (20.7%), HPV53 (15.7%), and HPV16 (14.3%). Single and multiple coinfections of hrHPV genotypes were detected in 57.2% and 42.8% of women with positive hrHPV results, respectively. Cervical intraepithelial neoplasia grade ≥2 (CIN2+) was identified in 8.5% of hrHPV-positive women. The CIN2+ detection rate in women who had multiple hrHPV infections (9.9%) was significantly higher than the rate in those who had infection with a single HPV type (7.2%). The top 5 CIN2+-associated HPV infections were HPV16 (25.2%), HPV82 (17.8%), HPV33 (16.3%), HPV31 (14.6%), and HPV26 (13.8%). For the composite group with HPV types HPV16, HPV26, HPV82, HPV31, HPV18, HPV33, HPV58, HPV35, HPV52, and HPV51, the risk of CIN2+ was 11.5% and represented 97.1% of all CIN2+ in biopsied, hrHPV-positive patients. The composite group of 8 remaining HPV genotypes (HPV39, HPV45, HPV53, HPV56, HPV59, HPV66, HPV68, and HPV73) was identified in 29.7% of hrHPV-positive patients, and the risk of CIN2+ for this composite group was similar to the risk of CIN2+ in hrHPV-negative patients.This large retrospective study in a predominantly unvaccinated cohort demonstrated that extended hrHPV genotyping improves genotype-specific risk stratification in women with L-SIL.

Although carbon dioxide laser vaporization is frequently used for treating vaginal intraepithelial neoplasia (VaIN), the optimal depth of epithelial destruction with laser vaporization requires elucidation. We aimed to evaluate VaIN depth and better illustrate epithelial destruction during laser vaporization.We included 246 women diagnosed with VaIN (low-grade VaIN [VaIN 1], 123 women; high-grade VaIN [VaIN 2/3], 123 women) using colposcopy-directed biopsy at our hospital from January 1, 2019, to April 30, 2020. The thickness of the noninvolved epithelium, if available, was determined. All available data, including cytology and histological information, were recorded. The t test and Pearson χ 2 test were used for statistical analysis. Statistical significance was set at p.05.The involved epithelial thicknesses in VaIN 2/3 and VaIN 1 were 0.41 ± 0.21 and 0.40 ± 0.19 mm, respectively, which were both greater than their noninvolved epithelial thickness values (0.17 ± 0.10 and 0.17 ± 0.08 mm, p.01 and p.01, respectively). In subgroup comparisons between the VaIN 2/3 and VaIN 1 groups, the involved epithelial thickness did not differ between premenopausal patients, postmenopausal women receiving estrogen, and postmenopausal women who did not receive estrogen ( p.05). In the VaIN 2/3 group, the lesion thickness in premenopausal was greater than that in postmenopausal women receiving estrogen ( p = .016) and those who were not receiving estrogen ( p = .017).The thickness of VaIN is generally less than 1 mm for women of all ages, except in rare cases of visible lesions with papillary hyperplasia.

ObjectivesWe investigated HPV genotypes in a large cohort of patients with definitive cervical histologic diagnosis.MethodsHPV testing was performed by real-time PCR assay, including 18 high-risk HPV (hrHPV) and 3 low-risk HPV (lrHPV). Totally 61,422 patients with documented HPV genotyping results within 6 months before cervical histologic diagnoses were included.ResultsHrHPV positive rate was 55.1% among all tested cases with the highest in adenosquamous carcinoma (94.1%), followed by squamous cell carcinoma (SCC) (93.7%), cervical intraepithelial neoplasia 2/3 (CIN2/3) (92.8%). HrHPV positive rates were significantly higher in high-grade squamous lesions than in those in glandular lesions. HPV16 was the most common genotype followed by HPV52 and HPV58 in CIN2/3. The most frequent hrHPV genotype in adenocarcinoma in situ (AIS) was HPV18, followed by HPV16, HPV45 and HPV52. In SCC cases, HPV16 was the most common type followed by HPV58, HPV52, HPV18 and HPV33. However, HPV18 showed significantly higher prevalence in adenocarcinoma and adenosquamous carcinoma than in that in SCC. Theoretically, the protective rates of 2/4-valent and 9-valent vaccine were 69.1% and 85.8% for cervical cancers.ConclusionsThe prevalence of HPV genotypes in Chinese population was different from that in Western population. Some hrHPV types were identified in cervical precancerous lesions and cancers, which are not included in current HPV vaccines. These data provide baseline knowledge for future HPV vaccine development.

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

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.

ObjectivesTriple-negative breast cancer (TNBC) is a heterogeneous disease, and different histological subtypes of TNBC have different clinicopathological features and prognoses. Therefore, this study aimed to establish a nomogram model to predict the histological heterogeneity of TNBC: including Metaplastic Carcinoma (MC) and Non-Metaplastic Carcinoma (NMC).MethodsWe evaluated 117 patients who had pathologically confirmed TNBC between November 2016 and December 2020 and collected preoperative multiparameter MRI and clinicopathological data. The patients were randomly assigned to a training set and a validation set at a ratio of 3:1. Based on logistic regression analysis, we established a nomogram model to predict the histopathological subtype of TNBC. Nomogram performance was assessed with the area under the receiver operating characteristic curve (AUC), calibration curve and decision curve. According to the follow-up information, disease-free survival (DFS) survival curve was estimated using the Kaplan-Meier product-limit method.ResultsOf the 117 TNBC patients, 29 patients had TNBC-MC (age range, 29–65 years; median age, 48.0 years), and 88 had TNBC-NMC (age range, 28–88 years; median age, 44.5 years). Multivariate logistic regression analysis demonstrated that lesion type (p = 0.001) and internal enhancement pattern (p = 0.001) were significantly predictive of TNBC subtypes in the training set. The nomogram incorporating these variables showed excellent discrimination power with an AUC of 0.849 (95% CI: 0.750−0.949) in the training set and 0.819 (95% CI: 0.693−0.946) in the validation set. Up to the cutoff date for this analysis, a total of 66 patients were enrolled in the prognostic analysis. Six of 14 TNBC-MC patients experienced recurrence, while 7 of 52 TNBC-NMC patients experienced recurrence. The DFS of the two subtypes was significantly different (p=0.035).ConclusionsIn conclusion, we developed a nomogram consisting of lesion type and internal enhancement pattern, which showed good discrimination ability in predicting TNBC-MC and TNBC-NMC.

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.

The monitoring of immunotherapies is still based on changes in the tumor size in imaging, with a long evaluation period and low sensitivity.To investigate the effectiveness of diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the therapeutic efficacy of anti-programmed death-1 (PD-1) therapy in a mouse triple negative breast cancer (TNBC) model.Prospective.A total of 54 BALB/c mouse subcutaneous 4 T1 transplantation models of TNBC.A 3.0-T; turbo spin echo (TSE) T2-weighted imaging, DKI with seven b values (0, 500, 1000, 1500, 2000, 2500, and 3000 sec/mmDKI and DCE-MRI parameters were evaluated by two radiologists independently. Regions of interest (ROIs) were drawn manually on the maximum cross-sectional area of the lesion; care was taken to avoid necrotic areas. The tumor cell density, the CD45 and CD31 levels were analyzed by two pathologists.The two-tailed unpaired t-test, Mann-Whitney U test, Fisher's exact test and Pearson correlation coefficient were performed. A P 0.05 was considered statistically significant.The apparent diffusion coefficient (ADC), mean diffusivity (MD), KDKI and DCE-MRI could reflect the changes in tumor microstructure and tumor tissue vasculature after anti-PD-1 therapy, respectively.1 TECHNICAL EFFICACY: Stage 4.

Extended high-risk human papillomavirus (hrHPV) genotype testing (hrHPVGT) has emerged as a new strategy to help optimize the efficiency of hrHPV triage.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.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+.hrHPVGT for women who have ASC-US cytology allows for risk stratification capable of optimizing the efficiency of triage for hrHPV-positive women.

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.

Aspect-based sentiment analysis (ABSA) aims to determine the sentiment polarity of the specific aspect for a given sentence. Attention-based models are widely used in this task because they can extract semantic information between context words to make up for the deficiency of sequence models in semantic encoding. In order to enhance the extraction of high-quality semantic information, we propose a novel joint model with Second-Order Features and Matching Attention (SOMA) for aspect-based sentiment analysis. Firstly, we introduce the second-order statistics to extract vital information and interact with the first-order features to generate the interaction representation. Secondly, we adopt Euclidean distance to replace the traditional matrix transformation to capture the semantic similarity between aspect terms and context words. Finally, we form a joint representation to focus on the meaningful words in the sentence. We conduct extensive experiments and comparisons on SemEval 2014, SemEval 2016, and Twitter datasets. Experimental results demonstrate the effectiveness of our model.

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.

Objective: In sonography, homogeneous endometrium is defined as uniform endometrial echogenicity and heterogeneous, asymmetrical or cystic endometrium is defined as non-uniform. However, the relationship between the non-uniform endometrial echogenicity and the presence or absence of pathology is not known. A retrospective study of the patients with ultrasound non-uniform endometrium who underwent hysteroscopy-directed biopsy was performed to explore its clinical meaning in the diagnosis of endometrial lesions. Materials and methods: Patients with non-uniform endometrial echogenicity who underwent hysteroscopy-directed biopsy were enrolled in the Obstetrics and Gynecology Hospital of Fudan University from January 2015 to May 2018 as the primary cohort. In total, 692 patients with non-uniform endometrial echogenicity were diagnosed and underwent hysteroscopy-directed biopsy. Characteristics were assessed using univariate logistic regression between patients with and without atypical endometrial hyperplasia and carcinoma (atypical EH+). Multivariate analyses were used to develop the predicting model. We incorporated statistically significant variables and presented with nomogram. Internal validation was assessed. An independent validation cohort consisted of 237 consecutive patients from June 2018 to February 2019. Results: Hysteroscopy-directed biopsy showed that 55.20% (382/692) of the patients with non-uniform endometrium had normal endometrium, while 44.80% (310/692) had endometrial lesions, including 39.31% (272/692) benign lesions and 5.49% (38/692) atypical EH+. Univariate logistic analysis showed that older age (P=0.027), abnormal uterine bleeding (AUB) before menopause (P=0.011), postmenopausal bleeding (P

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.

Background: Cancer stem cells (CSCs) play an important role in tumor recurrence, metastasis, and chemoresistance. CSCs can shift between non-CSC and CSC states in certain tumor microenvironments. The mechanisms of this shift are not well understood. We previously demonstrated that platelet-activating factor (PAF), a lipid mediator of inflammation in the tumor microenvironment, can promote ovarian cancer progression and induce chemoresistance via PAF/PAFR-mediated inflammatory signaling pathways. Here, we investigated the role of PAF/PAFR signaling in the stemness of ovarian cancer cell. Methods: The effects of PAF and PAFR antagonists on the stemness of SKOV3 and A2780 cells were evaluated using sphere-formation assays, FACS analysis and real-time PCR in vitro and a SKOV3 tumor-formation experiment in nude mice in vivo. The potential mechanism of the PAF effect on the stemness of ovarian cancer cells was evaluated by human cytokine antibody microarray analysis. Results: PAF can promote spheroid formation and inhibit the transition of quiescent ovarian cancer cells into the cell cycle. The percentage of cancer stem cells increased significantly, and the expression of stemness genes increased in PAF-treated group. These effects could be blocked by PAFR inhibitors. Ginkgolide B (GB) inhibited tumor growth and decreased the CSC percentage in vivo. Human cytokine antibody microarray analysis showed that some stemness-maintaining proteins increased in PAF-treated group. Conclusion: Our results suggest that PAF can regulate the stemness of ovarian cancer cells through the PAF/PAFR pathway, suggesting a new target for the treatment of ovarian cancer.

Transcriptional factors play important roles in plant growth, development and responses to stresses. BBX transcriptional factors are characterized with one or two B-box domains in the protein sequence. They are comprehensively involved in photomorphogenesis, flowering, shade avoidance, signal transduction of phytohormones, biotic and abiotic stress responses in plants by regulating gene transcription and interacting with other transcription factors. The classification, structure and functions of BBX of plants are reviewed in this paper.转录因子在调控植物生长、发育及环境适应性等方面发挥重要作用。具有B-box 结构域的一类锌指结构转录因子称为BBX，它们通过调控基因转录，与同类或其他转录因子的互作参与植物光形态建成、花发育、避荫效应、植物信号转导以及非生物和生物逆境响应等。文中从BBX 蛋白结构、分类以及其功能方面对该类转录因子在植物中的作用进行了综述。.

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.

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.

The widespread use of social media provides a large amount of data for public sentimentanalysis. Based on social media data, researchers can study public opinions on humanpapillomavirus (HPV) vaccines on social media using machine learning-based approaches that willhelp us understand the reasons behind the low vaccine coverage. However, social media data isusually unannotated, and data annotation is costly. The lack of an abundant annotated dataset limitsthe application of deep learning methods in effectively training models. To tackle this problem, wepropose three transfer learning approaches to analyze the public sentiment on HPV vaccines onTwitter. One was transferring static embeddings and embeddings from language models (ELMo)and then processing by bidirectional gated recurrent unit with attention (BiGRU-Att), called DWEBiGRU-Att. The others were fine-tuning pre-trained models with limited annotated data, called finetuninggenerative pre-training (GPT) and fine-tuning bidirectional encoder representations fromtransformers (BERT). The fine-tuned GPT model was built on the pre-trained generative pretraining(GPT) model. The fine-tuned BERT model was constructed with BERT model. Theexperimental results on the HPV dataset demonstrated the efficacy of the three methods in thesentiment analysis of the HPV vaccination task. The experimental results on the HPV datasetdemonstrated the efficacy of the methods in the sentiment analysis of the HPV vaccination task. Thefine-tuned BERT model outperforms all other methods. It can help to find strategies to improvevaccine uptake.

Biomedical knowledge graphs (BMKGs), which may facilitate precision medicine and clinical decision support, have become more and more important in healthcare practice and research. A lot of challenges still remain in their construction and curation due to the complex and high knowledge demanding nature of the task. Most of the current BMKGs are manually compiled, which is particularly time-consuming and labor-intensive. Some are automatically generated but rely heavily on the quality of the source data. Furthermore, most of them may not fully integrate or represent the most recent biomedical advancement. To tackle these problems, we propose a novel approach to building a BMKG leveraging the SemMedDB and Health Science Linked Open Data (LOD). Carefully checking the inconsistent predications in the SemMedDB, we detected 462,188 conflicting pairs of semantic triples. What’s more, further mining of semantic relationships among different datasets, we found over 30 new relationships linking disorders, genes and drugs. Our methods explore a new way to improve the quality of SemMedDB and facilitate BMKGs-based knowledge discovery.

An increasing number of people suffering from mental health conditions resort to online resources (specialized websites, social media, etc.) to share their feelings. Early depression detection using social media data through deep learning models can help to change life trajectories and save lives. But the accuracy of these models was not satisfying due to the real-world imbalanced data distributions. To tackle this problem, we propose a deep learning model (X-A-BiLSTM) for depression detection in imbalanced social media data. The X-A-BiLSTM model consists of two essential components: the first one is XGBoost, which is used to reduce data imbalance; and the second one is an Attention-BiLSTM neural network, which enhances classification capacity. The Reddit Self-reported Depression Diagnosis (RSDD) dataset was chosen, which included approximately 9,000 users who claimed to have been diagnosed with depression (”diagnosed users and approximately 107,000 matched control users. Results demonstrate that our approach significantly outperforms the previous state-of-the-art models on the RSDD dataset.

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.

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.

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.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.The PMBC group exhibited significantly higher ADC values for the mean (P = 0.004), 25Whole-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.4 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:391-400.

When a security attribute of the assets assignment is valuated, the commonly used method is based on the analysis of the corporate business strategy, combined with the data value given directly by the experience and intuition of the evaluators. This assessment process is lack of scientific basis. Grey Statistical evaluation can composite the views of related personnel in different department and give confidence interval. The scientific, objective and impartial assignment process is ensured by the statistical results. For example of asset integrity assignment, the process can be completed by the method used of grey statistical evaluation.