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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.

Objective. The relationship between human papillomavirus (HPV) and cervical lesions has been extensively elucidated, but infection with multiple genotypes is less investigated due to methodology limitations. In the current study, with a method of genotyping 21 HPVs in a routine cervical screening population, we aimed to investigate the prevalence and diversity of HPV infections in Chinese women and further evaluate the impact of multiple infections of HPV on cervical lesion progression. Methods. Totally, 73,596 patients who underwent 21-genotype HPV testing from January 2018 to April 2019 were retrieved from the database of the Department of Pathology, Obstetrics and Gynecology Hospital of Fudan University. HPV testing was performed by real-time PCR assay, including 13 high-risk HPVs (hrHPV), 5 potential hrHPVs, and 3 low-risk HPVs. Results. Of the 17,079 (infection rate, 23.2%) hrHPV- or potential hrHPV- (hr/phrHPV-) positive cases, 26.3% had multiple infections. Women younger than 25 and older than 65 were more prone to multiple infections. Of the hr/phrHPV-positive cases involving cervical intraepithelial neoplasia (CIN) 2 or worse (CIN2+), HPV73, 53, and 66 (=59) were the top three genotypes most likely to be included in multiple infections, while HPV16, 18, and 58 were the 3 least. Patients with single infection of HPV16 had higher incidences of CIN2+ than those with multiple-infection pattern ( P < 0.001 ), indicating that mixing with other genotypes alleviated pathogenicity. The infection of HPV52, 53, 56, 51, 39, 66, 59, 68, and 35 showed an opposite pattern, indicating that they were less likely to be pathogens individually. All other types showed no significant differences, indicating the capability of pathogenesis independently. HPV26 showed a higher OR for CIN2+ than most traditional hrHPV genotypes. The vial load and the percentage of HPV16 showed positive correlation with the severity of cervical lesions. Conclusion. Extensive genotyping identified 3 most frequent genotypes, HPV16, 52, and 58, in CIN2+ of Chinese population. HPV16 mixing with other genotypes alleviated its pathogenicity. The vial load and the percentage of HPV16 were positively correlated with the severity of cervical lesions. HPV26 may be considered as a hrHPV, which needs to be evaluated and confirmed by more cases.

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.

More users suffering from depression turn to online forums to express their problems and seek help. In such forums, there is often a large volume of posts with sensitive content, indicating that the user has a risk of suicide and self-harm. Early detection of depression using appropriate deep learning models and social media data can prevent potential self-harm. However, existing depression detection models are not powerful enough to capture critical sentiment information from the large volume of posts published by each user, which makes the performance of these models not satisfying. To address this problem, we propose a hierarchical posts representations model named Multi-Gated LeakyReLU CNN (MGL-CNN) for identifying depressed individuals in online forums. The model consists of two parts: the first one is a post-level operation, which is used to learn the representation of each post of the user, and the second one is a user-level operation, which is used to obtain the overall representation of the user's emotional state. Besides, we propose another depression detection model by changing the number of gated units in the MGL-CNN, which is named Single-Gated LeakyReLU CNN (SGL-CNN). We show how to use our models to identify depressed users through a lot of posted content. Experimental results showed that our models performed better than the previous state-of-the-art models on the Reddit Self-reported Depression Diagnosis dataset, and also performed well on the Early Detection of Depression dataset.

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.

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.

Some Science, Technology, Engineering, and Mathematics (STEM) subjects in secondary schools or high schools, such as biology, physics, or mathematics are considered tough to students. It is due to the lack of tools to visualise details or effects in the learning process, with traditional learning materials of textbooks, blackboards, and static models. The classroom education is evolving with the technology advancements. Development works in three-dimensional (3D) graphics rendering, virtual and augmented reality (VAR) have been reported to provide interactive visualisations for classroom education. Teaching of the subject of biology is one of such examples in the classroom education which could benefit to the emerging technologies with different types of supportive tools. This project is developed to apply virtual and augmented reality technology-enhanced learning (VARTEL) in biology education of secondary schools. Pilot study has been performed with the collaborating secondary schools. The VARTEL technologies developed in the research project can be rolled out to more mainstream schools in Singapore and other countries.

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.

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.

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.

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.

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.

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.

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.

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.

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.

How to ensure the information published is accurate and cannot be modified in the heterogeneous Network Environment,this is a difficult program to provide ticketing services through Middleware. This paper expounds the connection middleware design that between collaborative services platform and heterogeneous ticketing system, studies the interface specification and protocol specification of connection middleware and different subjects of heterogeneous ticketing system, realizes the function of ticket of collaborative services platform as well as maximizes the system's security and compatibility.

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.

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.