Search

Yaru Sheng,1 Jiangjing Yuan,1 Jing Wang,1 Liya Wang,1 Yuhong Li,1 Yudong Wang1– 3 1Department of Gynecologic Oncology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Shanghai Municipal Key Clinical Specialty, Female Tumor Reproductive Specialty, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Embryo Original Disease, Shanghai, People’s Republic of ChinaCorrespondence: Yudong Wang; Yuhong Li, Department of Gynecologic Oncology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, 910 Hengshan Road, Shanghai, People’s Republic of China, Tel +86-21-64070434-18602 ; +86-21-64070434-25517, Email wangyudong@shsmu.edu.cn; 13022107898@163.comBackground: Ovarian mature cystic teratomas (MCTs) are the most common tumors in pregnant women. The premature rupture of membranes (PROM) is a typical complication of pregnancy; however, the relationship between MCT and PROM is unknown. Therefore, we aimed to determine whether MCT is associated with the occurrence of PROM during pregnancy.Methods: The data of patients with adnexal masses during pregnancy between January 2017 and August 2021 were retrospectively analyzed. Ovarian cystectomy was performed during cesarean delivery or after vaginal delivery. Univariate and multivariate logistic regression models were used for statistical analysis.Results: A total of 234 patients with histopathological results were included. Among these patients, 21 occurred PROM during pregnancy, of which 11 were diagnosed with MCT. Compared with other subtypes, MCT (p=0.025) showed a stronger correlation with PROM and was an independent risk factor for PROM (odds ratio [OR], 2.811; 95% confidence interval [CI], 1.096– 7.215; p=0.032). Furthermore, we found that MCT with a diameter > 5 cm (p=0.0037) was more likely to promote the development of PROM than those that with a diameter < 5 cm.Conclusion: MCT was an independent risk factor for PROM during pregnancy. Positive actions and preventative clinical treatments should be fully taken into consideration by clinicians for pregnant women with MCTs, especially those ≥ 5 cm in diameter, to reduce the clinical complications related to MCT-associated PROM.Keywords: benign ovarian tumor, mature cystic teratoma, premature rupture of membranes, pregnancy

To evaluate the diagnostic accuracy of 2D BLADE turbo gradient- and spin-echo diffusion weighted imaging (TGSE BLADE DWI) for primary middle ear cholesteatoma diagnosis, using qualitative and quantitative methods.Retrospective case series.University hospital.Participants included those with suspected primary middle ear cholesteatoma after assessment by clinical otorhinolaryngologists combined with magnetic resonance imaging (MRI) examination. Finally, of the 85 ears from 65 patients enrolled in the study, 73 had cholesteatoma, and 12 had otitis media.Two radiologists independently assessed images and measured apparent diffusion coefficient (ADC) values. Sensitivity, specificity and accuracy were evaluated. Kappa (k) statistics, the intraclass correlation coefficient (ICC), the Kolmogorov-Smirnov normality test, the independent t test, and receiver operating characteristic (ROC) analysis were used for statistical analysis. Pair-wise comparison of the area under the ROC curve (AUC) was also performed using the Delong test.Imaging and histopathologic findings.The mean ADC value of cholesteatoma group (mean, 0.923 ± 0.246 × 10 -3 mm 2 /s) was significantly lower than that of noncholesteatoma group (mean, 1.744 ± 0.205 × 10 -3 mm 2 /s; p0.001). In ≤3 mm cholesteatoma group, the AUC of qualitative DWI was 0.846; the sensitivity, specificity, and accuracy for diagnosing cholesteatoma were 69.23%, 100%, and 84%, respectively; while the AUC of quantitative diagnosis was significantly increased to 1.0 ( p = 0.0209); and based on the optimal threshold of ADC, ≤1.352 × 10 -3 mm 2 /s, the sensitivity, specificity and accuracy improved to 100%. For3 mm cholesteatoma group, there were no significant differences in diagnostic performance. Excellent interobserver agreement and ICC for the qualitative and quantitative evaluations (k = 0.90 and ICC = 0.80, respectively) was noted between reviewers.TGSE BLADE DWI is useful for the detection of primary middle ear cholesteatomas, especially ≤3 mm lesions.

To construct a radiomics nomogram based on multiparametric MRI data for predicting isocitrate dehydrogenase 1 mutation (IDH +) and loss of nuclear alpha thalassemia/mental retardation syndrome X-linked expression (ATRX -) in patients with lower-grade gliomas (LrGG; World Health Organization [WHO] 2016 grades II and III).A total of 111 LrGG patients (76 mutated IDH and 35 wild-type IDH) were enrolled, divided into a training set (n = 78) and a validation set (n = 33) for predicting IDH mutation. IDH + LrGG patients were further stratified into the ATRX - (n = 38) and ATRX + (n = 38) subtypes. A total of 250 radiomics features were extracted from the region of interest of each tumor, including that from TThe radiomics nomogram identified LrGG patients for IDH mutation (C-index: training sets = 0.881, validation sets = 0.900) and ATRX loss (C-index: training sets = 0.863, validation sets = 0.840) with good calibration. Decision curve analysis further confirmed the clinical usefulness of the two nomograms for predicting IDH and ATRX status.The nomogram incorporating age, gender, and the radiomics signature provided a clinically useful approach in noninvasively predicting IDH and ATRX mutation status for LrGG patients. The proposed method could facilitate MRI-based clinical decision-making for the LrGG patients.• Non-invasive determination of IDH and ATRX gene status of LrGG patients can be obtained with a radiomics nomogram. • The proposed nomogram is constructed by radiomics signature selected from 250 radiomics features, combined with age and gender. • The proposed radiomics nomogram exhibited good calibration and discrimination for IDH and ATRX gene mutation stratification of LrGG patients in both training and validation sets.

A rapiddevelopment of the permanent magnetic synchronous generator (PMSG)-based offshore wind farm has been witnessed in the past decade. To prevent the offshore wind farms from being disconnected during a fault, many countries have proposed specification requirements for the fault ride-through (FRT). Traditional FRT scheme Chopper circuit for PMSG needs to consume all the mismatching energy and the impulse current is too high during the fault, which will even affect the safe of the PMSG. In this paper, the superconducting fault current limiter (SFCL) is applied to enhance the ability of the FRT in the PMSG-based offshore wind farm. In the proposed scheme, the resistive SFCL can reduce the energy consumption and improve the working performance of the Chopper circuit by absorbing the power of the grid-side converter (GCS) during the fault. An offshore wind farm model is built through PSCAD/EMTDC software. The comparison simulation results validate the feasibility of the proposed scheme.

This study is to compare the accuracy of 2D BLADE turbo gradient- and spin-echo imaging (TGSE BLADE) diffusion-weighted imaging (DWI) with that of readout-segmented echo-planar (RESOLVE) DWI in the detection of primary and residual/recurrent temporal bone cholesteatoma.The prospective study population consisted of 58 patients who were underwent magnetic resonance (MR) imaging for the evaluation of suspected temporal bone cholesteatoma. Two radiologists independently evaluated the two sequences. Kappa (k) statistics, the intra-class correlation coefficient (ICC), and a paired t test were used for statistical analysis.Of the 58 patients included, all had histo-pathologically confirmed cholesteatomas. In ≤ 3 mm group (n = 13), TGSE BLADE sequence correctly identified all cases except one that was recorded as equivocal on both sequences because of high signal intensity on T1WI; while on RESOLVE sequences, 6 were positive, 4 were equivocal, and 3 were false negative. For 3 mm group (n = 45), detection performance was similar between the two sequences. The mean ADC of cholesteatoma on TGSE BLADE DWI was 0.923 × 10TGSE BLADE outperforms RESOLVE in the detection of small temporal bone cholesteatoma ≤ 3 mm.

Background: Intratympanic and intravenous gadolinium administration is used to visualise endolymphatic hydrops. Aims/objectives: The goal of this study was to compare the image quality between intratympanic (IT-method) and intravenous (IV-method) gadolinium administration using three-dimensional inversion recovery with real reconstruction (3D real IR) sequences. Materials and methods: A number of 152 patients with Meniere's disease were included. The 3D real IR sequence was performed 24 h after IT administration or 4 h after IV administration. The detection rate of endolymphatic hydrops, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) of the two methods were compared. Specifically, the average image scores of the two methods were evaluated by two radiologists. Results: The SNRROI and CNRs of the IT-method were higher than those of the IV-method, whereas no significant difference between the IT-method and IV-method with regard to the SNRB was found. The average image scores were 3.49 ± 0.12 and 3.30 ± 0.12 for the IT-method and IV-method, respectively (p = .229). No statistically significant difference was found between two methods in terms of the detection rate of endolymphatic hydrops. Conclusions and significance: IT-method images can display endolymphatic hydrops more precisely than IV-method images. The IV-method can be used as an alternative to the IT-method in clinical applications to some extent.

Previous literatures reported insulin-like growth factor-2 messenger RNA-binding protein 3 (IGF2BP3) is a poor prognostic marker for colorectal cancer (CRC) patients. However, basic research on the effect and biological role of IGF2BP3 in CRC was still scare. Real-time quantitative polymerase chain reaction and western blot analysis were used to examine IGF2BP3 expression level in tumors and paired normal tissues from CRC patients. Tissue microarrays with 192 CRC patients were subjected to immunohistochemical staining to analyze the prognostic value of IGF2BP3. Proliferation assays, migration assays, and xenograft tumor formation in nude mice were performed to assess the biological role of IGF2BP3 in CRC cells. IGF2BP3 expression was significantly upregulated in tumor tissues compared with the matched normal tissues both in messenger RNA and protein level and was associated with worse prognosis. IGF2BP3 knockdown made cell cycle arrest to impair the proliferation ability of CRC cells and further inhibited the xenograft tumor growth in nude mice, also inhibited the migration ability of CRC cells via inducing epithelial-mesenchymal transition. Therefore, the research demonstrated that increased IGF2BP3 expression promoted the aggressive phenotypes of CRC cells. Targeted IGF2BP3 could be a novel and effective gene therapy for CRC patients to make a better prognosis.

Soft open point (SOP) is applied to the power service restoration of the distribution network because of the advantages of flexible control mode and optimizing the operation of the distribution network. Taking advantage of parallel collaborative between independent peer smart terminals unit (STU) in distribution network and information interaction ways of working, distributed power service restoration method of distribution network considering soft open point is put forward, which brings the superiority of SOP in the aspect of power service restoration into full play and avoids the problem of large information collection and calculation in the centralized power service restoration method. Firstly, the structure, control mode and power service restoration model of SOP are introduced, and then the distributed power service restoration method of distribution network with SOP is described, which mainly includes distributed network topology search and the expression and calculation of constraint conditions. Finally, a numerical simulation is carried out to verify the effectiveness of the proposed method.

Background Based on its high resolution in soft tissue, MRI, especially diffusion-weighted imaging (DWI), is increasingly important in the evaluation of cholesteatoma. The purpose of this study was to evaluate the role of the 2D turbo gradient- and spin-echo (TGSE) diffusion-weighted (DW) pulse sequence with the BLADE trajectory technique in the diagnosis of cholesteatoma at 3 T and to qualitatively and quantitatively compare image quality between the TGSE BLADE and RESOLVE methods. Method A total of 42 patients (23 males, 19 females; age range, 7–65 years; mean, 40.1 years) with surgically confirmed cholesteatoma in the middle ear were enrolled in this study. All patients underwent DWI (both a prototype TGSE BLADE DWI sequence and the RESOLVE DWI sequence) using a 3-T scanner with a 64-channel brain coil. Qualitative imaging parameters (imaging sharpness, geometric distortion, ghosting artifacts, and overall imaging quality) and quantitative imaging parameters (apparent diffusion coefficient [ADC], signal-to-noise ratio [SNR], contrast, and contrast-to-noise ratio [CNR]) were assessed for the two diffusion acquisition techniques by two independent radiologists. Result A comparison of qualitative scores indicated that TGSE BLADE DWI produced less geometric distortion, fewer ghosting artifacts (P P P P The ADC (P − 3 mm2/s) than RESOLVE DWI (0.928 × 10− 3 mm2/s). Conclusion Compared with RESOLVE DWI, TGSE BLADE DWI significantly improved the image quality of cholesteatoma by reducing magnetic sensitive artifacts, distortion, and blurring. TGSE BLADE DWI is more valuable than RESOLVE DWI for the diagnosis of small-sized (2 mm) cholesteatoma lesions. However, TGSE BLADE DWI also has some disadvantages: the whole image intensity is slightly low, so that the anatomical details of the air-bone interface are not shown well, and this shortcoming should be improved in the future.

The basal cell compartment in many epithelial tissues is generally believed to serve as an important pool of stem cells. However, basal cells are heterogenous and the stem cell subpopulation within basal cells is not well elucidated. Here we uncover that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb1 is expressed in a prostate basal cell subpopulation. The Zeb1+ prostate epithelial cells are multipotent prostate basal stem cells (PBSCs) that can self-renew and generate functional prostatic glandular structures at the single-cell level. Genetic ablation studies reveal an indispensable role for Zeb1 in prostate basal cell development. Utilizing unbiased single-cell transcriptomic analysis of over 9000 mouse prostate basal cells, we confirm the existence of the Zeb1+ basal cell subset. Moreover, Zeb1+ epithelial cells can be detected in mouse and human prostate tumors. Identification of the PBSC and its transcriptome profile is crucial to advance our understanding of prostate development and tumorigenesis., Heterogeneous populations of basal cells in the prostate epithelium contain stem cells. Here the authors show that Zeb1 marks a pool of prostate epithelial stem cells that self-renew, generate prostate glandular structures with all 3 epithelial cell types and are required for prostate basal cell development.

Background: Based on the high resolution of soft tissue, MRI has gained increasing importance in the evaluation of cholesteatoma, especially diffusion-weighted imaging(DWI). The purpose of this study was to evaluate the role of 2D turbo gradient- and spin-echo (TGSE) diffusion-weighted (DW) pulse sequence with BLADE trajectory technique in the diagnosis of cholesteatoma at 3T and to qualitatively and quantitatively compare the image quality between the TGSE BLADE and RESOLVE methods.Method: A total of 42 patients (23 males, 19 females; age range, 7-65 years; mean, 40.1 years) with surgically confirmed cholesteatoma in the middle ear were enrolled in this study. All patients underwent DWI (both the prototype TGSE BLADE DWI sequence and RESOLVE DWI sequence) using a 3-T scanner with a 64-channel brain coil.Qualitative imaging parameters (imaging sharpness, geometric distortion, ghosting artifacts, and overall imaging quality) and quantitative imaging parameters (apparent diffusion coefficient [ADC], signal-to-noise ratio [SNR], contrast, and contrast-to-noise ratio [CNR] for the two diffusion acquisition techniques were assessed by two independent radiologists. Result: Comparison of the qualitative scores indicated that TGSE BLADE DWI produced less geometric distortion and ghosting artifacts (P

Objectives Epigenetic modifiers were important players in the development of haematological malignancies and sensitivity to therapy. Mutations of SET domain‐containing 2 (SETD2), a methyltransferase that catalyses the trimethylation of histone 3 on lysine 36 (H3K36me3), were found in various myeloid malignancies. However, the detailed mechanisms through which SETD2 confers chronic myeloid leukaemia progression and resistance to therapy targeting on BCR‐ABL remain unclear. Materials and methods The level of SETD2 in imatinib‐sensitive and imatinib‐resistant chronic myeloid leukaemia (CML) cells was examined by immunoblotting and quantitative real‐time PCR. We analysed CD34+CD38− leukaemic stem cells by flow cytometry and colony formation assays upon SETD2 knockdown or overexpression. The impact of SETD2 expression alterations or small‐molecule inhibitor JIB‐04 targeting H3K36me3 loss on imatinib sensitivity was assessed by IC50, cell apoptosis and proliferation assays. Finally, RNA sequencing and ChIP‐quantitative PCR were performed to verify putative downstream targets. Results SETD2 was found to act as a tumour suppressor in CML. The novel oncogenic targets MYCN and ERG were shown to be the direct downstream targets of SETD2, where their overexpression induced by SETD2 knockdown caused imatinib insensitivity and leukaemic stem cell enrichment in CML cell lines. Treatment with JIB‐04, an inhibitor that restores H3K36me3 levels through blockade of its demethylation, successfully improved the cell imatinib sensitivity and enhanced the chemotherapeutic effect. Conclusions Our study not only emphasizes the regulatory mechanism of SETD2 in CML, but also provides promising therapeutic strategies for overcoming the imatinib resistance in patients with CML.

The basal cell compartment in many epithelial tissues such as the prostate, bladder, and mammary gland are generally believed to serve as an important pool of stem cells. However, basal cells are heterogenous and the stem cell subpopulation within basal cells is not well elucidated. Here we uncover that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb is exclusively expressed in a prostate basal cell subpopulation based on both immunocytochemical and cell lineage tracing analysis. The Zeb1+prostate epithelial cells are multipotent prostate basal stem cells (PBSCs) that can self-renew and generate functional prostatic glandular structures with all three epithelial cell types at the single-cell level. Genetic ablation studies reveal an indispensable role for Zeb1 in prostate basal cell development. Utilizing unbiased single cell transcriptomic analysis of over 9000 mouse prostate basal cells, we find that Zeb1+basal cell subset shares gene expression signatures with both epithelial and mesenchymal cells and stands out uniquely among all the basal cell clusters. Moreover, Zeb1+epithelial cells can be detected in mouse and clinical samples of prostate tumors. Identification of the PBSC and its transcriptome profile is crucial to advance our understanding of prostate development and tumorigenesis.

Tumor metastasis is the major cause of death for prostate cancer (PCa) patients. However, the treatment options for metastatic PCa are very limited. Epithelial-mesenchymal transition (EMT) has been reported to be an indispensable step for tumor metastasis and is suggested to associate with acquisition of cancer stem cell (CSC) attributes. We propose that small-molecule compounds that can reverse EMT or induce mesenchymal-epithelial transition (MET) of PCa cells may serve as drug candidates for anti-metastasis therapy. Methods: The promoters of CDH1 and VIM genes were sub-cloned to drive the expression of firefly and renilla luciferase reporter in a lentiviral vector. Mesenchymal-like PCa cells were infected with the luciferase reporter lentivirus and subjected to drug screening from a 1274 approved small-molecule drug library for the identification of agents to reverse EMT. The dosage-dependent effect of candidate compounds was confirmed by luciferase reporter assay and immunoblotting. Wound-healing assay, sphere formation, transwell migration assay, and in vivo intracardiac and orthotopic tumor xenograft experiments were used to evaluate the mobility, metastasis and tumor initiating capacity of PCa cells upon treatment. Possible downstream signaling pathways affected by the candidate compound treatment were analyzed by RNA sequencing and immunoblotting. Results: Drug screening identified Amlexanox, a drug used for recurrent aphthous ulcers, as a strong agent to reverse EMT. Amlexanox induced significant suppression of cell mobility, invasion, serial sphere formation and in vivo metastasis and tumor initiating capacity of PCa cells. Amlexanox treatment led to downregulation of the IKK-ɛ/ TBK1/ NF-κB signaling pathway. The effect of Amlexanox on EMT reversion and cell mobility inhibition can be mimicked by other IKK-ɛ/TBK1 inhibitors and rescued by reconstitution of dominant active NF-κB. Conclusions: Amlexanox can sufficiently suppress PCa metastasis by reversing EMT through downregulating the IKK-ɛ/TBK1/NF-κB signaling axis.

Cell polarity and correct mitotic spindle positioning are essential for the maintenance of a proper prostate epithelial architecture, and disruption of the two biological features occurs at early stages in prostate tumorigenesis. However, whether and how these two epithelial attributes are connected in vivo is largely unknown. We herein report that conditional genetic deletion of E-cadherin, a key component of adherens junctions, in a mouse model results in loss of prostate luminal cell polarity and randomization of spindle orientations. Critically, E-cadherin ablation causes prostatic hyperplasia which progresses to invasive adenocarcinoma. Mechanistically, E-cadherin and the spindle positioning determinant LGN interacts with the PDZ domain of cell polarity protein SCRIB and form a ternary protein complex to bridge cell polarity and cell division orientation. These findings provide a novel mechanism by which E-cadherin acts an anchor to maintain prostate epithelial integrity and to prevent carcinogenesis in vivo., Author summary Luminal cells are the most abundant type of the prostate epithelial cells. Most prostate cancers also display a luminal phenotype. Horizontal cell division of luminal cells allows the surface expansion of the secretory prostate lumen and meanwhile maintains the monolayer and polarized epithelial architecture. Disruption of the epithelial integrity and appearance of multilayer epithelia are early events in prostate adenocarcinoma development. However, the molecular mechanism that ensures the horizontal division in luminal cells remains largely unknown. Here, we generated a genetically engineered mouse model in which E-cadherin, a key component of the adherens junction that serves to connect the lateral plasma membrane of neighboring epithelial cells, was knocked out in the prostate luminal cells. E-cadherin deletion leads to loss of cell polarity and disoriented cell division, which subsequently causes dysregulated cell proliferation and strongly predisposes mice for prostate tumorigenesis. Importantly, we revealed that E-cadherin acts as an anchor to recruit cell polarity protein SCRIB and spindle positioning determinant LGN to the lateral cell membrane, thereby ensure a proper alignment of the cell division plane. All these findings uncover a novel mechanism by which E-cadherin links cell polarity and spindle orientation to keep prostate epithelial integrity and prevent carcinogenesis.

Background: A positive circumferential resection margin (CRM) may result in local recurrence (LR), but the significance remains controversial. We attempted to utilize the lymphocyte ratio (LYMR), neutrophil–lymphocyte ratio (NLR), tumor-infiltrating lymphocyte (TIL) count, and their combinations (TIL–LYMR/TIL–NLR) in predicting LR after rectal resection. Methods: Patients with rectal cancer who underwent curative resection between January 2016 and December 2018 were enrolled. Biopsy samples and data from the blood tests of 124 patients with rectal cancer who underwent curative resection were retrospectively obtained. Patients were divided into 2 groups: LR group and non-local recurrence (nLR) group. CD8 + TILs were immunostained using an antibody against CD8. The density of TILs was defined as the number of positive CD8 lymphocytes per square millimeter and was then graded as either high or low (cutoff = 80/mm2). The count of LYMR and NLR was also graded as either high or low. The associations between TILs, LYMR, NLR, and their combinations (TIL–LYMR/TIL–NLR) were evaluated. Results: With a median follow-up of 24.4 months, TIL–LYMR showed a positive correlation with LR (P = .001), but not with the CD8 + TIL count (P = .215) or TIL-NLR count (P = .638). Among inflammatory and immune markers variables, univariate analysis revealed that gender, CD8 + TIL count, and TIL-NLR count were associated with anastomotic leakage (P = .001, P = .014, and P = .036, respectively). In multivariate analysis, TIL–LYMR remained an independent predictor of LR (OR = 8.918, CI = 1.124–70.747, P = .038). We also showed that gender associated with anastomotic leakage in rectal cancer (OR 5.429; 95% CI 1.885–15.637; P = .002). Conclusion: In this study, our data indicate that absence of CD8 + T-cell infiltration in CRM may influence LR. These parameters may help identify LR provide additional information for therapeutic decision-making.